Ijcp dec 2015

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Volume 26, Number 7

December 2015, Pages 601–700

Peer Reviewed Journal

yy American Family Physician yy Cardiology yy Community Medicine yy Dentistry yy Dermatology yy Diabetology yy Gastroenterology yy Internal Medicine

an i c i ys ians

yy Neurology

Phly Physic y l mi ami

yy Obstetrics and Gynecology yy Pictorial CME

Fademy of F n ica Aca

yy Medilaw

er merican m A eA

yy Around the Globe yy Lighter Reading

ingurnal of th t a or d Jo

rp-reviewe o c In eer AP

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IJCP Group of Publications Dr Sanjiv Chopra Prof. of Medicine & Faculty Dean Harvard Medical School Group Consultant Editor

Volume 26, Number 7, December 2015 FROM THE DESK OF THE GROUP EDITOR-IN-CHIEF

606 Opinion on Registered Pharmacist

Dr Deepak Chopra Chief Editorial Advisor

Dr KK Aggarwal Group Editor-in-Chief

KK Aggarwal

AMERICAN FAMILY PHYSICIAN

608 Nonpharmacologic Management of Hypertension: What Works?

Rupal Oza, Miriam Garcellano

IJCP Group and eMedinewS 612 Practice Guidelines

Dr Veena Aggarwal

613 Photo Quiz

MD, Group Executive Editor

IJCP Editorial Board Obstetrics and Gynaecology Dr Alka Kriplani Dr Thankam Verma, Dr Kamala Selvaraj Cardiology Dr Praveen Chandra, Dr SK Parashar Paediatrics Dr Swati Y Bhave Diabetology Dr CR Anand Moses, Dr Sidhartha Das Dr A Ramachandran, Dr Samith A Shetty ENT Dr Jasveer Singh Dr Chanchal Pal Dentistry Dr KMK Masthan Dr Rajesh Chandna Gastroenterology Dr Ajay Kumar Dr Rajiv Khosla Dermatology Dr Hasmukh J Shroff Dr Pasricha Dr Koushik Lahiri Nephrology Dr Georgi Abraham Neurology Dr V Nagarajan Dr Vineet Suri Journal of Applied Medicine & Surgery Dr SM Rajendran, Dr Jayakar Thomas Orthopedics Dr J Maheshwari

Anand Gopal Bhatnagar Editorial Anchor Advisory Bodies Heart Care Foundation of India Non-Resident Indians Chamber of Commerce & Industry World Fellowship of Religions

This journal is indexed in IndMED (http://indmed.nic.in) and full-text of articles are included in medIND databases (http://mednic.in) hosted by National Informatics Centre, New Delhi.

CARDIOLOGY

616 A Case of Cardiac Tamponade Due to Hypothyroidism

Mallikarjunreddy M, Venugopal K, Bharath Raj MY, Manjunath Ganiger, Kadappa Jaligidad, Mahesh Sreenivas Prasad

COMMUNITY MEDICINE

620 Study of Hair Dye Poisoning: A Complete Profile

KB Yadavendra Reddy, P Vijayanarasimha Reddy, P Kiran Kumar, M Asha, B Visalakshi

625 Study of Healthcare-associated Infections

PH Mishra, Pallavi Banerjee, Heema Gosain

636 Extended-spectrum β-lactamase and AmpC-producing Klebsiella pneumoniae: A Therapeutic Challenge

Sheevani, Shashi Chopra, Gomty Mahajan, Jaspal Kaur, Yadwinder Singh Chouhan

DENTISTRY

640 Effect of Various Surface Treatment on the Push-out Bond Strength of Glass Fiber Posts Bonded to Human Root Dentin: An in vitro Study

AVK Narene, P Shankar, A Karthick

DERMATOLOGY

645 Helicobacter pylori Infection can Cause Chronic Urticaria

Pradip Kumar Das

DIABETOLOGY

647 A Hospital-based Study of Prevalence of Gestational Diabetes Mellitus

Atish Singla, Parneet Kaur, Khushpreet Kaur, Arvinder Kaur, Preetkanwal Sibia

GASTROENTEROLOGY

655 Role of β-blockers in Prevention of Hepatopulmonary Syndrome in Chronic Liver Disease: An Observation

Ashish Gautam, Prabhat Agrawal, Ashwini Nigam

INTERNAL MEDICINE

658 A Case Report of Oculopharyngeal Muscular Dystrophy

KB Gurumurthy, SG Jayaraj, Jobin V Joseph


INTERNAL MEDICINE Published, Printed and Edited by Dr KK Aggarwal, on behalf of IJCP Publications Ltd. and Published at E - 219, Greater Kailash, Part - 1 New Delhi - 110 048 E-mail: editorial@ijcp.com

661 Henoch-SchĂśnlein Purpura with Upper Gastrointestinal Hemorrhage in an Adult

BV Nagabhushana Rao, BVS Raman

NEUROLOGY

664 Cerebral Palsy

Printed at New Edge Communications Pvt. Ltd., New Delhi E-mail: edgecommunication@gmail.com

Sudivya Sharma

OBSTETRICS AND GYNECOLOGY

Copyright 2015 IJCP Publications Ltd. All rights reserved.

667 An Operated Case of Vaginocutaneous Fistula: A Rare Case

The copyright for all the editorial material contained in this journal, in the form of layout, content including images and design, is held by IJCP Publications Ltd. No part of this publication may be published in any form whatsoever without the prior written permission of the publisher.

Namrata Tiwari Mishra, Shiksha Tiwari, Anupam Tiwari, Mahesh Tiwari

670 Addition of Simple Laboratory Test to Reduce Overtreatment of Pelvic Inflammatory Disease by Syndromic Approach

Kavita Agarwal, Rekha Bharti, Achla Batra, Aruna Batra

673 Viral Infections in Pregnancy

Editorial Policies

The purpose of IJCP Academy of CME is to serve the medical profession and provide print continuing medical education as a part of their social commitment. The information and opinions presented in IJCP group publications reflect the views of the authors, not those of the journal, unless so stated. Advertising is accepted only if judged to be in harmony with the purpose of the journal; however, IJCP group reserves the right to reject any advertising at its sole discretion. Neither acceptance nor rejection constitutes an endorsement by IJCP group of a particular policy, product or procedure. We believe that readers need to be aware of any affiliation or financial relationship (employment, consultancies, stock ownership, honoraria, etc.) between an author and any organization or entity that has a direct financial interest in the subject matter or materials the author is writing about. We inform the reader of any pertinent relationships disclosed. A disclosure statement, where appropriate, is published at the end of the relevant article.

V Padma

679 Tuberculosis of the Female Genital Tract in Patients Attending an Infertility Clinic and its Effect on Pregnancy Outcome in in vitro Fertilization and Embryo Transfer

Alka Gahlot, ML Swarankar, Ravikant Soni

PICTORIAL CME

684 Lactation-induced Osteoporotic Vertebrae Fracture: A Rare Clinical Entity

Monika Maheshwari

MEDILAW

686 Right to Health is Integral to the Right to Life

KK Aggarwal

AROUND THE GLOBE

690 News and Views LIGHTER READING

Note: Indian Journal of Clinical Practice does not guarantee, directly or indirectly, the quality or efficacy of any product or service described in the advertisements or other material which is commercial in nature in this issue.

694 Lighter Side of Medicine

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FROM THE DESK OF THE GROUP EDITOR-IN-CHIEF

Prof. Dr KK Aggarwal

Group Editor-in-Chief IJCP Group and eMedinewS

Opinion on Registered Pharmacist PHARMACY PRACTICE REGULATIONS, 2015 According to Regulation 2(b) of the Pharmacy Practice Regulations, 2015, ‘Practice of Pharmacy’ means: i. Interpretation, evaluation and implementation of medical orders; dispensing of prescriptions, drug orders; ii. Participation in drug and device selection, drug administration, drug regimen reviews and drug or drug related research; iii. Provisions of patient counseling and the provision of those acts or services necessary to provide pharmaceutical care in all areas of patient care including primary care; and iv. Responsibility for compounding and labeling of drugs and devices (except labeling by a manufacturer, repacker or distributor of nonprescription drugs and commercially packaged legend drugs and devices) proper and safe storage of drugs and devices and maintenance of proper records for them. According to Regulation 2(h) of the Pharmacy Practice Regulations, 2015, ‘Pharmacy Practitioner’ means an individual (Community Pharmacist/Hospital Pharmacist/Clinical Pharmacist/Drug information Pharmacist) currently licensed, registered or otherwise authorized under the Act to counsel or otherwise and administer drugs in the course of professional practice. According to Regulation 2(i) of the Pharmacy Practice Regulations, 2015, Registered Pharmacist means a person whose name is for the time being entered in the register of the State in which he is for the time being residing or carrying on his profession or business of pharmacy under the Pharmacy Act, 1948. According to Regulation 2(j) of the Pharmacy Practice Regulations, 2015, ‘Prescription’ means a written or electronic direction from a Registered Medical Practitioner or other properly licensed practitioners such as Dentist, Veterinarian, etc. to a Pharmacist to compound and dispense a specific type and quantity of preparation or prefabricated drug to a patient. According to Regulation 3.3 of the Pharmacy Practice Regulations, 2015, ‘Displaying name of owner and registered pharmacist’: (a) Name of the owner of pharmacy business shall be displayed at or near the main entrance of each premises in which the business is carried on. (b) Name of the registered pharmacist along with his registration number and qualification along with his/her photograph shall be displayed adjacent to the area where dispensing is carried on in the pharmacy. Registered pharmacist shall also comply with a dress code of being dressed formally and wearing clean white overall (coat/apron) with a badge displaying the name and registration number.

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FROM THE DESK OF THE GROUP EDITOR-IN-CHIEF (c) Registered pharmacists shall display as suffix to their names only recognized pharmacy qualification/degrees or such certificates/diplomas and memberships/honours which confer professional knowledge or recognizes any exemplary qualification/achievements. According to Regulation 4.1 ‘Character of registered pharmacist’: (a) The prime object of the pharmacy profession is to render service to humanity; reward or financial gain is a subordinate consideration. Who-so-ever chooses his profession, assumes the obligation to conduct himself in accordance with its ideals. A registered pharmacist should be an upright man, instructed in the art of medicines. He shall keep himself pure in character and be diligent in caring for the sick; he should be modest, sober, patient, prompt in discharging his duty without anxiety; conducting himself with propriety in his profession and in all the actions of his life. (b) A person having qualification in any other system of pharmacy is not allowed to practice modern system of pharmacy in any form. (c) A registered pharmacist shall uphold the dignity and honor of his profession. ■■■■

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Nonpharmacologic Management of Hypertension: What Works? RUPAL OZA, MIRIAM GARCELLANO

ABSTRACT Hypertension is one of the most common conditions encountered in primary care. Nonpharmacologic strategies have been shown to help lower blood pressure. Lifestyle modifications are recommended for all patients with hyperten­sion. The American Heart Association/American College of Cardiology lifestyle management guideline recommends a diet emphasizing vegetables, fruits, and whole grains; limiting sodium intake to less than 2,400 mg per day; and exercising three or four times per week for an average of 40 minutes per session. Other nonpharmacologic strategies include weight loss, tobacco cessation, decreased alcohol consumption, biofeedback, and self-measured blood pres­sure monitoring. For patients with obstructive sleep apnea, the use of continuous positive airway pressure has been shown to improve blood pressure. Dietary supplements such as garlic, cocoa, vitamin C, coenzyme Q10, omega-3 fatty acids, and magnesium have been suggested for lowering blood pressure, but evidence is lacking.

Keywords: Hypertension, nonpharmacologic strategies, lifestyle modifications, self-measured blood pres­sure monitoring, dietary supplements

H

ypertension is one of the most preventable contributors to disease and death.1-3 Based on data from 2007 to 2010, 33% of U.S. adults 20 years and older—an esti­ mated 78 million—have hypertension, which is defined as blood pressure greater than 140/90 mm Hg.4 The prevalence is nearly equal between men and women. Worldwide, hypertension is most prevalent among black adults (44%).4 It is the most common condition treated in primary care and can lead to myocardial infarc­tion, stroke, renal failure, and death if not detected early and treated appropriately.4 A reduction in systolic blood pressure of 5 mm Hg has been associated in observa­ tional studies with mortality reductions of 14% from stroke, 9% from heart disease, and 7% from all causes.5 In 2014, the eighth report of the Joint National Committee on Preven­ tion, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 8) addressed guidelines to offer clinicians an analysis of what is and what is not known

RUPAL OZA, MD, is lead physician at Carepoint East Family Medicine and an assistant clinical professor of family medicine at The Ohio State Univer­sity Wexner Medical Center in Columbus. MIRIAM GARCELLANO, DO, is director of Urban Track Family Medicine Residency Program and assistant clinical professor of family medicine at The Ohio State University Wexner Medical Center. Source: Adapted from Am Fam Physician. 2015;91(11):772-776 .

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about blood pressure treatment thresholds, goals, and drug treatment strategies based on evidence from randomized controlled trials.1 JNC 8 did not directly address lifestyle treatments such as healthy diet, weight con­ trol, and regular exercise.1 However, a sub­group of the JNC 8 committee later published the American Heart Association/ American College of Cardiology (AHA/ACC) lifestyle management guideline,6 which will be out­lined in this article. In addition, other non­pharmacologic strategies such as weight loss, tobacco cessation, meditation, acupuncture, biofeedback, self-measured blood pressure monitoring, dietary supplements (e.g., garlic, cocoa, vitamin C, coenzyme Q10, omega-3 fatty acids, magnesium), and the use of con­tinuous positive airway pressure for patients with obstructive sleep apnea (OSA) will be discussed. DIET A diet with a high intake of vegetables, fruits, and whole grains is recommended.6,7 Other recommendations include consuming low-fat dairy products, poultry, fish, legumes, non­tropical vegetable oils, and nuts; and limiting intake of sweets, sugar-sweetened beverages, and red meat. This dietary pattern should be adapted to appropriate calorie requirements, personal and cultural food preferences, and nutritional therapy for


AMERICAN FAMILY PHYSICIAN other medical condi­tions, including diabetes mellitus. One way to achieve this is by following plans such as the Dietary Approaches to Stop Hypertension (DASH) diet (Table 18), the U.S. Department of Agriculture (USDA) Food Patterns, or the AHA diet. Compared with a typical American diet of the 1990s, the DASH diet lowers systolic blood pressure by 5 to 6 mm Hg and dia­stolic blood pressure by 3 mm Hg.9-11 The USDA Food Patterns offer lacto-ovo veg­etarian and vegan adaptations. The DASH diet is based on the AHA diet and empha­sizes consuming less red meat, sweets, and sugar-sweetened beverages. More infor­ mation about these diets is available at http://fnic.nal. usda.gov/diet-and-disease/ heart-health. SODIUM INTAKE

physical activity is better than none, and more activity results in greater benefits.15 Health benefits of exercise include reduced rates of all-cause mortality, coronary heart disease, hypertension, stroke, type 2 dia­ betes, metabolic syndrome, colon cancer, breast cancer, and depression.15 The U.S. Preventive Services Task Force recommends offering or referring overweight and obese adults who have additional car­diovascular risk factors to intensive behav­ ioral counseling interventions to promote a healthy diet and physical activity.16 One way to encourage patients to exercise is to write exercise prescriptions, especially for activities they enjoy. Weight loss is another important lifestyle modification for reducing blood pressure. Weight loss of approximately 10 kg (22 lb) may reduce systolic blood pressure by 5 to 20 mm Hg.2

There is strong and consistent evidence that reducing sodium intake reduces blood pres­ sure. Adults who would benefit from low­ering blood pressure should be advised to limit their sodium intake to no more than 2,400 mg per day (about 1 teaspoon of table salt).6 Further reduction of sodium intake to 1,500 mg per day is desirable because it is associated with an even greater reduc­tion in blood pressure. The average blood pressure reduction in patients consuming a sodiumrestricted diet of 2,400 mg per day is 2/1 mm Hg, or 7/3 mm Hg for those restricting sodium to 1,500 mg per day.12,13 Reducing baseline sodium intake by at least 1,000 mg per day will lower blood pressure even if the desired daily sodium intake is not yet achieved. Food prepared in res­ taurants, canned foods, and prepackaged foods (dry or frozen) tend to contain more sodium than home-cooked meals or frozen vegetables.

Cigarette smoking is the leading prevent­able cause of death in the United States17 and significantly increases the risk of cardiovas­cular disease.18 Smoking causes an immedi­ate increase in sympathetic nervous activity, which in turn increases myocardial oxygen demand through increased blood pressure, heart rate, and myocardial contractility.19 A meta-analysis of 20 prospective cohort stud­ies found that quitting smoking after a heart attack or cardiac surgery decreases a patient’s risk of death by more than 33% over five years.20 Pri­mary care physicians can use the five A’s framework (ask, advise, assess, assist, arrange) to incorporate smoking cessation counseling into their daily practices (Table 3).21

PHYSICAL ACTIVITY AND WEIGHT LOSS

ALCOHOL CONSUMPTION

Adults should engage in moderate to vigor­ous aerobic physical activity three or four times per week for an average of 40 minutes per session to lower blood pressure.6,14 Most health benefits occur with at least 150 min­utes per week of moderate-intensity physical activity, such as brisk walking (Table 2).14 Some

Moderate alcohol consumption has been shown to lower blood pressure.2 However, excessive alcohol consumption can raise blood pressure, and persons who do not drink alcohol should not be encouraged to start for the purposes of lowering blood pressure. For potentially beneficial health effects, alcohol consumption should be limited to two drinks per day (about 1 oz or 30 mL of ethanol) for most men and one drink per day for women and lighter-weight men.2,22

Table 2. Examples of Aerobic Exercise

SMOKING CESSATION

Aerobic exercise class

Golfing without using a cart

Bicycling

Jogging

DIETARY SUPPLEMENTS

Dancing

Moderate-intensity swimming

Gardening or yard work (e.g., raking, pushing a lawn mower)

Tennis

Garlic is commonly used as a dietary supplement to lower blood pressure. Data from two randomized controlled trials comparing the use of garlic vs. placebo in patients with hypertension showed that garlic may

Information from reference 14.

Walking briskly

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AMERICAN FAMILY PHYSICIAN have some blood pressure–lowering effect.23 However, com­pared with dietary changes, reduced sodium intake, and physical activity, there is insufficient evidence to support the use of garlic in reducing morbidity or mortality asso­ciated with cardiovascular events. Cocoa has a small but statistically significant blood pressure–lowering effect (average of 2 to 3 mm Hg) in adults with hypertension, but there is no evidence that it improves patient-oriented outcomes in the long term.24 Although vitamin C, coenzyme Q10, omega-3 fatty acids, and magnesium have been used for lowering blood pressure, there is no evidence to support their use in the management of hypertension. RELAXATION TECHNIQUES The mechanism by which relaxation techniques lower blood pressure is unclear. One theory suggests that they may help lower the stress and physiologic arousal pro­duced by the autonomic nervous system, thereby reduc­ing blood pressure. Evidence shows that transcendental meditation may modestly lower blood pressure.15 However, no specific method has been proven beneficial. Because of mixed results in trials and numerous limita­tions, the AHA does not recommend yoga or acupunc­ ture to lower blood pressure.15 Biofeedback techniques have been proven effective and may be considered in clinical practice to lower blood pressure.15 SELF-MEASURED BLOOD PRESSURE MONITORING A review of 52 trials by the Agency for Healthcare Research and Quality showed that self-measured blood pressure monitoring—with or without additional support such as education, counseling, telemedicine, home visits, or Web-based logging—lowers blood pressure compared with usual care, but effects and longterm benefits beyond 12 months remain uncertain.25 Self-monitoring of blood pressure resulted in a mean reduc­tion in systolic blood pressure of 3.9 mm Hg at six months, and self-monitoring of blood pressure with additional support resulted in a reduction in systolic blood pressure of 2.1 to 8.3 mm Hg, which remained significant at 12 months. Future studies are needed to determine the long-term benefits of self-measured blood pressure monitoring. OBSTRUCTIVE SLEEP APNEA OSA occurs when the upper airway is repeatedly obstructed during sleep, causing arousals and

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intermittent hypoxemia. Recent data have shown that it may contribute to poorly controlled high blood pressure.26 International guidelines now recognize OSA as one of the most common risk factors for resistant hyperten­sion.7 The link between OSA and hypertension is likely related to increased sympathetic activity (due to inter­mittent hypoxia),27 endothelial dysfunction and systemic inflammation,28 and abnormal autonomic function.29 A recent meta-analysis of randomized controlled trials showed that the use of continuous positive airway pres­ sure lowered 24-hour blood pressure levels in persons with resistant hypertension and OSA.30 Note: See for complete article visit: www.aafp.org/afp. REFERENCES 1. James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8) [published correction appears in JAMA. 2014;311(17):1809]. JAMA. 2014;311(5):507-520. 2. Chobanian AV, Bakris GL, Black HR, et al.; National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Eval­uation, and Treatment of High Blood Pressure; National High Blood Pres­sure Education Program Coordinating Committee. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report [published correction appears in JAMA. 2003;290(2):197]. JAMA. 2003;289(19):2560-2572. 3. Olives C, Myerson R, Mokdad AH, Murray CJ, Lim SS. Prevalence, aware­ness, treatment, and control of hypertension in United States counties, 2001-2009. PLoS One. 2013;8(4):e60308. 4. Go AS, Mozaffarian D, Roger VL, et al.; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart dis­ease and stroke statistics—2013 update: a report from the Ameri­can Heart Association [published corrections appear in Circulation. 2013;127(1):doi:10.1161/CIR.0b013e31828124ad, and Circulation. 2013;127(23):e841]. Circulation. 2013;127(1):e6-e245. 5. Whelton PK, He J, Appel LJ, et al.; National High Blood Pressure Educa­tion Program Coordinating Committee. Primary prevention of hyperten­sion: clinical and public health advisory from the National High Blood Pressure Education Program. JAMA. 2002;288(15):1882-1888. 6. Eckel RH, Jakicic JM, Ard JD, et al. 2013 AHA/ ACC guideline on lifestyle management to reduce cardiovascular risk: a report of the American Col­ lege of Cardiology/American Heart Association Task Force on Practice Guidelines. http://circ.ahajournals.org/ content/early/2013/11/11/01. cir.0000437740.48606.d1.full. pdf+html. Accessed May 5, 2014.


AMERICAN FAMILY PHYSICIAN 7. Calhoun DA, Jones D, Textor S, et al. Resistant hypertension: diagnosis, evaluation, and treatment. A scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research. Hypertension. 2008;51(6): 1403-1419. 8. National Heart, Lung, and Blood Institute. Your guide to lowering blood pressure. http://www.nhlbi.nih.gov/files/ docs/public/heart/hbp_low.pdf. Accessed September 29, 2014. 9. Svetkey LP, Simons-Morton D, Vollmer WM, et al. Effects of dietary pat­terns on blood pressure: subgroup analysis of the Dietary Approaches to Stop Hypertension (DASH) randomized clinical trial. Arch Intern Med. 1999;159(3):285-293. 10. Appel LJ, Moore TJ, Obarzanek E, et al.; DASH Collaborative Research Group. A clinical trial of the effects of dietary patterns on blood pres­sure. N Engl J Med. 1997;336(16):1117-1124. 11. Sacks FM, Appel LJ, Moore TJ, et al. A dietary approach to prevent hypertension: a review of the Dietary Approaches to Stop Hypertension (DASH) Study. Clin Cardiol. 1999;22(7 suppl):III6-III10. 12. Bray GA, Vollmer WM, Sacks FM, Obarzanek E, Svetkey LP, Appel LJ; DASH Collaborative Research Group. A further subgroup analysis of the effects of the DASH diet and three dietary sodium levels on blood pres­sure: results of the DASH-Sodium Trial [published correction appears in Am J Cardiol. 2010;105(4):579]. Am J Cardiol. 2004;94(2):222-227.

17. U.S. Preventive Services Task Force. Counseling and interventions to pre­vent tobacco use and tobacco-caused disease in adults and pregnant women: U.S. Preventive Services Task Force reaffirmation recommenda­tion statement. Ann Intern Med. 2009;150(8):551-555. 18. Larzelere MM, Williams DE. Promoting smoking cessation. Am Fam Phy­sician. 2012;85(6):591-598. 19. Najem B, Houssière A, Pathak A, et al. Acute cardiovascular and sympathetic effects of nicotine replacement therapy [published cor­rection appears in Hypertension. 2006;48(4):e23]. Hypertension. 2006;47(6):1162-1167. 20. Critchley J, Capewell S. Smoking cessation for the secondary pre­vention of coronary heart disease. Cochrane Database Syst Rev. 2004;(1):CD003041. 21. Fiore MC, Jaén CR, Baker TB, et al.; U.S. Department of Health and Human Services. Treating tobacco use and dependence: 2008 update. http://www.ahrq. gov/professionals/clinicians-providers/guidelinesrecommendations/tobacco/clinicians/update/treating_ tobacco_use08. pdf. Accessed June 12, 2014. 22. Wexler R, Aukerman G. Nonpharmacologic strategies for managing hypertension. Am Fam Physician. 2006;73(11):1953-1956. 23. Stabler SN, Tejani AM, Huynh F, Fowkes C. Garlic for the prevention of cardiovascular morbidity and mortality in hypertensive patients. Cochrane Database Syst Rev. 2012;(8):CD007653. 24. Ried K, Sullivan TR, Fakler P, Frank OR, Stocks NP. Effect of cocoa on blood pressure. Cochrane Database Syst Rev. 2012;(8):CD008893.

13. Sacks FM, Svetkey LP, Vollmer WM, et al.; DASH-Sodium Collaborative Research Group. Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet. N Engl J Med. 2001;344(1):3-10.

25. Uhlig K, Patel K, Ip S, Kitsios GD, Balk EM. Self-measured blood pressure monitoring in the management of hypertension: a systematic review and meta-analysis. Ann Intern Med. 2013;159(3):185-194.

14. Office of Disease Prevention and Health Promotion. Physical Activ­ity Guidelines Advisory Committee report. http://www.health.gov/paguidelines/report/. Accessed June 1, 2014.

26. Peppard PE, Young T, Palta M, Skatrud J. Prospective ciation between sleep-disordered study of the asso­ breathing and hypertension. N Engl J Med. 2000;342(19): 1378-1384.

15. Brook RD, Appel LJ, Rubenfire M, et al.; American Heart Association Professional Education Committee sure Research, of the Council for High Blood Pres­ Council on Cardiovascular and Stroke Nursing, Council on Epidemiology and Prevention, and Council on Nutrition, Physical Activity. Beyond medications and diet: alternative approaches to low­ering blood pressure: a scientific statement from the American Heart Association. Hypertension. 2013;61(6):1360-1383.

27. Cross MD, Mills NL, Al-Abri M, et al. Continuous positive airway pres­sure improves vascular function in obstructive sleep apnoea/hypopnoea syndrome: a randomised controlled trial. Thorax. 2008;63(7):578-583. 28. Budhiraja R, Quan SF. When is CPAP an antihypertensive in sleep apnea patients? J Clin Sleep Med. 2009;5(2): 108-109. 29. Parati G, Lombardi C. Control of hypertension in nonsleepy patients with obstructive sleep apnea. Am J Respir Crit Care Med. 2010;181(7):650-652.

16. LeFevre ML; U.S. Preventive Services Task Force. Behavioral counsel­ing to promote a healthful diet and 30. physical activity for cardiovascular disease prevention in adults with cardiovascular risk factors: U.S. Pre­ventive Services Task Force recommendation statement. Ann Intern Med. 2014;161(8):587-593. ■■■■

Varounis C, Katsi V, Kallikazaros IE, et al. Effect of CPAP on blood pressure in patients with obstructive sleep apnea and resistant hypertension: a systematic review and metaanalysis. Int J Cardiol. 2014;175(1):195-198.

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AMERICAN FAMILY PHYSICIAN

Practice Guidelines ACIP RELEASES 2015 CHILDHOOD IMMUNIZATION SCHEDULES The 2015 immunization schedule for children and the catch-up schedule from the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) have a few changes that are pertinent for family physicians. The sched­ules are available at http://www.aafp.org/patientcare/immunizations/schedules.html. The most notable change involves the quadrivalent live attenuated influenza vaccine (LAIV). In June 2014, ACIP made a preferential recommendation for LAIV over inactivated influenza vaccine for children two to eight years of age. This was based on data showing that LAIV provided better protection against influenza for those children. The recommendation stated that LAIV was preferred only if immediately available. The emphasis is that any other influenza vaccine should be given instead of waiting for LAIV to arrive. However, a review of the 2013-2014 vaccine efficacy data surprised everyone by showing that LAIV was less effec­tive than inactivated influenza vaccine against the H1N1 strain. Effectiveness against other strains of influenza was the same or better than inactivated influenza vaccine. The cause for this unexpected finding is unknown, but is under investigation. For now, the CDC has not changed any of its recommendations regarding influenza vaccination (http://www.cdc.gov/ flu/news/nasal-spray-effectiveness.htm). Updates are expected at the February 2015 ACIP meeting, and offices may want to delay preordering any 2015-2016 influenza vaccine until after that meeting. The footnotes of the childhood vaccine schedule were extensively modified for the meningitis vaccine. The meningococcal vaccine is recommended for use in children at high risk of invasive meningococcal disease

(i.e., infants with complement component deficiencies or functional or anatomic asplenia, including sickle cell disease; healthy infants who are part of an outbreak; or travelers in hyperendemic or epidemic areas). The vaccine should be given at two, four, six, and 12 months. However, each of the three childhood meningococcal vaccines has different indications based on the child’s age and medical condition. The footnotes now delineate the recommendations by specific condition and vaccine, which should make it easier to decide which vaccine to use in which situation. The CDC has published a comprehensive toolkit that can help guide you through safe storage and handling practices for your office (http://www.cdc.gov/vaccines/ recs/storage/toolkit/storage-handling-toolkit.pdf). There is a small but real association between febrile seizures and concurrent administration of influenza plus pneumococcal 13-valent conjugate vaccine and/or diphtheria and tetanus toxoids and acellular pertussis (DTaP). The number needed to vaccinate to produce one additional febrile seizure is approximately 2,200 children. Given the generally benign nature of febrile seizures and the benefits of the vaccines, ACIP has not recommended any change in practice at this time. A free vaccination schedule app for iOS and Android devices is available from the CDC at http://www.cdc. gov/vaccines/schedules/hcp/schedule-app.html. Some new vaccines will likely be available in 2015. A meningitis B vaccine was approved by the U.S. Food and Drug Administration in October 2014, and a second is expected be approved shortly. The nine-valent human papillomavirus vaccine may also be approved soon. ACIP will likely make recommendations for the appropriate use of these vaccines at the February 2015 meeting.

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Source: Adapted from Am Fam Physician. 2015;91(4):265.

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AMERICAN FAMILY PHYSICIAN

Photo Quiz SKIN-COLORED, DOME-SHAPED PAPULE ON THE UPPER LIP A 42-year-old man with a history of basal cell carcinoma on his scalp (five years earlier) presented for an annual examination. He reported inconsistent sunscreen use and did not have any new or concerning lesions. He did have a papule on his upper lip that had not changed in shape, size, or color since he first noticed it 10 years earlier. He had nicked it many times while shaving. Physical examination revealed a solitary, 3.5-mm, skincolored, dome-shaped, non­tender, firm papule (Figures 1 and 2). On dermoscopy, there was prominent telan­ giectasia and loss of skin markings within the papule, and no evidence of a pigment network or hair growth.

Question Based on the patient’s history and physical examination findings, which one of the fol­lowing is the most likely diagnosis?

Figure 1.

A. Basal cell carcinoma. B. Epidermal inclusion cyst. C. Intradermal melanocytic nevus. D. Neurofibroma. E. Palisaded encapsulated neuroma.

Figure 2.

SEE THE FOLLOWING PAGE FOR DISCUSSION.

Source: Adapted from Am Fam Physician. 2015;91(12):869-870.

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AMERICAN FAMILY PHYSICIAN DISCUSSION The answer is E: palisaded encapsulated neuroma, also known as a solitary circum­ scribed neuroma. This is a common benign neural tumor that may be misdiagnosed as a carcinoma.1 It presents as a small (2 to 6 mm), asymptomatic, skin-colored, firm, dome-shaped papule. It most often occurs on the mucocutaneous junction of the face in patients between 40 and 60 years of age. Men and women are equally affected.2 Palisaded encapsulated neuromas usually have no hair on the surface and minimal or absent telangiectasia; however, trauma to the area can cause prominent telangiectatic vessels and ulceration.2 Histologically, these neuromas appear as a partially encapsulated dermal nodule. The cause is unknown, but it has been suggested that they are a trauma-induced hyperplasia of the nerve fibers.3 Excision is typically curative.4 cinoma The most common form of basal cell car­ presents as a dome-shaped papule or nodule that may ulcerate and bleed. The raised, rolled, pearly borders can be accentu­ated by applying traction to the surrounding skin.5 Telangiectasia forms an arboreal pat­tern on dermoscopy.6 An epidermal inclusion cyst usually presents as a 1- to 4-cm, solitary, firm, mobile, Summary Table Condition

Characteristics

Basal cell carcinoma Dome-shaped papule or nodule that may ulcerate or bleed; raised, pearly, rolled borders; telangiectasia forms an arboreal pattern on dermoscopy Epidermal inclusion cyst

1- to 4-cm, solitary, firm, mobile, subcutaneous nodule; surface punctum that may express accumulated keratin debris

Intradermal melanocytic nevus

Soft with smooth edges and preservation of skin markings; brown pigment, commashaped vessels, and hair are often noted on dermoscopy

Neurofibroma

Soft sessile or pedunculated papule, usually on the trunk, that invaginates with pressure (“buttonholing”)

Palisaded encapsulated neuroma

Small, asymptomatic, skin-colored, firm, dome-shaped papule; usually no hair on the surface and minimal or absent telangiectasia

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subcutaneous nodule on the trunk, neck, or face. A white, cheesy material (accu­mulated keratin debris) can be expressed from the cyst with a surface punctum.7 An intradermal melanocytic nevus is a benign lesion that may or may not be pig­mented. It is usually soft with smooth edges and retains skin markings.8 Brown pigment, comma-shaped vessels, and hair are often noted on dermoscopy.9 A solitary neurofibroma presents as a soft sessile or pedunculated papule, usually on the trunk, that invaginates with pressure (“buttonholing”).5 Multiple neurofibromas are associated with von Recklinghausen dis­ease, or neurofibromatosis 1. Other clinical features include café au lait spots, axillary freckling, and iris hamartomas (Lisch nodules). REFERENCES 1. Golod O, Soriano T, Craft N. Palisaded encapsulated neuroma—a classic presentation of a com­ monly misdiagnosed neural tumor. J Drugs Dermatol. 2005;4(1):92-94. 2. Megahed M. Palisaded encapsulated neuroma (solitary circumscribed neuroma). A clinicopathologic and immunohistochemical study. Am J Dermatopathol. 1994;16(2):120-125. 3. Argenyi ZB, Santa Cruz D, Bromley C. Comparative light-microscopic and immunohistochemical study of traumatic and palisaded encapsulated neuromas of the skin. Am J Dermatopathol. 1992;14(6):504-510. 4. Newman MD, Milgraum S. Palisaded encapsulated neuroma (PEN): an often misdiagnosed neural tumor. Dermatol Online J. 2008;14(7):12. 5. Habif TP. Clinical Dermatology: A Color Guide to Diagnosis and Therapy. Edinburgh, Scotland: Mosby; 2009. 6. Marghoob AA, Usatine RP, Jaimes N. Dermos­copy for the family physician. Am Fam Physician. 2013;88(7):441-450. 7. Weedon D, Strutton G, Rubin AI. Weedon’s Skin Pathol­ ogy. 3rd ed. Edinburgh, Scotland: Churchill Livingstone/ Elsevier; 2010. 8. Dubovy SR, Clark BJ. Palisaded encapsulated neuroma (solitary circumscribed neuroma of skin) of the eyelid: report of two cases and review of the literature. Br J Ophthalmol. 2001;85(8):949-951.

9. Suwattee P, Schram SE, Warshaw EM. Digital polarized light dermoscopy of clinically nonpigmented dermal nevi. Dermatol Surg. 2007;33(9):1120-1125. ■■■■



CARDIOLOGY

A Case of Cardiac Tamponade Due to Hypothyroidism MALLIKARJUNREDDY M*, VENUGOPAL K†, BHARATH RAJ MY†, MANJUNATH GANIGER†, KADAPPA JALIGIDAD†, MAHESH SREENIVAS PRASAD†

ABSTRACT Hypothyroidism is one of the most common endocrine dysfunction encountered in clinical practice. It can be either primary or secondary, the latter being due to end-organ failure. Most common presentations of hypothyroidism are dry skin, sallow complexion, brittle nails, loss of hairs, hoarseness of voice, constipation, obesity, ascites, pleural effusion, delayed muscle contraction and relaxation, lethargy and somnolence. Cardiac manifestations include hemodynamic alterations like narrowing of pulse pressure, increased diastolic blood pressure, prolongation of circulation time, and decrease in blood flow to the tissues. Pericardial effusion is a common occurrence in severe hypothyroidism. However, cardiac tamponade secondary to hypothyroidism is very rare. Here we report a case of cardiac tamponade due to hypothyroidism in a 32-year-old male who presented with features of congestive cardiac failure and restrictive shock.

