Ijcp August 2013

Indexed with IndMED

ISSN 0971-0876

www.ijcpgroup.com

Volume 24, Number 3 Peer Reviewed Journal

August 2013, Pages 201-300

yy American Family Physician yy Anesthesiology yy Cardiology yy Dermatology yy Diabetology yy ENT yy Hematology yy Medicine yy Obstetrics and Gynecology yy Orthopedics yy Pediatrics yy Pharmacology yy Medifinance yy Medilaw

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Full text online: http://ebook.ijcpgroup.com/ijcp/

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IJCP Group of Publications Dr Sanjiv Chopra Prof. of Medicine & Faculty Dean Harvard Medical School Group Consultant Editor Dr Deepak Chopra Chief Editorial Advisor Padma Shri and Dr BC Roy National Awardee

Volume 24, Number 3, August 2013 from the desk of group editor-in-chief

205 Ethylene Oxide Used in Baby Powder by MNCs can Cause Allergy, Cancer and Blood Abnormalities in Long Run from the desk of group editor-in-chief community health

207 Sexual Desire and Sexual Activity of Men and Women Across their Lifespan KK Aggarwal

Dr KK Aggarwal Group Editor-in-Chief Dr Veena Aggarwal MD, Group Executive Editor

American Family Physician

211 Pediculosis and Scabies: A Treatment Update Karen Gunning, Karly Pippitt, Bernadette Kiraly, Morgan Sayler

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 Dentistry Dr KMK Masthan Dr Rajesh Chandna Gastroenterology Dr Ajay Kumar Dermatology Dr Hasmukh J Shroff Nephrology Dr Georgi Abraham Neurology Dr V Nagarajan Journal of Applied Medicine & Surgery Dr SM Rajendran, Dr Jayakar Thomas Asian Journal of 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

217 Practice Guidelines 220 Photo Quiz ANESTHESIOLOGY

223 Dexmedetomidine and Anesthesia Sudivya Sharma, Prashast Jain

CARDIOLOGY

226 Glucose Tolerance in Nondiabetic Patients after First Attack of Acute Myocardial Infarction and its Outcome Ajay S Dabhi, M Vadivelan, SR Rathava

Dermatology

230 Cutaneous Drug Eruption Caused by Amoxicillin: A Case Report SWAPNIL C Jaykare, VM Motghare, SL Padwal, JR Patil, HN Pise

diabetology

233 A Study of Somatic Status and Complications Among Female Hospitalized and Non-hospitalized Diabetic Patients from Mysore Urban Area Prabhavathi SN, Charlotte G Karunakaran, Ashoka HG

ENT

241 A Randomized, Open Label, Prospective, Comparative,

Multicentric Study to Evaluate the Efficacy and Safety of Montelukast and Fexofenadine Fixed-dose Combination vs Montelukast and Levocetirizine Fixed-dose Combination in Allergic Rhinitis Prateek Nayak, CV Srinivas, MV Jagade, S Chandrasekharan

HEMATOLOGY

247 Distribution of Blood Groups in and Around Bellary, Karnataka Gadwalkar Srikant R, Sunil Kumar N, Ravidhar

MEDICINE

251 Clinical Profile of Multiorgan Involvement in Malaria P Ratan, KC Nayak, S Kumar, V Singh, BK Gupta, M Sisodiya, V Tundwal, V Kulkarni, A Vyas

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.

obstetrics and gynecology

257 Effectiveness of Music Therapy on Anxiety and Depression Among High-risk Pregnant Women Kalaivani G, Jesinda, Nalini Jeyavanthsantha

obstetrics and gynecology 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 Printed at IG Printers Pvt. Ltd., New Delhi E-mail: igprinter@rediffmail.com, printer_ig@yahoo.com Š Copyright 2013 IJCP Publications Ltd. All rights reserved.