Keywords: Hypothyroidism, cardiac tamponade, pericardiocentesis, thyroxine

H

ypothyroidism is a multisystem disease affecting various parts and altering various functions of the body. Even though the occurrence of pericardial effusion has been described in the previous literatures, the occurrence of tamponade in such patients is extremely rare. Diagnosis of tamponade in hypothyroid cases is difficult as it is overlooked due to the presence of features of heart failure like tachycardia, pedal edema and cardiomegaly in chest X-ray. Emergent action in the form of closed pericardiocentesis can ensure the stability and prognostic improvement in such patients along with the addition of thyroxine supplements.

CASE REPORT A 32-year-old male patient presented to the emergency department with history of breathlessness of 3 months duration aggravated since 7 days, easy fatigability and decreased exercise tolerance. Breathlessness was insidious in onset and gradually progressed over

*Professor and Unit Head †Postgraduate Dept. of General Medicine Vijayanagara Institute of Medical Sciences, Bellary, Karnataka Address for correspondence Dr Venugopal K Postgraduate, Dept. of General Medicine Room No. 17, 17th Block Vijayanagara Institute of Medical Sciences, Bellary - 583 104, Karnataka E-mail: venu25061987@gmail.com

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3 months, it was present even at rest when he was admitted to the hospital. There was no history of palpitation or chest pain; neither was he a known case of hypertension or diabetes. The patient was treated at a peripheral center for anemia. On examination, he was pale with puffiness of face and bilateral pitting type of pedal edema. His pulse was 90 bpm, low volume, feeble and regular. In addition, pulsus paradoxus was present. Blood pressure was 80/50 mmHg. His oxygen saturation was 91% at room air. Respiratory rate was 30 cycles/min. Cardiovascular system examination revealed raised jugular venous pressure (JVP) of about 12 cm above sternal margin. Heart sounds were muffled. He had delayed deep tendon reflexes, hoarseness of voice, delayed speech. Other systemic examination was within normal limits. His random blood sugar was 120 mg%, hemoglobin of 11.2 mg%. Renal and liver parameters were within normal limits. Electrocardiogram (ECG) revealed low voltage complexes (Fig. 1). Chest X-ray showed cardiomegaly with typical money bag appearance (Fig. 2). Two-dimensional echocardiography showed the presence of early diastolic collapse of right ventricle and a large pericardial effusion, suggestive of cardiac tamponade (Fig. 3). In the view of worsening of general condition; emergency therapeutic closed pericardiocentesis was performed and about 1.6 liters of serous fluid was drained. Analysis of pericardial fluid revealed proteins of 4.8 g/dL, sugar of 50 mg/dL, cytology was negative


CARDIOLOGY

Figure 1. ECG showing low voltage complexes.

Figure 2. Chest X-ray posteroanterior view showing enlarged cardiac silhouette with typical money bag appearance.

for malignant cells, culture yielded no growth, negative for acid-fast bacilli and Gram staining, lipase of 27.23 IU/L, amylase of 51 IU/L, cholesterol of 121 mg/dL and adenosine deaminase levels of 18 IU/L. Test for collagen vascular markers were normal. After therapeutic pericardiocentesis, his general condition improved and thyroid function test results came and were as follows: Tri-iodothyronine (T3)-0.25 ng/mL, thyroxine (T4)-1.80 Âľg/dL, thyroid-stimulating hormone (TSH)-2.11 ÂľIU/mL, free T3 (FT3)-<1 pg/mL, FT4-0.40 ng/dL. Patient was started with thyroxine supplements and advised to follow-up after a month.

a

b

c

d

Figure 3. (a) 2D echocardiography parasternal long-axis view showing small heart size with massive pericardial effusion. (b) Parasternal short-axis view showing fluid collection all around the ventricle. (c) Apical four-chamber view demonstrating the pericardial effusion around all chambers. (d) Apical four-chamber view during diastole, which demonstrating right ventricular collapse.

Follow-up general condition was satisfactory and 2D echocardiography confirmed that patient did not develop further fluid accumulation. DISCUSSION The occurrence of a pericardial effusion due to hypothyroidism seems to be related to the severity and duration of the disease. The incidence is reported

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CARDIOLOGY to be as low as 3% in early mild stage to as high as 80% when myxedema is present.1 Cardiac tamponade is usually a dreadful consequence of increased pericardial pressure with accumulation of pericardial fluid within the pericardial sac that may be caused by acute pericarditis, tumor, uremia, hypothyroidism, trauma, cardiac surgery or other inflammatory/ noninflammatory conditions.2 Cardiac tamponade in patients diagnosed with hypothyroidism is probably rare as it is due to pericardial distensability and the slow accumulation of fluid, allowing significant fluid accumulation without hemodynamic compromise. It is important to suspect cardiac tamponade when patients have hemodynamic compromise regardless of the amount of pericardial effusion.3 For patients diagnosed with cardiac tamponade without sinus tachycardia, hypothyroidism should be suspected.4 The pathophysiologic derangements responsible for the collection of fluid in the serous cavities of hypothyroid patients are probably increased systemic capillary permeability and disturbances in electrolyte metabolism.5 Alexander first used the term “Gold Paint Effusion” to describe the golden brown appearance of the pericardial fluid due to the shimmering satin cholesterol crystals. The high cholesterol content of the fluid has been attributed to disturbances in lipid metabolism; possibly, a churning action of the heart plays a role in the precipitation of cholesterol from pericardial fluid or the poor absorptive capacity of the pericardium may be a major factor.3,5,6 Thyroid replacement alone is sufficient for resolution of these effusions, although it may take many months. In our case, patient generally improved with symptoms and there was no further accumulation of serous fluid within pericardium in the subsequent follow-up examinations. Pericardiocentesis is indicated only if cardiac tamponade develops. This rare but significant condition should be considered, especially when it occurs after acute cold exposure. Pericardial effusion, lipid metabolic abnormality and

abnormal liver function can be easily reversed with thyroid replacement.7-9 CONCLUSION Hypothyroidism should be suspected and evaluated in a case of cardiac tamponade when there is relative bradycardia, high TSH, low thyroid hormones since tamponade itself might be the only presenting feature. A physician needs to familiarize themselves with this presentation as a part of their workup for early diagnosis, which is important for improving the management aspect and outcome. REFERENCES 1. Hardisty CA, Naik DR, Munro DS. Pericardial effusion in hypothyroidism. Clin Endocrinol (Oxf). 1980;13(4):349-54. 2. Saito Y, Donohue A, Attai S, Vahdat A, Brar R, Handapangoda I, et al. The syndrome of cardiac tamponade with “small” pericardial effusion. Echocardiography. 2008;25(3):321-7. 3. Retnam VJ, Chichgar JA, Patkar LA, Chikhalikar AA, Golwalla AF. Myxedema and pericardial effusion with cardiac tamponade (a case report). J Postgrad Med. 1983;29(3):188-190B. 4. Wang JL, Hsieh MJ, Lee CH, Chen CC, Hsieh IC, Lin JD, et al. Hypothyroid cardiac tamponade: clinical features, electrocardiography, pericardial fluid and management. Am J Med Sci. 2010;340(4):276-81. 5. Chou SL, Chern CH, How CK, Wang LM, Huang CI, Lee CH. A rare case of massive pericardial effusion secondary to hypothyroidism. J Emerg Med. 2005;28(3):293-6. 6. Usalan C, Atalar E, Vural FK. Pericardial tamponade in a 65-year-old woman. Postgrad Med J. 1999;75(881):183-4. 7. Chatterji A. An unusual cause of pericardial tamponade. Scott Med J. 2009;54(1):58. 8. Lin CT, Liu CJ, Lin TK, Chen CW, Chen BC, Lin CL. Myxedema associated with cardiac tamponade. Jpn Heart J. 2003;44(3):447-50.

9. Al-Mahroos HM, Al-Bannay RA. Massive pericardial effusion as a sole manifestation of hypothyroidism: a case report. Bahrain Med Bull. 2000;22(4):188-91. ■■■■

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2015


COMMUNITY MEDICINE

Study of Hair Dye Poisoning: A Complete Profile KB YADAVENDRA REDDY*, P VIJAYANARASIMHA REDDY†, P KIRAN KUMAR‡, M ASHA‡, B VISALAKSHI‡

ABSTRACT Background: Poisoning due to hair dye ingestion, which was rare earlier is now rising to alarming proportion in Andhra Pradesh especially in Rayalaseema region. Hair dye poisoning is an uncommon form of poisoning, occasionally reported from African countries and sporadically in India. Objective: To study the complete clinical profile of hair dye poisoning and its complications. Material and methods: We report 225 cases of hair dye poisoning from Rajiv Gandhi Institute of Medical Sciences, Kadapa, which enumerates the epidemiology, clinical features, investigations, treatment, morbidity, mortality and highlights the toxic potential of hair dye. Results: It is more common in females, and young individuals. There is 70% incidence of orofacial edema. Thirteen percent needed emergency tracheostomy because of severe laryngeal edema. Ten percent of patients suffered from renal failure. There was 10% (24) mortality of which 18 were due to laryngeal edema. Conclusion: There is high incidence and rapid rise of hair dye in this region. ‘Word of mouth’ publicity regarding the suicidal potential of easily available hair dye. Common in females because it is cheap and easily available. High incidence of development of orofacial edema, renal failure. Rhabdomyolysis was noticed occasionally. Mortality was high due to delay in reaching the hospital; emergency tracheostomy was life-saving in severe cases of orofacial edema.

Keywords: Hair dye, poisoning, clinical profile

H

air dye ingestion is an uncommon form of poisoning in the West; however, in some parts of the world such as East Africa1 and Indian Subcontinent it is not uncommon. Poisoning due to hair dye is relatively rare in rest of India when compared to Andhra Pradesh.2 Compound responsible for hair dye toxicity is paraphenylenediamine (PPD), PPD imparts black color to hair dye. It is also used in tattoos and (black) henna. PPD is used because it is cheap, has high temperature stability, high strength, chemical and electrical resistance. Toxic dose of PPD is 10 g. PPD is also used for dyeing furs, accelerating vulcanization and azodye manufacturing. Poisoning due to PPD is reported in northern Africa and Arabia due to local custom of using henna (black). This poison can be accidental, suicidal or homicidal. It is also used as abortifacient. Systemic toxicity occurs in two phases.In phase 1 (acute

*Associate Professor †Assistant Professor ‡Final Year Postgraduate Dept. of General Medicine Rajiv Gandhi Institute of Medical Sciences, Kadapa, Andhra Pradesh Address for correspondence Dr KB Yadavendra Reddy D No.: 3/139, Christian Lane, Kadapa - 516 001, Andhra Pradesh E-mail: yaduhuf@gmail.com

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phase), within 4-6 hours, numbness and burning of the mouth and throat, epigastric pain, gastritis, persistent vomiting leading to dehydration, angioedema, airway obstruction, blindness, dysphagia, respiratory distress or failure and cyanosis usually occur. Rare manifestations include exophthalmos, optic neuritis and permanent blindness. In phase 2 (within days or weeks), clinical manifestations include dark urine (a characteristic chocolate or reddish brown) oliguria or anuria, acute tubular necrosis and renal failure, muscle pain, tenderness, rigidity, rhabdomyolysis, intravascular hemolysis and drowsiness. The hair dye also contains ethylenediaminetetraacetic acid (EDTA), which causes hypocalcemia resulting in numbness, trismus, carpopedal spasm and positive Chvostek’ sign and Trousseau’s sign. The toxicity resolves with adequate calcium correction. Another toxic component of the hair dye is resorcinol, which is a corrosive and also causes methemoglobinemia and renal toxicity. Laboratory features includes raised alanine aminotransferase (ALT), creatine phosphokinase (CPK), lactate dehydrogenase (LDH) and urea, hyperkalemia, methemoglobinemia, hemoglobinemia, metabolic acidosis and hypocalcemia. Peripheral smear can show anisocytosis and poikilocytosis. Urine analysis can show raised urine osmolality, proteinuria,


COMMUNITY MEDICINE hematuria, hemoglobinuria, myoglobinuria and albuminuria. PPD applied locally can cause contact dermatitis. Transcutaneous absorption of PPD can be rapid and may lead to systemic effects including angioedema, gastrointestinal disturbances, tremors, drowsiness, convulsions, dyspnea, liver atrophy, acute renal failure, cardiac arrest and death in few cases.

Sex Ratio As the suicidal tendencies are more in female population the distribution of hair dye poisoning is also commonly seen in female patients when compared to male patients. Figure 2 shows the distribution of hair dye poisoning as per sex distribution.

However, systemic effects develop following chronic topical application. Chronic dermal exposure can cause lethargy, myalgia, purplish discoloration of gums and teeth, anorexia, gastrointestinal disturbances, liver and spleen enlargement subacute atrophy of the liver, jaundice, chronic renal failure (CRF), progressive neurological symptoms and coma.

120

Incidence The incidence of hair dye poisoning is increasing every year. Number of hair dye poisonings had a 10 times rise in year 2013. Figure 1 depicts the incidence of hair dye poisoning is increasing every year.

80 60

45 30

20 0 2011

2012

2013

Years

Figure 1. Year-wise distribution of cases.

Male

Female

160

146

140

No. of patients

120 100 79

80 60 40 20 0

2011-2013 Years

Figure 2. Sex-wise distribution of cases.

100 90 80 No. of patients

RESULTS

100

40

MATERIAL AND METHODS Patients with consumption of hair dye, admitted in Rajiv Gandhi Institute of Medical Sciences, Kadapa from January 2011 to December 2013, were part of this study. Age, sex, mode of consumption, amount of consumption (in milliliters), time of consumption, clinical features, reasons for choosing hair dye as poison were recorded. Detailed clinical examination was done. Laboratory investigations complete blood picture (CBP), complete urine examination (CUE), liver function test (LFT), serum electrolytes, methemoglobin were performed. Treatment, complications and outcome were recorded. The importance of a thorough toxicological review of hair dye poisoning is illustrated and manifestations and treatment of hair dye poisoning are reviewed. Literature and publications are reviewed.

150

140

No. of patients

Poisoning due to PPD has high mortality. Therefore, early recognition can be life-saving. There is no specific antidote. The most important aspect of management is early recognition of poisoning by this compound, supportive measures that include Ryles tube aspiration with 2% soda bicarbonate and alkalinization of urine. Asphyxia is the major early challenge, which may require emergency tracheostomy3,4 and ventilatory support. Drugs, used include hydrocortisone, antihistaminics and vasopressors. Renal support in the form of dialysis is required in acute renal failure.5,6

160

70 60 50 40 30 20 10 0 0-10

11-20

21-30

31-40 41-50 Age in years

51-60

61-70

Figure 3. Age group-wise distribution of cases.

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COMMUNITY MEDICINE 160

150

2011

2012

2013

140 120

Table 1. Clinical Features Clinical features

112 102

100 80

65

60

50

45

43 40

30

28

20 0 OP poison

Hair dye

Others

Incidence (%)

Nausea, vomiting, abdominal pain

100

Orofacial edema

70

Muscle cramps

50

Severe rhabdomyolysis

02

Renal failure

10

Toxic myocarditis

02

Seizures

01

Figure 4. Changing trend of poisoning from OP poisoning to hair dye poisoning.

Mouth

40%

Media

60%

a

Figure 5. Source of information of hair dye as a poison.

b

Figure 6. Double tongue Figure 7. Tongue stuck sign. sign.

Age Poisoning with hair dye is more commonly seen in young age people between age groups of 21-30 years as shown in the Figure 3. The trend of poisoning in our region is changing from organophosphate (OP) poisoning to hair dye poisoning as depicted in Figure 4.

Reason for Choosing Hair Dye Eighty percent of patients told that they have chosen hair dye as a poison because it is easily available and cheaper than pesticides and easily applicable. Sixty percent of patients told that they have got this information of hair dye as poison from neighborhood and 40% of them told that they have got this information from the media (Fig. 5).

develops within first 6 hours and is rare after 6 hours. Figure 6 shows double tongue sign (small tongue like projection below the tongue) the earliest sign of severe oropharyngeal edema. Figure 7 show tongue stuck sign (tongue fully stuck between the lips).

Lab Features Table 2 shows the lab parameters of hair dye poisoning patients. TREATMENT

Clinical Features

There is no specific antidote for hair dye poisoning. Treatment is done symptomatically. Ryles tube aspiration was preferred over gastric lavage in these patients. Gastric lavage and induction of vomiting increases the contact of poison with oropharynx and increases the severity of edema. Nausea and vomiting were treated with antacids.

Clinical features were mild like nausea, vomiting, abdominal pain if consumption of hair dye is <20 mL. Symptoms were severe like orofacial edema if consumed >20 mL (Table 1). Submandibular edema

The orofacial edema and laryngeal edema are treated with antihistaminics and steroids. Local administration of steroids, adrenaline and hyaluronidase were attempted but were of little use. Hypocalcemia was

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COMMUNITY MEDICINE Table 2. Lab Parameters of Hair Dye Poisoning Patients Lab parameters

Incidence (%)

Hypocalcemia

20%

Urine (hemoglobinuria)

50%

CPK, AST, ALT, LDH

Mildly elevated in 50%, severely elated in 2%

RFT

Raised in 10% of cases

CPK = Creatine phosphokinase; AST = Aspartate aminotransferase; ALT = Alanine aminotransferase; LDH = Lactate dehydrogenase; RFT = Renal function test.

procedures, which accounts for 13% of total cases as it is life-saving procedure. Some of them needed mechanical ventilatory support. A patient who presented with submandibular edema and who was treated with tracheostomy is shown in Figure 9.

Mortality The mortality among the hair dye poisonings is very high. It accounts for about 10% deaths, which is significant. In our study, death of the patients was mainly due to laryngeal edema as it is a detrimental phenomenon, which leads to respiratory distress requiring emergency tracheostomy. If there is late presentation of the patients to emergency department or if there is any delay in performing the tracheostomy procedure, it ultimately results in death. In some patients, late complications like renal failure and toxic myocarditis also were responsible for the mortality but less compared to the acute laryngeal edema. ANALYSIS

Figure 8. Patient with rhabdomyolysis.

a

b

Figure 9. Submandibular edema (a) tracheostomy (b).

treated with the calcium gluconate intravenously.7 Renal failure8 was treated with hydration and sodium bicarbonate, if not reversed then dialysis was done in those patients and in rhabdomyolysis the patients were treated symptomatically. Figure 8 shown a patient with rhabdomyolysis.

Tracheostomy Surgical treatment is reserved for those patients in whom laryngeal edema causes respiratory distress, which do not allow the inhalation and exhalation. In our study, we have done 30 emergency tracheostomy

There is 10-fold rise in the number of hair dye poisoning cases in the year 2013. Now one of every 10 cases, admitted into acute medical ward and 50% of poison cases are the cases of hair dye poisoning. They are replacing the other modes of suicidal attempts such as pesticide poisoning and burns. It is more common in females (65%) and more in the age group of 15-35 years. There is high incidence of (70%) development of orofacial edema in these cases. It is not fully dependent on the dose of PPD consumed. The development of edema was more common in patients who had self-induced vomiting. So, it is more preferable to do Ryle’s tube aspiration than routine gastric lavage. The mean duration for development of edema is 1-6 hours. The earliest sign is development of submandibular edema. Development of severe edema is very rare after 6 hours. So, delay in reaching the hospital and self-induced vomiting had high impact on morbidity and mortality. Of the cases of orofacial edema, half of them developed severe laryngeal edema. These cases did not respond fully to antihistamine, steroids, adrenaline and local application or sprays. Emergency tracheostomy was life-saving in these conditions. Occurrence of renal failure, muscle cramps, rhadomyolysis polyneuropathy, myocardial infarction and seizure were also noted. Five percent of these cases had high renal parameters. Half of them ending in renal failure.

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COMMUNITY MEDICINE CONCLUSION There is high incidence and rapid rise of hair dye poisoning in this region. “Word of mouth” publicity regarding the suicidal potential of easily available hair dye might have contributed to clustering of cases from this area. More common in females because of cheap and easily available. More in adult age group. High incidence of development of orofacial edema. Renal failure, rhabdomyolysis, were noticed, occasionally; toxic myocarditis, seizures, are also seen. Mortality was high when there was delay in reaching the hospital, emergency tracheostomy was life-saving in severe cases of orofacial edema. These alarming facts suggest rationale use and sale of hair dye. REFERENCES

2. Soni S, Nagarik A, Gopal Kishan A, Anuradha. Hair dye poisoning: Why is it common in South India, Mediciti Hospitals, Hyderabad. 3. El-Ansary EH, Ahmed ME, Clague HW. Systemic toxicity of para-phenylenediamine. Lancet. 1983;1(8337):1341. 4. Ashraf W, Dawling S, Farrow LJ. Systemic paraphenylenediamine (PPD) poisoning: a case report and review. Hum Exp Toxicol. 1994;13(3):167-70. 5. Lava NS Dollar J. Hair dye induced rhabdomyolysis. J Electroencephalogr Clin Neurophysiol. 1996;98:18. 6. Saito K, Murai T, Yabe K, Hara M, Watanabe H, Hurukawa T. Rhabdomyolysis due to paraphenylenediamine (hair dye) - report of an autopsy case. Nihon Hoigaku Zasshi. 1990;44(5-6):469-74. 7. Lifshits M, Yagupsky P, Sofer S. Fatal paraphenylenediamine (hair dye) intoxication in a child resembling Ludwig’s angina. J Toxicol Clin Toxicol. 1993;31(4): 653-6.

1. Filali A, Semlali 1, Ottaviano V, Furnari C, Corradini D, Soulaymani R. A retrospective study of acute poisoning 8. Ezhilarasi A, Edwin Fernando M, Balaraman V, Jayakumar of paraphenylenediamine (occidental tawakt) in Morocco. M. Department of Nephrology, MMC & GGH, Chennai. Afr J Trad CAM. 2006;3(1):142-9. ■■■■

Telemedicine Shortens Door-to-needle Time: Nearly Half-hour Saved A mobile stroke treatment unit (MSTU) at Cleveland Clinic in the US uses telemedicine to connect emergency team members to a hospital-based vascular neurologist. It reduces time to tPA treatment by more than 25 minutes. Researcher Ken Uchino, MD, and colleagues report their experience in the journal JAMA Neurology, published online Dec 7. More than 400 patients have been transported by the telemedicine-assisted MSTUs since the program began operations in July 2014. MSTUs are staffed with a registered nurse, paramedic, emergency medical technician (EMT) and a CT technologist. CT is performed on board the MSTU and a neuroradiologist remotely assesses the images obtained by CT. The ambulance is also equipped with its own lab to measure prothrombin time, blood glucose, electrolyte levels, hemoglobin levels, platelet and leukocyte counts. Ninety-nine of the 100 patients had CT performed in the MSTU and 16 received IV tPA in the MSTU. One additional patient was a candidate for MSTU-delivered IV tPA, but could not be evaluated because of video failure. This patient received IV-tPA after hospital arrival. ÂÂ

Time from door to CT completion was 13 minutes in the MSTU group (IQR 9-21 minutes) and 18 minutes in the ED group (IQR 12-26 minutes).

ÂÂ

Time from door to IV thrombolysis was 32 minutes in the MSTU group (IQR 24-47 minutes) and 58 minutes in the ED group (IQR 53-68 minutes).

ÂÂ

Time to CT interpretation did not differ significantly between the two groups.

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COMMUNITY MEDICINE

Study of Healthcare-associated Infections PH MISHRA*, PALLAVI BANERJEE†, HEEMA GOSAIN‡

ABSTRACT Management of hospital-acquired infection is a very important aspect of healthcare management. A nosocomial infection affects approximately 2 million patients annually in acute care facilities in our country and their annual patient care costs several millions of rupees. Studies shows that nearly one-third of nosocomial infections can be prevented by a well-organized infection control program. But only <10% are actually prevented. Healthcare waste is an important source of healthcare-associated infection (HAI) and should be considered as a reservoir of pathogenic microorganisms, which can cause contamination and give rise to infection. If waste is inadequately managed, these microorganisms can be transmitted by direct contact, air or by a variety of vectors. Infectious waste contributes in this way to the risk of nosocomial infections, putting the health of hospital personnel and patients, at risk. The aim of the Hospital Infection Control Program is dissemination of information, surveillance activities, investigation, prevention and control of nosocomial infections in the hospitals.

Keywords: Hospital-acquired infection, hospital waste management, Hospital Infection Control Committee

T

his study describes the measures taken in a tertiary care hospital to control infection and its effect. There are big human and economic burdens of healthcare-associated infections (HAIs). The appropriate resources and activities required for an effective Infection Prevention and Control Program (IPCP) are very important to minimize the incidence and adverse outcomes of these infections.

surgical site, urinary tract, pulmonary and skin and soft tissue infections. Transmission of infectious diseases, such as SARS, tuberculosis, influenza, Clostridium difficile (C. difficile), Norovirus and antibioticresistant organisms (e.g., MRSA [methicillin-resistant Staphylococcus aureus] and VRE [vancomycin-resistant enterococci]) to patients within the healthcare delivery system are also considered HAIs.

The goals of IPCPs are to minimize these and other negative effects by contributing to patient safety through protecting patients from infections; protecting healthcare workers and visitors to healthcare facilities from infections; and accomplishing these goals in the most cost-effective manner whenever possible, thus reducing the economic impacts of HAIs on individual health facilities, health systems and the national healthcare industry. HAIs occur in relation to healthcare interventions including invasive, diagnostic, surgical and medical procedures. Examples of HAIs include bloodstream,

IPCPs were first introduced in the1950s. Initially referred to as Infection Control Programs, these hospital-based programs focused on the control of hospital-acquired infections, which were referred to as nosocomial infections. As healthcare increased in complexity and sophistication and expanded beyond acute care, the mandate of IPCPs should have expanded to encompass infections in all settings across the healthcare continuum. Contrary to expectations, however, IPCPs have seen their resources either decrease or remain static and consequently have failed to achieve the needs of the expanding mandate.

*Medical Superintendent †Microbiologist ‡Senior Executive Secretary Indian Spinal Injuries Centre, C Block, Vasant Kunj, New Delhi Address for correspondence Dr PH Mishra Medical Superintendent Indian Spinal Injuries Centre, C Block, Vasant Kunj, New Delhi - 110 070 E-mail: paramhansmishra@yahoo.com

HAIs contribute to significant morbidity, mortality and economic costs and the risk of hospital-acquired infections is increasing. These infections are the most common complication affecting hospitalized patients. Effective IPCPs reduce nosocomial infections by at least 30% and have repeatedly been shown to be effective in controlling infection outbreaks in the healthcare setting. Appropriate resources, both in quantity and in quality, are required to support effective IPCPs.

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COMMUNITY MEDICINE AIM OF THE STUDY The aim of the study is to see the effect of Hospital Infection Control Program in the intensive care unit (ICU) of a tertiary care hospital. MATERIAL AND METHODS This study was conducted in the ICU of a tertiary care super specialty hospital (Indian Spinal Injuries Centre) by observing and monitoring the effect of implementing Hospital Infection Control Program in postoperative cases over a period of 7 days from the date of surgery. Indian Spinal Injuries Centre is a tertiary care specialized centre for spinal injury patient, orthopedics and joint replacement.

Infection Control Program Hospital control program team consists of two infection control nurses and one infection control officer (microbiologist) who are responsible for infection control work. There is a multidisciplinary Hospital Infection Control Committee chaired by medical superintendent and microbiologist is the member secretary and other members are from different clinical and nonclinical specialties, nursing and housekeeping. REVIEW OF LITERATURE A nosocomial infection (derived from the Greek words nosos [disease] and komein [to care for], and later the Latin word for hospital nosocomium) is defined as an “Infection that is not present or incubating when the patient is admitted to hospital or other healthcare facility”. The time frame for diagnosis of a nosocomial infection will thus clearly be dependent on the incubation period of the specific infection; 48-72 hours after admission is generally deemed indicative of nosocomial, rather than community-acquired infection. Although generally associated with hospital admission (hence the term hospital-acquired infection), nosocomial infections can arise after admission to any healthcare facility and the term HAI is increasingly being used. Such infections are common and associated with great morbidity and mortality. Indeed, one provocative headline stated “Hospital-acquired infections kill 5,000 patients a year in England”. The information for this news piece was taken from a government report on hospital-acquired infection in England, which suggested that there are at least 1,00,000 cases of hospital-acquired infection every

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year in England, costing the UK National Health Service some £1 billion each year. In addition to their association with increased morbidity and mortality, nosocomial infections are frequently associated with drug-resistant microorganisms, including MRSA and extended-spectrum β-lactamase (ESBL)-producing Gram-negative bacteria, which can pose considerable therapeutic problems. Medicolegal issues can also arise, since patients or their families sometimes blame the hospital or staff for the infection, and demand compensation. Nosocomial infections can affect any part of the body, but respiratory tract infections are most frequent, followed by central line infections, urinary tract infections and wound infections. PATHOPHYSIOLOGY The development of nosocomial infection is dependent on two key pathophysiological factors: decreased host defences and colonization by pathogenic, or potentially pathogenic, bacteria. Although these two factors can arise independently, for infection to result both must be present to some degree. Direct contact can include spread from the hands of healthcare workers or visitors, but also from contaminated equipment and infusions. UNDERLYING HEALTH IMPAIRMENT Certain conditions predispose to bacterial colonization, and hence nosocomial infection, by impairing hostdefense mechanisms. Patients with chronic lung disease are at an increased risk of developing nosocomial infection. Poor nutrition and chronic debilitation are associated with reduced immune defense, explaining the increased risk of nosocomial infections in such patients. THE ACUTE DISEASE PROCESS The underlying disease process as well as the severity of disease can affect the risk of developing nosocomial infection. Patients with a primary diagnosis of trauma or burns are at an increased risk. Trauma patients too have altered immune responses, making them more likely to develop infection. Perhaps unsurprisingly, severity of illness as assessed by severity scores has also been associated with the development of nosocomial infection, but rather associated with other risk factors for infection, such as prolonged length of stay.


COMMUNITY MEDICINE INVASIVE DEVICES

Italy ICU-acquired infection (%)

In a report from the National Nosocomial Infection Surveillance (NNIS) system, involving data from 4,98,998 patients, 83% of episodes of nosocomial pneumonia were associated with mechanical ventilation, 97% of urinary tract infections arose in patients with a urinary catheter in place and 87% of primary bloodstream infections were in patients with a central line.

35 30 Spain France Austria Portugal Ireland Germany Netherlands Belgium UK Luxembourg Scandinavia R2 = 0-678 Switzerland

25 20 15 10 5 5

TREATMENT METHODS Various therapeutic strategies are associated with a raised risk of nosocomial infection. Cook and colleagues noted that the administration of paralytic agents was an independent predictor of nosocomial pneumonia in their study of 1,014 mechanically ventilated patients. Sedative drugs, corticotherapy, antacids, stress-ulcer prophylaxis, previous antibiotic therapy and multiple blood transfusions have all been identified as risk factors. EPIDEMIOLOGY The quoted incidence of nosocomial infection varies, according to the setting i.e., the type of hospital or ICU the population of patients, and the precise definition used (hospital-acquired, ICU acquired, nosocomial pneumonia). One of the largest databases related to nosocomial infection in intensive care. In this 1-day point prevalence study, information was obtained on all patients who occupied a bed in an ICU over 24 hours in 1992: 10,038 patients were recruited from 1,417 western European ICU. Of these patients, 4,501 were infected and of those 2,064 (21% of the total number) had an ICU-acquired infection. There was a relation between the prevalence of nosocomial infection and mortality according to country, with greater incidence of infection and higher mortality rates in the southern European countries of Portugal and Greece than in Scandinavia and Switzerland (Fig. 1). Other studies have quoted incidence rates between 9% and 37%, dependent largely on the populations studied and the definitions used. Differences in surveillance techniques can also affect detection of nosocomial infection and, hence, rates. However, we are becoming less invasive in our treatment techniques (less aggressive surgical procedures are used, fewer Swan-Ganz catheters are being placed, noninvasive mechanical ventilation is being applied when possible and appropriate) and are more aware of techniques that could prevent nosocomial infection (antibiotic-

Greece

10

15

20

25

30

Mortality (%)

Figure 1. Correlation between prevalence rate of ICUacquired infection and mortality rate by country.

coated catheters, avoidance of nasotracheal intubation thus limiting sinusitis), which could result in a reduced incidence of infections. In a study on one ICU, comparing data over 25 years, the incidence of bacteremia increased from 1.8% in 1971-75 to 5.5% in 1991-95, with the largest increase seen between 1986-90 and 1991-95. Dagan and co-workers, however, reported a fall in the nosocomial infection ratio from 25.2% in 1987 to 20% in 1992. EFFECT OF NOSOCOMIAL INFECTION The effect of nosocomial infection in terms of morbidity, mortality and increased resource use is substantial. Nosocomial infection is associated with an increased length of stay, which results in an additional cost of about US$ 3.5 billion per year, without taking into account antibiotic or other therapeutic costs. Crude mortality rates associated with nosocomial infection vary from 12% to 80%, dependent on the population studied and the definitions used. ORGANISMS Any organism can be implicated in nosocomial infection, and many infections are polymicrobial. Recent years have seen a swing in the pattern of infecting organisms towards Gram-positive infections. The surveillance and control of pathogens of epidemiologic importance (SCOPE) project data revealed that Gram-positive cocci were isolated in 64% of 10,617 episodes of nosocomial bacteremia, whereas Gram-negative bacilli were isolated in only 27% of cases. The EPIC study11 identified the following as the most commonly reported nosocomial pathogens: S. aureus (30%), Pseudomonas aeruginosa (29%), coagulase-negative staphylococci (19%), yeasts (17%), Escherichia coli (13%), enterococci (12%), Acinetobacter spp. (9%) and

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COMMUNITY MEDICINE Klebsiella spp. (8%). Other studies have noted similar patterns of causative microorganisms. ANTIMICROBIAL RESISTANCE Antimicrobial resistance patients who remain in hospital for long periods can have successive infections and are more likely to develop nosocomial infections due to resistant pathogens. In the EPIC study, 60% of the S. aureus for which methicillin resistance patterns were reported, were resistant (as high as 80% in Italy, France, and Greece), and 46% of P. aeruginosa were resistant to gentamicin. Legras and colleagues similarly reported that 58% of the S. aureus in their study in French ICUs were methicillin-resistant. The NNIS reports increased rates of resistance for many microorganisms when comparing data from 2000 with those pooled from the period 1995 to 1999 (Fig. 2). One approach to try and reduce the frequency of resistant organisms is to use antibiotic rotation or cycling. Gruson and colleagues noted that antibiotic rotation and restricted use of ceftazidime and ciprofloxacin caused a fall in the number of cases of VAP-associated with resistant Gram-negative bacilli, and an increase in the numbers of methicillinsensitive S. aureus. Raymond and co-workers introduced a quarterly rotation of empirical antibiotics in their ICU and noted great reductions in the incidence of antibiotic-resistant Gram-positive coccal infections (7.8 infections per 100 admissions vs 14.6 infections per 100 admissions, p < 0.0001), antibiotic resistant Gram-negative bacillary infections (2.5 infections per 100 admissions vs 7.7 infections per 100 admissions p < 0.0001), and mortality associated with infection (2.9 deaths per 100 admissions vs 9.6 deaths per 100 admissions, p < 0.0001) during rotation. Other groups have reported similar benefits from such strategies, which require continued input from infectious disease specialists if they are to be employed effectively.

Urinary Tract This is the second most common site of nosocomial infection (accounting for 8-35% of infections), although the consequences of nosocomial urinary tract infection are usually less severe than for other types of nosocomial infection. Urinary tract infections are generally associated with the presence of a urinary catheter. Silver hydrogel-coated catheters might reduce the incidence of nosocomial urinary tract infection in general hospital patients, although results of several studies, including one in patients in intensive care, noted no significant differences. Antibiotic-coated catheters (with nitrofural or ciprofloxacin) have been effective in animals and in vitro, but no results from clinical tests have been published and concerns exist as to the effects of such catheters on the development of antimicrobial resistance. Prevention of nosocomial urinary tract infections should thus aim at avoiding catheter placement whenever possible, but when necessary, reducing the duration of catheterization.

Catheter-related Infections Catheter-related bloodstream infections are associated with pronounced increases in length of time in ICU and hospital costs.

Other Sites Nosocomial infections from other sources are generally decreasing in incidence. One good example of how change in practice can affect infection rates is the case of nosocomial sinusitis, a nosocomial infection specific to ICU. Results of studies indicate that nosocomial sinusitis, carrying an increased risk of nosocomial pneumonia, was significantly more common in patients with nasal devices, such as nasogastric or nasotracheal tubes, than in those without.

SPECIFIC NOSOCOMIAL INFECTIONS

In a randomized trial, Rouby and colleagues reported that radiological sinusitis developed in 95% of patients intubated with a nasal tube compared with 23% in patients with an oral tube. Use of the orotracheal route for intubation, rather than the nasotracheal route, has reduced the incidence of nosocomial sinusitis.

Respiratory

FUTURE PERSPECTIVES

The respiratory tract is the most common site of nosocomial infection in the ICU. In the EPIC study, pneumonia accounted for 47% of nosocomial infections, the figure rising to 65% if all respiratory infections were included.

The roles of understaffing and staff composition as predisposing factors for nosocomial infection need to be emphasised. Fridkin and colleagues noted that the patient-to-nurse ratio was an independent risk factor for catheter-related bloodstream infection in

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COMMUNITY MEDICINE their population of surgical patients in intensive care. Infection surveillance can reduce nosocomial infection rates when incorporated with infection prevention programs, but needs to be improved and implemented and combined with continuing educational programs to encourage compliance with basic infection control procedures. Infection surveillance is increasingly undertaken and various surveillance systems have been developed. DEFINITIONS OF HOSPITAL-ACQUIRED (NOSOCOMIAL) INFECTIONS

ÂÂ

Skin and soft tissue infection, other infections

ÂÂ

Intra-abdominal infection

ÂÂ

Osteomyelitis

ÂÂ

Septicemia

ÂÂ

Meningitis

ÂÂ

Intravascular-access-device infection/infection in tracheal incision

ÂÂ

Infections in newborns.

OBSERVATIONS

The Centers for Disease Control and Prevention (CDC) defined hospital infection as follows: Hospital-acquired infection (nosocomial infection) is the occurrence of infection after hospital admission, without evidence that the infection was present or incubating at the time of admission. A nosocomial infection usually occurs within 30 days after hospital stay or within 1 year in case of infection associated with insertion of a prosthetic device. Types of HAI: All types were recorded. Infections in more than one site in the same person were registered as separate infections.

This study shows that if IPCP is implemented and monitored it can bring down HAI even in a hospital treating spine injuries (Where patients are unable to take care and move hence there are more chances of infection) (Table 1 and Fig. 2). DISCUSSION

Impacts of HAIs: An Overview Society as a whole suffers negative consequences from HAIs. These infections, including their investigation and treatment, have both immediate and future implications

The following are clinical infection categories: ÂÂ

Urinary tract infection (excluding asymptomatic bacteriuria

ÂÂ

Upper respiratory tract infection

ÂÂ

Lower respiratory tract infection

ÂÂ

Gastroenteritis

ÂÂ

Postoperative superficial

wound

infection;

Table 1. Infection Control Data for Indian Spinal Injuries Centre Dec 11

incision

ÂÂ

Postoperative wound infection, deep-seated

ÂÂ

Skin and soft tissue infection, burn infection

site

Jan 12

Feb 12

March 12

April 12

May 12

UTI

4.4

3.6

3.7

3.2

2.4

2

BSI

1.4

0.7

0

0

0

0

SSI

1.8

1.3

1.1

1

0.8

0.6

VAP

0

0

16.2

6.2

0

0

UTI = Urinary tract infection; BSI = Bloodstream infection; SSI = Surgical site infection; VAP = Ventilator-associated pneumonia.

20

UTI 16.2

BSI

15

SSI VAP

10 5

6.2

4.4 3.7

3.6 1.4 1.8

0 Dec 11

0

0.7 1.3 0 Jan 12

3.2 0

1.1

Feb 12

0 1 March 12

2.4 0 0.8 0 April 12

2

0 0.6 0

May 12

Figure 2. Infection control data for Indian Spinal Injuries Centre.

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COMMUNITY MEDICINE for the individual, the healthcare system, and the local, national and global communities. Although there are limited data describing the societal impact of HAIs, some emerging examples illustrate their breadth and gravity.

Can be performed with:

Alcoholic hand sanitizer

Use of plain soap and water for routine hand washing.

Use of antimicrobial agent for specific circumstances.

Costs and Rates of HAIs The management of HAIs exacerbates rising healthcare costs, although the exact attributable cost to society is unknown. Related financial impacts of HAIs include an increased time away from home for the individual with an infection and if employed, the individual experiences loss of work and wages or at least an increased use of sick leave.

Gloves

The indirect costs, such as a family members’ time lost from work in caring for the affected individual, must be considered in addition to the direct costs of increased use of resources, but have not been wellquantified. Overall, HAIs have a detrimental effect on the individual’s quality-of-life and are very costly. The HAI financial burden to the healthcare system has been estimated by measuring a number of indices including increased:

ÂÂ

ÂÂ

Wear gloves when touching blood, body fluids, secretions, excretions and contaminated items. Put on clean gloves just before touching mucous membranes and nonintact skin.

Mask, Eye Protection, Face Shield Wear a mask and eye protection or a face shield during procedures and patient care activities that are likely to generate splashes or sprays of blood, body fluids, secretions and excretions.

Gown ÂÂ

Wear a gown during procedures and patientcare activities that are likely to generate splashes or sprays of blood, body fluids, secretions or excretions.

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Number of readmissions to hospital

ÂÂ

Length of stay

Patient-care Equipment

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Use of antimicrobials

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ÂÂ

Surveillance and isolation measures for AROs

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Laboratory and radiological services attributable to diagnosing and managing HAIs

Environmental Control

ÂÂ

Overall direct or indirect costs

ÂÂ

ÂÂ

Cost attributable to outbreaks.

Effective infection control program should include the following: ÂÂ

Organized surveillance and control activities

ÂÂ

One infection control practitioner for every major Health Facility

ÂÂ

A trained hospital epidemiologist

ÂÂ

A system for reporting surgical wound infection rates and other infection back to the practicing surgeons and physicians.

Ensure that reusable equipment is not used for the care of another patient until it has been cleaned and reprocessed appropriately. Ensure that the hospital has adequate procedures for the routine care, cleaning and disinfection of environmental surfaces.

Linen ÂÂ

Handle used linen, soiled with blood, body fluids, secretions and excretions in a manner that prevents skin and mucous membrane exposures and that avoids transfer of microorganisms to other patients and environments.

Occupational Health and Blood Borne Pathogens ÂÂ

Take care to prevent injuries when using needles, scalpels, and other sharp instruments or devices.

Essentials of the Standard Precautions to be Used in the Care of all Patients

ÂÂ

Use ventilation devices as an alternative to mouthto-mouth resuscitation methods.

Hand Hygiene

Place of Care of the Patient

ÂÂ

630

Performed between patient contacts, after touching blood, secretions, excretions and contaminated items, whether or not gloves are worn.

Indian Journal of Clinical Practice, Vol. 26, No. 7, December 2015

ÂÂ

Place a patient, who contaminates the environment or who does not assist in maintaining appropriate hygiene, in an isolated (or separate) room.


COMMUNITY MEDICINE Goals for Infection Control There are three principal goals for hospital infection control and prevention programs regardless of the healthcare setting or service mix: ÂÂ

Protect the patient

ÂÂ

Protect the healthcare worker, visitors and others in the healthcare environment

ÂÂ

Accomplish the previous goals in a timely, efficient, and cost-effective manner, whenever possible.

Priority Outcome Areas

Hospital Infection Control Committee play a major role in this. HAI rates could be reduced over a period of 6 months by simple approach like implementing and monitoring hand hygiene compliance among staff and those handling the patients. DO’S AND DON’TS

Infection Control Do’s ÂÂ

Ensure that all isolation/cohort areas are supplied with gloves/gowns, aprons and hand-hygiene supplies.

ÂÂ

Encourage and facilitate hand-hygiene practices

ÂÂ

Ensure ongoing and terminal cleaning of isolation areas.

The priority outcome areas identified are: ÂÂ

Management accountability

commitment,

leadership

and

ÂÂ

Monitoring infection control and reducing infection rates

ÂÂ

Prevention of adverse events

ÂÂ

Protecting healthcare workers and visitors

ÂÂ

Surveillance.

Don’ts ÂÂ

Transfer isolated/cohorted clinically essential.

ÂÂ

Prolong patient’s placement in isolation area on cessation of symptoms/clearance of specimens/ completion of treatment and/or advice by specialist.

Management Commitment, Leadership and Accountability The hospital management is responsible for ensuring management supports and allocates appropriate resources for effective prevention, monitoring and control of infection.

Prevent Adverse Events The hospital management has a risk management approach and ensures that senior management support an effective risk management program, which incorporates strategies for addressing infection control issues.

Monitor IC and Reduce Infection Rates Interruption of the transmission of or potential transmission of infectious disease, outbreak investigations and control, and performance improvement activities.

Protect Staff and Visitors

There is a defined program for nosocomial infection surveillance which includes the collection, analysis and reporting back of data to those who need to know and take action. The Infection Control Team and

unless

Infection Control in Healthcare Environment Cleaning of Patient Care Devices Do’s ÂÂ

Perform most cleaning, disinfection and sterilization of patient-care devices in a central processing department in order to control quality.

ÂÂ

Meticulously clean patient-care items with water and detergent or with water and enzymatic cleaners before high-level disinfection or sterilization procedures.

ÂÂ

Remove visible organic residue (e.g., residue of blood and tissue) and inorganic salts with cleaning.

ÂÂ

Use cleaning agents that are capable of removing visible organic and inorganic residues.

ÂÂ

Clean medical devices as soon as possible after use (e.g. at the point of use because soiled materials become dried onto the instruments). Dried or baked materials on the instrument make the removal process more difficult.

ÂÂ

Perform either manual cleaning (i.e., using friction) or mechanical cleaning (e.g., with ultrasonic cleaners, washer-disinfector, washer-sterilisers).

ÂÂ

Inspect equipment surfaces for breaks in integrity that can impair either cleaning or disinfection/ sterilization.

The hospital management is responsible for the provision of a safe environment for patients, staff and visitors.

Surveillance

individual

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COMMUNITY MEDICINE Disinfectant Fogging

Don’ts

Don’t

ÂÂ

Disconnect the catheter and drainage tube unless the catheter requires irrigation.

ÂÂ

Screen for asymptomatic bacteriuria in catheterized patients.

ÂÂ

Treat asymptomatic bacteriuria in catheterized patients except before invasive urologic procedures.

ÂÂ

Perform disinfectant fogging for routine purposes in patient-care areas.

Disposal of Biohazard Materials Do’s ÂÂ

Ensure segregation of waste at point of origin into designated colored bags depending on type of waste as per BMW (Management of Handling Rules, 1998).

ÂÂ

Irrigate catheter.

ÂÂ

Perform continuous irrigation of the bladder with antimicrobials as a routine infection prevention measure.

ÂÂ

Ensure that janitor wears gloves, mask, apron when handling biomedical waste.

ÂÂ

Use systemic prophylaxis.

ÂÂ

Bag all used linen at point of origin. While changing linen avoid unnecessary agitation.

ÂÂ

Change catheters frequently.

ÂÂ

ÂÂ

Bag all linen, tie it up and keep aside.

Routinely use silver-coated or other antibacterial catheters.

ÂÂ

Use dedicated trolley for waste and for used linen.

ÂÂ

Disinfect waste trolley with FDA approved disinfectant after each use.

ÂÂ

Use material that do not generate fumes in wards and critical care units.

ÂÂ

Discard sharps in the dedicated sharps container.

Best Practices for Prevention and Monitoring of Catheter-associated Urinary Tract Infections Do’s Limit the use of indwelling urethral catheters to the following: ÂÂ

Perioperative use for selected surgical procedures

ÂÂ

Urine output monitoring in critically ill patients

ÂÂ

Management of acute urinary retention and urinary obstruction

ÂÂ

Assistance in pressure ulcer healing for incontinence

ÂÂ

Properly secure indwelling catheters after insertion

ÂÂ

Maintain a sterile, continuously closed drainage system

ÂÂ

Collect a small sample of fresh urine for examination by aspirating urine from the sampling port with a sterile needle and syringe after cleansing the port with disinfectant

ÂÂ

Maintain unobstructed urine flow

ÂÂ

Empty the collecting bag regularly, using a separate collecting container for each patient

ÂÂ

Keep the collecting bag below the level of the bladder at all times.

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Indian Journal of Clinical Practice, Vol. 26, No. 7, December 2015

antimicrobials

routinely

as

Best Practices for Prevention and Monitoring of Surgical Site Infections Do’s ÂÂ

Keep preoperative hospital stay as short as possible.

ÂÂ

Control serum blood glucose level in all diabetic patients adequately.

ÂÂ

Use electric clippers rather than razors or depilatories for hair removal. Hair should be removed immediately before the operation.

ÂÂ

Use an acceptable antiseptic agent for skin preparation, such as alcohol (usually 70-92%), chlorhexidine (4%, 2% or 0.5% in alcohol base) or iodine/iodophors (usually 10% aqueous with 1% iodine or with 7.5%).

ÂÂ

Perform the surgical scrub for duration of 3-5 minutes.

ÂÂ

Select a prophylactic antimicrobial agent based on its efficacy against the most common pathogens causing surgical site infection for a specific operation.

ÂÂ

Administer a antimicrobial prophylaxis, ideally within 30 minutes, but not longer than 2 hours before the initial incision.

ÂÂ

Maintain positive pressure ventilation in the operating room with respect to the corridors and adjacent areas.

ÂÂ

Maintain a minimum of 15 air changes per hour in the operating room, of which at least 3 should be of fresh air.

ÂÂ

Keep operating room doors closed except when needed for passage of equipment, personnel and the patient.


COMMUNITY MEDICINE ÂÂ

Limit the number of personnel entering the operating room, to necessary ones only.

ÂÂ

Promptly remove any intravascular catheter that is no longer essential.

ÂÂ

Wet vacuum the operating room floor after the last operation of the day or in night with an EPAapproved hospital disinfectant.

ÂÂ

ÂÂ

Protect an incision closed primarily with a sterile dressing for 24-48 hours postoperatively.

Replace all catheters as soon as possible and after no longer than 48 hours when adherence to aseptic technique can not be ensured (i.e., when catheters are inserted during a medical emergency)

ÂÂ

ÂÂ

Wash hands with an antiseptic agent before and after dressing changes or on any contact with the surgical site.

Use a subclavian site (rather than a jugular or a femoral site) in adult patients to minimize infection risk for tunneled central venous catheter (CVC) placement.

Identify SSI using CDC definition without modification among surgical in patients and out patients.

ÂÂ

ÂÂ

Conduct surveillance in ICUs and other patient populations to determine catheter-related bloodstream infection (CRBSI) rates, monitor trends in those rates and assist in identifying lapses in infection control practices.

Don’ts ÂÂ

Extend antibiotic prophylaxis postoperatively.

ÂÂ

Routinely use vancomycin for prophylaxis.

ÂÂ

Perform special cleaning or disinfection of operating rooms after contaminated or dirty operations.

ÂÂ

Perform routine environmental sampling of the operating room. Perform microbiologic sampling of operating room environmental surfaces or air only as part of an epidemiologic investigation.

ÂÂ

Do’s Educate healthcare workers regarding the indications for intravascular catheter use, proper procedures for the insertion and maintenance of intravascular catheters.

ÂÂ

Observe hand hygiene before and after palpating catheter insertion sites, as well as before and after inserting, replacing, accessing, repairing or dressing an intravascular catheter.

ÂÂ

Maintain aseptic technique for the insertion and care of intravascular catheters.

ÂÂ

Disinfect clean skin with an appropriate antiseptic before catheter insertion and during dressing changes. Although a 2% chlorhexidine-based preparation is preferred, but tincture of iodine, an iodophor or 70% alcohol can also be used.

ÂÂ

ÂÂ

Routinely culture catheter tips.

ÂÂ

Routinely use arterial or venous cut down procedures as a method to insert catheters.

ÂÂ

Apply organic solvents (e.g., acetone and ether) to the skin before insertion of catheters or during dressing changes.

ÂÂ

Use topical antibiotic ointment or creams on insertion sites (except when using dialysis catheters) because of their potential to promote fungal infections and antimicrobial resistance.

ÂÂ

Routinely replace central venous or arterial catheters solely for the purposes of reducing the incidence of infection.

ÂÂ

Routinely replace venous catheters in patients who are bacteremic or fungemic if the source of infection is unlikely to be the catheter.

ÂÂ

Use filters routinely for infection-control purposes.

ÂÂ

Administer intranasal or systemic antimicrobial prophylaxis routinely before insertion or during use of an intravascular catheter to prevent catheter colonization or bloodstream infection.

ÂÂ

Routinely use antibiotic lock solutions to prevent CRBSI. Use prophylactic antibiotic lock solution only in special circumstances (e.g. in treating a patient with a long-term cuffed or tunneled catheter or port, having a history of multiple CRBSIs despite optimal maximal adherence to aseptic technique.

Use flash sterilization for routine reprocessing of surgical instruments.

Best Practices for Prevention and Monitoring of Intravascular Catheter-related Infections ÂÂ

Don’ts

Select the catheter, insertion technique and insertion site with the lowest risk for complications (infectious and noninfectious) for the anticipated type and duration of intravenous therapy (IV) therapy.

CONCLUSION HAIs increased morbidity, mortality and resource expenditure throughout the hospital setting and particularly in the ICU. A multidisciplinary approach to prevention that involves the whole intensive-care team including management is essential if we are to succeed

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COMMUNITY MEDICINE in preventing infections. Awareness of risk factors and attention to simple preventive measures such as hand hygiene can reduce the incidence and effect of these infections. SUGGESTED READING 1. Garner JS, Jarvis WR, Emori TG, Horan TC, Hughes JM. CDC definitions for nosocomial infections, 1988. Am J Infect Control. 1988;16:128-40. 2. Mayor S. Hospital acquired infections kill 5000 patients a year in England. BMJ. 2000;321:1370. 3. House of Commons Committee of Public Accounts. The management and control of hospital acquired infection in acute NHS trusts in England. www. publications.parliament.uk/pa/cm 199900/cmselect/cm pubacc/306/30603.htm. 4. Wang JT, Chang SC, Ko WJ, et al. A hospital-acquired outbreak of methicillin-resistant Staphylococcus aureus infection initiated by a surgeon carrier. J Hosp Infect. 2001;47:104-9. 5. Harnett SJ, Allen KD, Macmillan RR. Critical care unit outbreak of Serratia liquefaciens from contaminated pressure monitoring equipment. J Hosp Infect. 2001;47: 301-7. 6. Riley TV, Webb SA, Cadwallader H, Briggs BD, Christiansen L, Bowman RA. Outbreak of gentamicinresistant Acinetobacter baumanii in an intensive care unit: clinical, epidemiological and microbiological features. Pathology. 1996;28:359-63. 7. Torres A, Aznar R, Gatell JM, et al. Incidence, risk and prognosis factors of nosocomial pneumonia in mechanically ventilated patients. Am Rev Respir Dis. 1990;142:523-8. 8. Bochicchio GV, Joshi M, Knorr KM, Scalea TM. Impact of nosocomial infections in trauma: does age make a difference? J Trauma. 2001;50:612-7. 9. Kollef MH. Ventilator-associated pneumonia: multivariate analysis. JAMA. 1993;270:1965-70.

a

10. Hanson LC, Weber DJ, Rutala WA, Samsa GP. Risk factors for nosocomial pneumonia in the elderly. Am J Med. 1992;92:161-6.

15. Cunnion KM, Weber DJ, Broadhead WE, Hanson LC, Pieper CF, Rutala WA. Risk factors for nosocomial pneumonia: comparing adult critical-care populations. Am J Respir Crit Care Med. 1996;153:158-62. 16. Girou E, Pinsard M, Auriant I, Canonne M. Influence of the severity of illness measured by the Simplified Acute Physiology Score (SAPS) on occurrence of nosocomial infections in ICU patients. J Hosp Infect. 1996;34:131-7. 17. Hurr H, Hawley HB, Czachor JS, Markert RJ, McCarthy MC. APACHE II and ISS scores as predictors of nosocomial infections in trauma patients. Am J Infect Control. 1999;27: 79-83. 18. Richards MJ, Edwards JR, Culver DH, Gaynes RP. Nosocomial infections in combined medical-surgical intensive care units in the United States. Infect Control Hosp Epidemiol. 2000;21:510-5. 19. Ponce de Leon-Rosales SP, Molinar-Ramos F, DominguezCherit G, Rangel-Frausto MS, Vazquez-Ramos VG. Prevalence of infections in intensive care units in Mexico: a multicenter study. Crit Care Med. 2000;28:1316-21. 20. Tejada AA, Bello DS, Chacon VE, et al. Risk factors for nosocomial pneumonia in critically ill trauma patients. Crit Care Med. 2001;29:304-9. 21. Ibrahim EH, Tracy L, Hill C, Fraser VJ, Kollef MH. The occurrence of ventilator-associated pneumonia in a community hospital: risk factors and clinical outcomes. Chest. 2001;120:555-61. 22. Kropec A, Schulgen G, Just H, Geiger K, Schumacker M, Daschner F. Scoring systems for nosocomial pneumonia in ICUs. Intensive Care Med. 1996;22:1155-61. 23. Markowicz P, Wolff M, Djedaini K, et al. Multicenter prospective study of ventilator-associated pneumonia during acute respiratory distress syndrome: incidence, prognosis, and risk factors. Am J Respir Crit Care Med. 2000;161:1942-48. 24. Papia G, McLellan BA, El Helou P, et al. Infection in hospitalized trauma patients: incidence, risk factors, and complications. J Trauma. 1999;47:923-7. 25. Legras A, Malvy D, Quinioux AI, et al. Nosocomial infections: prospective survey of incidence in five French intensive care units. Intensive Care Med. 1998;24:1040-6.

11. Cook DJ, Walter SD, Cook RJ, et al. Incidence of and risk factors for ventilator-associated pneumonia in critically ill patients. Ann Intern Med. 1998;129:433-40.

26. Girou E, Stephan F, Novara A, Safar M, Fagon JY. Risk factors and outcome of nosocomial infections: results of a matched case control study of ICU patients. Am J Respir Crit Care Med. 1998;157:1151-8.

12. Wallace WC, Cinat M, Gornick WB, Lekawa ME, Wilson SE. Nosocomial infections in the surgical intensive care unit: a difference between trauma and surgical patients. Am Surg. 1999;65:987-90.

27. Dagan O, Cox PN, Ford-Jones L, Ponsonby J, Bohn DJ. Nosocomial infection following cardiovascular surgery: comparison of two periods, 1987 vs 1992. Crit Care Med. 1999;27:104-8.

13. Appelgren P, Hellstrom I, Weitzberg E, Soderlund V, Bindslev L, Ransjo U. Risk factors for nosocomial intensive care infection: along-term prospective analysis. Acta Anaesthesiol Scand. 2001;45:710-9.

28. Gastmeier P, Sohr D, Just HM, Nassauer A, Daschner F, Ruden H. How to survey nosocomial infections. Infect Control Hosp Epidemiol. 2000;21:366-70.

14. Napolitano LM, Faist E, Wichmann MW, Coimbra R. Immune dysfunction in trauma. Surg Clin North Am. 1999;79:1385-416.

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29. Pittet D, Tarara D, Wenzel RP. Nosocomial bloodstream infection in critically ill patients: excess length of stay, extra costs and attributable mortality. JAMA. 1994;271: 1598-601.


COMMUNITY MEDICINE 30. Appelgren P, Hellstrom I, Weitzberg E, Soderlund V, Bindslev L, Ransjo U. Risk factors for nosocomial intensive care infection: a long-term prospective analysis. Acta Anaesthesiol Scand. 2001;45:710-9.

46. Karchmer TB, Giannetta ET, Muto CA, Strain BA, Farr BM. A randomized crossover study of silver-coated urinary catheters in hospitalized patients. Arch Intern Med. 2000;160:3294-8.

31. Rello J, Ochagavia A, Sabanes E, et al. Evaluation of outcome of intravenous catheter-related infections in critically ill patients. Am J Respir Crit Care Med. 2000; 162:1027-30.

47. Thibon P, Le Coutour X, Leroyer R, Fabry J. Randomized multicentre trial of the effects of a catheter coated with hydrogel and silver salts on the incidence of hospitalacquired urinary tract infections J Hosp Infect. 2000;45: 117-24.

32. Digiovine B, Chenoweth C, Watts C, Higgins M. The attributable mortality and costs of primary nosocomial bloodstream infections in the intensive care unit. Am J Respir Crit Care Med. 1999;160:976-81. 33. Correa L, Pittet D. Problems and solutions in hospitalacquired bacteraemia. J Hosp Infect. 2000;46:89-95. 34. Friedman G, Silva E, Vincent JL. Has the mortality of septic shock changed with time? Crit Care Med. 1998;26:2078-86. 35. Edmond MB, Wallace SE, McClish DK, Pfaller MA, Jones RN, Wenzel RP. Nosocomial bloodstream infections in United States hospitals: a three-year analysis. Clin Infect Dis. 1999;29:239-44. 36. Spencer RC. Predominant pathogens found in the European Prevalence of Infection in Intensive Care Study. Eur J Clin Microbiol Infect Dis. 1996;15:281-85. 37. National Nosocomial Infections Surveillance (NNIS) System Report, Data Summary from January 1992-June 2001, issued August 2001. Am J Infect Control. 2001;29:404-21. 38. Gruson D, Hilbert G, Vargas F, et al. Impact of colonystimulating factor therapy on clinical outcome and frequency rate of nosocomial infections in intensive care unit neutropenic patients. Crit Care Med 2000;28:3155-60. 39. Raymond DP, Pelletier SJ, Crabtree TD, et al. Impact of a rotating empiric antibiotic schedule on infectious mortality in an intensive care unit. Crit Care Med. 2001;29:1101-08. 40. Kollef MH, Vlasnik J, Sharpless L, Pasque C, Murphy D, Fraser V. Scheduled change of antibiotic classes: a strategy to decrease the incidence of ventilator-associated pneumonia. Am J Respir Crit Care Med. 1997;156:1040-48. 41. Richards MJ, Edwards JR, Culver DH, Gaynes RP. Nosocomial infections in coronary care units in the United States. Am J Cardiol. 1998;82:789-93. 42. Rosser CJ, Bare RL, Meredith JW. Urinary tract infections in the critically ill patient with a urinary catheter. Am J Surg. 1999;177:287-90. 43. Laupland KB, Zygun DA, Davies HD, Church DL, Louie TJ, Doig CJ. Incidence and risk factors for acquiring nosocomial urinary tract infection in the critically ill. J Crit Care. 2002;17:50-7. 44. Bouza E, San Juan R, Munoz P, Voss A, Kluytmans J. A European perspective on nosocomial urinary tract infections, 2: report on incidence, clinical characteristics and outcome (ESGNI-004 study). Clin Microbiol Infect. 2001;7:532-42. 45. Leone M, Garnier F, Dubuc M, Bimar MC, Martin C. Prevention of nosocomial urinary tract infection in ICU patients: comparison of effectiveness of two urinary drainage systems. Chest. 2001;120:220-4.

48. Lai KK, Fontecchio SA. Use of silver-hydrogel urinary catheters on the incidence of catheter-associated urinary tract infections in hospitalized patients. Am J Infect Control. 2002;30:221-5. 49. Bologna RA, Tu LM, Polansky M, Fraimow HD, Gordon DA, Whitmore KE. Hydrogel/silver ion-coated urinary catheter reduces nosocomial urinary tract infection rates in intensive care unit patients: a multicenter study. Urology. 1999;54:982-7. 50. Pugach JL, DiTizio V, Mittelman MW, Bruce AW, DiCosmo F, Khoury AE. Antibiotic hydrogel coated Foley catheters for prevention of urinary tract infection in a rabbit model. J Urol. 1999;162:883-7. 51. Johnson JR, Delavari P, Azar M. Activities of a nitrofurazone containing urinary catheter and a silver hydrogel catheter against multidrug-resistant bacteria characteristic of catheter-associated urinary tract infection. Antimicrob Agents Chemother. 1999;43:2990-95. 52. Kunin CM. Nosocomial urinary tract infections and the indwelling catheter: what is new and what is true? Chest. 2001;120:10-2. 53. Dimick JB, Pelz RK, Consunji R, Swoboda SM, Hendrix CW, Lipsett PA. Increased resource use associated with catheter-related bloodstream infection in the surgical intensive care unit. Arch Surg 2001;136:229-34. 54. Holzapfel L, Chastang C, Demingeon G, Bohe J, Piralla B, Coupry A. A randomized study assessing the systematic search for maxillary sinusitis in nasotracheally mechanically ventilated patients. Influence of nosocomial maxillary sinusitis on the occurrence of ventilatorassociated pneumonia. Am J Respir Crit Care Med. 1999;159:695-701. 55. George DL, Falk PS, Umberto MG, et al. Nosocomial sinusitis in patients in the medical intensive care unit: a prospective epidemiological study. Clin Infect Dis. 1998;27:463-70. 56. Rouby JJ, Laurent P, Gosnach M, et al. Risk factors and clinical relevance of nosocomial maxillary sinusitis in the critically ill.Am J Respir Crit Care Med. 1994;150:776-83. 57. Fridkin SK, Pear SM, Williamson TH, Galgiani JN, Jarvis WR. The role of understaffing in central venous catheterassociated bloodstream infections. Infect Control Hosp Epidemiol. 1996;17:150-8. 58. Haley RW, Culver DH, White JW, et al. The efficacy of infection surveillance and control programs in preventing nosocomial infections in US hospitals. Am J Epidemiol. 1985;121:182-205.

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Extended-spectrum β-lactamase and AmpC-producing Klebsiella pneumoniae: A Therapeutic Challenge SHEEVANI*, SHASHI CHOPRA*, GOMTY MAHAJAN†, JASPAL KAUR†, YADWINDER SINGH CHOUHAN‡

ABSTRACT Klebsiella pneumoniae accounts for substantial proportion of nosocomial infections. Increasing multidrug resistance in these bacteria is posing a great threat to hospitalized patients due to the limitation of therapeutic options. Therefore, present study was undertaken with the aim to know the burden of extended-spectrum β-lactamase (ESBL)-producing K. pneumoniae and coexistence of AmpC in these isolates using phenotypic methods in a tertiary care hospital of Punjab, India. Material and methods: ESBL and AmpC screening and confirmation was done using phenotypic methods as per Clinical and Laboratory Standards Institute (CLSI) guidelines in 200 clinical isolates of K. pneumoniae. Results: Out of 200 isolates of K. pneumoniae, 116 (58%) were ESBL producers, while 84 (42%) were ESBL nonproducers. Of these 116 ESBL-positive isolates, 29 (25%) were co-producers of AmpC β-lactamase. ESBL-producing isolates were significantly more resistant to other group of antibiotics as compared to ESBL nonproducers. Conclusion: A high prevalence rate of ESBL-producing K. pneumoniae was observed in our institute. Multidrug resistance in these isolates was frequent, indicating the extensive injudicious use of antibiotics. Increasing prevalence of ESBL-producing K. pneumoniae needs to be checked to reduce the mortality and morbidity due to the infections caused by these strains.

Keywords: Extended-spectrum β-lactamase, AmpC, Klebsiella pneumoniae

K

lebsiella pneumoniae, a Gram-negative pathogen is notorious for causing nosocomial as well as community-acquired infections.1 Acquisition of β-lactamases such as extended-spectrum β-lactamases (ESBLs), AmpC and other enzymes has strengthened the bacteria enormously.2,3 ESBLs are plasmid-mediated enzymes that are able to hydrolyze a wide variety of penicillins and cephalosporins including thirdgeneration cephalosporins and monobactams.4 However, the ESBL-producing bacteria remain susceptible to cephamycins, β-lactam plus β-lactamase inhibitor combinations and carbapenems. Presence of AmpC (Functional Group 1 β-lactamases) in the same strains renders them resistant to cephamycins as well as inhibitor combinations, further narrowing the treatment scope.5 Cross transmission of ESBL-producing bacteria and AmpC-producing bacteria in hospitalized settings have been implicated for nosocomial infections worldwide making the detection of β-lactamases of

*Associate Professor †Assistant Professor ‡Tutor Dept. of Microbiology Punjab Institute of Medical Sciences, Jalandhar, Punjab

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great importance for epidemiological purposes as well as for infection control purposes. Molecular detection of these enzymes is the gold standard in their diagnosis but lack of availability of molecular methods in routine diagnostic laboratories due to cost factor is the major limitation in the developing countries. In the absence of molecular techniques, phenotypic methods if performed using stringent precautions and by standard methods, provide an effective and reliable alternatives. Therefore, the present study was undertaken to know the burden of ESBL-producing K. pneumoniae and coexistence of AmpC in these isolates using phenotypic methods in a tertiary care hospital of Punjab, India. Comparative analysis of antimicrobial susceptibility pattern of ESBL producers and ESBL nonproducers was also done to study the variation in resistance amongst these two groups. MATERIAL AND METHODS A total of 200 consecutive, nonrepeat clinical isolates of K. pneumoniae obtained from various clinical specimens sent to microbiology laboratory in a tertiary care hospital of Jalandhar, Punjab (India) from June 2011 to May 2012, were included in the study. Identification of the isolates was done with standard biotyping methods.6


COMMUNITY MEDICINE Antimicrobial susceptibilities of the isolates to different antimicrobial agents (μg) viz. cefoperazone (CPZ) (75), ceftazidime (CAZ) (30), cefotaxime (CTX) (30), aztreonam (ATM) (30), ceftriaxone (CRO) (30), cefepime (30), cefoxitin (30), cotrimoxazole (1.25/23.75), amikacin (30), gentamicin (30), ciprofloxacin (5), chloramphenicol (30), piperacillin (100), piperacillin + tazobactam (100/10), amoxicillin + clavulanic acid (AMCA) (20/10), imipenem (10), ceftazidime + clavulanic acid (CAZ/CA) (30/10), cefoperazone + sulbactam (50/50), netilmicin (30), nitrofurantoin (NFT) (100) were determined by standard disc diffusion (SDD) method using commercially available disks (HiMedia Lab Pvt. Ltd., Mumbai) and were categorized as sensitive, intermediate and resistant as per Clinical and Laboratory Standards Institute (CLSI) guidelines, wherever applicable.7 Quality control was achieved by using standard strain of Escherichia coli ATCC 25922.

ESBL Screening CLSI has developed screening tests for identifying the ESBL-producing Klebsiella species. According to CLSI guidelines, strains showing zone of inhibition of ≤22 mm for ceftazidime, ≤27 mm for cefotaxime and ≤25 mm for ceftriaxone were selected for confirmation tests of ESBL.7 Standard double disc synergy test (DDST) was performed using discs of 30 µg each of CAZ and CTX along with AMCA (amoxicillin 20 µg × clavulanic acid 10 µg). The discs of CAZ and CTX were placed at the distance 20 mm from that of AMCA and incubated at 37°C overnight. The organism was considered potential ESBL producer if the zone of inhibition around the CAZ and/CTX disc showed distinct shape/size potentiating towards amoxyclav disc.8,9

Phenotypic Confirmation of ESBL Combined disc diffusion method was used as recommended by the CLSI.10 A disc of CAZ/CA (30/10µg) and CAZ alone was applied to the surface of the inoculated plate. Increase in zone diameter by 5 mm with antimicrobial agent tested in combination with

clavulanic acid (CA) versus its zone when tested alone was taken as an indication of ESBL-producing isolates. Quality control was achieved using standard strains of E. coli ATCC 25922 and K. pneumoniae ATCC 700603.

AmpC Detection Screening Cefoxitin disc (30 µg) was used for screening of AmpC producers. Zone of inhibition of <18 mm was taken as potential AmpC producer.

Confirmation (Phenotypic) AmpC Disc Test Lawn culture of E. coli ATCC 25922 was made on Müller-Hinton agar (MHA) plate and then cefoxitin disc and sterile disk of Whatman filter paper number one were placed adjacent to each other. Sterile disk was smeared with test strain and plate incubated at 37°C for 24 hours. Distortion of zone of inhibition confirmed the presence of AmpC. Statistical analysis was done using chi-square test wherever applicable. RESULTS Out of 200 isolates of K. pneumoniae, 116 (58%) were ESBL producers while 84 (42%) were ESBL nonproducers. Of these 116 ESBL positive isolates, 29 (25%) were co-producers of AmpC β-lactamase while 5 of 200 (2.5%) were pure AmpC producers. Overall prevalence of AmpC was found to be 17% (34/200). The categorization was done on the basis of criteria mentioned in Table 1. In vitro susceptibility shown to various third-generation cephalosporins in confirmed ESBL-producing K. pneumoniae is depicted in Table 2. Maximum false sensitivity was observed in case of ceftazidime (7/116) followed by cefotaxime (5/116), ceftriaxone (4/116) and cefpodoxime (4/116), while only one isolate showed false sensitivity to cefoperazone. Maximum number of ESBLproducing K. pneumoniae were isolated from intensive

Table 1. Categorization as per Phenotypic Methods Category

Susceptibility to 3rd Susceptibility to cefepime gen. cephalosporin (4th gen. cephalosporin)

Susceptibility to cefoxitin

ESBL confirmatory test

AmpC disc test

ESBL +ve ESBL+ AmpC +ve

Negative Negative

Negative Negative

Positive Negative

Positive Negative

Not done Positive

AmpC +ve ESBL & AmpC -ve

Negative Positive

Positive Positive

Negative Positive

Negative Not done

Positive Not done

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COMMUNITY MEDICINE Table 2. Sensitivity Result by Disc Diffusion Method (Third-generation Cephalosporins) Among the Confirmed ESBL-positive Isolates Sensitivity

Cefotaxime

Ceftriaxone

Ceftazidime

Cefoperazone

Cefpodoxime

Sensitive

5

4

7

1

4

Intermediate

-

-

-

-

-

111

112

109

115

112

Resistant

Table 3. Ward-wise Distribution of ESBL-producing K. pneumoniae Dept.