255 Double-headed Monster Delivered Vaginally N Singh, S Barya, K Pandey, P Dubey, D Kumar

260 A Study to Evaluate the Efficacy of Actim Partus (A Rapid Bedside Test) in the Prediction of Preterm Labor Shikha Singh, Saroj Singh, Mukesh Chandra, Rekha Rani, Suchit Verma

264 A Case-control Study of Pelvic Inflammatory Disease and Its Association with Multiparity among Patients Attending SSG Hospital, Vadodara, Gujarat SV Patel, RK Baxi, PV Kotecha, VS Mazumdar, HN Bakshi, KG Mehta

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.

ORTHOPEDICS

267 An Update on Bisphosphonate-related Osteonecrosis of the Jaw Jacob Kurien, E Anuradha Sunil, Archana Mukunda, Sunitha Raj Philip

Pediatrics

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. 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.

271 Exclusive Breast-feeding: Is Motivation the Only Issue?

M Girish, N Mujawar, V Dandge, P Pazare, K Gaikwad

279 An Interesting Case of Meckel-Gruber Syndrome Sangeeta Arya, K Pandey, A Verma, RK Singh, S Chauhan

276 Vitamin E Level in Normal Indian Children Geeta Gathwala, Subrika Yadav, Ojawanai, G Lal

PHARMACOLOGY

281 To Assess the Attitude, Knowledge and Practices of Medical Professionals About Adverse Drug Reactions and Their Reporting in a Teaching Hospital Manoj Goyal, Monika Bansal, Shailesh Yadav, Varnika Grover, Preetkanwal

mediLAW

285 When can Hospitals be Liable for Medical Negligence Deaths?

KK Aggarwal

Medifinance

287 Retirement Forthcoming Conferences

288 International Conferences emedinews inspiration

289 Dakshinayana is the Start of Negative State of Mind eMedi quiz

290 Quiz Time

IJCP’s Editorial & Business Offices Delhi Dr Veena Aggarwal 9811036687 E - 219, Greater Kailash, Part - I, New Delhi - 110 048 Cont.: 011-40587513 editorial@ijcp.com drveenaijcp@gmail.com Subscription Dinesh: 9891272006 subscribe@ijcp.com Ritu: 09831363901 ritu@ijcp.com

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from the desk of group editor-in-chief Dr KK Aggarwal

Padma Shri and Dr BC Roy National Awardee Sr. Physician and Cardiologist, Moolchand Medcity, New Delhi President, Heart Care Foundation of India Group Editor-in-Chief, IJCP Group and eMedinewS National Vice President, Elect, IMA Director, IMA AKN Sinha Institute (08-09) Hony. Finance Secretary, IMA (07-08) Chairman, IMA AMS (06-07) President, Delhi Medical Association (05-06) emedinews@gmail.com http://twitter.com/DrKKAggarwal Krishan Kumar Aggarwal (Facebook)

Ethylene Oxide Used in Baby Powder by MNCs can Cause Allergy, Cancer and Blood Abnormalities in Long Run Multinationals should stop treating Indians as guinea pigs, the food and drug administration (FDA) told the Bombay HC, while opposing Johnson & Johnson’s (J&J) plea to restart its Mulund facility as reported in TOI. A division bench of Justice SJ Vazifdar and Justice MS Sonak, the court heard J&J’s plea challenging FDA’s order directing closure from June 24. In 2007, J&J had used ethylene oxide (EtO) treatment for 15 batches of baby powder and did not check for residue. But J&J argued that it had checked three of the batches for residue in 2009, and had found none to be contaminated. To check for contamination, instead of the steam sterilization treatment, they sent the bottles for EtO treatment to a lab. After the treatment, they were no checks for residue. As per FDA, the company was required to test each batch they put into the market. About EtO ÂÂ Hypotension, dyspnea and chest pain may be produced by sensitivity to the ethylene oxide used as a membrane

sterilant.1

ÂÂ Chemicals that have been associated with sporadic spontaneous pregnancy loss include anesthetic gases

(nitrous oxide), arsenic, aniline dyes, benzene, ethylene oxide, formaldehyde, pesticides, lead, mercury and cadmium.2 anaphylaxis in susceptible individuals: The sterilization agents EtO and ortho-phthalaldehyde.3

ÂÂ A variety of other medications and agents have been implicated in anaphylaxis or reactions resembling ÂÂ Type A allergic reactions during dialysis are caused by leachable substances from the dialyzer or by contamination

with bacterial peptides. A classic cause of this type of reaction is ethylene oxide, which is used to sterilize hollow fiber dialyzers. Reactions to ethylene oxide, which are now uncommon, occur exclusively during the first use, usually when there has been inadequate rinsing of the dialyzer prior to use. Immunoglobulin (IgE) antibodies directed against ethylene oxide are present in some cases, particularly those with more severe reactions. One study, found that 16 of 106 unselected patients developed mild allergic symptoms after hemodialysis; 10 of these patients also developed eosinophilia.4 Two observations suggested an important role for ethylene oxide in this response: Allergy to ethylene oxide could be demonstrated in seven of the cases; and the symptoms and eosinophilia were ameliorated in three patients by ethylene oxide-free hemodialysis.

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from the desk of group editor-in-chief ÂÂ Spina bifida patients have been reported to be at increased risk of anaphylactic reactions during general

anesthesia. Following a reaction, latex is often incriminated as spina bifida patients are known to have an increased incidence of latex allergy. EtO has recently been suggested to be an alternative cause. EtO is a highly reactive gas widely used to sterilize heat-sensitive medical devices, and traces of EtO can be found in many of the same products as latex.5

ÂÂ There is a link between low-dose EtO exposure and breast cancer.6 ÂÂ For breast cancer the substances classified as ‘carcinogenic to humans’ (Group 1) include EtO.7 ÂÂ Chronic exposure to EtO causes elevation in the absolute mean number of monocytes and eosinophils and a

decrease in the absolute mean number of lymphocytes. There is also an elevation in the percentage of hematocrit and the mean absolute number of the red blood cells, and a decrease in the mean absolute number of platelets, in the exposed group compared with the control group.8

References 1. Nicholls AJ, Platts MM. Anaphylactoid reactions due to haemodialysis, haemofiltration, or membrane plasma separation. Br Med J (Clin Res Ed) 1982;285(6355):1607-019. 2. Savitz DA, Sonnenfeld NL, Olshan AF. Review of epidemiologic studies of paternal occupational exposure and spontaneous abortion. Am J Ind Med 1994;25(3):361-83. 3. Ebo DG, Bosmans JL, Couttenye MM, Stevens WJ. Haemodialysis-associated anaphylactic and anaphylactoid reactions. Allergy 2006;61(2):211-20. 4. Röckel A, Klinke B, Hertel J, Baur X, Thiel C, Abdelhamid S, et al. Allergy to dialysis materials. Nephrol Dial Transplant 1989;4(7):646-52. 5. Bache S, Petersen JT, Garvey LH. Anaphylaxis to ethylene oxide - a rare and overlooked phenomenon: Acta Anaesthesiol Scand 2011;55(10):1279-82. 6. Mikoczy Z, Tinnerberg H, Björk J, Albin M. Cancer incidence and mortality in Swedish sterilant workers exposed to ethylene oxide: updated cohort study findings 1972-2006. Int J Environ Res Public Health 2011;8(6):2009-19. 7. Weiderpass E, Meo M, Vainio H. Risk factors for breast cancer, including occupational exposures. Saf Health Work 2011;2(1):1-8. 8. Shaham J, Levi Z, Gurvich R, Shain R, Ribak J. Hematological changes in hospital workers due to chronic exposure to low levels of ethylene oxide. J Occup Environ Med 2000;42(8):843-50. ■■■■

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community health

Sexual Desire and Sexual Activity of Men and Women Across their Lifespan KK Aggarwal

Abstract Objective: To study the sexual desire and activity of men and women aged 30-80 years. Methodology: A representative sample was surveyed and correlated with their social, individual and interpersonal characteristics. A total of 100 subjects were recruited. Observations: The study showed that sexual desire declined with advancing age with overall men reporting more frequent and stronger sexual desire compared to women. For both men and women, sexual activity in older participants was mostly an issue of denial or disagreement of the other partner. There were additional social and personality determinants of lack of sexual desire and sexual inactivity, which included illness, lack of privacy, erectile dysfunction, spiritual reasons and menopause. Conclusions: Sexual history should be a routine part of history taking and should be undertaken during assessment of the patient.