No. of isolates

No. of ESBL +ve

ESBL +ve (%)

ICU

40

37

92.5

Medicine

48

36

75

Surgery

32

23

71.88

Orthopedics

14

08

57.14

Pediatrics

20

04

20

OBG

32

06

18.75

ENT

06

01

16.67

Others

08

01

12.50

Total

200

116

58

Table 4. Comparative Analysis of Resistance Pattern of ESBL-positive and ESBL-negative K. pneumoniae Non-β-lactam antibiotics

Resistance in K. pneumoniae (%) ESBL –ve*

ESBL +ve*

Nitrofurantoin

09

55

Ciprofloxacin

18

86

Moxifloxacin

18

86

Ofloxacin

09

71

Cotrimoxazole

33

93

Gentamicin

27

80

Amikacin

00

49

Netilmicin

00

58

*Difference between %age resistance to different antimicrobial agents in ESBL producers and ESBL nonproducers was significant i.e., p value <0.01.

care unit (ICU) wards (92.5%), followed by Medicine, Surgery, Orthopedics, Pediatrics and Obstetrics and Gynecology with isolation rate of 75%, 71.88%, 57.14%, 20% and 18.75%, respectively (Table 3). Susceptibility pattern of ESBL producers and ESBL nonproducers showed that ESBL producers show significantly high resistance (p < 0.01) to different class of antimicrobial agents as compared to ESBL nonproducers (Table 4). Carbapenem resistance was observed in 13 isolates

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of 116 (11.21%) ESBL producers and resistance was common to both, meropenem and imipenem. All the carbapenem-resistant isolates were from ICU. DISCUSSION The present study was undertaken to know the trends of ESBL and AmpC-producing K. pneumoniae in indoor patients of a tertiary care hospital. High isolation rate (58%) of ESBL-producing K. pneumoniae was observed in our institute. Prevalence rate of 4-80% of ESBLs has been reported in various studies from India.11-14 Increased rate of ESBL-producing Klebsiella could be due to the fact that ours is a tertiary care hospital and most of the complicated resistant cases with history of extensive usage of antibiotics are referred here. An indiscriminate use or abuse of antibiotics, especially cephalosporins, is a known risk factor for acquisition of ESBLs.15 A very high rate (~92%) of ESBL production in isolates from ICU samples was observed in our study as compared to other studies.11-15 However, another study from Punjab’s tertiary care hospital reported 80% of prevalence rate of ESBLs in ICU patients.16 It is perhaps due to the prolonged stay of patients in hospitals and demand of extensive usage of invasive devices in these patients. Intensive infection control practices and judicious use of antimicrobial agents are the need of an hour to reduce the prevalence of resistant pathogen in the ICUs. Twenty-nine isolates were found to be co-producer of AmpC. In these isolates, CLSI recommended methods would have failed to detect the ESBL production due to masking effect of AmpC enzyme as it is resistant to inhibition by clavulanic acid. Therefore, inclusion of cefoxitin disk as an indicator of AmpC and confirmation of the same by AmpC disk test is of great assistance to know the accurate incidence of ESBLs as well as AmpC β-lactamases. Resistance to three or more antimicrobials of different classes was significantly more frequent (p < 0.01) in ESBL-positive isolates as compared to the ESBLnegative Klebsiella isolates as also reported by other studies.17-20 ESBLs are encoded by plasmids, which may


COMMUNITY MEDICINE carry resistance genes to other antimicrobial groups as well, which explains the multidrug resistance in ESBL harboring isolates.20 ESBL-producing organisms have become an important clinical problem due to their resistance to multiple antibiotics. Thus antibiotic options in the treatment of these organisms are extremely limited. Resistance to carbapenems in ESBL producers has further engraved the situation. Due to increased prevalence of multidrug resistance ESBLs, selective pressure on carbapenems has led to the resistance against this group as well, limiting the treatment option. Treatment of these multiple drug-resistant strains is a therapeutic challenge for the clinicians and pharmaceuticals. CONCLUSION Unchecked growth of resistant strains of Klebsiella is a real threat to medical fraternity and calls for strict adherence to antibiotic policies to curtail injudicious use of antibiotics. The occurrence of multiple β-lactamases among bacteria not only limits the therapeutic options but also poses diagnostic challenge to the microbiologist. Clinical and laboratory doctors need to join hands to curb the growing menace of multidrug-resistant, ESBL and AmpC-producing strains of Klebsiella. It will help to check the increasing prevalence of the resistant bug and will also reduce the mortality and morbidity due to the infections caused by these strains. REFERENCES 1. Podschun R, Ullmann U. Klebsiella spp. as nosocomial pathogens: epidemiology, taxonomy, typing methods, and pathogenicity factors. Clin Microbiol Rev. 1998;11(4):589-603. 2. Turner PJ. Extended-spectrum beta-lactamases. Clin Infect Dis. 2005;41 Suppl 4:S273-5. 3. Bell JM, Turnidge JD, Gales AC, Pfaller MA, Jones RN; Sentry APAC Study Group. Prevalence of extended spectrum beta-lactamase (ESBL)-producing clinical isolates in the Asia-Pacific region and South Africa: regional results from SENTRY Antimicrobial Surveillance Program (1998-99). Diagn Microbiol Infect Dis. 2002;42(3):193-8.

6. Crichton PB. Enterobacteriaceae: Escherichia, Klebsiella, Proteus and other genera. In: Colle JG, Fraser AG, Marmion BP, Simmons A (Eds.), Mackie and McCartney Practical Medical Microbiology, 14th Edition. Edinburgh, UK: Churchill Livingstone; 1996. pp. 361-84. 7. Clinical Laboratory Standards Institute (CLSI). Performance standards for antimicrobial susceptibility testing. In: Proceedings of the 16th International Supplement (M100-S16). Wayne, Pa, USA: National Committee for Clinical Laboratory Standards; 2006. 8. Jarlier V, Nicolas MH, Fournier G, Philippon A. Extended broad-spectrum beta-lactamases conferring transferable resistance to newer beta-lactam agents in Enterobacteriaceae: hospital prevalence and susceptibility patterns. Rev Infect Dis. 1988;10(4):867-78. 9. Ananthakrishanan AN, Kanungo R, Kumar A, Badrinath S. Detection of extended spectrum beta-lactamase producers among surgical, wound infections and burns patients in JIPMER. Indian J Med Microbiol. 2000;18(4):160-5. 10. National Committee for Clinical Laboratory Standards (NCCLS). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically. Approved Standard M7-A5 and Informational Supplement M100-S10, Wayne Pa, USA: National Committee for Clinical Laboratory Standards; 2000. 11. Hansotia JB, Agarwal V, Pathak AA, Saoji AM. Extended spectrum beta-lactamase mediated resistance to third generation cephalosporins in Klebsiella pneumoniae in Nagpur, central India. Indian J Med Res. 1997;105:158-61. 12. Manchanda V, Singh NP, Goyal R, Kumar A, Thukral SS. Phenotypic characteristics of clinical isolates of Klebsiella pneumoniae & evaluation of available phenotypic techniques for detection of extended spectrum betalactamases. Indian J Med Res. 2005;122(4):330-7. 13. Rodrigues C, Joshi P, Jani SH, Alphonse M, Radhakrishnan R, Mehta A. Detection of b-lactamases in nosocomial gram negative clinical isolates. Indian J Med Microbiol. 2004;22(4):247-50. 14. Lal P, Kapil A, Das BK, Sood S. Occurrence of TEM & SHV gene in extended spectrum beta-lactamases (ESBLs) producing Klebsiella sp. isolated from a tertiary care hospital. Indian J Med Res. 2007;125(2):173-8.

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15. Kumar MS, Lakshmi V, Rajagopalan R. Occurrence of extended spectrum beta-lactamases among Enterobacteriaceae spp. isolated at a tertiary care institute. Indian J Med Microbiol. 2006;24(3):208-11.

5. Coudron PE, Moland ES, Thomson KS. Occurrence and detection of AmpC beta-lactamases among Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis isolates at a veterans medical center. J Clin Microbiol. 2000;38(5):1791-6.

16. Oberoi L, Singh N, Sharma P, Aggarwal A. ESBL, MBL and AmpC β lactamases producing superbugs - havoc in the intensive care units of Punjab India. J Clin Diagn Res. 2013;7(1):70-3. Con’td on page 644...

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DENTISTRY

Effect of Various Surface Treatment on the Push-out Bond Strength of Glass Fiber Posts Bonded to Human Root Dentin: An in vitro Study AVK NARENE*, P SHANKAR†, A KARTHICK*

ABSTRACT This in vitro study evaluated whether surface treatment for glass fiber posts has an effect on the push-out strength bonded to human root dentin. Fifty freshly extracted maxillary central incisors were endodontically treated and post-space preparation done. A total of 50 FRC Postec randomly divided into five groups (10 teeth each) were subjected to four different surface treatments: Silane only (II), cojet and silane (III), 10% sodium ethoxide and silane (IV), 10% hydrogen peroxide (V). The control group (I) did not receive any surface treatment. The root canals were treated with 37% phosphoric acid and Excite DSC and all the posts were luted with Variolink II dual cure resin. A push-out test was done to measure bond strength at different levels of the root. Data were analyzed with one-way ANOVA and post-hoc Tukey HSD test. The results showed no significant difference between control group and silane treatment. Cojet and silane (III) showed the highest bond strength of 15.50 ± 4.2 MPa, which was statistically significant than all the other group (p < 0.001). The coronal segment showed the highest mean bond strength of 13.74 ± 6.1 MPa (p < 0.001).

Keywords: Post, Push-out bond strength, surface treatment

T

he challenge of restoring endodontically treated teeth has spawned a considerable diversity in foundation restorations and a plethora of publications in dental literature.1 Pulpless teeth pose several challenges due to the loss of tooth structure by caries, defective restoration and endodontic access preparations.

Use of post system for the rehabilitation of endodontically treated teeth requires planning for restoring function of the tooth as well as structural and esthetic strategy. Currently, increasing demand for esthetic posts and cores has led to the development of zirconia and fiber posts.2 These post systems have been developed to improve the optical effect of esthetic restorations.3 Newer adhesive systems and resin-based

*Senior Lecturer Dept. of Conservative and Endodontics Sree Balaji Dental College and Hospital, Chennai, Tamil Nadu †Professor Dept. of Conservative and Endodontics Ragas Dental College and Hospital, Chennai, Tamil Nadu Address for correspondence Dr AVK Narene 8/4, East Tank Street, Thiruvottiyur, Chennai - 600 019, Tamil Nadu

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luting agents create a genuine adhesive continuum between the tooth and the post-core complex. The use of these bondable materials allows the practitioner to unify the structure and morphology of root systems.4 Zirconium oxide posts demonstrate high fracture resistance due to high flexural strengths, which is comparable to that of cast gold and titanium posts. But the fracture of zirconium oxide posts often results in unrestorable damage to the tooth, whereas in vitro studies on fracture strength of fiber re-inforced composite (FRC) posts show more favorable mode of failure. The modulus of elasticity of FRC posts is closer to that of dentin and distributes stress evenly over a broad surface area.5,6 Fiber posts are bonded with resin luting cements, which allows the formation of a single unit where tooth, post and core function as a cohesive unit monoblock configuration.7 The clinical success of post retention depends on the bonding of post to the luting cement and luting cement with the dentin.8 Surface treatments are methods by which general adhesive properties of a material are enhanced by facilitating chemical and micromechanical retention between different constituents.9,10 Various methods of surface treatments for fiber posts are sand blasting, hydrogen


DENTISTRY peroxide (H2O2), silane, potassium permanganate, sodium ethoxide, etc. Taking into consideration that the primary cause of failure of fiber posts is debonding, the objective of this study was to test the effect of various surface treatments on the push-out bond strength of glass fiber posts. The null hypotheses tested in this study were: ÂÂ

The use of silane coupling agent alone does not have effect on the bond strengths of fiber posts

ÂÂ

There is no measurable difference in bond strength after different surface treatment

ÂÂ

There is no measurable difference in bond strength at different levels of root.

METHODOLOGY Fifty freshly extracted single rooted human maxillary central incisors free of caries and fractures without any significant canal curvatures and with type 1 canal configuration were selected and stored in 0.9% physiologic saline until root canal treatment was performed. Crowns were decoronated to the level of cementoenamel junction for all samples using a diamond disc and pulp was extirpated using barbed broaches. An initial 10 size K-file was passed in the canal till its tip could be seen at the apex and the length was measured. Working length was calculated by subtracting 1 mm from the measured length of the initial 10 size K-file. The coronal third of the canal was prepared using GG drills from sizes 4-1, while apical and middle third was prepared with K files manually using step back technique. Three percent sodium hypochlorite, 17% EDTA (ethylenediaminetetraacetic acid) and 0.9% physiological saline were the standard irrigants used in the study. Master apical size of #35 was standardized and obturation was done by lateral condensation technique with AH Plus sealer. Post-space preparation was done using the corresponding drill supplied by the manufacturer leaving 5 mm of apical gutta-percha for all the samples. The canals were then irrigated with distilled water and dried with paper points. The canal walls of all the experimental samples were then etched with 37% orthophosphoric acid gel for 15 seconds using an applicator tip. The canal walls were then irrigated with distilled water to remove the excess etchant from the canal and dried with paper points. The bonding agent Excite DSC

Box 1. Surface Treatment of Posts yy Group I (n = 10): No surface treatment yy Group II (n = 10): Silane treatment only (The posts were surface-treated with silane coupling agent (Monobond-S) for 60 seconds and then gently air-dried) yy Group III (n = 10): Cojet and silane treatment (The posts were sandblasted (Cojet) for 30 seconds and then treated with silane coupling agent for 60 seconds and then gently air-dried) yy Group IV (n = 10): 10% H2O2 and silane treatment (The posts were immersed in 10% H2O2 for 5 minutes, washed with distilled water and treated with silane solution for 60 seconds and then gently air-dried) yy Group V (n = 10): Sodium ethoxide and silane treatment (The posts were immersed in freshly prepared solution of sodium ethoxide for 5 minutes, washed with distilled water and treated with silane solution (Monobond-S) for 60 seconds and then gently air-dried).

(Ivoclar Vivadent) was applied with the Microbrush all over the prepared post-space of the root canal and light cured for 20 seconds from the orifice. All the samples were randomly assigned into five experimental groups of 10 teeth each. The fiber post-FRC Postec (Ivoclar Vivadent) - 1.0 mm diameter (Tip) (n = 50) was grouped as shown in Box 1. All the posts were then luted with Variolink II (Ivoclar Vivadent) dual cure resin cement. After luting the samples were stored in 100% humidity at 37oC and were subjected to a temperature of 45oC for 3 minutes, 5 times a day for 15 days.

Push-out Bond Strength Testing The apical 5 mm of the samples containing gutta-percha was cut down with a diamond disc. From the remaining coronal segment of the samples, 3 cross sections of 2 mm thickness from apical area were obtained and the thickness was checked with a digital vernier calipers. The specimens were then placed in an acrylic mold of 2 mm diameter and then subjected to push-out bond strength testing. Each section was attached to the acrylic mold with cyanoacrylate adhesive ensuring that the coronal surface faces the mold and the post was centered over the hole of 2 mm diameter in the mold The push-out mold was then placed in Lloyds Instron universal testing machine. The cross head was lowered at a speed of 1 mm/min until the post was dislodged. Push-out bond strengths were calculated for each section. All the values obtained were tabulated and subjected to statistical analysis.

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DENTISTRY RESULTS The highest mean push-out strength values were recorded in Group III (Cojet and Silane treatment) 15.50 ± 4.2 MPa followed by Group V (Sodium ethoxide and Silane treatment) 12.04 ± 3.9 MPa and Group IV (10% H2O2 and Silane treatment) 11.9 ± 3.5 MPa as shown in Table 1. These results were analyzed using oneway-ANOVA and post-hoc Tukey HSD test. Group III (Cojet and Silane treatment) was significant with all the other groups at p < 0.001 level. There was no significant difference between Group I (No surface treatment) 10.43 ± 3.8 MPa and Group II (Silane treatment) 10.73 ± 3.5 MPa at p < 0.05 proving that there was no increase in bond strength of fiber posts that had undergone silane treatment only. In all the experimental groups, the coronal segment showed the highest mean bond strength of 13.74 ± 6.1 MPa. The lowest bond strength was observed with the apical segments (10.58 ± 5.1 MPa). Coronal segments show a statistical significance (p < 0.001) when compared with the apical and middle segments. DISCUSSION The restoration of endodontically treated teeth is one of the extensively studied topics in endodontics and yet remains controversial from many perspectives. There are varieties of posts that are available today which may vary in composition, mechanical properties and structural geometry (Custom made cast post, prefabricated post, titanium post, zirconia and fiber posts).11 Fiber-reinforced technology is already used for a wide range of applications in dentistry - splints, complete dentures, fixed dentures, retainers, etc. Fibers have also been used for endodontic post build-up restorations to reinforce composite resins. Surface treatments are methods by which general adhesive properties of a material are enhanced by facilitating chemical and micromechanical retention between different constituents. As it has been

hypothesized that the primary mode of failure of fiber posts is debonding, various surface treatment methods have been suggested to improve the bond between the post and the luting cement like sand blasting, silanization, H2O2, sodium ethoxide etching, etc.12,13 Silanes are hybrid organic-inorganic compounds that can mediate adhesion between matrices through their intrinsic dual reactivity. Although the use of silane coupling agents as adhesion promoters in fiber reinforced materials is well-established, their use in pretreatment of fiber posts still remains controversial.14,15 Bond integrity is challenged by the limited capacity to dissipate polymerization shrinkage stresses (C factor) in long narrow post-spaces that exhibit highly unfavorable cavity geometry.16-18 The efficacy of one step (self-etch) adhesives in forming a durable bond with root dentin is questioned.19 It was shown that the hybrid layers created by self-etch adhesives are not uniform and contain nanovoids that are permeable to water. This may adversely affect the longevity of bonded root canal fillings and posts. The increased collagenolytic activity in root dentin due to the less acidic primers of self-etch adhesives have also been demonstrated recently.20 Therefore, a total etch technique was followed in this study. Excite DSC, dual polymerizing single bottle agent was used as the bonding agent. The uniform formation of hybrid layer lies in the wetting of the adhesive entirely over the etched surfaces. The importance of microbrush in reaching the narrowest and deepest portion of root canal preparations has been shown by Vichi et al21 and Ferrari et al.8 This results in a deep diffusion of resin into the tubules and the formation of uniform hybrid layer and lateral branches. In an attempt to simulate the oral condition, a thermocycling protocol was done to all the test samples. In a recent study of the bonding of resin cements to fiber posts, it was found that the strength of the bond depended on the post material, the surface treatment of the post and the resin cement.22 The role of silane

Table 1. Push-out Bond Strength of Coronal, Middle and Apical Specimens Groups

I (MPa)

II (MPa)

III (MPa)

IV (MPa)

V (MPa)

Coronal

11.9 ± 6.3

12.5 ± 7.2

17.1 ± 7.0

13.5 ± 4.9

13.7 ± 5.5

Middle

10.5 ± 5.5

10.7 ± 6.9

15.2 ± 5.8

11.9 ± 5.2

12.0 ± 7.2

Apical

8.9 ± 7.3

9.0 ± 6.8

14.2 ± 4.9

10.3 ± 6.6

10.5 ± 7.3

Mean

10.43 ± 3.8

10.73 ± 3.5

15.5 ± 4.2

11.9 ± 3.5

12.04 ± 3.9

Subgroups

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DENTISTRY in the bonding of ceramics and composites has been established but its role in fiber post adhesion yet remains controversial. Silane due to its low viscosity would assist substrate wetting, and once an intimate contact between the interfacing materials is established, the Van der Waals forces would become effective providing physical adhesion, which may lead to a tertiary monoblock structure from the existing secondary monoblock. The results showed no significant difference in Group I and II (No surface treatment and silane (10.43 ± 3.8 MPa and 10.73 ± 3.5) proving no increase in bond strength of fiber posts that had undergone only silane treatment. Hence, the first null hypothesis tested holds good. These results were in accordance with the study by Perdigao et al23 and Newman et al.24 The highest mean push-out strength values were recorded in Group III (Cojet and Silane) 15.50 ± 4.2 MPa followed by Group V (Sodium ethoxide and Silane) 12.04 ± 3.9 MPa and Group IV (10% H2O2 and Silane) 11.9 ± 3.5 MPa. The results show a statistically significant difference at p < 0.001 levels. The highly cross-linked polymers of the matrix of the glass FRC posts used in this study do not have any free functional group for reaction.22,23 This could be the possible reason for insignificant effect of the silane when no surface treatment was done. Etching solutions such as sodium ethoxide, hydrogen peroxide, potassium permanganate have been commonly employed for partially removing the resinous superficial layer of the fiber posts containing epoxy resin matrix. Increased bond strength has been observed after the combined etching and silanization coupling from various studies than silane treatment alone. In the present study, mechanical roughening using cojet followed by silane treatment achieved the highest bond strength of 15.5 MPa compared to chemical etching (10% H202, sodium ethoxide) and silane treatment. These were significant to p < 0.001 level. In addition to that findings, etching with chemical solutions yielded higher bond strength values than Group I and II (Silane and Non-Silane). Thus, second null hypothesis tested has been proven to be false. The coronal segment showed the highest mean bond strength of 13.47 ± 6.1 MPa. The lowest bond strength was observed with the apical segments. Coronal segments show a statistical significance (p < 0.001) when compared with the apical and middle group. But no statistical difference was observed between the middle and apical segments (p > 0.001). These results were consistent with the studies of Boff et al,6 Kalkan

et al16 and Perdiago et al.23 But these were in contrary with those of Teixeira et al in which apical segments revealed the highest bond strength which may be due to the fact that bond strength was related more to the area of solid dentin than the density of tubules. Adhesion to root dentin is a viable procedure but structural differences exist between coronal and radicular dentin. Tubule density is greatest in the coronal and middle third than the apical third of the root. As adhesion is enhanced by the penetration of resin into the tubules, if there were a greater number of tubules per mm2, a stronger bond would be expected. Additionally, the coronal portion of the canal is the most accessible part for the canal space, making it easier for thorough application of the adhesive and therefore formation of resin tags is more uniform than the deeper areas of the canal. Hence, the third null hypothesis tested has been proven to be false. Thus, mechanical roughening of the post (Cojet) and silanization has proven to be more effective than the use of the etching solutions and silane. CONCLUSION Within the limitations of the present study it has been found that: ÂÂ

Silanization without any surface treatment has negligible effect on the bond strength of fiber post.

ÂÂ

Cojet with silane treatment has proven to be more effective than silanization done along with etching solutions.

ÂÂ

There is a marginal increase in bond strength when the posts were silanated after etching with 10% H2O2 and sodium ethoxide.

ÂÂ

Highest push-out strength was achieved at the coronal third of the root when compared with the middle and apical third.

Further studies on these fiber post systems are required to validate the results of the present study. More parameters like microleakage, flexural strength, modulus of elasticity, etc. needs to be evaluated. REFERENCES 1. Bateman G, Ricketts DN, Saunders WP. Fibre-based post systems: a review. Br Dent J. 2003;195(1):43-8; discussion 37. 2. Berekally T. Contemporary perspectives on post-core systems. Aust Endod J. 2003;29(3):120-7 3. Gluskin AH, Ahmed I, Herrero DB. The aesthetic post and core: unifying radicular form and structure. Pract Proced Aesthet Dent. 2002;14(4):313-21; quiz 322.

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DENTISTRY 4. Qualtrough AJ, Mannocci F. Tooth-colored post systems: a review. Oper Dent. 2003;28(1):86-91 5. Balbosh A, Kern M. Effect of surface treatment on retention of glass-fiber endodontic posts. J Prosthet Dent. 2006;95(3):218-23. 6. Boff LL, Grossi ML, Prates LH, Burnett LH Jr, Shinkai RS. Effect of the activation mode of post adhesive cementation on push-out bond strength to root canal dentin. Quintessence Int. 2007;38(5):387-94. 7. Tay FR, Pashley DH. Monoblocks in root canals: a hypothetical or a tangible goal. J Endod. 2007;33(4):391-8. 8. Ferrari M, Grandini S, Simonetti M, Monticelli F, Goracci C. Influence of a microbrush on bonding fiber post into root canals under clinical conditions. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2002;94(5):627-31. 9. Ferrari M, Vichi A, Grandini S, Goracci C. Efficacy of a self-curing adhesive-resin cement system on luting glassfiber posts into root canals: an SEM investigation. Int J Prosthodont. 2001;14(6):543-9. 10. Monticelli F, Toledano M, Tay FR, Cury AH, Goracci C, Ferrari M. Post-surface conditioning improves interfacial adhesion in post/core restorations. Dent Mater. 2006;22(7):602-9. 11. Fokkinga WA, Kreulen CM, Vallittu PK, Creugers NH. A structured analysis of in vitro failure loads and failure modes of fiber, metal, and ceramic post-and-core systems. Int J Prosthodont. 2004;17(4):476-82. 12. Goracci C, Fabianelli A, Sadek FT, Papacchini F, Tay FR, Ferrari M. The contribution of friction to the dislocation resistance of bonded fiber posts. J Endod. 2005;31(8):608-12.

14. Matinlinna JP, Lassila LV, Ozcan M, Yli-Urpo A, Vallittu PK. An introduction to silanes and their clinical applications in dentistry. Int J Prosthodont. 2004;17(2):155-64. 15. Goerig AC, Michelich RJ, Schultz HH. Instrumentation of root canals in molar using the step-down technique. J Endod. 1982;8(12):550-4. 16. Kalkan M, Usumez A, Ozturk AN, Belli S, Eskitascioglu G. Bond strength between root dentin and three glassfiber post systems. J Prosthet Dent. 2006;96(1):41-6. 17. Le Bell AM, Tanner J, Lassila LV, Kangasniemi I, Vallittu P. Bonding of composite resin luting cement to fiberreinforced composite root canal posts. J Adhes Dent. 2004;6(4):319-25. 18. Monticelli F, Toledano M, Tay FR, Sadek FT, Goracci C, Ferrari M. A simple etching technique for improving the retention of fiber posts to resin composites. J Endod. 2006;32(1):44-7. 19. Monticelli F, Osorio R, Toledano M, Goracci C, Tay FR, Ferrari M. Improving the quality of the quartz fiber postcore bond using sodium ethoxide etching and combined silane/adhesive coupling. J Endod. 2006;32(5):447-51. 20. Tay FR, Pashley DH, Loushine RJ, Weller RN, Monticelli F, Osorio R. Self-etching adhesives increase collagenolytic activity in radicular dentin. J Endod. 2006;32(9):862-8. 21. Vichi A, Grandini S, Ferrari M. Clinical procedure for luting glass-fiber posts. J Adhes Dent. 2001;3(4):353-9. 22. Qualtrough AJ, Chandler NP, Purton DG. A comparison of the retention of tooth-colored posts. Quintessence Int. 2003;34(3):199-201.

23. 13. Goracci C, Raffaelli O, Monticelli F, Balleri B, Bertelli E, Ferrari M. The adhesion between prefabricated FRC posts and composite resin cores: microtensile bond 24. strength with and without post-silanization. Dent Mater. 2005;21(5):437-44. ■■■■

Perdigão J, Gomes G, Lee IK. The effect of silane on the bond strengths of fiber posts. Dent Mater. 2006;22(8):752-8. Newman MP, Yaman P, Dennison J, Rafter M, Billy E. Fracture resistance of endodontically treated teeth restored with composite posts. J Prosthet Dent. 2003;89(4):360-7.

...Con’td from page 639

17. Giamarellou H. Multidrug resistance in Gram-negative bacteria that produce extended-spectrum beta-lactamases (ESBLs). Clin Microbiol Infect. 2005;11 Suppl 4:1-16. 18. Paterson DL, Mulazimoglu L, Casellas JM, Ko WC, Goossens H, Von Gottberg A, et al. Epidemiology of ciprofloxacin resistance and its relationship to extendedspectrum beta-lactamase production in Klebsiella pneumoniae isolates causing bacteremia. Clin Infect Dis. 2000;30(3):473-8.

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19. Gupta V, Singla N, Chander J. Detection of ESBLs using third & fourth generation cephalosporins in double disc synergy test. Indian J Med Res. 2007;126(5): 486-7. 20. Bradford PA. Extended-spectrum beta-lactamases in the 21st century: characterization, epidemiology, and detection of this important resistance threat. Clin Microbiol Rev. 2001;14(4):933-51.


DERMATOLOGY

Helicobacter pylori Infection can Cause Chronic Urticaria PRADIP KUMAR DAS

ABSTRACT Helicobacter pylori (H. pylori) is a bacteria that is identified in the stomach and cause peptic ulcer in most of cases. Apart from the gastrointestinal tract, other areas are also the target of H. pylori infection. The skin is an example and several studies have found a link between H. pylori infection and chronic urticaria. Infection with H. pylori is thought to increase the permeability of the mucosal lining of the stomach and thus increases the exposure to allergens in the gastrointestinal tract. We present a case of a 47-year-old young man with history of suffering of functional bowel disorder persistently for the last 3 years, who presented with the appearance of papulovesicular rash with marked itching and swelling of both the forearms and hands with some maculopapular rash in the other parts of the body with itching. He was investigated and found to have H. pylori infection, which was the cause of his urticaria.

Keywords: Helicobacter pylori infection, chronic urticaria, allergens, permeability

H

elicobacter pylori (H. pylori) is a bacteria that is identified in the stomach and cause peptic ulcer in most of cases.1 The exact route of infection remains unknown but oral or fecal/oral exposure is the most likely cause of man-to-man transmission. Not only the gastrointestinal tract, other areas are also the target of H. pylori infection. The skin is an example and several studies have found a link between H. pylori infection and chronic urticaria.2 It is postulated that infection with H. pylori increases the permeability of the mucosal lining of the stomach and thus increases the exposure to allergens in the gastrointestinal tract. Moreover, the immune response to H. pylori produces antibodies that encourage release of histamine in the skin.3

forearms and hands with some maculopapular rash in the other parts of the body with itching. Examination revealed linear excoriations, erythematous papules in both the forearms and 1-2 vesicles in the palm and swelling of the forearms (Figs. 1 and 2).

CASE REPORT A 47-year-old young man with history of suffering of functional bowel disorder persistently for the last 3 years, presented with the appearance of papulovesicular rash with marked itching and swelling of both the

Secretary, Swasthya Bhabna Welfare Society, Principal Investigator, Consultant Physician and Dermatologist, Master Trainers and Supportive Supervisor in GFATM-Project - 7 Address for correspondence Dr Pradip Kumar Das 15/C, Raja KL Goswami Street, Serampore, Hooghly - 712 201, West Bengal E-mail: pradipdr2@gmail.com

Figures 1 and 2. Erythematous papules in right forearm and palm with some vesicles and swelling prior to treatment.

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DERMATOLOGY Gastrointestinal, cardiovascular system and respiratory, neurological examinations revealed nothing significant. Findings from a complete blood cell count, assays for blood urea nitrogen level, thyroid function, liver function, stool routine parasites were normal and negative stool occult blood test except ultrasonography (USG) upper abdomen showed Grade 1 fatty liver and gastroscopy revealed H. pylori associated moderate chronic active gastritis and moderate chronic active duodenitis with moderate villous atrophy. The patient was given oral clarithromycin 500 mg twice-daily, amoxicillin 1 g twice-daily, pantoprazole 40 mg twice-daily, amitriptyline 25 mg at bedtime daily along with levocetirizine 5 mg and calamine lotion was applied locally twice-daily for 2 weeks. Following 2 weeks of treatment, the excoriated papules and vesicles improved significantly, but slight pruritus was present. Besides these, no adverse effects were noted. At 4 weeks follow-up, the lesions remained improved (Figs. 3 and 4).

DISCUSSION According to the definition of chronic urticaria, it is “A recalcitrant skin disease characterized by pruritic wheals lasting more than 6 weeks in the absence of physical cause.”1 The symptoms of chronic urticaria are caused by the release of histamine and other skin mediator chemicals, where triggering factors are infections or infestations, food additives or nonsteroidal anti-inflammatory drugs (NSAIDs). However in many cases, there is no known triggering factor to be identified and in that case it is designated as ‘idiopathic’ chronic urticaria. A number of studies have indicated that H. pylori infection can play a role in the development of urticaria/hives because of the damage caused to the stomach by the H. pylori infection, which leads to an increase in permeability of the delicate mucosal lining.2 After that the immune system leads to inflammation on the skin layers. Besides these several other mechanisms are actively playing in the immune system for the development of chronic urticaria in H. pylori-infected persons. Some studies have shown partial or complete remission in urticaria in patients who have successfully eradicated H. pylori, compared to patients who have not eradicated the infection.4 Moreover, several other studies have revealed that complete removal of H. pylori infection has a greater outcome on certain skin diseases like chronic urticaria, Behcet disease, lichen planus, atopic dermatitis, Sweet disease and systemic sclerosis, but diseases like psoriasis and rosacea associated with H. pylori infection even on complete eradication of H. pylori after full treatment showed unsatisfactory response.5,6 CONCLUSION Because chronic urticaria is a condition that can have a significant impact on quality-of-life, detection of H. pylori and its total removal from the body indeed leads to a positive outcome.6 In fact, a review paper on the role of H. pylori in skin disease makes the following recommendation: “To cure at least some patients from quality-of-life reducing chronic urticaria, it seems worthwhile to eradicate H. pylori in all patients with chronic urticarial and H. pylori infection.”7

Figures 3 and 4. Four weeks of follow-up after treatment: papules and swelling appear significantly improved.

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Limitations of this study include that only a single case is presented, so no definitive conclusion can be drawn about the complete removal of H. pylori in skin diseases at present. Con’td on page 657...


DIABETOLOGY

A Hospital-based Study of Prevalence of Gestational Diabetes Mellitus ATISH SINGLA*, PARNEET KAUR†, KHUSHPREET KAUR‡, ARVINDER KAUR#, PREETKANWAL SIBIA#

ABSTRACT Introduction: The prevalence of diabetes is rapidly rising all over the globe at an alarming rate. Therefore, it is crucial to detect women with gestational diabetes mellitus (GDM) as the condition is associated with diverse range of adverse maternal and neonatal outcomes. Aims and objectives: To find the prevalence of GDM among Indian pregnant women and the association of various risk factors with GDM. Material and methods: The study was performed on 200 pregnant women attending the antenatal clinic between 24 and 28 weeks of gestation, according to the DIPSI guidelines and diagnosis of GDM was made when plasma glucose exceeded 140 mg/dL after 2 hours. The results were analyzed for the presence of GDM and the relation of various risk factors. Results: A total of 200 patients were enrolled for the study. The study subjects had a mean age of 25.71 ± 3.9 years and body mass index (BMI) of 23.36 ± 3.94 kg/m2, respectively. The prevalence of GDM was found to be 20%. Regarding association of risk factors with GDM, 15% of GDM cases had BMI >30 and 7.5% had family history of diabetes mellitus but 62.5% cases had no risk factors. Conclusion: There is a high prevalence of GDM in the population, irrespective of presence of any associated risk factors, thus necessitating the need of universal screening.

Keywords: Gestational diabetes mellitus, glucose intolerance, screening

T

he prevalence of diabetes is increasing globally and the total number of people with this condition is projected to rise from 171 million in 2000 to 366 million in 2030. India is no exception, with projected rates of 79.4 million in 2030—a 151% increase from 31.7 million in 2000. The increased prevalence is attributed to the aging population structure, urbanization, the obesity epidemic and physical inactivity. While all these factors contribute to the epidemic of diabetes, intrauterine exposures are emerging as potential risk factors. The “fetal origin of adult disease” hypothesis proposes that gestational programming may critically influence adult health and disease. Gestational programming is a process whereby stimuli or stresses occurring at critical

*Junior Resident †Professor ‡Professor and Head #Associate Professor Dept. of Obstetrics and Gynecology Govt. Medical College and Rajindra Hospital, Patiala, Punjab Address for correspondence Dr Parneet Kaur House No. 52, Phulkian Enclave, Near Mini Secretariat Patiala- 147 001, Punjab E-mail: parneetkd@yahoo.co.in

or sensitive periods of fetal development, permanently change structure, physiology and metabolism, which predisposes individuals to disease in adult life. If the stimulus happens to be glucose intolerance in pregnancy, it predisposes the offspring to an increased risk of developing glucose intolerance in the future. This vicious cycle is likely to influence and perpetuate the incidence and prevalence of glucose intolerance in any population. Therefore, preventive measures against type 2 diabetes should start during the intrauterine period and continue from early childhood throughout life. In this respect, detection of gestational diabetes mellitus (GDM) becomes an important public health concern. GDM is defined as “any degree of glucose intolerance with onset or first recognition during pregnancy”. The importance of GDM is that two generations are at risk of developing diabetes in the future. Women with a history of GDM are at increased risk of future diabetes; predominately type 2 diabetes, cardiovascular disease and their children have increased risk for obesity and diabetes. Besides, any abnormal glucose intolerance in pregnant women is associated with a graded increase in adverse maternal and fetal outcomes. Thus, GDM offers an important opportunity for development, testing and implementation of clinical strategies for diabetes prevention.