Keywords: Sexual Activity, sexual desire, erectile dysfunction, spiritual reasons, menopause

L

ow sexual desire is expected to be associated with low sexual activity. Like sexual desire, sexual activity also declines with age. Important predictors of sexual activity of aging men are availability of a partner, infrequent sexual activity, low satisfaction with sexual performance, limited ability to speak about sexuality, certain personality characteristics, in particular low openness and lack of social resonance. Sexual satisfaction is an important domain of sexual functioning in both men and women. Methodology The study was based on a representative survey of the population, recruiting a total of 100 people aged 30-80 years. The sample comprised of 68 men and 32 women. For further analysis, the study sample was divided into five age groups of comparable size: 30-40 years (n = 7), 41-50 years (n = 20), 51-60 years (n = 38), 61-70 years (n = 24) and >70 years (n = 11). The mean age of the men was 56.86 years and of women was 56.18 years. All study participants were given a questionnaire on an outpatient basis followed by face-to-face interview in the hospital setting.

ÂÂ All study subjects were married, none were

divorced or separated; 7 were widowed (2 men and 7 women). Overall 93% lived with a partner.

ÂÂ Employment rates differed between men and

women; more men than women were employed, 72.05% (49/68) versus 25% (8/32), respectively. Forty-nine (72.05%) of the 68 males were professionals; 19 (27.94%) were retired.

zz zz

Out of 32 women, 24 (75%) were housewives and 8 (25%) were working.

ÂÂ The average age at which the men stopped sexual

life was 56.91 years.

Questionnaire ÂÂ What is the frequency of sexual intercourse in a

week/month/year?

ÂÂ What is the reason for cessation of intercourse? ÂÂ What is the average duration of erectile process

(for men)?

ÂÂ Presence of premature ejaculation? Yes/No ÂÂ Personal and Partner satisfaction? Yes/No ÂÂ Extramarital affairs (if any): Yes/No ÂÂ Chronic diseases suffered in the past along with

their duration

ÂÂ Investigations undergone and their results Padma Shri and Dr BC Roy National Awardee President Heart Care Foundation of India E-mail: emedinews@gmail.com

ÂÂ Current medications (prescription/OTC) ÂÂ Past history of medication intake

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207

community health ÂÂ The average age at which the women stopped

sexual life was 56 years.

Frequency of Sexual Activity in Women All women below the age of 40 years were fully sexually active with zero percent reporting no sexual activity. After the age of 40 years (n = 31), only 16% of women were fully sexually active. In the 41-50 years age group, 14.28% women were not sexually active; this percentage in 50-60 years age group was 53.84% and in 60-70 years age group, it was 62.5%. After the age of 70 years, 100% women reported no sexual activity. Fifty-seven percent women in the age group 41-50 years; 23% in the age group 50-60 years; 37.5% in the age group 60-70 years and zero percent after the age of 70 were partially sexually active. In the 41-50 years age group, 28.57% women were fully sexually active; this percentage in 50-60 years age group was 23%. In the 60-70 years age group and after 70 years of age, the percentage of women who were fully sexually active was zero percent. Table 2 summarizes the observations in women. Men vs Women ÂÂ Both men and women were equally fully sexually

Observations The frequency and intensity of sexual desire in men and women according to age were analyzed separately for the five age groups. The frequency was rated as follows: ÂÂ Very frequent or frequent: Sexually active ÂÂ Occasional or rare: Partially sexually active ÂÂ Nil: Not sexually active

Frequency of Sexual Activity in Men Below the age of 50 years, all men (n = 19) were sexually active with zero percent reporting no sexual activity. Only one person (5.26%) was partially sexually active. After the age of 50 years (n = 49), 24.48% of men were fully sexually active; 30.61% were partially sexually active and 46.93% were not sexually active. After the age of 60 years, none of the men were fully sexually active. ‘No sexual activity’ increased from 20% in the 51-60 years age group to 87.5% in those aged >70 years. Sixty-nine percent men aged 60-70 years were not sexually active. After the age of 70 years, 86% males were not sexually active. Table 1 summarizes the observations in men.

Table 1. Frequency of Sexual Activity in Men Age group (Years) 30-40 (n = 6) Intensity Very frequent/frequently Occasional/rarely Nil 41-50 (n = 13) Very frequent/frequent Occasional/rare Nil 51-60 (n = 25) Very frequent/frequently Occasional/rarely Nil 61-70 (n = 16) Very frequent/frequently Occasional/rarely Nil ≥70 (n = 8) Very frequent/frequently Occasional/rarely Nil

active at age 40.

ÂÂ Between the age of 40-50 years, 92% of men were

fully sexually active and only 28.57% of women were fully sexually active. 57.14% of women were partially sexually active in this age group and 14% of them were not sexually active.

Number of males (n = 68) 6 0 0 12 1 0 12 8 5 0 5 11 0 1 7

Percentage of males 100 0 0 92.3 7.69 0 48 32 20 0 31.25 68.75 0 12.5 87.5

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community health Table 2. Frequency of Sexual Activity in Women Age groups (Years) 30-40 (n = 1) Intensity Very frequently/frequently Occasionally/rarely Nil 41-50 (n = 7) Very frequently/frequently Occasionally/rarely Nil 51-60 (n = 13) Very frequently/frequently Occasionally/rarely Nil 61-70 (n = 8) Very frequently/frequently Occasionally/rarely Nil ≥70 (n = 3) Very frequently/frequently Occasionally/rarely Nil ÂÂ Between 50-60 yeas, 32% of men and 23% of women Number of females (n = 32) 1 0 0 2 4 1 3 3 7 0 3 5 0 0 3 Percentage of females 100 0 0 28.57 57.14 14.28 23.07 23.07 53.84 0 37.5 62.5 0 0 100

were partially sexually active. Twenty percent of men and 54% women were sexually non-active in this age group. women were fully sexually active.

that women were more likely than men to report lack of sexual desire.1 Another German study also showed that sexual desire declined with advancing age; overall, men reported more frequent and stronger sexual desire than women. In the study for both men and women, sexual activity in older participants was mostly an issue of the presence of a partnership. There were additional social and personality determinants of a lack of sexual desire and sexual inactivity: In men, sexual desire was compromised by social factors (unemployment, low income), while in women these were previous sexual traumas (childhood sexual abuse, rape).2 In our study also, men reported more frequent and intense sexual desire and activity than women. Sexual desire declined with age for both men and women. In both men and women, infrequent sexual activity was most clearly determined by age. At >70 years of age, most men and women reported no sexual activity. Aging women had less sexual desire in general than in aging men. Lack of sexual desire was rare among young men and women. Gender differences emerged around 41-50 years of age and became greater with increasing age. In both men and women sexual inactivity was predicted most strongly by three factors: Age, illness and spiritual reasons. No association between sexual satisfaction and

ÂÂ After the age of 60 years, none of the men of

Other Observations ÂÂ Men were sexually more active than women at all

ages.

ÂÂ Men were also more partially sexually active than

women at all ages.

ÂÂ The reasons for no sexual activity were advanced

age, illness and spiritual.

ÂÂ Sixteen percent men reported having erectile

dysfunction and 18% had premature ejaculation. Only two men admitted to extramarital relationships. in their sexual life and 94.11% stated that their partners were also satisfied with the relationship. association was found between sexual satisfaction and diabetes, blood pressure or heart disease.