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DIABETOLOGY Out of a 200 subjects, 40 women were found to have plasma glucose levels ≥140 mg/dL, 2 hours after a 75 g glucose load. Therefore, the prevalence of GDM in our study was found to be 20%. The mean age of the GDM cases was 27.33 ± 5.23 years and that of controls (nonGDM) cases was 25.22 ± 3.40 years (Table 1).

MATERIAL AND METHODS The study was conducted in the Dept. of Obstetrics and Gynecology at Govt. Medical College and Rajindra Hospital, Patiala from January 2013 to June 2014. The study randomly recruited 200 pregnant women at 24-28 weeks of gestation attending the antenatal clinic. The women who were known to have diabetes prior to index pregnancy were excluded from the study. The selected women were given 75 g of anhydrous glucose dissolved in a volume of 300 mL of water, to be consumed within 5 minutes, irrespective of their fasting status. Two hours later, a venous blood sample (minimum volume 1 mL in a fluoride/oxalate tube) was taken to estimate plasma glucose by glucose oxidase peroxidase (GOD-POD) method. The subjects were asked to avoid physical activity for 2 hours after intake of glucose. Diagnosis of GDM was made if 2-hour plasma glucose value was ≥140 mg/dL. The results were analyzed for the presence of GDM and its relation with various risk factors. All the women with positive results were advised diet modification and regular follow-up in the OPD for further management.

In our study, there was similar distribution of the GDM and non-GDM cases in the urban (55%) and rural (45%) region (Table 2). When we compared our cases by gravidity, it was seen that only 20% of GDM cases were primigravidas and 80% were multigravidas. In our study, the mean body mass index (BMI) of the GDM and non-GDM cases was 24.41 ± 4.48 kg/m2 and 23.04 ± 3.77 kg/m2, respectively. There were 47.5% of GDM cases with normal BMI. Since, a large proportion of the GDM cases had BMI within normal range therefore, we urge upon the importance of need of universal screening for GDM irrespective of their BMI status (Table 3). When the GDM cases were analyzed for the presence of risk factors, obesity and unexplained IUDs or neonatal deaths (NNDs) were found to be the most

RESULTS 7

Obesity

The mean age of the study population was 25.705 ± 3.90 years. The patients were asked about the presence of various risk factors associated with GDM. It was seen that unexplained intrauterine death (IUD) (4.5%) in the past was the most common factor, followed by congenitally malformed baby (3%) in the past, recurrent abortions 1% and the least associated being history of babies with birth weight >4 kg in the past. Overall, obesity before the start of pregnancy was the most common high-risk factor in the study population with an incidence of 7%. Family history of diabetes in single or both the parents was seen in 4% of the study population (Fig. 1).

4

Family h/o DM Recurrent vaginal infections

3

Recurrent UTI

2.5

Congenital anomaly

3

Previous baby weight >4 kg

0.5 4.5

Unexplained IUD/NND Recurrent abortions

1 0

2

4

6

Percentage of prevalence

Figure 1. High-risk factors in the study population. DM = Diabetes mellitus; UTI = Urinary tract infection; IUD = Intrauterine death; NND = Neonatal death.

Table 1. Association of Incidence of GDM with Age Age (years)

No. of GDM cases

Percentage (%)

No. of NGT cases

Percentage (%)

18-20

1

2.50

15

9.38

21-25

16

40

73

45.63

26-30

11

27.50

62

38.75

31-35

10

25

10

6.25

36-40

1

2.50

-

-

>41

1

2.50

-

-

Total

40

100

160

100

Mean (years)

27.33 ± 5.23

NGT = Normal glucose tolerance.

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Indian Journal of Clinical Practice, Vol. 26, No. 7, December 2015

8

25.22 ± 3.40


DIABETOLOGY Table 2. Distribution of GDM Cases According to Area Area

No. of GDM cases

Percentage (%)

No. of NGT cases

Percentage (%)

Rural

18

45

71

45

Urban

22

55

89

55

Total

40

100

160

100

Table 3. Distribution of GDM by Body Mass Index BMI (kg/m2)

No. of GDM cases

Percentage (%)

No. of NGT cases

Percentage (%)

<18.99

4

10

16

10

19.00-24.99

19

47.50

107

66.88

25.0-29.99

11

27.50

29

18.13

30 and above

6

15

8

5

Total

40

100

160

100

Mean

(kg/m2)

24.41 Âą 4.48

23.04 Âą 3.77

Table 4. High-risk Factors in GDM Cases High-risk factor

No. of subjects

Percentage (%)

12.5

1

Unexplained IUD/NND

15

4.50

Previous baby weight >4 kg

2.5

0.50

Congenital anomaly

10

3

Recurrent UTI

2.5

2.50

Recurrent vaginal infections

7.5

3

Family history of DM

7.5

4

Obesity

15

7

Recurrent abortions

common factor while history of recurrent urinary tract infections in the present pregnancy and macrosomic babies in the past were the least associated (Table 4). In this study, it was seen that 62.5% of the positive cases had no associated risk factors, thus justifying the need for universal screening for GDM, otherwise a large majority of cases would be missed out. DISCUSSION The concept of GDM goes back at least to the year 1946. The importance of GDM is that two generations are at risk of developing diabetes in the future. Women with a history of GDM are at an increased risk of future diabetes, predominantly type 2 diabetes, as are their children. Increasing maternal carbohydrate intolerance in the pregnant women is associated with graded increase in adverse maternal and fetal outcomes. Ethnically Indian women have high prevalence of diabetes. Indian women especially have

11-fold higher chances of developing GDM compared to the Caucasian women. Identification and systemic management of the disease reduces both maternal and perinatal morbidity. Hence, universal screening during pregnancy has become important in our country. For this we need a simple procedure, which is economical and feasible. Despite more than 30 years of research, there is no consensus regarding the optimal approach to the screening for GDM. Hence, this prospective study of 200 pregnant women between 24 and 28 weeks gestation was carried out to find out the prevalence of GDM by a procedure which is simple, economical and feasible to be performed in our Indian context. The prevalence of GDM in our study was found to be 20%, which was comparable to the studies done by Seshiah et al1 and Balaji et al2 using the Diabetes In Pregnancy Study group India (DIPSI) criteria but in contrast to the studies done by Wahi et al3 and Rajput et al4 and Kalra et al.5 This could be due to

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DIABETOLOGY ethnic variation and difference in the criteria used for diagnosis. The mean age of the GDM cases in our study was 27.33 ± 5.23 years, which was comparable to the study done by Bhat et al6 and Wahi et al,3 but is more than the study by Rajput et al,3 whereas study by Cypryk et al7 showed higher mean age for GDM. In our study, the GDM cases were more of urban origin (55%) than the rural (45%), which was comparable to the study of Seshiah et al8 done in 2008. The incidence of GDM was found to increase with gravidity, which was comparable to the studies done by Bhat et al6 and Sohag et al.9 Studies by various authors like Cypryk et al7 and Bhat et al6 had an incidence of GDM of 39.4% and 37.9%, respectively in subjects with BMI >25 kg/m2, thus our study corresponds to the findings of these authors with a comparable incidence of 42.5%. Our study had low incidence of family history of diabetes in the GDM cases (7.5%) as compared to various other authors.3,5,7 Trends of association of GDM with obesity in our study (15%) was comparable to studies by authors like Kalra et al5 (18.8%) and Wahi et al3 (25.8%) but very low as compared to study of Nilofer et al10 (88.89%). This gross difference could be due to the differences in the study population as Nilofer et al included only high-risk cases and our study was done on general population irrespective of the risk factors. It was seen that if the screening was just limited to the high risk cases, then 62.5% of the GDM cases would have gone undetected and therefore untreated. This is in accordance with the study by Weeks et al,11 which reported that they would have missed 43% GDM cases had they tested only the at-risk subjects.

diabetes on a large scale will go a long way in reducing the scourge of this condition. With effective screening and management of GDM, from “the diabetes capital of the world”, we (India) can claim to be the “diabetes care capital of the world.”

CONCLUSION

8. Seshiah V, Balaji V, Balaji MS, Paneerselvam A, Arthi T, Thamizharasi M, et al. Prevalence of gestational diabetes mellitus in South India (Tamil Nadu) - a community based study. J Assoc Physicians India. 2008;56:329-33.

Women with GDM are at increased risk for adverse obstetric and perinatal outcomes and Punjab is no exception to it, with 20% prevalence of gestational diabetes in our tertiary care hospital. Nevertheless, a substantial number of women with GDM present with none of these risk factors. Therefore, we need to universally screen the antenatal women for GDM. Although the eradication of GDM is impossible, we can definitely prevent its adverse effects on pregnancy outcome. Treatment of GDM prevents future DM in the mother and also acts as prevention for future DM in the unborn child. Opening of maternal-infant centers with standard protocols or prevention and treatment of

REFERENCES 1. Seshiah V, Balaji V, Balaji MS, Sekar A, Sanjeevi CB, Green A. One step procedure for screening and diagnosis of gestational diabetes mellitus. J Obstet Gynecol India. 2005;55(6):525-9. 2. Balaji V, Balaji M, Anjalakshi C, Cynthia A, Arthi T, Seshiah V. Diagnosis of gestational diabetes mellitus in Asian-Indian women. Indian J Endocrinol Metab. 2011;15(3):187-90. 3. Wahi P, Dogra V, Jandial K, Bhagat R, Gupta R, Gupta S, et al. Prevalence of gestational diabetes mellitus (GDM) and its outcomes in Jammu region. J Assoc Physicians India. 2011;59:227-30. 4. Rajput R, Yadav Y, Nanda S, Rajput M. Prevalence of gestational diabetes mellitus & associated risk factors at a tertiary care hospital in Haryana. Indian J Med Res. 2013;137(4):728-33. 5. Kalra P, Kachhwaha CP, Singh HV. Prevalence of gestational diabetes mellitus and its outcome in western Rajasthan. Indian J Endocrinol Metab. 2013;17(4):677-80. 6. Bhat M, K N R, Sarma SP, Menon S, C V S, S GK. Determinants of gestational diabetes mellitus: A case control study in a district tertiary care hospital in south India. Int J Diabetes Dev Ctries. 2010;30(2):91-6. 7. Cypryk K, Szymczak W, Czupryniak L, Sobczak M, Lewiński A. Gestational diabetes mellitus - an analysis of risk factors. Endokrynol Pol. 2008;59(5):393-7.

9. Sohag AA, Memon S, Bhutto A. Prevalence of gestational diabetes mellitus and its association with risk factors. Medical Channel. 2013;19(2):30-2. 10. Nilofer AR, Raju VS, Dakshayini BR, Zaki SA. Screening in high-risk group of gestational diabetes mellitus with its maternal and fetal outcomes. Indian J Endocrinol Metab. 2012;16 Suppl 1:S74-8.

11. Weeks JW, Major CA, de Veciana M, Morgan MA. Gestational diabetes: does the presence of risk factors influence perinatal outcome? Am J Obstet Gynecol. 1994;171(4):1003-7. ■■■■

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2015


Every citizen of India should have the right to accessible, affordable, quality and safe heart care irrespective of his/her economical background

Sameer Malik Heart Care Foundation Fund An Initiative of Heart Care Foundation of India

E-219, Greater Kailash, Part I, New Delhi - 110048 E-mail: heartcarefoundationfund@gmail.com Helpline Number: +91 - 9958771177

“No one should die of heart disease just because he/she cannot afford it” About Sameer Malik Heart Care Foundation Fund

Who is Eligible?

“Sameer Malik Heart Care Foundation Fund” it is an initiative of the Heart Care Foundation of India created with an objective to cater to the heart care needs of people.

Objectives Assist heart patients belonging to economically weaker sections of the society in getting affordable and quality treatment. Raise awareness about the fundamental right of individuals to medical treatment irrespective of their religion or economical background. Sensitize the central and state government about the need for a National Cardiovascular Disease Control Program. Encourage and involve key stakeholders such as other NGOs, private institutions and individual to help reduce the number of deaths due to heart disease in the country. To promote heart care research in India.

All heart patients who need pacemakers, valve replacement, bypass surgery, surgery for congenital heart diseases, etc. are eligible to apply for assistance from the Fund. The Application form can be downloaded from the website of the Fund. http://heartcarefoundationfund.heartcarefoundation. org and submitted in the HCFI Fund office.

Important Notes The patient must be a citizen of India with valid Voter ID Card/ Aadhaar Card/Driving License. The patient must be needy and underprivileged, to be assessed by Fund Committee. The HCFI Fund reserves the right to accept/reject any application for financial assistance without assigning any reasons thereof. The review of applications may take 4-6 weeks. All applications are judged on merit by a Medical Advisory Board who meet every Tuesday and decide on the acceptance/rejection of applications. The HCFI Fund is not responsible for failure of treatment/death of patient during or after the treatment has been rendered to the patient at designated hospitals.

To promote and train hands-only CPR.

Activities of the Fund Financial Assistance

The HCFI Fund reserves the right to advise/direct the beneficiary to the designated hospital for the treatment.

Financial assistance is given to eligible non emergent heart patients. Apart from its own resources, the fund raises money through donations, aid from individuals, organizations, professional bodies, associations and other philanthropic organizations, etc.

The financial assistance granted will be given directly to the treating hospital/medical center.

After the sanction of grant, the fund members facilitate the patient in getting his/her heart intervention done at state of art heart hospitals in Delhi NCR like Medanta – The Medicity, National Heart Institute, All India Institute of Medical Sciences (AIIMS), RML Hospital, GB Pant Hospital, Jaipur Golden Hospital, etc. The money is transferred directly to the concerned hospital where surgery is to be done.

Drug Subsidy

The HCFI Fund has the right to print/publish/webcast/web post details of the patient including photos, and other details. (Under taking needs to be given to the HCFI Fund to publish the medical details so that more people can be benefitted). The HCFI Fund does not provide assistance for any emergent heart interventions.

Check List of Documents to be Submitted with Application Form Passport size photo of the patient and the family A copy of medical records Identity proof with proof of residence Income proof (preferably given by SDM)

The HCFI Fund has tied up with Helpline Pharmacy in Delhi to facilitate

BPL Card (If Card holder)

patients with medicines at highly discounted rates (up to 50%) post surgery.

Details of financial assistance taken/applied from other sources (Prime Minister’s Relief Fund, National Illness Assistance Fund Ministry of Health Govt of India, Rotary Relief Fund, Delhi Arogya Kosh, Delhi Arogya Nidhi), etc., if anyone.

The HCFI Fund has also tied up for providing up to 50% discount on imaging (CT, MR, CT angiography, etc.)

Free Diagnostic Facility

Free Education and Employment Facility

The Fund has installed the latest State-of-the-Art 3 D Color Doppler EPIQ 7C Philips at E – 219, Greater Kailash, Part 1, New Delhi.

HCFI has tied up with a leading educational institution and an export house in Delhi NCR to adopt and to provide free education and employment opportunities to needy heart patients post surgery. Girls and women will be preferred.

This machine is used to screen children and adult patients for any heart disease.

Laboratory Subsidy HCFI has also tied up with leading laboratories in Delhi to give up to 50% discounts on all pathological lab tests.


About Heart Care Foundation of India

Help Us to Save Lives The Foundation seeks support, donations and contributions from individuals, organizations and establishments both private and governmental in its endeavor to reduce the number of deaths due to heart disease in the country. All donations made towards the Heart Care Foundation Fund are exempted from tax under Section 80 G of the IT Act (1961) within India. The Fund is also eligible for overseas donations under FCRA Registration (Reg. No 231650979). The objectives and activities of the trust are charitable within the meaning of 2 (15) of the IT Act 1961.

Heart Care Foundation of India was founded in 1986 as a National Charitable Trust with the basic objective of creating awareness about all aspects of health for people from all walks of life incorporating all pathies using low-cost infotainment modules under one roof. HCFI is the only NGO in the country on whose community-based health awareness events, the Government of India has released two commemorative national stamps (Rs 1 in 1991 on Run For The Heart and Rs 6.50 in 1993 on Heart Care Festival- First Perfect Health Mela). In February 2012, Government of Rajasthan also released one Cancellation stamp for organizing the first mega health camp at Ajmer.

Objectives Preventive Health Care Education Perfect Health Mela Providing Financial Support for Heart Care Interventions Reversal of Sudden Cardiac Death Through CPR-10 Training Workshops Research in Heart Care

Donate Now... Heart Care Foundation Blood Donation Camps The Heart Care Foundation organizes regular blood donation camps. The blood collected is used for patients undergoing heart surgeries in various institutions across Delhi.

Committee Members

Chief Patron

President

Raghu Kataria

Dr KK Aggarwal

Entrepreneur

Padma Shri, Dr BC Roy National & DST National Science Communication Awardee

Governing Council Members Sumi Malik Vivek Kumar Karna Chopra Dr Veena Aggarwal Veena Jaju Naina Aggarwal Nilesh Aggarwal H M Bangur

Advisors Mukul Rohtagi Ashok Chakradhar

Executive Council Members Deep Malik Geeta Anand Dr Uday Kakroo Harish Malik Aarti Upadhyay Raj Kumar Daga Shalin Kataria Anisha Kataria Vishnu Sureka

This Fund is dedicated to the memory of Sameer Malik who was an unfortunate victim of sudden cardiac death at a young age.

Rishab Soni

HCFI has associated with Shree Cement Ltd. for newspaper and outdoor publicity campaign HCFI also provides Free ambulance services for adopted heart patients HCFI has also tied up with Manav Ashray to provide free/highly subsidized accommodation to heart patients & their families visiting Delhi for treatment.

http://heartcarefoundationfund.heartcarefoundation.org



GASTROENTEROLOGY

Role of β-blockers in Prevention of Hepatopulmonary Syndrome in Chronic Liver Disease: An Observation ASHISH GAUTAM*, PRABHAT AGRAWAL*, ASHWINI NIGAM*

ABSTRACT Aim: Study was initiated to study the presence of hepatopulmonary syndrome (HPS) in chronic liver disease patients, and role of β-blockers in its occurrence. Methods: Patients admitted in Dept. of Medicine and patients attending the Medicine OPD were examined and investigated for presence of HDS irrespective of its typical clinical features as explained in the literature. Patients having ascites or pleural effusion were managed by means of paracentesis and pleural tap first and then included in the study. Patients having any other primary pulmonary disease like bronchial asthma or chronic obstructive pulmonary disease were excluded from the study. Arterial blood gas analysis and contrast-enhanced echocardiography was done to confirm presence of arterial hypoxemia and pulmonary shunt, the diagnostic criteria. Results: During 1 year study, total 125 patients were enrolled in the study after appropriate selection criteria. Twenty-eight out of 125 patients were not taking propranolol. Propranolol is contraindicated in these patients for one or two reasons. Four out of these 28 patients developed HPS. One out of 97 patients who were on propranolol developed HPS. Total five patients were confirmed having HPS. The Fisher’s exact test statistic value is 0.008887. The result is significant at p < 0.01. Conclusion: Patients of cirrhosis with portal hypertension on treatment with propranolol were having significantly lower chances of development of HPS then those without propranolol. Propranolol may have preventive role for development of HPS.

Keywords: Hepatopulmonary syndrome, β-blockers, chronic liver disease

H

epatopulmonary syndrome (HPS) and portopulmonary syndrome are two rare, but fatal extrahepatic complications of chronic liver disease and portal hypertension. Till date, no definitive treatment options are available for managing these complications. Few studies claim liver transplantation as the definitive treatment. Flückiger in 1884 for the first time recognized this clinical entity as complication of liver cirrhosis. Liver disease, with presence of arterial hypoxemia evident on arterial blood gas (ABG) analysis, and intrapulmonary vascular shunt as evident on contrast-enhanced echocardiography or use of technetium-99m–labeled macro aggregated albumin for lung scanning with quantitative brain uptake makes the triad of HPS. Clinical presentations are nonspecific

and may include dyspnea on exertion or rest, presence of spider angiomas, clubbing, cyanosis and severe arterial hypoxemia. This study was conducted with the aim to evaluate patients of chronic liver disease for presence of HPS. Diagnostic criteria for HPS are given in Table 1.1 Retrospective data regarding diagnosis and treatment were collected and evaluated for treatment given so far for management of cirrhosis. METHODS One hundred twenty-five patients with liver disease of varied etiologies were enrolled in the study after Table 1. Diagnostic Criteria for the Hepatopulmonary Syndrome1 Oxygenation defect

*Assistant Professor PG Department of Medicine SN Medical College, Agra, Uttar Pradesh Address for correspondence Dr Ashish Gautam Assistant Professor PG Department of Medicine SN Medical College, Agra, Uttar Pradesh E-mail: dr_ashishgautam@yahoo.co.in

Partial pressure of oxygen <80 mmHg or alveolar-arterial oxygen gradient ≥15 mmHg, while breathing ambient air

Pulmonary vascular Positive findings on contrast-enhanced dilatation echocardiography or abnormal uptake in the brain (>6%) with radioactive lungperfusion scanning Liver disease

Portal hypertension (most common) with or without cirrhosis

Indian Journal of Clinical Practice, Vol. 26, No. 7, December 2015

655


GASTROENTEROLOGY appropriate selection criteria. Patients with any evidence of primary respiratory or cardiac disease were excluded. Cirrhosis and portal hypertension was confirmed by history, clinical examination, pathological investigations and radiology. Patients were further evaluated for presence of platypnea, cyanosis, clubbing and angiomas; the typical associations of HPS. Irrespective of the grade of cirrhosis and presence of signs and symptoms all selected patients were evaluated for pulmonary shunt. For this a transthoracic contrast echocardiography was done using agitated saline. Visibility of microbubbles in the left atrium between 3-6 cardiac cycles after they were seen in right-atrium indicated microbubble passage through an abnormally dilated vascular bed. A due consent was taken from patients for this examination. An ABG analysis was done in these patients. ABG was done in both resting supine position and in sitting upright position after 5 minutes. As per the diagnostic criteria in Table 1, cut-off value for considering HPS were resting PO2 <80 mmHg and/or ΔPO2 i.e., PO2 (A-a) ≥15 mmHg. We used resting PO2 in our study. Using these criteria five patients were diagnosed to have HPS. Out of 125 patients, 97 were using propranolol, whereas 28 were not using propranolol as it was contraindicated in them due to one or more side effects in them. Propranolol is a drug used in portal hypertension as prophylaxis for secondary variceal bleeding. Four out of 28 developed HPS, whereas only one out of 97 developed HPS. The Fisher’s exact test statistic value is 0.008887. The result is significant at p < 0.01. RESULTS Out of 125 patients, five patients fulfilled the diagnostic criteria for presence of HPS. The mean age of patients was 52.6 years with standard deviation (SD) = 10.6. Eighty-four were male and 41 were females. Cause of chronic liver disease were alcoholic liver disease 56 (44.8%), chronic hepatitis B 38 (30.4%), chronic hepatitis C 14 (11.2%), noncirrhotic portal fibrosis 5 (4.0%); others and undetermined causes 12 (9.6%) (Table 2). Others included one case of autoimmune hepatitis. On the basis of examination and investigation, patients were categorized into Child’s grade: A = 12, B = 20 and C = 93. On retrospective evaluation of medical records, it was found that 28 out of 125 patients were not taking propranolol or any other β-blocker. They all had one or two contraindications for using β-blocker. β-blockers are among preferred drugs used to reduce

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Indian Journal of Clinical Practice, Vol. 26, No. 7, December 2015

Table 2. Clinical Characteristics of 125 Study Patients Parameters

No. of patients

Sex Male

84

Female

41

Clinical features Platypnea

5

Cyanosis

12

Clubbing

42

Angiomas

3

Causes of CLD Alcohol

56

Hepatitis B

38

Hepatitis C

14

NCPF

5

Others

12

Reason for β-blocker contraindications Sinus bradycardia

21

Postural hypotension

18

Diabetes

2

Prolonged PR interval

3

CLD = Chronic liver disease; NCPF = Noncirrhotic portal fibrosis.

Table 3. Characteristics of Five Patients with HPS No. of patients Sex Male

4

Female

1

Clinical features Platypnea

3

Cyanosis

5

Clubbing

5

Angiomas

0

Mean PaO2

78%

portal hypertension. Patients were categorized further in Group A (β-blocker using group) n = 97, and Group B (β-blocker contraindicated group) n = 28. In Group A, one out of 97 was diagnosed to have HPS. In Group B, four out of 28 patients were diagnosed to have HPS (Table 3). The Fisher’s exact test statistic value is 0.008887. The result is significant at p < 0.01. Causes of contraindications for β-blocker use were sinus bradycardia, clinical postural hypotension, diabetes, prolonged PR interval.


GASTROENTEROLOGY DISCUSSION Cirrhosis leads to a hyperdynamic state of circulation especially in presence of acute or chronic hepatocellular failure.2 Peripheral vasodilatation and reduced peripheral vascular resistance manifests with peripheral flushing, erythema, decreased blood pressure and bounding pulse. Cardiac output is increased to compensate for above. The numerous functionally inactive arteriovenous fistulas open up due to this profound vasodilatation. HPS is manifestation of similar mechanism in liver cirrhosis, which develops when the pulmonary venous shunt is at its extreme.3 Cyanosis and reduced oxygen saturation is a frequent finding in decompensated cirrhosis.4 Various medications are tried in HPS with variable effectiveness but most do not seems to be effective in its reversal. Pentoxyphyllin5 and methylene blue6 till date are found effective up to a certain extent in HPS reversal. β-blockers are among the preferred drugs for patients with portal hypertension. They are given in titrated doses to prevent primary and secondary bleeding from esophageal varices. β-blockers were clearly declared ineffective in management of HPS.7 Still, there are few hopes in theory favoring them to use in HPS. A case report published in 1994 by Saunders et al, in which a patient improved from HPS proved by serial exercise testing.8 This patient was on β-blocker for some time after which he showed signs of improvement. Although author itself was not able to describe the role of β-blocker in improvement from HPS still comparing the data from our study with this case may open the new

ways of thoughts in using β-blockers as prophylaxis or may be for treatment of HPS. REFERENCES 1. Rodríguez-Roisin R, Krowka MJ. Hepatopulmonary syndrome - a liver-induced lung vascular disorder. N Engl J Med. 2008;358(22):2378-87. 2. Murray JF, Dawson AM, Sherlock S. Circulatory changes in chronic liver disease. Am J Med. 1958;24(3):358-67. 3. Rodríguez-Roisin R, Krowka MJ, Hervé P, Fallon MB; ERS Task Force Pulmonary-Hepatic Vascular Disorders (PHD) Scientific Committee. Pulmonary-Hepatic vascular Disorders (PHD). Eur Respir J. 2004;24(5):861-80. 4. Rodman T, Sobel M, Close HP. Arterial oxygen unsaturation and the ventilation-perfusion defect of Laennec’s cirrhosis. N Engl J Med. 1960;263:73-7. 5. Sztrymf B, Rabiller A, Nunes H, Savale L, Lebrec D, Le Pape A, et al. Prevention of hepatopulmonary syndrome and hyperdynamic state by pentoxifylline in cirrhotic rats. Eur Respir J. 2004;23(5):752-8. 6. Schenk P, Madl C, Rezaie-Majd S, Lehr S, Müller C. Methylene blue improves the hepatopulmonary syndrome. Ann Intern Med. 2000;133(9):701-6. 7. Rodríquez-Roisin R, Krowka MJ, Hervé P, Fallon MB; ERS (European Respiratory Society) Task Force-PHD Scientific Committee. Highlights of the ERS Task Force on pulmonary-hepatic vascular disorders (PHD). J Hepatol. 2005;42(6):924-7.

8. Saunders KB, Fernando SS, Dalton HR, Joseph A. Spontaneous improvement in a patient with the hepatopulmonary syndrome assessed by serial exercise tests. Thorax. 1994;49(7):725-7. ■■■■

...Con’td from page 646

REFERENCES 1. Chey WD, Wong BC; Practice Parameters Committee of the American College of Gastroenterology. American College of Gastroenterology guideline on the management of Helicobacter pylori infection. Am J Gastroenterol. 2007;102(8):1808-25. 2. Cover TL, Blaser MJ. Helicobacter pylori in health and disease. Gastroenterology. 2009;136(6):1863-73. 3. Yadav MK, Rishi JP, Nijawan S. Chronic urticaria and Helicobacter pylori. Indian J Med Sci. 2008;62(4):157-62. 4. Federman DG, Kirsner RS, Moriarty JP, Concato J. The effect of antibiotic therapy for patients infected with

Helicobacter pylori who have chronic urticaria. J Am Acad Dermatol. 2003;49(5):861-4. 5. Hernando-Harder AC, Booken N, Goerdt S, Singer MV, Harder H. Helicobacter pylori infection and dermatologic diseases. Eur J Dermatol. 2009;19(5):431-44. 6. Magen E, Mishal J, Schlesinger M, Scharf S. Eradication of Helicobacter pylori infection equally improves chronic urticaria with positive and negative autologous serum skin test. Helicobacter. 2007;12(5):567-71. 7. Wedi B, Kapp A. Helicobacter pylori infection in skin diseases: a critical appraisal. Am J Clin Dermatol. 2002;3(4):273-82.

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INTERNAL MEDICINE

A Case Report of Oculophar yngeal Muscular Dystrophy KB GURUMURTHY*, SG JAYARAJ†, JOBIN V JOSEPH‡

ABSTRACT This is a case report of oculopharyngeal muscular dystrophy, which is a very rare degenerative disorder. It is a genetic condition usually inherited in an autosomal dominant pattern, though sporadic cases are also reported, degenerative disorder.

Keywords: Oculopharyngeal muscular, autosomal dominant, ptosis, dysphagia

O

culopharyngeal muscular dystrophy (OPMD) is characterized by late-onset (usually after the age of 45 years) eyelid drooping (ptosis), swallowing difficulty (dysphagia) and a positive family history with involvement of two or more generations, rarely sporadic cases have also been reported. This is a case of sporadic OPMD. Only very few cases have been reported from India.

CASE REPORT A 69-year-old gentleman presented with drooping of both eyelids since 15 months, which started with right followed by left. Drooping gradually increased over months and on presentation, he could not open the eyes spontaneously. No diurnal variation or fatigability was observed. Initially, there was no other neurological deficit. Six months later, he started having difficulty in deglutition, in the form of cough and nasal regurgitation while swallowing, especially for liquid. This difficulty gradually progressed and at present he was on Ryles tube feeding (Fig. 1). No history of facial deviation was present. He also noticed difficulty in looking towards both side, he had to turn the head for looking

*Professor †Associate Professor ‡Assistant Professor Dept. of General Medicine SSIMS & RC, Davangere, Karnataka Address for correspondence Dr Jobin V Joseph Assistant Professor Dept. of General Medicine SSIMS & RC, Bypass Road, Davangere - 4, Karnataka E-mail: drjobinvj@yahoo.com

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Figure 1. Patient was on Ryles tube feeding.

to sides, since 6 months. On examination, patient was well-built and nourished, vitals were normal. Higher mental functions were also normal. Bilateral ptosis was present, right more than left (Fig. 2). Right palpebral fissure was almost closed, and he could open the eyes a little bit with difficulty. Movement of Eyeball: All movements were restricted (almost absent) except, in left eye slight adduction was possible. Gag reflex-movement of posterior pharyngeal wall was reduced bilaterally. There was no wasting of muscles, power was normal, there was no weakness of proximal muscle, reflexes were sluggish and gait was normal. Other systemic examinations were within normal limits. Clinical diagnosis: dystrophy.

Oculopharyngeal

muscular


INTERNAL MEDICINE In Europe, the prevalence of OPMD is estimated to be 1 in 1,00,000 people. The autosomal dominant form of this condition is much more common in the French-Canadian population of the Canadian province of Quebec, where it is estimated to affect 1 in 1,000 individuals. Autosomal dominant OPMD is also seen more frequently in the Bukharan (Central Asian) Jewish population of Israel, affecting 1 in 600 people. The autosomal recessive form of this condition is very rare; only a few cases of autosomal recessive OPMD have been identified.

Figure 2. Bilateral ptosis was present, right more than left.

Investigations Complete hemogram: Normal. RBS: 104 mg%. Blood urea: 30 mg%, serum creatinine - 1.0 mg%. CPK was raised. Muscle biopsy: revealed abnormal vacuoles within muscle fibers. Final diagnosis: Oculopharyngeal muscular dystrophy. DISCUSSION Oculopharyngeal muscular dystrophy is a genetic condition characterized by muscle weakness that begins in adulthood, typically after the age of 40. The first symptom in people with this disorder is usually drooping eyelids (ptosis), followed by difficulty in swallowing (dysphagia). The swallowing difficulties begin with solid food, but as the condition progresses, liquids can be difficult to swallow as well. Many people with this condition have weakness and wasting (atrophy) of the tongue. These problems with food intake may cause malnutrition. Some affected individuals also have weakness in other facial muscles.

Mutations in the polyadenine-binding protein nuclear 1 (PABPN1) gene cause OPMD. The PABPN1 gene provides instructions for making a protein that is active (expressed) throughout the body. In cells, the PABPN1 protein plays an important role in processing molecules called messenger RNAs (mRNAs), which serve as genetic blueprints for making proteins. The protein alters a region at the end of the mRNA molecule that protects the mRNA from being broken down and allows it to move within the cell. The PABPN1 protein contains an area where the protein building block (amino acid) alanine is repeated 10 times. This stretch of alanines is known as a polyalanine tract. The role of the polyalanine tract in normal PABPN1 protein function is unknown. Mutations in the PABPN1 gene that cause OPMD result in a PABPN1 protein that has an extended polyalanine tract. The extra alanines cause the PABPN1 protein to form clumps within muscle cells that accumulate because they cannot be broken down. These clumps (called intranuclear inclusions) are thought to impair the normal functioning of muscle cells and eventually cause cell death. The progressive loss of muscle cells most likely causes the muscle weakness seen in people with OPMD. It is not known why dysfunctional PABPN1 proteins seem to affect only certain muscle cells.

Individuals with OPMD frequently have weakness in the muscles near the center of the body (proximal muscles), particularly muscles in the upper legs and hips. The weakness progresses slowly over time and people may need the aid of a cane or a walker. Rarely, affected individuals need wheelchair assistance.

When investigated in a laboratory, findings include high creatine phosphokinase (CPK) levels (approximately 5 times that of normal levels). A muscle biopsy reveals abnormal vacuoles within muscle fibers (Fig. 3). A distinction between OPD and myasthenia gravis or mitochondrial myopathy must be made. The absence of family history and the fluctuation of symptoms in myasthenia gravis usually distinguish the two conditions.

There are two types of OPMD, which are distinguished by their pattern of inheritance. They are known as the autosomal dominant and autosomal recessive types.

Treatment is supportive to the patient with death eventually occurring from infections. Difficulty with swallowing may result in nasogastric feeding.

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INTERNAL MEDICINE SUGGESTED READING 1. Becher MW, Morrison L, Davis LE, Maki WC, King MK, Bicknell JM, et al. Oculopharyngeal muscular dystrophy in Hispanic New Mexicans. JAMA. 2001;286(19): 2437-40. 2. Lindsay KW, Bone I, Callander R, Gijn JV. Neurology and Neurosurgery Illustrated. 5th Edition, Churchill Livingstone; 2010. p. 483. 3. Goh KJ, Wong KT, Nishino I, Minami N, Nonaka I. Oculopharyngeal muscular dystrophy with PABPN1 mutation in a Chinese Malaysian woman. Neuromuscul Disord. 2005;15(3):262-4. 4. Brais B, Bouchard JP, Xie YG, Rochefort DL, Chrétien N, Tomé FM, et al. Short GCG expansions in the PABP2 gene cause oculopharyngeal muscular dystrophy. Nat Genet. Figure 3. Rimmed vacuoles in small polygonal or angular muscle fibers. 1998;18(2):164-7. ■■■■

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Cannabidiol (CBD), a cannabis derivative, could help children with epilepsy, suggested a series of studies presented at the American Epilepsy Society’s 69th Annual Meeting. Results revealed that after 3 months, the frequency of all seizures was a median of 45% lower in all participants; 47% experienced a >50% reduction in seizures, and 9% of patients were seizure-free.

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Six out of ten adults with controlled type 2 diabetes receive too many hemoglobin A1C (HbA1C) tests, leading to waste and the possibility of overtreatment with hypoglycemic drugs, suggested a retrospective analysis published in The BMJ.

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Heavily pretreated patients with relapsed or refractory multiple myeloma responded well to treatment with the investigative combination of ibrutinib, carfilzomib and dexamethasone, suggested a phase I/IIb study, presented at the American Society of Hematology meeting.

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Universal decolonization of patients in intensive care units (ICUs) with chlorhexidine baths and an antibiotic nasal ointment reduces bacteriuria and candiduria in men, but not in women, reported a new study published online in The Lancet Infectious Diseases.

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Measuring the levels of RNA biomarkers in blood may help quickly differentiate sepsis from infectionnegative systemic inflammation, suggested new research published in PLOS Medicine.

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A new study suggests that there is a higher risk of ischemic stroke for men who take α-blockers but who are not already taking other blood pressure medications. The study is published in the Canadian Medical Association Journal. Researchers noted an increased risk for ischemic stroke for men during the first 21 days of starting treatment and a reduced risk 22-60 days after starting treatment.

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Patients with primary glomerulonephritis generally have favorable long-term kidney transplant outcomes, suggested new findings published online in Transplantation. Inhaled isopropyl alcohol from a medication pad relieves nausea in emergency department patients, at least in the short-term, suggested a small randomized controlled trial published online December 8 in the Annals of Emergency Medicine.

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INTERNAL MEDICINE

Henoch-Schönlein Purpura with Upper Gastrointestinal Hemorrhage in an Adult BV NAGABHUSHANA RAO*, BVS RAMAN†

ABSTRACT Henoch-Schönlein purpura (HSP) is a small vessel vasculitis characterized by palpable purpura, arthralgia, gastrointestinal (GI) signs and symptoms and glomerulonephritis. It is disease of children. But when it effects adults it can be more severe and outcome may be relatively poor. Both significant upper GI bleed and scrotal involvement were not reported in adults many a times in the literature. Here we present adult patient with HSP who presented with GI hemorrhage and scrotal swelling with good clinical outcome.

Keywords: Henoch-Schönlein purpura, acute abdomen, gastrointestinal hemorrhage, scrotal swelling, adult

H

enoch-Schönlein purpura (HSP) is an immunoglobulin A vasculitis, most commonly affecting the children of age group 3-15. The annual incidence is 10-20/1,00,000 children aged below 17 years.1 It is rare in adults, approximately 10% HSP cases occur in adults and disease can be more severe and may not be self-limiting as in children.2 HSP is a disease of unknown etiology, thought to be triggered by various infections and immunizations. It is characterized by a tetrad of symptoms, a palpable purpura without coagulopathy or thrombocytopenia, arthralgia or arthritis, abdominal pain or renal disease. There is no specific test for HSP; diagnosis is clinical. Diagnostic dilemma may occur if the disease presents incomplete. In such situations, biopsy of affected organ is warranted, which will reveal predominantly immunoglobulin A deposits.

linezolid, cefixime, serratiopeptidase and diclofenac by the surgeon. A day after, he developed abdominal pain, hence diclofenac was stopped and symptomatic treatment with pantoprazole, antacid syrup and buscopan was given. Two days later, he developed skin rash on legs. Thought to be due to allergy, hence he was referred for physician consultation.

CASE REPORT

Investigations

A 55-year-old male patient consulted our surgical colleague for a patch of cellulitis at the base of his right great toe 5 days ago. Patient is a known diabetic on oral hypoglycemic agents for the last 10 years. He was given

Normal: Hemoglobin, hepatitis B surface antigen (HBsAg), white blood cell (WBC) count, peripheral smear, amylase, prothrombin time (PT) and activated partial thromboplastin time (aPTT), complement 3 and 4 (c3c4), creatinine 1.2 (0.6-1.4).

*Dept. of Medicine †Dept. of General Surgery Queen’s NRI Hospital, Seethammadhara, Visakhapatnam, Andhra Pradesh Address for correspondence Dr BV Nagabhushana Rao Dept. of Medicine Queen’s NRI Hospital, Seethammadhara, Visakhapatnam - 530 013, Andhra Pradesh E-mail:bhavanavnrao@gmail.com

When I examined him in outpatient department, he was hemodynamically stable. He looked a little pale, abdomen was mildly distended with vague tenderness all over. Petechiae were there all over the lower limbs up to thigh and even on the scrotum (Fig. 1). Scrotum was swollen and tender, ankles were a bit swollen too. Ankle and knee joint movements were painful. He was admitted to the hospital and treated symptomatically with intravenous fluids, pantoprazole, ondansetron, etc.

Negative: HBsAg, antinuclear factor (ANF), hepatitis C virus (HCV), R factor, antineutrophilic cytoplasmic antibodies (ANCA) with cytoplasmic staining pattern cytoplasmic ANCA (cANCA) and perinuclear ANCA (pANCA). Abnormal: Erythrocyte sedimentation rate (ESR) 30 (0-15), C-reactive protein (CRP) 6.5 (0-6 mg), platelets 4.5 lakhs (1.5-4.0).

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INTERNAL MEDICINE

Figure 2. Edema of intestines on CT scan of abdomen.

Figure 1. Purpura over feet.

In the view of abdominal pain, joint pain, petechiae over legs HSP was suspected and intravenous hydrocortisone 100 mg thrice a day was started. In spite of the above measures his abdominal pain persisted. Contrast-enhanced computed tomography (CECT) and angiography of abdomen were done. CT showed trasmural thickening of jejunum and terminal ileum suggestive of inflammation/infection (Fig. 2). He had vomited blood 3 times each 100-150 mL. Upper gastrointestinal (GI) endoscopy showed inactive chronic duodenal ulcer and diffuse gastropathy suggestive of vasculitis (Fig. 3). He was started on methylprednisolone 1 g every day for 3 days. Patient improved clinically, abdomen scrotal and joint pain resolved. He was discharged on 1 mg/kg prednisolone to be tapered off gradually. He had significant proteinuria of 3 g/24 hours. His blood sugar was controlled with insulin both within the hospital and at home. He was given telmisartan 40 mg once a day in view of proteinuria. Fundus examination did not reveal retinopathy. Renal biopsy deferred by the patient and skin rash did not reappear during observation.

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Figure 3. Vasculitis lesions of stomach in upper GI endoscopy.

DISCUSSION Our patient had focal cellulitis at the base of great toe for which he was given medication. Many drugs are known to precipitate HSP, one of them being diclofenac. He developed skin rash over the leg, which was thought to be simple allergy a usual mistake. He had arthralgia of knees and ankles. HSP often presents with arthralgia before or after onset of skin rash. He had edema of feet, a feature of HSP. Scrotal involvement in adults is rare.3 Painful scrotal swelling in HSP may require scrotal Doppler study


INTERNAL MEDICINE to exclude torsion of testis where decreased arterial flow points to torsion. Persisting and significant pain abdomen can be due to many a causes in adults with HSP including pancreatitis, appendicitis, cholecystitis, peritonitis or mesenteric vascular occlusion.4 Our patient’s CT abdomen showed transmural thickening/edema of jejunum and the ileum suggestive of inflammation due to HSP.5 CECT scans also help to exclude other causes of pain abdomen. In HSP, intussusception is not a common presentation in adults. Obvious upper GI bleed is rarely seen in adults with HSP, though 56% of children may have occult blood positive stool. Upper GI endoscopy showed classical diffuse gastropathy suggestive of vasculitis. Sometimes, acute abdomen or upper GI bleed may be preceded by skin rash giving a diagnostic dilemma. GI symptoms without rash also have been reported. Patient responded to high dose methylprednisolone.6 In similar situation in nonresponders, immunosuppression, plasmapheresis have also been attempted. Patient had significant proteinuria, as patient had diabetes for a long time and had no diabetic retinopathy; diabetic nephropathy cannot be excluded without renal biopsy, which was deferred by the patient. Proteinuria decreased with prednisolone and telmisartan during observation.

CONCLUSION In palpable purpuric rash, abdominal and joint pain, with or without renal involvement, we have to consider HSP in differential diagnosis even if the patient is an adult. They may present with upper GI bleed, which needs cautious approach as involvement of GI tract can be diffuse and obscure. Scrotal involvement is rare but a known complication of HSP. REFERENCES 1. Piram M, Mahr A. Epidemiology of immunoglobulin A vasculitis (Henoch-Schönlein): current state of knowledge. Curr Opin Rheumatol. 2013;25(2):171-8. 2. Pillebout E, Thervet E, Hill G, Alberti C, Vanhille P, Nochy D. Henoch-Schönlein purpura in adults: outcome and prognostic factors. J Am Soc Nephrol. 2002;13(5):1271-8. 3. Aaron S, Al-Watban L, Manca D. Scrotal involvement in an adult with Henoch-Schönlein purpura. Clin Rheumatol. 2013;32 Suppl 1:S93-5. 4. Zhang Y, Huang X. Gastrointestinal involvement in Henoch-Schönlein purpura. Scand J Gastroenterol. 2008;43(9):1038-43. 5. Colleter L, Corcos O, Vilgrain V, Ronot M. HenochSchönlein purpura in adults. Diagn Interv Imaging. 2014;95(6):637-40.

6. Wang L, Huang FC, Ko SF, Cheng MT. Successful treatment of mesenteric vasculitis caused by HenochSchönlein purpura with methylprednisolone pulse therapy. Clin Rheumatol. 2003;22(2):140-2. ■■■■

Traumatic Brain Injuries in Sports When a purely scientific advance stands to jeopardize a very powerful interest, rejection can turn threatening. Such was the case of forensic pathologist Bennet Omalu, a native Nigerian working in the Allegheny County coroner’s office. Dr Omalu had no idea just how powerful the National Football League (NFL) was when he published the first diagnosis of chronic traumatic encephalopathy in Neurosurgery. The NFL immediately mobilized a cadre of physicians on the organization’s payroll to attack his research, but Dr Omalu persisted despite such prosecution by the NFL. Even experts without any ties to the NFL initially discounted his research. Because of Dr Omalu’s persistence, the NFL has been forced to acknowledge chronic traumatic encephalopathy, and the wider sports culture has begun questioning the costs of repeated brain injuries in sports, both professional and recreational.

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NEUROLOGY

Cerebral Palsy SUDIVYA SHARMA

ABSTRACT Cerebral palsy (CP) is a central motor dysfunction affecting muscle tone, posture and movement resulting from a permanent, nonprogressive defect or lesion of the immature brain. The resulting limitations in movement and posture cause activity limitation and are often accompanied by disturbances of sensation, depth perception and other sight-based perceptual problems and communication ability. An understanding of the natural history of CP is essential for a proper prognosis and provision of support services.

Keywords: Central motor dysfunction, continuum of reproductive casualty

C

erebral palsy (CP), formerly known as “cerebral paralysis”, was first identified by English surgeon William Little in 1860. CP can be defined as a central motor dysfunction affecting muscle tone, posture and movement resulting from a permanent, nonprogressive defect or lesion of the immature brain. It should be viewed as part of a “continuum of reproductive casualty”, comprising miscarriages, stillbirths and severe and minor brain injuries.1

It is caused by damage to the motor control centers of the developing brain and can occur during pregnancy, during childbirth or after birth up to 3 years. The resulting limitations in movement and posture cause activity limitation and are often accompanied by disturbances of sensation, depth perception and other sight-based perceptual problems and communication ability; impairments can also be found in cognition and epilepsy is found in about one-third of cases. EPIDEMIOLOGY CP is the most common motor disability in childhood.2 Population-based studies from around the world report prevalence estimates of CP ranging from 1.5 to more than 4 per 1,000 live births or children of a defined age range.3-7

CLASSIFICATION The various schemes of classifying the cerebral palsies are summarized in Table 1. Table 1. Schemes for Classifying the Cerebral Palsies Type of brain injury Genetic: Malformation, deformation, destruction Metabolic Infarction, hemorrhagic Infective, inflammatory (periventricular leukomalacia) Trauma/compression Timing of brain injury 1st, 2nd, 3rd trimester, perinatal, postnatal Site of brain injury Cortical, cortical-subcortical, white matter, basal ganglia, brainstem, cerebellar, midline or global Topography of signs Monoplegia, diplegia, triplegia, quadriplegia, double hemiplegia, trunkal Motor manifestations Hypotonic, ataxic*, spastic, dystonic, dyskinetic Functional impact None, mild, moderate, severe Impairment: Disturbance at organ level Disability: The consequence of impairment for function and † activity

Clinical Assistant HN Reliance Hospital, Mumbai, Maharashtra Address for correspondence Dr Sudivya Sharma Flat. No.77, B-Wing, Mahavir Krupa Building TJ Road, Sewri (W), Mumbai - 400 015, Maharashtra E-mail: drsudivyasharma@gmail.com

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Handicap: The disadvantage to the individual arising from impairment and disability *Ataxic CP should be viewed with caution as these conditions may represent an underlying genetic disorder. †After

World Health Organization. International classification of impairments, disabilities and handicaps. Geneva; WHO, 1980.


NEUROLOGY TYPES ÂÂ

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Spastic CP is the commonest type, accounting for 70% of cases. The spastic variety of CP commonly results in the development of contractures over time especially at the elbows, wrists, hips, knees and ankles. Spastic diplegia and spastic hemiplegia have the best prognosis for functional improvement. Spastic diplegia is usually associated with prematurity and implies spasticity of both lower limbs with minimal upper extremity involvement. In hemiplegia, involvement is unilateral with the upper limb usually being affected more than the lower limb. In quadriplegia, all four limbs are affected, upper limbs usually more severely. Intellectual disability and epilepsy are common in the latter group. Bulbar muscles are involved to a varying degree resulting in poor control of the mouth, tongue and pharynx. Feeding difficulties may be severe, requiring nasogastric feeding or a gastrostomy. Aspiration pneumonia is most likely in this group. The likelihood for functional improvement in patients with spastic quadriplegia is often poor. Dyskinetic CP may be associated with deafness, dysarthria and drooling. Seizures occur in about one-quarter of these patients. In the majority of these cases, the intelligence quotient (IQ) is low/normal. Since, the introduction of exchange transfusion for blood group incompatibility and the subsequent dramatic reduction of kernicterus, the incidence of this type of CP has decreased. In ataxic CP, balance is impaired and speech disorders are common (“scanning cerebellar speech”). Intellectual disability and epilepsy are often associated findings. This group also has a poor likelihood for functional improvement.

ETIOLOGY Recent research has demonstrated that intrapartum asphyxia is not the most important cause, probably accounting for no more than 10% of all cases; rather infections in the mother, even infections that are not easily detected, may triple the risk of the child developing the disorder, mainly as the result of the toxicity of cytokines to the fetal brain that are produced as part of the inflammatory response. Low birth weight, prematurity and multiple birth infants are risk factors.8 After birth, other causes include toxins, severe jaundice, lead poisoning, physical brain injury, shaken baby syndrome, incidents involving hypoxia to the brain (such as near drowning), and encephalitis or meningitis.

DIAGNOSIS The probability of CP rises with increasing prematurity, multiple pregnancies and events such as intracranial hemorrhage, meningitis or neonatal seizures. Other suggestive features are: ÂÂ

Feeding difficulties

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Excessive drooling owing to poor bulbar function with recurrent aspiration pneumonia and failure to thrive

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Pronounced hypotonia

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A lack of variability of limb movements or sustained or “cramped” postures

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Persistence of primitive reflexes such as the rooting, grasp and asymmetric tonic neck response

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Neonatal and infantile seizures

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Visual field loss, squints

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Hearing loss

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Anxiety, depression, conduct disorders, severe hyperactivity and inattention, and autism.

The classical symptoms are spasticity, spasms, other involuntary movements (e.g., facial gestures), unsteady gait, problems with balance and/or soft tissue findings consisting largely of decreased muscle mass. Secondary conditions can include seizures, epilepsy, apraxia, dysarthria or other communication disorders, eating problems, sensory impairments, intellectual disability, learning disabilities, urinary incontinence, fecal incontinence and/or behavioral disorders. Pain is associated with tight and/or shortened muscles, abnormal posture, stiff joints, unsuitable orthosis, etc. There is also a high likelihood of chronic sleep disorders secondary to both physical and environmental factors.9 The National Collaborative Perinatal Project in the US endorses delayed labeling of these children as twothirds of children diagnosed with “spastic diplegia” and half of all children with signs of “cerebral palsy” at their first birthday “outgrew” their symptoms by the age of 7 years.10

Predicting the Ability to Walk To attempt to resolve uncertainty Grant11 summarized an available opinion:

Sala

and

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Persistence of primitive reflexes is incompatible with the development of walking

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Sitting unsupported at 2 years indicates that the child will eventually walk outdoors

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If sitting is delayed beyond 3 years, the prospects for functional outdoor walking are remote.

15 years have not reduced the rate of CP. In most cases, the injury causing the disorder may not be preventable.

PREVENTION

REFERENCES

Mitchell lists preventive measures as having three main objectives: Primary prevention is concerned with preventing situations, which may dispose to cerebral palsy; secondary prevention involves correction of predisposing conditions such as hypoxia or jaundice and tertiary prevention relates to minimizing results of inevitable brain damage.12

1. Forfar JO, Hume R, McPhail FM, Maxwell SM, Wilkinson EM, Lin JP, et al. Low birthweight: a 10-year outcome study of the continuum of reproductive casualty. Dev Med Child Neurol. 1994;36(12):1037-48.

It must be accepted that there is still no “cure” for a diagnosed case of CP. The central nervous system is complex and damage is permanent. Minimal damage can become less predominant as undamaged nervous tissue matures.

3. Arneson CL, Durkin MS, Benedict RE, Kirby RS, YearginAllsopp M, Van Naarden Braun K, et al. Prevalence of cerebral palsy: Autism and Developmental Disabilities Monitoring Network, three sites, United States, 2004. Disabil Health J. 2009;2(1):45-8.

MANAGEMENT Treatment for CP is a lifelong multidimensional process focused on the maintenance of associated conditions. Identification of type, extent and severity of neuromotor deficit guides it. Treatment may include one or more of the following: Physical therapy; occupational therapy; speech therapy; water therapy; drugs to control seizures, alleviate pain or muscle spasms; hyperbaric oxygen; the use of Botox to relax contracting muscles; surgery to correct anatomical abnormalities or release tight muscles; braces and other orthotic devices; rolling walkers and communication aids such as computers with attached voice synthesizers. CONCLUSION CP encompasses a variety of neurological syndromes. An understanding of the natural history of CP is essential for a proper prognosis and provision of support services. Important items include the prognosis for life expectancy, walking and hand function. However, dramatic improvements in care over the last

2. In: Capute and Accardo’s Neurodevelopmental Disabilities in Infancy and Childhood. Pasquale J Accardo (Ed.). 3rd Edition, Baltimore: Paul H. Brookes Publishing Co; 2008. p. 17.

4. Bhasin TK, Brocksen S, Avchen RN, Van Naarden Braun K. Prevalence of four developmental disabilities among children aged 8 years - Metropolitan Atlanta Developmental Disabilities Surveillance Program, 1996 and 2000. MMWR Surv Summar. 2006;55(1):1-9. 5. Paneth N, Hong T, Korzeniewski S. The descriptive epidemiology of cerebral palsy. Clin Perinatol. 2006;33(2):251-67. 6. Surveillance of Cerebral Palsy in Europe. Prevalence and characteristics of children with cerebral palsy in Europe. Dev Med Child Neurol. 2002;44(9):633-40. 7. Winter S, Autry A, Boyle C, Yeargin-Allsopp M. Trends in the prevalence of cerebral palsy in a population-based study. Pediatrics. 2002;110(6):1220-5. 8. “Infection in the Newborn as a Cause of Cerebral Palsy. 12/2004”. United Cerebral Palsy Research and Education Foundation (U.S.). Retrieved 2007-07-05. 9. Newman CJ, O’Regan M, Hensey O. Sleep disorders in children with cerebral palsy. Dev Med Child Neurol. 2006;48(7):564-8. 10. Nelson KB, Ellenberg JH. Children who “outgrew’ cerebral palsy. Pediatrics. 1982;69(5):529-36. 11. Sala DA, Grant AD. Prognosis for ambulation in cerebral palsy. Dev Med Child Neurol. 1995;37(11):1020-6.

12. Mitchell RG. The prevention of cerebral palsy. Develop Med Child Neurol. 1971;13(2):137-46. ■■■■

Diagnosing Stroke in Acute Dizziness In patients presenting with acute dizziness and nystagmus or imbalance, a combination of readily available clinical information can help risk-stratify acute stroke. Patients with dizziness from stroke are challenging because they often lack typical stroke warning signs or symptoms. “In acute dizziness presentations, the combination of ABCD2 [age, blood pressure, clinical features, duration and diabetes] score, general neurologic examination, and a specialized OM [ocular motor] examination has the capacity to risk-stratify acute stroke on MRI." (Kevin A. Kerber, MD, University of Michigan Health System, Ann Arbor, and colleagues in Neurology).

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OBSTETRICS AND GYNECOLOGY

An Operated Case of Vaginocutaneous Fistula: A Rare Case NAMRATA TIWARI MISHRA*, SHIKSHA TIWARI†, ANUPAM TIWARI‡, MAHESH TIWARI‡

ABSTRACT Vaginocutaneous fistula is a very rare fistula of genital tract. We report a case of a vaginocutaneous fistula presented with vague discomfort at perineum. She had history of recurrent perineal abscess.

Keywords: Vaginocutaneous fistula, fistulectomy, fistulogram

A

fistula is an abnormal connection between organ, vessel or intestine and another structure. A vaginal fistula starts with tissue damage which results from injury, surgery and infection. After days to years of tissue necrosis, a fistula breaks open. Vaginal fistula is reported very rarely in developed countries. However, vaginal fistula is much more common in developing countries. It is painless. But sometimes, it may cause embarrassing soiling problems.

vaginal discharge, pruritus and dyspareunia. All her swab cultures were negative. However, there was symptomatic improvement with multiple courses of antibiotics.

CASE REPORT

Routine investigations done to check for signs of infection were normal. Work-up for connective tissue disease was also done. Fistulogram was done. To our great surprise, fistulogram revealed a rightsided vaginocutaneous fistula with no peritoneal communication (Fig. 1).

A 28-year-old female reported to our outpatient unit with complaints of lower abdominal pain, persistent vaginal discharge and some vague discomfort in perineal region. Her background history included two normal vaginal deliveries with no medical or surgical comorbidities. There was no relieving or aggravating factor. Her previous menstrual cycles were regular. Her bowel and bladder habits were normal. Her vague discomfort in perineal region lasted for 2 years, which was extensively investigated and no cause was found. This was followed by persistent

*Assistant Professor Dept. of Obstetrics and Gynecology Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra †Consultant Dept. of Obstetrics and Gynecology ‡Consultant Dept. of Surgery Red Cross Hospital, Mhow, Indore, Madhya Pradesh Address for correspondence Dr Namrata Tiwari Mishra 1004, Sunbeam, Swastik Park Nahur West, Mumbai, Maharashtra E-mail: dr.namrata28@gmail.com

Her symptoms had worsened since last 2 months. General physical examination was normal. Abdominal examination was unremarkable. Local examination revealed an external opening. There was no lymphadenopathy.

A 3-week course of oral antibiotics did not resolve the symptoms, so the patient underwent surgical removal of the fistula tract under antibiotic suppression. Preoperatively, a vaginocutaneous fistula was confirmed with a fistula probe inserted through the fistula to find the internal opening (Fig. 2). Fistulectomy was performed (Fig. 3). Vaginal wall and the perineum were opened with appropriate incisions and fistula tract was removed. Specimen was sent for histopathological examination, which confirmed the diagnosis of vaginocutaneous fistula. Retrospectively, on taking detailed history, we came to know that she had perineal tear during her last delivery 4 years back. Details were not available. Recovery was uneventful. Patient was discharged on Day 4. Followups at 6 weeks, 3 months and 6 months after operation were completely normal.

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Figure 3. Fistulectomy done.

DISCUSSION Figure 1. Fistulogram showing vaginocutaneous fistula.

Figure 2. Fistula probe inserted through the external opening.

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The differential diagnosis of vaginal fistula should include vaginocutaneous fistula. Although the incidence is low but evaluation and treatment should be performed expeditiously as the condition affects the quality-of-life. Sometimes, fistula closes spontaneously and the drainage may be intermittent making them hard to identify at the time of examination. There are various etiologies for vaginocutaneous fistula. One of the most important cause is deep perineal tear following operative vaginal deliveries. Vaginoperineal integrity may be disturbed due to perianal operations, episiotomy and perianal disease.1,2 Other predisposing factors are infections and immune system disorders.3,4 Inflammatory bowel disorders like Crohn’s disease can have negative impact on the healing processes.5 Sjogren’s disease may be a predisposing factor for recurrent failures of fistula repair.6,7 It is rare systemic autoimmune disorder characterized by progressive dryness of mucous membranes that can interfere with the healing process.8,9 Treatment of underlying inflammation is mandatory for successful repair. Diagnosis and management of connective tissue disorder can significantly improve the outcomes of surgery for perianal fistulas. Radiation treatment for pelvic cancer is an another cause. Recently, chronic wuchereriasis presenting as a vaginoperineal fistula has been reported.10 Review of literature shows similar cases


OBSTETRICS AND GYNECOLOGY following tension-free vaginal tape insertion associated with infection. One report is of vaginocutaneous fistula 18 months following bladder neck suspension, the Stamey cystourethropexy procedure.11 Mostly after the abscess has been drained, a fistula may persist and may lead to some type of drainage from external opening. If the opening on the skin heals when a fistula is present, a recurrent abscess may develop. Until the fistula is eliminated, there may be recurring cycles of pain, swelling and drainage, with intervening periods of apparent healing. Local examination may not diagnose these anomalies accurately. Imaging modalities like fistulogram and pelvic magnetic resonance imaging are important tools for mapping the fistula tract and identifying internal openings. This particular case is unusual. The long delay in the fistula formation, the lack of comorbidities and negative swab cultures made the pathogenesis of the complication unclear.

3. Smink M, Lotgering FK, Albers L, de Jong DJ. Effect of childbirth on the course of Crohn’s disease; results from a retrospective cohort study in the Netherlands. BMC Gastroenterology. 2011;11:6. 4. Pinto RA, Peterson TV, Shawki S, Davila GW, Wexner SD. Are there predictors of outcome following rectovaginal fistula repair? Dis Colon Rectum. 2010;53(9):1240-7. 5. Tubaro E, Santiangeli C, Cavallo G, Belogi L, Guida G, Croce C, et al. Effect of a new de-N-acetyl-lysoglycosphingolipid on chemically-induced inflammatory bowel disease: possible mechanism of action. Naunyn Schmiedebergs Arch Pharmacol. 1993;348(6):670-8. 6. Vadacca M, Margiotta D, Sambataro D, Buzzulini F, Lo Vullo M, Rigon A, et al. BAFF/APRIL pathway in Sjögren syndrome and systemic lupus erythematosus: relationship with chronic inflammation and disease activity. Reumatismo. 2010;62(4):259-65. 7. Beksac K, Turgal M, Basaran D, Aran O, Beksac MS. Vaginoperineal fistula as a complication of perianal surgery in a patient with Sjögren’s syndrome: a case report. Case Rep Rheumatol. 2014;2014:359605.

CONCLUSION

8. Gwosdz M, Körber A, Hillen U, Dissemond J. Vasculitic leg ulcers in primary Sjogren syndrome. Hautarzt. 2008;59(5):404-8.

In conclusion, vaginocutaneous fistula should be included in the differential diagnosis of vaginal fistula.

9. Zoukhri D. Mechanisms involved in injury and repair of the murine lacrimal gland: role of programmed cell death and mesenchymal stem cells. Ocul Surf. 2010;8(2):60-9.

REFERENCES 1. Howard D, DeLancey JO, Burney RE. Fistula-in-ano after episiotomy. Obstet Gynecol. 1999;93(5 Pt 2):800-2.

10. Sharma P, Kumar N, Jain P, Gur R, Jain S. Chronic wuchereriasis presenting as a vaginoperineal fistula: report of a case with aspiration cytologic diagnosis. Acta Cytol. 2005;49(3):335-8.

11. Giles DL, Davila GW. Suprapubic-vaginocutaneous fistula 2. LeFevre C, Erekson EA, Hoffstetter S, McLennan M. 18 years after a bladder-neck suspension. Obstet Gynecol. Fistula-in-ano: an uncommon cause of chronic vulvar symptoms. Obstet Gynecol. 2010;115(2 Pt 2):421-3. 2005;105(5 Pt 2):1193-5. ■■■■

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OBSTETRICS AND GYNECOLOGY

Addition of Simple Laboratory Test to Reduce Overtreatment of Pelvic Inflammatory Disease by Syndromic Approach KAVITA AGARWAL*, REKHA BHARTI*, ACHLA BATRA†, ARUNA BATRA‡

ABSTRACT Objectives: To combine microscopic examination of vaginal smear to reduce overtreatment of pelvic inflammatory disease (PID) by syndromic approach. Material and methods: This is a cross-sectional study. Eighty-seven women with symptoms of pain lower abdomen, altered vaginal discharge or menstrual irregularities were enrolled in the study. Clinical diagnosis of PID was made based on the uterine and/or adnexal tenderness on pelvic examination. Vaginal, endocervical samples for microscopy and gonococcal and pyogenic culture were taken. Presence of ≥10 polymorphs/HPF on vaginal smear was taken as laboratory evidence of PID. Observations: Forty-four out of 47 women presenting with pain lower abdomen and 19 out of 40 presenting with altered vaginal discharge and menstrual irregularities were clinically diagnosed as PID. About 68.18% (30/44) in pain lower abdomen group and 68.42% (13/19) in the other group had laboratory evidence of PID. One-third (31.74%) of women with pelvic tenderness did not have significant pus cells on vaginal smear microscopy and would have been overtreated if microscopic examination of vaginal smear was not included to document clinical diagnosis of PID. Conclusions: Syndromic approach used along with vaginal smear microscopy for diagnosis of PID increases the specificity and thus reduces overtreatment.

Keywords: Pelvic inflammatory disease, vaginal discharge, vaginal smear

P

elvic inflammatory disease (PID) is polymicrobial in nature and is caused mainly by Neisseria gonorrhoeae, Chlamydia trachomatis and a wide variety of anaerobes and aerobic bacteria that constitute the normal vaginal flora. Standard tools for diagnosis of gonococcal and Chlamydia infection are expensive and not readily available in resource-limited settings. Syndromic approach guarantees an adequate management of women with clinical diagnosis of PID. According to the Centers for Disease Control and Prevention (CDC) guidelines 2006, specificity of clinical diagnosis of PID in population at low risk for sexually transmitted infections, can be enhanced by combining signs of lower genital tract inflammation with one of the three minimum criteria for diagnosing

*Assistant Professor †Associate Professor and Consultant ‡Professor and Consultant Dept. of Obstetrics and Gynecology, Safdarjung Hospital, New Delhi Address for correspondence Dr Kavita Agarwal 92, Vrindavan Apartment, Gali No. 4, Krishna Nagar Safdarjung Enclave, New Delhi - 110 029 E-mail: drku93@gmail.com

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PID (i.e., cervical motion tenderness, uterine tenderness or adnexal tenderness). Therefore, microscopic examination of vaginal smear for presence of pus cells can avoid overuse of antibiotics in women, presenting at tertiary hospital, with clinical diagnosis of PID, as majority of these women have already received multiple courses of antibiotics. The aim of present study was to evaluate the clinical diagnosis of PID by combining microscopic examination of vaginal smear to reduce overtreatment of PID by syndromic approach and to study socio-demographic profile of women with PID. MATERIAL AND METHODS This is a cross-sectional study. Eighty-seven women with complaints of lower abdominal pain, altered vaginal discharge or menstrual irregularities were enrolled in the study after informed consent. Detailed history and examination including pelvic examination was done. Vaginal and endocervical samples were taken for Gram staining and gonococcal and pyogenic culture. Chlamydia antigen testing was not done due to nonavailability of the test at our center. Blood samples were tested for syphilis and human immunodeficiency


OBSTETRICS AND GYNECOLOGY virus (HIV). The presence of ≼10 pus cells/HPF on microscopic examination of vaginal smear was taken as laboratory evidence of PID. Socio-demographic characteristics of the women with PID confirmed on vaginal smear microscopy were compared with women without PID and were described using standard descriptive statistics and characteristics associated with PID were examined using Chi-square test. RESULTS Eighty-seven women were enrolled in the study. Duration of symptoms varied from 3 days to 6 years, in majority of women (94.25%) duration of symptoms was more than 1 month (Table 1). Forty-seven women presented with lower abdominal pain; out of these, 44 (85.10%) had pelvic tenderness and 68.18% (30/44) showed presence of ≼10 pus cells/HPF on microscopic examination of vaginal smear. In the other group of 40 women with complaints of either altered vaginal discharge or menstrual irregularities, pelvic tenderness was present in 19 (47.5%) and 68.42% (13/19) showed laboratory evidence of PID (Tables 2 and 3). One-third (31.74%) of women with pelvic tenderness did not have significant pus cells on vaginal smear microscopy and would have been overtreated if microscopic examination of vaginal smear was not included to document clinical diagnosis of PID.

Table 1. Duration of Symptoms Duration

No of cases (n = 87)

<7 days

2

7-30 days

3

1 month-1 year

44

>1 year

38

Table 2. Clinical Presentations Signs and symptoms

Total (n = 87)

Lower abdominal pain

47

Vaginal discharge/menstrual complaints

40

Table 3. Vaginal Smear Microscopy Clinical PID

Vaginal smear positive cases of PID (n = 43)

Percentage of positive cases of PID

LAPS

30/44

68.18

Vaginal discharge/ menstrual complaints with tenderness

13/19

68.42

LAPS: Lower abdominal pain and tenderness.

Table 4. Age Distribution of Study Group

Gonococcal and pyogenic cultures were negative in all the cases. All women tested negative for syphilis and HIV as the study group comprised of women with low risk for sexually transmitted infections.

Age group (years)

PID (n = 43)

Control (n = 44)

<20

1

2

21-30

18

34

31-40

19

8

Socio-demographic Profile

41-45

4

0

Most of women in the PID group were between 31 and 40 years (p < 0.02) and were more often illiterate (p < 0.05). Women in non-PID group were mainly in 21-30 years age group (p < 0.001) and their spouses had skilled or semi-skilled profession as occupation (p < 0.01) (Tables 4-6).

>45

1

0

DISCUSSION Syndromic management provides treatment at first visit and cuts the cost of expensive laboratory testing. It avoids further transmission and complications of reproductive tract infections that can occur as a result of loss to follow-up, but at the same time it results in substantial overtreatment. One-third (31.74%) of women

Table 5. Education Status of Women Education status of patients

Smear positive cases

Smear negative cases

Illiterate

18

9

Completed primary school

10

16

Completed higher secondary

8

9

Senior Secondary

1

6

Graduation

3

3

Postgraduation

3

1

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OBSTETRICS AND GYNECOLOGY Table 6. Occupation of Spouses Occupation of spouses

Table 7. Occupation of Women PID (n = 43)

Control (n = 44)

Agricultural laborer

2

4

Non-agricultural laborer

2

Domestic servant

Occupation of women

PID (n = 43)

Control (n = 44)

Skilled/semi-skilled worker

2

2

Large business/selfemployed

3

3

1

1

1

Unemployed

38

39

Skilled/semi-skilled worker

13

19

Petty business/small shop

7

10

Large business/self-employed

5

1

Service (Govt./Pvt.)

9

5

Truck driver/helper

1

0

Local transport worker

1

2

Hotel staff

1

1

(p = 0.000003 and p < 0.05, respectively). Prasad et al3 reported that women who worked as agricultural laborers had an elevated likelihood of having a sexually transmitted infection (odds ratio, 2.4), whereas no association with occupation of women was found in the present study (Table 7).

Agricultural/cultivator/landholder

1

0

CONCLUSION

in the present study were benefited by this test and were not given unnecessary antibiotics. Repeated courses of antibiotics can lead to unnecessary side effects in an individual and result in early drug resistance. These women should be evaluated for chronic pelvic pain and managed accordingly. Microscopic examination of vaginal smear is a relatively simple and inexpensive laboratory method for increasing specificity of clinical diagnosis of PID especially in women presenting at tertiary hospitals. Results of vaginal smears can be given within a reasonable time and therefore, patients do not have to return to the health facility for treatment the next day. Sloan et al1 found young age to be strongly associated with C. trachomatis and/or N. gonorrhoeae. Whereas Viberga et al2 and the present study found PID to be more common in older women (p = 0.003 and p < 0.02, respectively) and women with lower education level

To conclude, syndromic approach used along with vaginal smear microscopy for diagnosis of PID increases the specificity and thus reduces overtreatment. PID had statistically significant association with older age and illiteracy (p < 0.05). REFERENCES 1. Sloan NL, Winikoff B, Haberland N, Coggins C, Elias C. Screening and syndromic approaches to identify gonorrhea and chlamydial infection among women. Stud Fam Plann. 2000;31(1):55-68. 2. Viberga I, Odlind V, Lazdane G. Characteristics of women at low risk of STI presenting with pelvic inflammatory disease. Eur J Contracept Reprod Health Care. 2006;11(2):60-8.

3. Prasad JH, Abraham S, Kurz KM, George V, Lalitha MK, John R, et al. Reproductive tract infections among young married women in Tamil Nadu, India. Int Fam Plan Perspect. 2005;31(2):73-82. ■■■■

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OBSTETRICS AND GYNECOLOGY

Viral Infections in Pregnancy V PADMA

ABSTRACT Viral infections in pregnancy are a major cause of maternal and fetal morbidity and mortality. Infections can develop in the neonate transplacentally, perinatally (from vaginal secretions or blood) or postnatally (from breast milk or other sources). The clinical manifestations of neonatal infections vary depending on the viral agent and gestational age at exposure. The risk of infection is usually inversely related to gestational age at acquisition, some resulting in a congenital malformation syndrome. Perinatal infections account for 2-3% of birth defects, which arise from a spectrum of organisms and have varying modes of transmission. Most fetuses if infected during the first trimester will suffer from a syndrome of congenital malformation.

Keywords: Viral infections, transplacental, postnatal, measles, hepatitis

V

iral infections in pregnancy are a major cause of maternal and fetal morbidity and mortality. Infections can develop in the neonate transplacentally, perinatally (from vaginal secretions or blood), or postnatally (from breast milk or other sources). The clinical manifestations of neonatal infections vary depending on the viral agent and gestational age at exposure. Infections known to produce congenital defects have been described as TORCH (Toxoplasma, Other, Rubella, Cytomegalovirus [CMV], Herpes). The “other” category has expanded rapidly to include several viruses. The viral infections of concern during pregnancy are those caused by rubella virus, CMV and herpes simplex virus (HSV). Other viruses known to cause congenital infections include parvovirus B19 (B19V), varicella-zoster virus (VZV), West Nile virus, measles virus, enteroviruses, adenovirus and human immunodeficiency virus (HIV). Hepatitis E virus causes high mortality rate in pregnant women. Lymphocytic choriomeningitis virus (LCMV) has been implicated as a teratogenic rodent-borne arena-virus.

Professor Dept. of Medicine Sree Balaji Medical College, Bharath University, Chennai, Tamil Nadu Address for correspondence Dr V Padma Professor, Dept. of Medicine Sree Balaji Medical College, Chrompet, Chennai, Tamil Nadu E-mail: padmaramesh86@yahoo.com, drpadmaramesh86@gmail.com

DISCUSSION TORCH infections are: T–Toxoplasmosis O–Other (varicella zoster, parvovirus coxsackievirus, West Nile virus, measles enteroviruses, adenovirus, influenza)

B19, virus,

R–Rubella C–Cytomegalovirus H–Herpes simplex virus-2, HIV, hepatitis (hepatitis E virus because of the high mortality rate associated with infection in pregnant women).

Rubella (German Measles) The fetus is most at risk in the first 16 weeks gestation. Causative organism: Rubella virus (togaviruses RNA). Route of infection: Via respiration as the virus is concentrated in the nasopharyngeal secretions. Symptoms: Mild pyrexia, arthralgia, rash on face, postauricular, deep cervical and suboccipital lymphadenopathy. Risk of fetal transmission ÂÂ

50-60% of fetuses are affected if infection is acquired in the first month

ÂÂ

22% in the second month

ÂÂ

6-10% in the third to fourth month of gestation.

Despite availability of effective vaccines, around 20% of women of childbearing age do not possess rubella antibody. Most children exposed to maternal rubella infection develop congenital rubella syndrome (CRS).

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OBSTETRICS AND GYNECOLOGY CRS is characterized by intrauterine growth restriction,1 intracranial calcifications, microcephaly, cataracts, neurologic disease (with a broad range of presentations, from behavior disorders to meningoencephalitis), cardiac defects (most commonly patent ductus arteriosus or pulmonary arterial hypoplasia), osteitis and hepatosplenomegaly. Diagnosis: A fourfold rise in rubella immunoglobulin (Ig)G antibody titer between acute, convalescent serum. A positive serologic test for rubella-specific IgM antibody. Viral cultures drawn from nasal, blood, throat, urine or cerebrospinal fluid are positive from 1 week before to 2 weeks after the onset of the rash.

virus isolation in cell cultures (shell vial) is also highly sensitive and specific. Amniocentesis for CMV PCR can be performed after 21 weeks of gestation; testing fetal serum for IgM antibodies is highly sensitive for congenital infection after 21 weeks of gestation. Identification of CMV in the amniotic fluid by culture or PCR is the most sensitive and specific test for congenital CMV, with a procedure loss rate of less than 1 in 200. Treatment ÂÂ

CMV hyperimmune globulin may reduce the risk of congenital infection and disease when given to pregnant women experiencing a primary CMV infection.

ÂÂ

Ganciclovir in congenital CMV infection: Ganciclovir at 12 mg/kg/day for 6 weeks stops the progression of hearing loss and can even reverse it.

Prevention ÂÂ

Vaccination before or after pregnancy (not during).

ÂÂ

In acute infection: Droplet precautions.

ÂÂ

In neonatal infection: Contact precautions.

Cytomegalovirus Infects 50-60% of women of childbearing age. Causative agent: CMV (DNA virus, Herpes family). Maternal symptoms: Usually mild or asymptomatic, fever with/without lymphadenopathy, sore throat. Transmission ÂÂ

Direct: Person-to-person contact (saliva, milk, urine, semen, tears, stools, blood, cervical and vaginal secretion).

ÂÂ

Indirect: Contaminated fomites.

In primary CMV infection, 30-40% of fetuses will be infected; 2-4% of them will develop severe malformations at birth. In recurrent CMV infections, about 1% of fetuses will be infected and the rest will be normal at birth, but later in life, they may suffer from delayed speech and learning difficulties due to cerebral calcification and sensorineural hearing loss. A small group may have chorioretinitis. Complications of fetal CMV infection:2 Micro- and hydrocephaly, chorioretinitis, cerebral calcification, mental retardation, heart block, petechiae. Diagnosis: IgM antibodies can persist for up to a year, leading to difficulty in determining fetal exposure during pregnancy. A 4-fold or greater rise in the CMV-IgG titer within 2 weeks is consistent with a recent infection. Urine culture or polymerase chain reaction (PCR) using urine or serum are also methods used for diagnosis. Rapid

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Indian Journal of Clinical Practice, Vol. 26, No. 7, December 2015

Toxoplasmosis Causative agent: Protozoan Toxoplasma gondii. Risk of fetal infection ÂÂ

First trimester (15%), second trimester (25%), third trimester (65%).

ÂÂ

Forty percent of fetuses are affected if the mother has the illness.

Maternal symptoms: Asymptomatic or fever, rash and eosinophilia. Diagnosis: If both IgG and IgM are positive, this indicates either a recent infection or a false-positive test result. A fourfold rise in IgG antibody titers between tests indicates a recent infection. Treatment: Spiramycin 3 g/day for 3-4 weeks, dose of 1 g (3 million U)3 orally every 8 hours prescribed for the duration of the pregnancy if the amniotic fluid PCR is reported negative. A combination of pyrimethamine, sulfadiazine and folinic acid should be offered as treatment for women in whom fetal infection has been confirmed or is highly suspected (usually by a positive amniotic fluid PCR). A nonpregnant woman who has been diagnosed with an acute T. gondii infection should be counseled to wait 6 months before attempting to become pregnant.

HIV Causative agent: RNA retrovirus. immunodeficiency virus (HIV).

Human

Fetal transmission ÂÂ

Twenty-five percent if the mother is infected.


OBSTETRICS AND GYNECOLOGY ÂÂ

Reduced to 8% if the mother is treated with zidovudine (AZT).

ÂÂ

Less than 3% with suppressive triple antiretroviral therapy.

Transmission during pregnancy and puerperium ÂÂ

Majority of infants are infected in third trimester or at time of delivery; vertical transmission can occur during vaginal delivery; cesarean section is protective (50%).

ÂÂ

Premature babies are more at risk of vertical transmission.

ÂÂ

Transmission may also occur with breastfeeding.

ÂÂ

Bottle feeding reduces possibly by up to 50%.

vertical

transmission

Screening: Routine HIV antibody test performed in first trimester. Repeat in third trimester if high risk for HIV. Serology: Enzyme-linked immunosorbent (ELISA), Western blot for confirmation.

assay

Treatment: If HIV-positive, treat with a combination4 of three anti-HIV medications in one pill (efavirenz, emtricitabine and tenofovir). Efavirenz may cause birth defects and should be avoided in the first trimester of pregnancy. After the first trimester, efavirenz or triple drug regime can be used safely. Nevirapine is safe for women with CD 4 <250; it causes liver failure in others. Cesarean section at 38 weeks in patients with viral load <1,000s prevents fetal transmission. Within 6-12 hours after delivery, babies born to women infected with HIV receive an anti-HIV medication called AZT, which helps prevent mother-to-child transmission of HIV. The babies receive AZT for 6 weeks. Transferred maternal antibodies persist up to 18 months in uninfected infants, so gene amplification via PCR can detect neonatal HIV infection. Intrauterine HIV is associated with prematurity and growth retardation. Clinical problems: Appear sooner in infected babies than in adults; acquired immune deficiency syndrome (AIDS) (e.g., at aged 6 months) with hepatosplenomegaly, failure to thrive, encephalopathy, recurrent fever, respiratory diseases (interstitial lymphocytic pneumonitis), septicemia (salmonella), pneumocystis and lymphadenopathy. Death is usually from respiratory failure or overwhelming infection (20% at 18 months).

Viral Hepatitis Most common cause of jaundice during pregnancy. Hepatitis B and C are transmitted by contaminated blood, saliva, breast milk, semen. Hepatitis A and E are transmitted by feco-oral route. Vertical transmission of hepatitis A virus (HAV) during pregnancy or puerperium is rare. The incidence of acute HAV infection in pregnancy is approximately 1:1,000 women. Pregnancy should not impact a physician’s management of HAV infection or vice versa. During pregnancy, the risk of fulminant hepatitis E virus (HEV) disease and maternal mortality occurs in 20% of patients when the disease presents during the third trimester. Premature deliveries with high infant mortality of up to 33% are also observed. Hepatitis B It is a DNA virus Complications: Hepatitis, cirrhosis and/or liver cancer (as an adult at age of 30-40 years). Rate of transmission from mother to fetus: 10-20% (if HBeAg positive-90%) Pregnant women who are infected transmit the virus transplacentally to the fetus and at birth. Neonatal jaundice is rare in women with chronic hepatitis or acquired hepatitis early in pregnancy. The risk is high when infection occurs late in pregnancy. Screening: trimester).

Routine

HBsAg

(performed

in

first

Prevention: Hepatitis B immunoglobulin (HBIG) and hepatitis B virus (HBV) vaccine should be given to the baby at birth. If nonimmune mother is exposed in pregnancy, give HBIG and HBV vaccine. No antiviral agent has been approved by the FDA for use in pregnancy. Lamivudine5 and tenofovir are the two agents with the most in vivo experience in the first trimester, and these appear to be safe. Quantification of HBV DNA is recommended in all infected women at the end of the second trimester (at 26-28 weeks of gestation). If the viral load is >10,000 copies/mL, antiviral prophylaxis of HBV transmission to newborn can be initiated early in the third trimester (28-30 weeks). In the absence of active disease or cirrhosis at baseline, discontinuation of treatment 4 weeks after delivery is

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OBSTETRICS AND GYNECOLOGY reasonable. If the patient has advanced liver disease, we do not recommend discontinuation. Hepatitis C

Prevention: If lesions are present at time of delivery, then cesarean section is recommended. Daily oral acyclovir can be considered in late third trimester.

It is a RNA virus.

Parvovirus B19

Vertical transmission is low with rate of approximately 6%. The risk of transmission correlates with hepatitis C virus (HCV) titer in the mother.

Most adults with parvovirus B19 (B19V) infection are asymptomatic; the effects of this virus on the fetus are much greater and include miscarriage, fetal anemia, hydrops fetalis, myocarditis and/or intrauterine fetal death.8

Complications: Hepatitis, cirrhosis and/or liver cancer (as an adult). Screening: patients:

Recommended

in

high-risk

ÂÂ

Intravenous drug users (IVDU)

ÂÂ

Blood transfusion before 1995

ÂÂ

Undiagnosed hepatitis.

pregnant

Infection occurs most frequently in the winter and spring. B19V infection accounts for 15-20% of nonimmune hydrops fetalis. Thirty to 40% of pregnant women are seronegative for B19V and are thus susceptible to infection.

Prevention: Avoid high-risk behavior, e.g., IVDU; currently no post-exposure prophylaxis available. Current approved therapy for HCV-related chronic liver disease6 includes α-interferon-2b alone or in combination with the oral agent ribavirin. Because there are no large studies of ribavirin use during human pregnancy, and ribavirin is teratogenic (causes birth defects) in multiple animal species, the use of ribavirin during pregnancy is presently contraindicated. The risk of vertical transmission of HCV appears to be related to the level of viremia in the pregnant mother and not to the route of delivery.

The critical period for the development of fetal hydrops is when maternal B19V infection is acquired between the 13th and 16th weeks of gestation, possibly because of the relative immaturity of the fetal immune response, as well as the shortened life span of the red blood cells at this gestational age.

Varicella-zoster Virus Herpes-virus family, DNA virus. If infection occurs in the first trimester, there is 4.9% risk of congenital varicella.

The virus does not appear to be transmitted when a woman’s titer is <106/mL or is negative.

Congenital syndrome: Limb hypoplasia, ocular abnormalities, central nervous system (CNS) abnormalities (convulsive disorders) and dermatomal scarring.9

α-interferon 2b-3 million IU subcutaneously or intramuscular (IM) 3 times a week. Ribavirin has been assigned to pregnancy Category X by the Food and Drug Administration (FDA). Nearly all animal studies have revealed evidence of embryo lethality and teratogenicity.

Perinatal: If infection is acquired in the last 10 days of pregnancy, this results in variably severe fetal infections with neonatal mortality as high as 34%. (Infection at this time prevents development of maternal antibodies that avert transplacental transfer of IgG antibodies, which confer passive immunity to the fetus). Diagnosis: Clinical, serology (IgG and IgM).

Herpes Simplex Herpes virus family, DNA virus. Seventy percent due to HSV-2. Primary: Fetal loss, congenital syndrome. Recurrent: Mucocutaneous disease, encephalitis.

lesions,

disseminated

Transmission occurs at time of delivery in 90-95% of cases (vaginal delivery).7 Neonatal HSV infection affects 1/5,000 births (half of these related to primary infection).

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Indian Journal of Clinical Practice, Vol. 26, No. 7, December 2015

Screening: Routine recommended.

screening

generally

not

Prevention: If pregnant woman (with no history of previous chickenpox) is exposed, perform varicella IgG. Exposed neonate should receive varicella-zoster immune globulin (VZIG) prophylaxis. Diagnosis is primarily clinical, by recognition of the rash. If necessary, it can be confirmed by detection of antigen (direct immunofluorescence), PCR or by viral culture of the aspirated vesicular fluid.


OBSTETRICS AND GYNECOLOGY Treatment: Acyclovir (800 mg 5 times daily at 4 hourly intervals for 7 days) or acyclovir 5 mg/kg 8 hourly IV (intravenous) until patient is improving. Acyclovir is a Class C antiviral agent used in the treatment of varicella zoster. Oral acyclovir has been shown to significantly reduce symptoms, duration and intensity.

Enterovirus Enterovirus infections are not believed to cross the placenta and cause fetal disease.

Measles Virus Measles virus infection (rubeola) during pregnancy, tends to be severe, with pneumonitis predominating. Although it is not known to be teratogenic, rubeola has been associated with spontaneous abortion, premature labor and low birth weight. Neonates born to mothers with active measles virus infection are at risk of developing neonatal measles, but no congenital syndrome has been described.

Lymphocytic Choriomeningitis Virus LCMV has been associated with sporadic cases of congenital infection worldwide. Affected infants demonstrate chorioretinitis, hydrocephalus, mental retardation and/or visual impairment; in addition, intrauterine death is possible.10 Unlike congenital CMV and rubella infections, hearing deficits and hepatosplenomegaly are rarely seen in congenital LCMV.

Other Viruses Other viruses11 postulated to cause congenital infections include echovirus, West Nile virus and adenovirus. In 2002, an article in Morbidity and Mortality Weekly Report discussed a single case of West Nile virus infection in a mother and associated chorioretinitis in her newborn. Infants born to mothers who develop symptomatic West Nile virus infection within 3 weeks prior to delivery may develop symptomatic West Nile virus disease shortly after birth.

Influenza Influenza poses a significant threat to the health of the mother and infant. During the 2009 H1N1 pandemic,12 pregnant women accounted for 5% of all deaths and were more likely to be hospitalized than the general population. Diagnosis: Throat swab positive for H1N1.

The Centers for Disease Control and Prevention (CDC) recommends treatment of influenza in pregnant and postpartum women (up to 2 weeks after birth) with a neuraminidase inhibitor13 such as oseltamivir and zanamivir (seasonal influenza). Early treatment within 2 days of onset of symptoms is associated with lower morbidity. The usual dose of oseltamivir is 75 mg twice-daily for 5 days. One study found that influenza vaccination of high-risk pregnant patients also provides some protective immunity for newborns and reduces subsequent hospitalizations in the infants.14 CONCLUSION Viral infections, if acquired early in pregnancy, cause congenital malformations in children. The risk of infection is usually inversely related to gestational age at acquisition, some resulting in a congenital malformation syndrome. Perinatal infections account for 2-3% of birth defects, which arise from a spectrum of organisms and have varying modes of transmission. Hence, prevention of infection, early diagnosis and treatment will reduce morbidity and mortality in children born to mothers infected with viral infections. REFERENCES 1. De Santis M, Cavaliere AF, Straface G, Caruso A. Rubella infection in pregnancy. Reprod Toxicol. 2006;21(4):390-8. 2. Gaytant MA, Steegers EA, Semmekrot BA, Merkus HM, Galama JM. Congenital cytomegalovirus infection: review of the epidemiology and outcome. Obstet Gynecol Surv. 2002;57(4):245-56. 3. Paquet C, Yudin MH; Society of Obstetricians and Gynaecologists of Canada. Toxoplasmosis in pregnancy: prevention, screening, and treatment. J Obstet Gynaecol Can. 2013;35(1):78-81. 4. Thorne C, Newell ML. The safety of antiretroviral drugs in pregnancy. Expert Opin Drug Saf. 2005;4(2):323-35. 5. Su GG, Pan KH, Zhao NF, Fang SH, Yang DH, Zhou Y. Efficacy and safety of lamivudine treatment for chronic hepatitis B in pregnancy. World J Gastroenterol. 2004;10(6):910-2. 6. Conte D, Colucci A, Minola E, Fraquelli M, Prati D. Clinical course of pregnant women with chronic hepatitis C virus infection and risk of mother-to-child hepatitis C virus transmission. Dig Liver Dis. 2001;33(4):366-71. 7. Brown ZA, Selke S, Zeh J, Kopelman J, Maslow A, Ashley RL, et al. The acquisition of herpes simplex virus during pregnancy. N Engl J Med. 1997;337(8):509-15. 8. Al-Khan A, Caligiuri A, Apuzzio J. Parvovirus B-19 infection during pregnancy. Infect Dis Obstet Gynecol. 2003;11(3):175-9.

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OBSTETRICS AND GYNECOLOGY 9. Harger JH, Ernest JM, Thurnau GR, Moawad A, Momirova V, Landon MB, et al; National Institute of Child Health and Human Development, Network of Maternal-Fetal Medicine Units. Risk factors and outcome of varicellazoster virus pneumonia in pregnant women. J Infect Dis. 2002;185(4):422-7. 10. Barton LL, Mets MB, Beauchamp CL. Lymphocytic choriomeningitis virus: emerging fetal teratogen. Am J Obstet Gynecol. 2002;187(6):1715-6.

12. Mosby LG, Rasmussen SA, Jamieson DJ. 2009 pandemic influenza A (H1N1) in pregnancy: a systematic review of the literature. Am J Obstet Gynecol. 2011;205(1):10-8. 13. Xie HY, Yasseen AS 3rd, Xie RH, Fell DB, Sprague AE, Liu N, et al. Infant outcomes among pregnant women who used oseltamivir for treatment of influenza during the H1N1 epidemic. Am J Obstet Gynecol. 2013;208(4):293. e1-7.

14. 11. Ornoy A, Tenenbaum A. Pregnancy outcome following infections by coxsackie, echo, measles, mumps, hepatitis, polio and encephalitis viruses. Reprod Toxicol. 2006;21(4):446-57. ■■■■

Benowitz I, Esposito DB, Gracey KD, Shapiro ED, Vázquez M. Influenza vaccine given to pregnant women reduces hospitalization due to influenza in their infants. Clin Infect Dis. 2010;51(12):1355-61.

Maternal Deaths Fell 44% Since 1990: UN Maternal mortality has fallen by 44% since 1990, United Nations agencies and the World Bank Group reported. Maternal deaths around the world dropped from about 5,32,000 in 1990 to an estimated 3,03,000 this year, according to the report, the last in a series that has looked at progress under the Millennium Development Goals (MDGs). This equates to an estimated global maternal mortality ratio (MMR) of 216 maternal deaths per 1,00,000 live births, down from 385 in 1990. The analyzes contained in Trends in Maternal Mortality: 1990 to 2015 – Estimates by WHO, UNICEF, UNFPA, World Bank Group and the United Nations Population Division are being published simultaneously in The Lancet. Despite global improvements, only 9 countries, Bhutan, Cabo Verde, Cambodia, Iran, Lao People’s Democratic Republic, Maldives, Mongolia, Rwanda and Timor-Leste, achieved the MDG 5 target of reducing the maternal mortality ratio by at least 75% between 1990 and 2015. Despite this important progress, the MMR in some of these countries remains higher than the global average.

Don’t Advise Doctors on Reproductive Medicine, Say Infertility Specialists Don’t tell doctors how to practice reproductive medicine. Using this dramatic line, the country’s infertility specialists have written a 10-point rejoinder to the central government’s Assisted Reproductive Technology (Regulation) Bill 2014. “The bill should not include technical details telling the physician how to practice reproductive medicines. Even the MTP (Medical Termination of Pregnancy) Act & the PCPNDT (Pre-Conception and Prenatal Diagnostic Techniques Act) do not advise physicians on how to perform MTP, ultrasonography, amniocentesis, etc,” said a letter by the Indian Society for Assisted Reproduction (ISAR) last week. ISAR, an umbrella organization of infertility specialists in the country, wrote the letter in response to the Centre’s call for suggestions to its draft bill. “The law should act as a guideline and not get into specifics,” said ISAR past president Dr Manish Banker from Ahmedabad. ISAR members have said the government should rework certain provisions that duplicate functions laid down by other Acts and hold another meeting with doctors before approving the draft bill. They want “graded punishment” for offences such as clerical errors, lack of proper permission, harm caused by wrong medical treatment and exploitation of surrogate. … (Times of India – Malathy Iyer)

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OBSTETRICS AND GYNECOLOGY

Tuberculosis of the Female Genital Tract in Patients Attending an Infertility Clinic and its Effect on Pregnancy Outcome in in vitro Fertilization and Embryo Transfer ALKA GAHLOT*, ML SWARANKAR†, RAVIKANT SONI‡

ABSTRACT Objective: To study the effect of genital tuberculosis (TB) on female fertility and the outcome of in vitro fertilization and embryo transfer (IVF-ET) in these patients. Material and methods: A total of 550 infertile women were included in the study. Routine hysteroscopy was done with or without laparoscopy in all patients with history of infertility and diagnosis was confirmed by acid-fast bacilli (AFB) culture (BACTEC) of biopsies obtained by endometrial curettage and EB-rRNA-PCR. Results of IVF-ET were analyzed in patients with genital TB. Results: Incidence of genital TB in patients presenting with infertility was 15.64%. History of extra-genital TB was present in 29% and tubercular peritonitis was seen in combination with female genital tract TB in approximately 45% of patients. Laparoscopic finding in 58 patients showed tubal involvement in 67.44% cases and frozen pelvis in 12.8% cases. 22.1% patients had synechias of varying degree at hysteroscopy and 52.63% of them had endometrial biopsy AFB culture positive for TB. The pregnancy rate after IVF-ET was 18.75% per transfer and live birth rate was 23.88%. Conclusion: TB is one of the major etiological factors of female infertility. IVF-ET offers the only realistic treatment to these women. Preliminary assessment of endometrium by hysteroscopy is helpful in assessing prognosis in these cases.

Keywords: Genital tuberculosis, pregnancy rate, in vitro fertilization, embryo transfer

T

he incidence of infertility in genital tuberculosis (TB) worldwide varies from 44% to 74%; in India it is reported to be 58%.1 The fallopian tubes constitute the initial focus of genital TB in 90-100% of patients, followed by the uterus 50-60%, the ovaries 20-30%, the cervix 5-15% and lastly the vagina in 1% of patients.2 It is well-established that genital TB is one of the common causes of female infertility.3 However, it is difficult to predict the accurate prevalence of genital TB because it often tends to exist without any clinical sign or symptoms (latent). Genital TB is reported to be a major pelvic factor causing infertility in Indian women.4,5

*Associate Professor †Professor Dept. of Obstetrics and Gynecology ‡Senior Demonstrator Dept. of Biochemistry Mahatma Gandhi University of Medical Sciences and Technology, Jaipur, Rajasthan Address for correspondence Dr Alka Gahlot 170, Heera Nagar, DCM, Ajmer Road, Jaipur- 302 021, Rajasthan E-mail: dralkagahlot@gmail.com, alkagahlot23@gmail.com

While 5-10% of infertile females all over the world have genital TB, the incidence varies from less than 1% in the US to nearly 18% in India.2 Active TB is observed only in 10% of the infected individuals;6 usually latent infection persists.7 Mycobacterium tuberculosis, prior to developing into active tubercular endometritis, may reside in the basal endometrium leading to impairment of endometrial and subendometrial blood flow. Hence, implantation failure following in vitro fertilization (IVF) in women with unexplained infertility could be due to latent TB considering the fact that Indian subcontinent is the zone prone to TB in any form.8 Genital TB is an extremely indolent infection and the disease may not become manifest for more than 10 years after initial seedling in genital tract. The main presenting complaints of young women are infertility, vaginal bleeding and chronic lower abdominal or pelvic pain.2 Genital TB should always be considered in young patients presenting with unexplained infertility or repeated IVF failure.8 In the present study, the role of genital TB is examined in infertile patients. Thickness of endometrium was

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OBSTETRICS AND GYNECOLOGY assessed to predict endometrial involvement and compared with endometrial thickness in nontubercular infertile patients. MATERIAL AND METHODS This study was done at Jaipur Fertility Centre, ART Division of Mahatma Gandhi Institute of Medical Sciences and Technology, Jaipur. A retrospective analysis of 86 women suffering from infertility due to genital TB during the 1½ year from July 2011 to December 2012 was done. A total of 550 infertile women were analyzed during the study. Past history of antitubercular treatment was noted in detail, including duration of treatment, organ or system involved and diagnostic criteria by which TB was confirmed. Previous operative interventions and operative findings were recorded in details. Mid cycle endometrial thickness was assessed with color Doppler study in genital TB patients and other infertile patients with nontubercular etiology. A detailed history including demographic particulars was taken and a thorough clinical examination done. Apart from routine hematological investigations, specialized investigations consisting of transvaginal sonography of uterus and adnexa, hormone profile, immunological assays and endoscopy were performed as needed. Postmenstrual hysteroscopy was done in all patients in whom it was not done earlier and endometrial biopsy sent for ribosomal RNA-polymerase chain reaction (rRNA-PCR) and acid-fast bacilli (AFB) culture (BACTEC). Saline infusion sonography was done during hysteroscopy to assess tubal patency in patients where laparoscopy was not required. Laparoscopy was done using the standard two puncture technique. All abnormal findings suspicious of TB such as pallor of tissue, salpingitis and retort-shaped tubes, eversion of fimbrial end of the tube, hydrosalpinx, tuboovarian masses, adhesions, unilateral and bilateral tubal block, isthmica nodosa at the proximal part of the tube, distal tubal obstruction and scattered caseating material on pelvic peritoneum or genital organs were observed. All correctable adhesions around ovaries and tubes were treated using scissor and monopolar cutting current. Tubal patency was checked by transcervical injection of 50 mL of sterile methylene blue solution and by observing the passage through the fimbrial ends of the tubes. Hysteroscopy was done during the same setting and endometrial tissue from all parts of the uterine cavity was taken and sent for

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rRNA and AFB culture examination for detection of M. tuberculosis. PCR enables detection of <10 pg DNA that corresponds to about three genome equivalents. It has a high-sensitivity (>90%) and a specificity ranging between 70% and 90%.9 Another rapid technique to aid diagnosis of TB is the BACTEC culture.10 BACTEC-460 cultures normally gives a specificity of 91.8%.11 RESULTS This study comprised 550 infertile women in total. Most of the patients were aged between 30-34 years (42%), rural (51.1%) and educated 64.9% (Table 1). The overall incidence of genital tract TB among the infertile population was 15.64% (86/550 cases). Family history of TB was present in 16% of cases. Only 15.12% patients had a history of pulmonary TB. Maximum number of patients (37.21%) had history of abnormal uterine bleeding mostly in the form of scanty periods, followed by history of taking antitubercular drugs. Some of the patients had more than one clinical presentation (Table 2). Table 1. Patient Characteristics Variables

All patients (n = 550)

Tuberculous patients (n = 86)

20-24

51/550 = 9.27%

33/86 = 38.37%

25-29

125/550 = 22.73%

12/86 = 13.95%

30-34

231/550 = 42%

18/86 = 20.93%

35-40

143/550 = 26%

23/86 = 26.74%

Urban

269/550 = 48.9%

31/86 = 36.04%

Rural

281/550 = 51.1%

55/86 = 63.95%

Not educated

193/550 = 35.1%

63/86 = 73.26%

Educated

357/550 = 64.9%

23/86 = 26.74%

Age group (years)

Resident

Educational level

Table 2. Clinical Data of Diagnosed Cases having Genital TB Clinical data

N = 86

Percentage (%)

Antitubercular drugs

29

33.72

Abnormal uterine bleeding

32

37.21

History of night fever and sweating

4

4.65

Adnexal mass

8

9.3

History of pulmonary TB

13

15.12


OBSTETRICS AND GYNECOLOGY Out of 86 patients tested, positive reports for PCR and BACTEC culture were obtained in 62 (72.1%) and 37 patients (43%), respectively. All patients with positive BACTEC culture were also PCR-positive (Table 3). Some patients had more than one abnormal finding. Thirty-seven patients had already undergone laparoscopy and received full course of antitubercular treatment for genital or extra-genital TB. Two patients had normal findings at laparoscopy. In our study, we performed laparoscopy in 21 patients (Table 4). In 28 patients, we did not perform laparoscopy as there were biopsy-proven tubercular endometritis in six patients, advanced age (>38 years) with positive serology in five, Table 3. Percentage of EB-PCR and AFB Culture Positive Cases Variable

No. of patients

Percentage (%)

EB-PCR positive

62/86

72.1

EB-AFB culture positive

37/86

43

Table 4. Laparoscopy Findings Findings

Hydrosalpinx

Previous laparoscopy (n = 37)

Laparoscopy during study (n = 21)

4

6

Tubal block/beading

15

13

Tubercular salpingitis

12

14

Adhesions

11

9

Frozen pelvis

6

5

Table 5. Results of IVF-ET in Patients with Genital TB Soussis et al17

Frydman et al18

Parikh et al4

Present study

No. of patients

13

20

30

67

No. of transfers

21

32

NM

112

Pregnancy rate/transfer

6/21 = 28.65%

8/32 = 25%

6/30 = 16%

21/112 = 18.75%

Delivery/no. of patients

4/13 = 30.7%

6/20 = 30%

5/30 = 16.7%

16/67 = 23.88%

Abortion/no. of patients

2/13 = 15.4%

1/20 = 5%

_

5/67 = 7.46%

Ectopic pregnancy/ No. of patients

_

1/20 = 5%

1/30 = 3.3%

_

NM = Not mentioned.

history of abdominal TB in 13 including three who had tuboplasty and history of ectopic pregnancy in four. Antitubercular treatment was taken by all. One of our patients conceived spontaneously during antitubercular treatment and delivered at term. All women were counseled for IVF-ET procedure. However, only 67 opted for it and underwent 112 cycles of IVF-ET. Out of 21 patients who conceived five aborted. Thirteen had a singleton pregnancy while three had a twin pregnancy. One woman with twin pregnancy delivered prematurely at 34 weeks but went home with healthy babies. Remaining 15 women were delivered by cesarean section at term. All of them had healthy babies. One patient conceived spontaneously after two failed attempt of IVF-ET (Table 5). DISCUSSION The most common initial symptom of genital TB is infertility.2 The diagnosis of genital TB is often difficult because of its subtle presentation. Considering the high prevalence of TB in the Indian subcontinent, the need to investigate asymptomatic infertile women for silent or subclinical genital TB, especially in high-risk population has also been suggested by Oosthuizen et al.12 The average incidence of genital TB in infertility clinics throughout the world is 5-10% and it varies from 0.69% in Australia to 17.4% in India.1 Out of 550 patients who came to us for infertility because of various reasons, 86 had genital TB, giving an incidence of 15.64%. Classically, female genital TB has been described as a disease of young women, with 80-90% of patients diagnosed between 20 and 40 years of age.1 The mean age of women with genital TB in our study was 32 years (range 20-40 years). About 20% of patients with genital TB give a history of TB in their immediate family.1 In our study, family history was present in 16% of cases. Genital TB is almost always secondary to TB elsewhereusually lungs and sometimes kidney, gastrointestinal tract, bones and joints. Occasionally, it is part of a generalized miliary disease process. The mode of spread is usually hematogenous or lymphatic and occasionally via direct contiguity with an intra-abdominal or peritoneal focuses.1 Primary genital TB is extremely rare. In most studies, a history of previous diagnosis of or treatment for extra-genital TB is present in 20-50% of patients.1,2 Inactive pulmonary lesions are demonstrable in about one-third of the patients who have genital TB.1 History of extra-genital TB was present in 29% (25/86) of the patients in our study. Tubercular peritonitis is seen in combination with female genital tract TB in

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OBSTETRICS AND GYNECOLOGY approximately 45% of patients and is responsible for extensive adhesions. History of tubercular abdomen was present in 47% of patients in our study. Laparotomy had been done in five patients for ectopic pregnancy, in two for intestinal pathology, in one for tubo-ovarian mass, in two for tuboplasty and in one for ovarian cyst. Laparoscopic adhesiolysis and fimbrioplasty were done in two patients. Fallopian tubes constitute the initial focus of genital TB in a majority of the cases and TB has accounted for approximately 5% of all cases of salpingitis in many parts of the world. The tubes are involved in at least 90% cases and the disease probably starts there.13 The finding of endometrial TB almost always means that the tubes are infected, although not necessarily closed. But tubercular salpingitis is sometimes found without associated endometritis. The gross appearance varies and is often consistent with chronic salpingitis. Rarely, the peritoneal surface of the tubes is studded with tubercles and filled with caseous material.4 Dense adhesions are also seen in some cases. In our study, laparoscopy finding in 58 (67.44%) patients showed tubal involvement and a frozen pelvis in 12.8%. Endometrial receptivity plays an important role in determining the reproductive outcome in IVF program.14 Rinaldi et al15 have shown that even a good quality embryo may often be rejected due to problems within the endometrium. They have reported endometrial thickness ≼10 mm to be favorable for embryo implantation. Blood flow impairment in uterine arteries may be correlated with infertility.16 The relationship between suboptimal perfusion of the endometrium and unsuccessful IVF treatment is well-established. The use of color Doppler for endometrial assessment has gained considerable importance in IVF program. Mid cycle endometrial thickness was significantly on the higher side in nontubercular infertile patients in comparison to infertile patients with genital TB in our study. Endometrium is involved in approximately 50-60% of women with genital TB.17 In our study, 72.1% patients showed positive PCR and 43% showed positive AFB culture on endometrial biopsy. Negative endometrial biopsy does not rule out pelvic involvement with TB, since sampling errors are common and there may be tubercular lesions in the other genital parts without an associated tubercular endometritis. Preliminary hysteroscopy was performed in all patients with genital TB because of the possibility of endometrial and cervical damage due to tubercular process. However, in one patient it could not be performed because of cervical stenosis. On hysteroscopy, 61 patients had

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normal uterine cavities, three had submucous fibroids and two had polyps, while synechias of varying degrees were present in 19 patients. Ten patients with synechiae had AFB culture-proven tubercular endometritis. Synechiotomy followed by intrauterine device insertion without copper wire on it and hormone replacement therapy (HRT) was the treatment given to seven patients who had dense synechiae and reduced uterine capacity. In the remaining 12 patients, flimsy synechiae were broken by the scope and as the uterine cavity was adequate HRT was not given. Of these 19 patients with synechiae, one had primary amenorrhea, three had secondary amenorrhea, two had only spotting at menstruation, six had scanty flow and seven had normal menstrual flow. Genital TB is one of the main etiological factors causing synechiae of uteri.16 On hysteroscopy, synechiae were present in 22.1% (19/86) of patients of whom 52.63% (10/19) had positive AFB culture for TB. Therefore, a hysteroscopic examination should be performed routinely, before admitting the patients with genital TB into an IVF program. The preliminary evaluation reduces the failure rate. A history of tubercular endometritis represents a special indication for a preliminary hysteroscopy before IVF.18 Preferred treatment for synechias is lysis of adhesions at hysteroscopy, followed by immediate insertion of an intrauterine device to prevent further adhesion.18 Uses of estrogen or combination of estrogen and progestogen for rapid endometrial growth have been controversial. The success of treatment regarding term deliveries and rate of abortion depends on the severity of adhesions.19 In our study, 21% (4/19) of the patients with intrauterine synechiae presented with amenorrhea while 10.53% (2/19) had severe amenorrhea, 31.6% (6/19) patients developed oligomenorrhea. In a study by Parikh et al,4 59% patients with genital TB developed oligomenorrhea. The treatment of genital TB consists of initial multidrug medical therapy for a period of 6 months to 1 year.20 Pregnancy after diagnosis of genital TB is rare and when it does occur, it is more likely to be an ectopic one or results in spontaneous abortion. The conception rate was 19.2% while the live birth rate was only 7.2% in a study by Tripathy.1 The risk factors not conducive to pregnancy are secondary amenorrhea, no endometrium on curettage and negative chromopertubation.1 Tuboplastic macro- or micro-surgical operation in these cases very rarely or almost never leads to term pregnancies. They even increase the chances of tubal pregnancy and may reactivate the silent pelvic TB.


OBSTETRICS AND GYNECOLOGY Therefore, they are contraindicated.21,22 None of the three patients who underwent micro-surgical tubal operations previously conceived spontaneously in our study. IVF represents a useful treatment and improves the chances of fertility in what was earlier considered a desperate situation. The total pregnancy rate per transfer was 18.75% in our study, while 23.88% had live births. Soussis et al17 reported 28.6% success rate with IVF in 13 patients with histologically proven genital TB. Frydman et al18 reported 25% pregnancy rate per transfer in tuberculous infertility. Thus, IVF represents the only treatment for tubal and possibly endometrial tubercular infertility. REFERENCES 1. Tripathy SN, Tripathy SN. Infertility and pregnancy outcome in female genital tuberculosis. Int J Gynaecol Obstet. 2002;76(2):159-63. 2. Jones HW III, Wentz AC, Burnett LS. In: Novak’s Textbook of Gynecology. Baltimore: Williams & Wilkins; 1988. pp. 557-69. 3. Sutherland AM. The changing pattern of tuberculosis of the female genital tract. A thirty year survey. Arch Gynecol. 1983;234(2):95-101. 4. Parikh FR, Nadkarni SG, Kamat SA, Naik N, Soonawala SB, Parikh RM. Genital tuberculosis - a major pelvic factor causing infertility in Indian women. Fertil Steril. 1997;67(3):497-500. 5. Chakravarty BN, Shirazze HH, Vijay PK, Goswami SK. The place for IVF in genital tuberculosis: Abstract Book 19th Annual ESHRE Meeting Madrid. 2003;18:371. 6. Stead WW. Pathogenesis of a first episode of chronic pulmonary tuberculosis in man: recrudescence of residuals of the primary infection or exogenous reinfection? Am Rev Respir Dis. 1967;95(5):729-45. 7. Stead WW, Kerby GR, Schlueter DP, Jordahl CW. The clinical spectrum of primary tuberculosis in adults. Confusion with reinfection in the pathogenesis of chronic tuberculosis. Ann Intern Med. 1968;68(4):731-45.

9. Roy H, Roy S, Roy S. Use of polymerase chain reaction for diagnosis of endometrial tuberculosis in high risk subfertile women in an endemic zone. J Obstet Gynecol India. 2003;53:260-3. 10. Malik S. Genital tuberculosis and implantation in assisted reproduction. Rev Gynecol Pract. 2003;3(3):160-4. 11. Rohner P, Ninet B, Metral C, Emler S, Auckenthaler R. Evaluation of the MB/BacT system and comparison to the BACTEC 460 system and solid media for isolation of mycobacteria from clinical specimens. J Clin Microbiol. 1997;35(12):3127-31. 12. Oosthuizen AP, Wessels PH, Hefer JN. Tuberculosis of the female genital tract in patients attending an infertility clinic. S Afr Med J. 1990;77(11):562-4. 13. Novak ER, Woodruff JD. In: Novak’s Gynecology and Obstetrics Pathology. 8th Edition, Philadelphia: WB Saunders; 1979. p. 328. 14. Yang JH, Wu MY, Chen CD, Jiang MC, Ho HN, Yang YS. Association of endometrial blood flow as determined by a modified colour Doppler technique with subsequent outcome of in-vitro fertilization. Hum Reprod. 1999;14(6):1606-10. 15. Rinaldi L, Lisi F, Floccari A, Lisi R, Pepe G, Fishel S. Endometrial thickness as a predictor of pregnancy after in-vitro fertilization but not after intracytoplasmic sperm injection. Hum Reprod. 1996;11(7):1538-41. 16. Goswamy RK, Williams G, Steptoe PC. Decreased uterine perfusion - a cause of infertility. Hum Reprod. 1988;3(8):955-9. 17. Soussis I, Trew G, Matalliotakis I, Margara R, Winston RM. In vitro fertilization treatment in genital tuberculosis. J Assist Reprod Genet. 1998;15(6):378-80. 18. Frydman R, Eibschitz I, Belaisch-Allart JC, Hazout A, Hamou JE. In vitro fertilization in tuberculous infertility. J In Vitro Fert Embryo Transf. 1985;2(4):184-9. 19. Schenker JG. Etiology of and therapeutic approach to synechia uteri. Eur J Obstet Gynecol Reprod Biol. 1996;65(1):109-13. 20. Behera D. Tuberculosis control in India - a view point. Indian J Tuberc. 2007;54(2):63-5. 21. Frantzen C, Schlösser HW. Microsurgery and postinfectious tubal infertility. Fertil Steril. 1982;38(4): 397-420.

8. Dam P, Shirazee HH, Goswami SK, Ghosh S, Ganesh A, Chaudhury K, et al. Role of latent genital tuberculosis in 22. Ballon SC, Clewell WH, Lamb EJ. Reactivation of silent repeated IVF failure in the Indian clinical setting. Gynecol pelvic tuberculosis by reconstructive tubal surgery. Am J Obstet Invest. 2006;61(4):223-7. Obstet Gynecol. 1975;122(8):991. ■■■■

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PICTORIAL CME

Lactation-induced Osteoporotic Vertebrae Fracture: A Rare Clinical Entity MONIKA MAHESHWARI

L

actation-associated osteoporosis is a rare clinical condition,1 causing significant disability and must be kept in mind in the differential diagnosis in postpartum ladies presenting with low back pain after pregnancy. The bone loss in lactating women can result from calcium loss during breast milk feeding to infants, decrease in estrogen level and increase in parathyroid hormone related protein levels.2 It may cause severe low back pain in the postpartum period and multiple fragility fractures, particularly in the vertebrae. The current case reports a 36-year-old female who presented with back pain that began in the second month postpartum. X-ray spine showed collapse of T8, T9, T10, T11 and T12 vertebrae (Fig. 1).

T8 T9

She underwent dual-energy X-ray absorptiometry (DEXA) scan for bone marrow density, which confirmed lactation-induced osteoporosis after exclusion of other causes. The patient was advised to wean off lactation immediately and appropriate therapy was initiated, which included calcium, vitamin D, calcitonin nasal spray, teriparatide injection3 and antiresorptive agentsbisphosphonates4 for 3 months. She responded well to therapy with symptomatic relief in backache and improved bone marrow density in review DEXA scan after 3 months. Hence, it is advised to treating doctor to consider this rare clinical entity in postpartum females presenting with severe backache.

T10

T11

T12

Figure 1. Skiagram of thoracolumbar spine (lateral view) showing osteoporotic collapse of T8, T9, T10, T11 and T12 vertebrae.

REFERENCES 1. Scozzari F, Aronica GL, Seidita A, Taormina G, Di Stefano L, D’Alcamo A, et al. Osteoporosis in pregnancy:

Associate Professor Dept. of Medicine JLN Medical College, Ajmer, Rajasthan Address for correspondence Dr Monika Maheshwari Naveen Niwas, 434/10 Bapu Nagar, Ajmer, Rajasthan E-mail: opm11@rediffmail.com

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A case report and review of the literature. Acta Medica Mediterranea. 2014;30:115-20. 2. Hirata G, Chaki O. Bone loss in lactating women and post-pregnancy osteoporosis. Clin Calcium. 2011;21(9):1347-52. 3. Lampropoulou-Adamidou K, Trovas G, Stathopoulos IP, Papaioannou NA. Case report: Teriparatide treatment in a case of severe pregnancy-and lactation-associated osteoporosis. Hormones (Athens). 2012;11(4):495-500. 4. O’Sullivan SM, Grey AB, Singh R, Reid IR. Bisphosphonates in pregnancy and lactation-associated osteoporosis. Osteoporos Int. 2006;17(7):1008-12.


2015

Rx


MEDILAW

Right to Health is Integral to the Right to Life KK AGGARWAL

Government hospitals run by the State and the Medical Officers employed therein are duty bound to extend medical assistance for preserving human life. Failure on the part of a Government hospital to provide timely medical treatment to a person in need of such treatment results in violation of his right to life guaranteed under Article 21.”

Can a person who cannot afford treatment seek treatment? Yes. Article 21 of the Constitution of India guarantees protection of life and personal liberty to every citizen. It states: “No person shall be deprived of his life or personal liberty except according to procedure established by law.” In People’s Union For Civil Liberties vs Union Of India And Anr on 5 February, 1997, Writ Petition (crl.) 612 of 1992, the Supreme Court of India observed as follows: “…It was held “In our opinion, the right to life and liberty guaranteed by Article 21 is so fundamental and basis that no compromise is possible with this right. It is ‘non-negotiable’. .... The State has no right to take any action which will deprive a citizen of the enjoyment of this basic right except in accordance with a law which is reasonable, fair and just.” In its various judgements, the Supreme Court has widened the scope of Article 21 by adding dimensions of right to health and medical care to right to life. ÂÂ

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In Bandhua Mukti Morcha v. Union of India AIR 1984 SC 802, the Supreme Court held “It is the fundamental right of everyone in this country, assured under the interpretation given to Article 21 by this Court …, to live with human dignity, free from exploitation. This right to live with human dignity enshrined in Article 21 derives its life breath from the Directive Principles of State Policy and particularly clauses (e) and (f) of Article 39 and Articles 41 and 42 and at the least, therefore, it must include protection of the health and strength of workers, men and women… “ In Paschim Banga Khet Mazdoor Samity ... vs State Of West Bengal & Anr on 6 May, 1996 (1996 SCC (4) 37, JT 1996 (6) 4), the Supreme Court held “Article 21 imposes an obligation on the State to safeguard the right to life of every person. Preservation of human life is thus of paramount importance. The

Senior Physician and Cardiologist, Moolchand Medcity, New Delhi Group Editor-in-Chief, IJCP Group and eMedinewS

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In State of Punjab & Others v. Mohinder Singh Chawla & Others AIR 1997 SC 1225, the Supreme Court held “It is now settled law that right to health is integral to the right to life. Government has a constitutional obligation to provide health facilities.”

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In State Of Punjab & Ors vs Ram Lubhaya Bagga Etc. Etc on 26 February, 1998, the Supreme Court of India held “... Further to secure protection of one’s life is one of the foremost obligation of the State, it is not merely a right enshrined under Article 21 but an obligation cast on the State to provide this both under Article 21 and under Article 47 of the Constitution. The obligation includes improvement of public health as its primary duty.”

What are the patient rights in terms of the care they should receive? The Patient Charter as developed by the Disease Management Association of India (DMAI) and the National Accreditation Board for Hospitals and Healthcare Providers (NABH) states that patients have the following right to care as follows:

Care ÂÂ Patients have a right to receive treatment irrespective of their type of primary and associated illnesses, socioeconomic status, age, gender, sexual orientation, religion, caste, cultural preferences, linguistic and geographical origins or political affiliations. ÂÂ Right to be heard to his/her satisfaction without the doctor interrupting before completion of narrating their entire problem and concerns. ÂÂ Expectation from the doctor to write the prescription legibly and explain to the patient on the details on dosage, dos & don’ts and generic options for the medicines.


MEDILAW ÂÂ

They have to be provided with information and access on whom to contact in case of an emergency.

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A documented procedure for obtaining patient’s and/or their family’s informed consent exists to enable them to make an informed decision about their care. This process is an important patient right and needs to be practiced with utmost diligence and transparency.

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Patients have to be educated on risks, benefits, expected treatment outcomes and possible complications to enable them to make informed decisions, and involve them in the care planning and delivery process.

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Patients have the right to request information on the names, dosages and adverse effects of the medication that they are treated with.

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Patients or their authorized individuals have the right to request access and receive a copy of their clinical records.

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Patients have the right to complete information on the expected cost of treatment. The information should be presented as an itemized structure of the various expenses and charges.

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Patients have the right to information on hospital rules and regulations.

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Information on organ donation.

The WMA 2005 Declaration of Lisbon on the Rights of the Patient also provides rights to medical care of good quality to patients as follows:

Right to medical care of good quality a) Every person is entitled without discrimination to appropriate medical care. b) Every patient has the right to be cared for by a physician whom he/she knows to be free to make clinical and ethical judgements without any outside interference. c) The patient shall always be treated in accordance with his/her best interests. The treatment applied shall be in accordance with generally approved medical principles. d) Quality assurance should always be a part of healthcare. Physicians, in particular, should accept responsibility for being guardians of the quality of medical services. e) In circumstances where a choice must be made between potential patients for a particular treatment that is in limited supply, all such patients are entitled to a fair selection procedure for that treatment. That choice must be based on medical criteria and made without discrimination. f) The patient has the right to continuity of healthcare. The physician has an obligation to cooperate in the coordination of medically indicated care with other healthcare providers treating the patient. The physician may not discontinue treatment of a patient as long as further treatment is medically indicated, without giving the patient reasonable assistance and sufficient opportunity to make alternative arrangements for care.

Should patients be given complete information about their illness? Yes. As per the NABH patient charter, the information to be provided to patients is meant to be in a language of the patient’s preference and in a manner that is effortless to understand. ÂÂ

Patients and/or their family members have the right to receive complete information on the medical problem, prescription, treatment and procedure details.

In this regard, the WMA 2005 Declaration of Lisbon on the Rights of the Patient states as follows: 7. Right to information a) The patient has the right to receive information about himself/herself recorded in any of his/her medical records, and to be fully informed about his/her health status including the medical facts about his/her condition. However, confidential information in the patient’s records about a third party should not be given to the patient without the consent of that third party. b) Exceptionally, information may be withheld from the patient when there is good reason to believe that this information would create a serious hazard to his/her life or health. c) Information should be given in a way appropriate to the patient’s culture and in such a way that the patient can understand. d) The patient has the right not to be informed on his/her explicit request, unless required for the protection of another person’s life. e) The patient has the right to choose who, if anyone, should be informed on his/her behalf.

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MEDILAW Can a patient seek redressal for grievances regarding treatment received?

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Protection from physical abuse and neglect.

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Accommodating and respecting their special needs such as spiritual and cultural preferences.

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Right to confidentiality about their medical condition.

Yes. The NABH Patient Charter has provisions for this. 5. Right to redress ÂÂ

Patient has the right to justice by lodging a complaint through an authority dedicated for this purpose by the healthcare provider organization or with government health authorities.

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The patient has the right to a fair and prompt hearing of his/her concern.

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The patient in addition has the right to appeal to a higher authority in the healthcare provider organization and insist in writing on the outcome of the complaint.

Can a doctor disclose information about patient learnt during consultation? No. All patients have a right to confidentiality. Various associations have supported the rights of patients with regard to confidentiality. The NABH Patient Charter states as follows: 2. Confidentiality and dignity ÂÂ

Right to personal dignity and to receive care without any form of stigma and discrimination.

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Privacy during examination and treatment.

The WMA 2005 Declaration of Lisbon on the Rights of the Patient states as follows: 8. Right to confidentiality a) All identifiable information about a patient’s health status, medical condition, diagnosis, prognosis and treatment and all other information of a personal kind must be kept confidential, even after death. Exceptionally, descendants may have a right of access to information that would inform them of their health risks. b) Confidential information can only be disclosed if the patient gives explicit consent or if expressly provided for in the law. Information can be disclosed to other healthcare providers only on a strictly “need to know” basis unless the patient has given explicit consent. c) All identifiable patient data must be protected. The protection of the data must be appropriate to the manner of its storage. Human substances from which identifiable data can be derived must be likewise protected.

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2015


AROUND THE GLOBE

News and Views ÂÂ

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The US Food and Drug Administration (FDA) has approved a new recombinant PEGylated antihemophilic factor for children aged 12 years or older and adults with hemophilia A. The factor VIII therapy is approved both as needed treatment and for prophylaxis. The UK National Institute for Health and Care Excellence (NICE) has issued its first-ever guidance on menopause which emphasizes that help and information are available to women suffering from symptoms and that treatment options, such as hormone-replacement therapy (HRT) as well as nondrug treatments, can be discussed with their doctors. A high intake of red meat appears to increase the risk for end-stage renal disease, and replacement of red meat protein with other sources of protein has the potential to reduce this risk, suggests a new study conducted in people of Chinese origin in the general population of Singapore, presented at the Kidney Week 2015. Intra-articular steroid injections are not effective over the long-term for preventing structural damage in knee osteoarthritis, reported a 2-year randomized trial presented at the annual meeting of the American College of Rheumatology. University of Florida researchers have found that with the correct dosage, electrical stimulation treatment can help ease back pain in older adults. The findings are published online in The Journal of Pain. New research presented at the American Heart Association’s Scientific Sessions 2015 reported that obese children had 27% more muscle mass in the left ventricle of their hearts and 12% thicker heart muscles, which are both signs of heart disease.

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The estrogen antagonist oral enclomiphene citrate raises serum total testosterone levels while maintaining normal sperm counts in men with secondary hypogonadism, suggested two new studies published online in BJU International.

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For patients with early breast cancer, taking the angiotensin-receptor blocker (ARB) candesartan cilexetil may decrease the risk of cardiac dysfunction, a common side effect of radiation and certain cancer medications, suggests the Prevention of Cardiac Dysfunction During Adjuvant Breast

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Cancer Therapy (PRADA) trial presented at the American Heart Association (AHA) 2015 Scientific Sessions. ÂÂ

Unequal growth between genetically identical monozygotic (MZ) twins in the womb may be triggered in the earliest stages of human embryo development, reported a new study published in the journal Stem Cell Reports.

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Omega-3 fatty acid supplementation is associated with a reduction in follicle-stimulating hormone (FSH) levels in normal-weight women.

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Being pleasantly or unpleasantly surprised by the taste of something can change a person’s mood, suggested new research published in Food Research International. Researchers noted that eating vanilla yogurts made people feel happy and that yogurts with lower fat content yielded a stronger positive emotional response.

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Macrolide antibiotic use is associated with a 2.42-fold increased risk of sudden cardiac death and ventricular tachyarrhythmias, suggests new research published online in the Journal of the American College of Cardiology.

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Mindfulness meditation can bring greater pain relief than a placebo, reported new research published in the Journal of Neuroscience. Mindfulness meditation appears to affect the brain in ways that reduce pain.

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Ranibizumab, a vascular endothelial growth-factor (VEGF) inhibitor, may be the first major treatment advance in 40 years for proliferative diabetic retinopathy, suggested new research presented at the American Academy of Ophthalmology (AAO) 2015 Annual Meeting.

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A new study, presented at the Liver Meeting 2015: American Association for the Study of Liver Diseases (AASLD), suggested that obeticholic acid maintains reduced levels of key biomarkers for primary biliary cholangitis (previously known as primary biliary cirrhosis) for up to 5 years. As a long-term therapy, both as monotherapy and in combination with ursodeoxycholic acid, the response is good.

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Data presented at the 14th International Kidney Cancer Symposium (IKCS) suggest that patients with metastatic renal cell carcinoma (mRCC) have variable clinical outcomes to treatment, and


AROUND THE GLOBE identifying the underlying molecular markers may help predict response to therapy. ÂÂ

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Results from the phase 2b DARWIN 1 study suggest that filgotinib is safe and effective for patients with rheumatoid arthritis who have an inadequate response to methotrexate therapy. The findings were presented at the American College of Rheumatology (ACR) 2015 Annual Meeting. A new study, published in the December issue of Sleep, suggests that lead exposure in early childhood is associated with increased risk for sleep problems and excessive daytime sleepiness in later childhood. Peripheral thermometers lack clinically acceptable accuracy and should not be used when precise measurement of core body temperature will influence clinical decisions, suggested a metaanalysis published online November 16 in the Annals of Internal Medicine. New findings, presented at the American Heart Association (AHA) 2015 Scientific Sessions, suggest that patients with type 2 diabetes and established CVD who received the antidiabetic sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin, had a reduced risk of being hospitalized for heart failure or dying from CVD during a median followup of 3.1 years, even if they had HF at baseline, in comparison with placebo.

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Women with knee pain had a significantly increased risk of all-cause and cardiovascular disease mortality, with or without radiographic osteoarthritis (ROA), but not with ROA alone, suggested new research published in the Annals of the Rheumatic Diseases.

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New research has identified how Salmonella infections that have spread to the blood and organs can lead to life-threatening thrombosis. Researchers stated that these systemic infections trigger the development of inflammation, which then leads to thrombosis. The findings are published in the Journal of Clinical Investigation.

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Laparoscopic cholecystectomy can effectively prevent recurrent attacks of idiopathic acute pancreatitis (IAP), suggests new research published in the November issue of the Annals of Surgery. The risk for epilepsy was higher in children with hospital-diagnosed pertussis infections compared with the general pediatric population; however, the absolute risk for epilepsy was low, reported a population-based cohort study published in JAMA.

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Endometrial and ovarian cancer can be detected by analysis of uterine lavage fluid, reported a proofof-concept study published online in the Journal of Clinical Oncology.

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The combination of ombitasvir, paritaprevir, and ritonavir plus dasabuvir, with or without ribavirin, appears to be safe and effective in patients with compensated cirrhosis caused by genotype 1 hepatitis C infection. The preliminary results from the phase 3b TOPAZ-II trial were presented at the Liver Meeting 2015.

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All iron intravenous (IV) products are associated with anaphylaxis risk, but the risk with iron dextran is significantly higher than with other formulations, and the risk is lowest with iron sucrose, reported a study of nearly 700,000 Medicare nondialysis patients, published in the November 17 issue of JAMA.

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Children, who develop severe wheezing and difficulty breathing after a common cold, with a risk of severe lower respiratory tract illness, could benefit from taking a common antibiotic at the first sign of cold symptoms, suggested a study published in JAMA.

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People who drink up to five cups of coffee per day are less likely to die from heart disease, neurological disease, type 2 diabetes, or suicide, suggested a new study published online November 16 in Circulation.

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A study conducted among overweight and obese patients in Brazil who had intragastric-balloon procedures suggested that though this is a valid endoscopic therapeutic option for weight loss, the weight loss wasn’t maintained long-term in most of the people. The findings were presented at the Obesity Week 2015.

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The selective BRAF inhibitors vemurafenib and dabrafenib have significantly improved survival in patients with BRAF V600–mutant metastatic melanoma, when compared with standard therapy. However, both the drugs appear to be associated with an increased risk for acute kidney injury, suggested a new report published in the November issue of JAMA Oncology.

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The phase III open-label ASTRAL-4 study revealed that daily sofosbuvir and velpatasvir, alone or in combination with ribavirin, for 12 weeks yielded similar rates of sustained virologic response (83% and 94%) for the treatment of hepatitis C in patients with liver cirrhosis. The findings were published online in the New England Journal of Medicine.

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AROUND THE GLOBE ÂÂ

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The sustained and tapered release of dexamethasone to the ocular surface of the eye after cataract surgery significantly reduces pain and inflammation, reported an analysis of data from two phase 3 trials presented at the American Academy of Ophthalmology 2015 Annual Meeting. Adolescent boys with an anterior cruciate ligament (ACL) repair may be at risk for lower bone mineral density (BMD) of the calcanei and associated fracture, suggested a new study published online in Arthroscopy. Having a good breakfast is linked to educational attainment, suggested new research published in the journal Public Health Nutrition. Researchers noted that pupils who ate breakfast had chances twice as high of gaining an above-average assessment score, compared with those who did not.

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A new study, published in the American Journal of Epidemiology, suggests that consuming moderate amounts of caffeine during pregnancy will not affect the baby’s intelligence.

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Ranolazine is effective for chronic angina in patients with obstructive CAD, but it did not significantly improve angina symptoms, angina frequency, or coronary flow in the Treatment With Ranolazine in Microvascular Coronary Dysfunction: Impact on Angina Myocardial Ischemia (RWISE) study of patients with chronic angina due to coronary microvascular dysfunction. The drug, however, improved coronary flow reserve in patients with the worst initial coronary blood flow (American Heart Association (AHA) 2015 Scientific Sessions).

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A fixed-dose combination of sofosbuvir plus velpatasvir is highly effective for patients with hepatitis C genotypes 1, 2, 4, 5, and 6, reported the ASTRAL-1 trial, presented at the Liver Meeting 2015 and published online simultaneously in the New England Journal of Medicine.

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The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) is an effective tool in everyday clinical practice for the identification of cognitive impairment in patients with MS, suggests a new study published online in BMC Neurology.

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An artificial pancreas was successfully used with islet transplantation in patients with type 1 diabetes in a randomized trial published online in the American Journal of Transplantation. Researchers noted that total pancreatectomy with islet autotransplantation, a closed-loop “pancreas” consisting of an insulin pump and a continuous glucose monitor was more effective at managing

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the risk of hypoglycemia than conventional therapy over 72 hours. ÂÂ

Patients with vitiligo commonly have other autoimmune diseases such as thyroid disease, alopecia areata, discoid lupus, Guillain-Barre syndrome, linear morphea, myasthenia gravis, pernicious anemia, Sjogren syndrome, and systemic lupus erythematosus, according to a cross-sectional study published in J Am Acad Dermatol 2015.

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Topical application of imiquimod at the injection site improves the immunogenicity of intradermal trivalent influenza vaccine, suggests new research published online in The Lancet Infectious Diseases.

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Collagen crosslinking (CXL) treatment may curb the progression of keratoconus in young patients, but nerve disorientation persists, suggests new research published online in JAMA Ophthalmology.

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A new study published in the November 18 issue of the Journal of Bone & Joint Surgery revealed a link between obesity and a higher risk for surgery in orthopedic trauma patients. Obesity was associated with increased surgery risk, longer hospital stays, higher charges, and increased odds of discharge to care facility rather than home.

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Giving tenofovir to pregnant women with high levels of hepatitis B virus can reduce transmission to children, suggests new research presented at the American Association for the Study of Liver Diseases meeting.

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Light therapy may treat more than just seasonal affective disorder, and when used alone or in conjunction with antidepressants, it seems to be effective and well-tolerated for those with major depressive disorder, suggested a study published online in JAMA Psychiatry.

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Melatonin supplements are a safe and effective way to address sleep problems in children with atopic dermatitis, suggests a new clinical trial published online in JAMA Pediatrics.

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In an extended follow-up of participants of COURAGE trial, no late benefit in survival was noted between patients with stable CAD who received PCI as an initial strategy plus optimal medical therapy and those who received optimal medical therapy alone. The findings were published online in the New England Journal of Medicine.

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A new study published in the journal Science revealed how parasitic worms can influence a woman’s likelihood of becoming pregnant. The study revealed that hookworm infection was found to reduce the likelihood of pregnancy, while roundworm infection increased it.


AROUND THE GLOBE ÂÂ

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Sildenafil, a drug commonly used to treat erectile dysfunction, improves insulin sensitivity and markers of endothelial function in people with prediabetes, suggested a new study published online November 18 in the Journal of Clinical Endocrinology and Metabolism. Findings from an Indian registry study suggest that speaking more than one language might protect against cognitive injury related to stroke. The findings, published online in Stroke, revealed that bilingual stroke patients were more than twice as likely to have normal cognition following their stroke and also performed better on tests measuring post-stroke attention and function, when compared with patients who spoke only one language. Neuromyelitis optica (NMO) spectrum disorder, or Devic’s disease, a brain disorder that causes inflammation in the central nervous system, may increase a woman’s risk for miscarriage and preeclampsia, suggested new research published in Neurology. Among patients with rheumatoid arthritis who fail to achieve an adequate response to their first anti-tumor necrosis factor (TNF) agent, a nonTNF targeted biologic may yield significantly better disease control than a second anti-TNF agent, reported the first randomized trial of its kind presented at the American College of Rheumatology 2015 Annual Meeting.

sectional study published online in the Journal of the American Academy of Dermatology. ÂÂ

New research, published in Respirology, suggests that compared with moderate physical activity, high physical activity levels may be linked with poorer asthma control in females, but not in males.

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Shockwave lithotripsy (SWL) to the kidney, unlike SWL to the ureter or ureteroscopy, increases the risk of hypertension, suggests a new study published online in Kidney International.

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A study from the St. Jude Children’s Research Hospital, Washington University Pediatric Cancer Genome Project, suggested that nearly 8.5% of pediatric cancer patients had pathogenic or likely pathogenic mutations of genes within their normal tissue that increased their risk of developing cancer. The findings were published November 19 in the New England Journal of Medicine.

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Nearly half of middle-aged European adults with normal glucose levels will develop prediabetes during the remainder of their lifetime, and most of them will eventually progress to type 2 diabetes, according to the latest data from a prospective cohort study in the Netherlands published online November 10, 2015 in Lancet Diabetes & Endocrinology.

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After patients blinded by retinitis pigmentosa underwent transchoroidal implantation of a subretinal device (Alpha IMS, Retina Implant AG), almost 50% could recognize shapes and details of objects 12 months after implantation, and another 25% could localize them (American Academy of Ophthalmology 2015 Annual Meeting).

Patients with vitiligo commonly have other autoimmune diseases, most commonly thyroid disease and alopecia areata, suggested a cross■■■■

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LIGHTER READING

Have you ever not wanted to do something so badly that you would rather die than go? Well that’s how I felt about joining Madcaps and volunteering at Saint Vincent De Paul Homeless shelter. But now I believe that you should have an open mind to things because in the end you might just end up enjoying it. “It’s a waste of time”, I said when my mom told I had to join Madcaps, a mothers and daughters club assisting philanthropies, and then when she told me I had to volunteer at a homeless shelter I thought this just could not get worse. We got there late, of course, and walked to the dirty homeless shelter, where we saw a lady yelling at the security guard. He dealt with her and then led us to the kitchen where we ran into my five fellow Madcaps class of 2017 mothers and daughters. Since I’m usually so socially awkward I had met only one person at the pool party, earlier this year. I looked around for her but she was not there. Damn, I was alone! When the head of the kitchen came out and asked for 3 mothers to work outside the kitchen to clean up the plates and silverware, my mom just so happened to volunteer, leaving me to serve food with people I had never met before. Soon the homeless families started to walk in and a little girl, around 5 years old, walked up and pointed to the food I was handing out. I handed her the cold sandwich, wrapped in the sticky plastic, she nodded in a form of saying thanks, and then walked to join her family at the large table. As she walked away I thought of how much I had. I get to go to one of the top schools in San Diego, I have a great house by the water, and I have a warm meal every night. Then I thought of how little she had. She probably didn’t go to school, and this is where she sleeps and eats every day. It took that little girl to make me realize just how lucky I am.

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After that moment I had a change of heart. Now, I love Madcaps and don’t miss one meeting, I have gotten over being socially awkward and now have many friends, who I hang out with on a regular basis. And this year I am sure I will do more than the required 20 hours of philanthropies. I believe that if you have an open mind about things you can learn a lot about yourself and the people in your community, you can make new friends and realize just how lucky you are. I believe that if you have an open mind to things you can accomplish more and become a better rounded person. I believe you can make a difference just by doing one thing you don’t want to do. HIGH BLOOD PRESSURE When a physician remarked on a new patient’s extraordinarily ruddy complexion, he said, “High blood pressure, Doc. It comes from my family.” “Your mother’s side or your father’s?” the doctor asked. “Neither,” he replied. “It’s from my wife’s family.” “Oh, come now,” the doctor said. “How could your wife’s family give you high blood pressure?” He sighed. “You oughta meet ‘em sometime, Doc!

Dr. Good and Dr. Bad SITUATION: A patient came with classical benign postural vertigo.

Take these drugs

Do Epley maneuver

© IJCP Academy

THAT LITTLE GIRL

HUMOR

INSPIRATIONAL STORY

Lighter Side of Medicine

LESSON: Epley maneuver in most situations can cure benign postural vertigo.


Information for Authors Manuscripts should be prepared in accordance with the ‘Uniform requirements for manuscripts submitted to biomedical journals’ compiled by the International Committee of Medical Journal Editors (Ann. Intern. Med. 1992;96: 766-767). Indian Journal of Clinical Practice strongly disapproves of the submission of the same articles simultaneously to different journals for consideration as well as duplicate publication and will decline to accept fresh manuscripts submitted by authors who have done so. The boxed checklist will help authors in preparing their manuscript according to our requirements. Improperly prepared manuscripts may be returned to the author without review. The checklist should accompany each manuscript. Authors may provide on the checklist, the names and addresses of experts from Asia and from other parts of the World who, in the authors’ opinion, are best qualified to review the paper. Covering letter –

The covering letter should explain if there is any deviation from the standard IMRAD format (Introduction, Methods, Results and Discussion) and should outline the importance of the paper. Principal/Senior author must sign the covering letter indicating full responsibility for the paper submitted, preferably with signatures of all the authors. Articles must be accompanied by a declaration by all authors stating that the article has not been published in any other Journal/Book. Authors should mentioned complete designation and departments, etc. on the manuscript.

Manuscript Three complete sets of the manuscript should be – submitted and preferably with a CD; typed double spaced throughout (including references, tables and legends to figures). –

The manuscript should be arranged as follow: Covering letter, Checklist, Title page, Abstract, Keywords (for indexing, if required), Introduction, Methods, Results, Discussion, References, Tables, Legends to Figures and Figures.

All pages should be numbered consecutively beginning with the title page.

Note: Please keep a copy of your manuscript as we are not responsible for its loss in the mail. Manuscripts will not be returned to authors. Title page Should contain the title, short title, names of all the authors (without degrees or diplomas), names and full location of the departments and institutions where the work was performed,

name of the corresponding authors, acknowledgment of financial support and abbreviations used. – The title should be of no more than 80 characters and should represent the major theme of the manuscript. A subtitle can be added if necessary. – A short title of not more than 50 characters (including inter-word spaces) for use as a running head should be included. – The name, telephone and fax numbers, e-mail and postal addresses of the author to whom communications are to be sent should be typed in the lower right corner of the title page. – A list of abbreviations used in the paper should be included. In general, the use of abbreviations is discouraged unless they are essential for improving the readability of the text. Summary – The summary of not more than 200 words. It must convey the essential features of the paper. – It should not contain abbreviations, footnotes or references. Introduction – The introduction should state why the study was carried out and what were its specific aims/objectives. Methods – These should be described in sufficient detail to permit evaluation and duplication of the work by others. – Ethical guidelines followed by the investigations should be described. Statistics The following information should be given: – The statistical universe i.e., the population from which the sample for the study is selected. – Method of selecting the sample (cases, subjects, etc. from the statistical universe). – Method of allocating the subjects into different groups. – Statistical methods used for presentation and analysis of data i.e., in terms of mean and standard deviation values or percentages and statistical tests such as Student’s ‘t’ test, Chi-square test and analysis of variance or non-parametric tests and multivariate techniques. –

Confidence intervals for the measurements should be provided wherever appropriate.

Results – These should be concise and include only the tables and figures necessary to enhance the understanding of the text.

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Discussion –

This should consist of a review of the literature and relate the major findings of the article to other publications on the subject. The particular relevance of the results to healthcare in India should be stressed, e.g., practicality and cost.

References These should conform to the Vancouver style. References should be numbered in the order in which they appear in the texts and these numbers should be inserted above the lines on each occasion the author is cited (Sinha12 confirmed other reports13,14...). References cited only in tables or in legends to figures should be numbered in the text of the particular table or illustration. Include among the references papers accepted but not yet published; designate the journal and add ‘in press’ (in parentheses). Information from manuscripts submitted but not yet accepted should be cited in the text as ‘unpublished observations’ (in parentheses). At the end of the article the full list of references should include the names of all authors if there are fewer than seven or if there are more, the first six followed by et al., the full title of the journal article or book chapters; the title of journals abbreviated according to the style of the Index Medicus and the first and final page numbers of the article or chapter. The authors should check that the references are accurate. If they are not this may result in the rejection of an otherwise adequate contribution. Examples of common forms of references are: Articles Paintal AS. Impulses in vagal afferent fibres from specific pulmonary deflation receptors. The response of those receptors to phenylguanide, potato S-hydroxytryptamine and their role in respiratory and cardiovascular reflexes. Q. J. Expt. Physiol. 1955;40:89-111.

Figures – Two complete sets of glossy prints of high quality should be submitted. The labelling must be clear and neat. – All photomicrographs should indicate the magnification of the print. – Special features should be indicated by arrows or letters which contrast with the background. The back of each illustration should bear the first – author’s last name, figure number and an arrow indicating the top. This should be written lightly in pencil only. Please do not use a hard pencil, ball point or felt pen. Color illustrations will be accepted if they make a – contribution to the understanding of the article. –

Do not use clips/staples on photographs and artwork.

Illustrations must be drawn neatly by an artist and photographs must be sent on glossy paper. No captions should be written directly on the photographs or illustration. Legends to all photographs and illustrations should be typed on a separate sheet of paper. All illustrations and figures must be referred to in the text and abbreviated as “Fig.”.

Please complete the following checklist and attach to the manuscript: 1. Classification (e.g. original article, review, selected summary, etc.)_______________________________ 2. Total number of pages ________________________ 3. Number of tables ____________________________ 4. Number of figures ___________________________

Books

5. Special requests _____________________________

Stansfield AG. Lymph Node Biopsy Interpretation Churchill Livingstone, New York 1985.

Indian 1.____________Foreign 1.________________

Articles in Books

2.____________ 2.________________

Strong MS. Recurrent respiratory papillomatosis. In: Scott Brown’s Otolaryngology. Paediatric Otolaryngology Evans JNG (Ed.), Butterworths, London 1987;6:466-470.

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