ÂÂ Overall 95.5% people showed personal satisfaction

ÂÂ No

Discussion An analysis based on two representative national sex surveys conducted in Finland in the 1990s has shown

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community health cardiovascular diseases including myocardial infarction, stroke, coronary revascularization and congestive heart failure was found. Conclusions Despite the growing older population, the topic of sexuality in older adults is often not discussed. Chronic diseases, such as cardiovascular diseases, hypertension and diabetes mellitus and associated psychological disturbances, are more prevalent in this age group and can have considerable impact on sexuality in both men and women. Also, many older people are hesitant to discuss this topic. The belief that older people are less sexually active than their younger counterparts often influences the clinician’s interaction with the patient and the issue is not addressed during evaluation. Sexual history should be a routine part of history taking and should be undertaken during assessment of the patient. An understanding of the sexual changes that accompany the aging process may help general practitioners and other doctors to give practical and useful advice on sexuality as well as refute the misconception that aging equates to celibacy.3 References 1. Kontula O, Haavio-Mannila E. The impact of aging on human sexual activity and sexual desire. J Sex Res 2009;46(1):46-56. 2. Beutel ME, Stobel-Richter Y, Brahler E. Sexual desire and sexual activity of men and women across their lifespans: results from a representative German community survey. BJU Int 2008;101(1):76-82. 3. Lochlainn MN, Kenny RA. Sexual activity and aging. J Am Med Dir Assoc 2013;14(8):565-72.

■■■■

Me Lord I Am Not Guilty: Complaint needs to be verified by Complainant Under the Delhi Medical Council Act Rule 32, the complaint shall be verified by the complainant ot as n nt h ess is a n i r dd pla com His a The d up. ceable e a turn untr

Pro

cee

d

We will have to proceed the case on merit and hear the doctors

Lesson: In one of the orders DMC/636/2010, the complainant did not turn up and the notice returned undelivered with noting from postal department “Address untraceable”. However, the Council pursued the complaint and recorded written statement of the doctors along with documents on record. Comments: As per Delhi Medical Council, Rule 32, • “The complaint shall be verified by the complainant”. That means the presence of the complainant is necessary”. • “On the date of hearing or any other date to which hearing could be adjourned, it shall be obligatory on the parties to appear before the Council. Where the complainant fails to appear before the Council on such days, the Council may on its discretion either dismiss” the complaint for default or decide it on merits, where the opposite party fails to appear on the date of hearing, the Council may decide the complaint ex-parte.”

Dr KK Aggarwal

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American Family Physician

Pediculosis and Scabies: A Treatment Update KAREN GUNNING, KARLY PIPPITT, BERNADETTE KIRALY, MORGAN SAYLER

Abstract Pediculosis and scabies are caused by ectoparasites. Pruritus is the most common presenting symptom. Head and pubic lice infestations are diagnosed by visualization of live lice. Finding nits (louse egg shells) alone indicates a historical infestation. A “no nit” policy for schools and day care centers no longer is recommended because nits can persist after successful treatment with no risk of transmission. First-line pharmacologic treatment of pediculosis is permethrin 1% lotion or shampoo. Multiple novel treatments have shown limited evidence of effectiveness superior to permethrin. Wet combing is an effective nonpharmacologic treatment option. Finding pubic lice should prompt an evaluation for other sexually transmitted infections. Body lice infestation should be suspected when a patient with poor hygiene presents with pruritus. Washing affected clothing and bedding is essential if lice infestation is found, but no other environmental decontamination is necessary. Scabies in adults is recognized as a pruritic, papular rash with excoriations in a typical distribution pattern. In infants, children, and immunocompromised adults, the rash also can be vesicular, pustular, or nodular. First-line treatment of scabies is topical permethrin 5% cream. Clothing and bedding of persons with scabies should be washed in hot water and dried in a hot dryer.

Keywords: Pediculosis, scabies, pruritus, permethrin, pubic lice, sexually transmitted infections

P

ediculosis and scabies are caused by ectoparasites. Pruritus is the most common presenting symptom in persons with either condition. Determining the etiology is important and straightforward based on history and physical examination; however, pediculosis may be overdiagnosed by anxious patients and overtreated by physicians without an office evaluation. An accurate diagnosis may have an impact on reducing resistance of lice to currently available treatments.

flattened dorsoventrally. The pubic louse is much shorter. Lice are unable to jump or fly; consequently, transmission requires close contact.2 The female insect’s life cycle lasts for one to three months, and she lays up to 300 eggs at the skin-hair junction that hatch and mature to adults in 20 days.1 Eggs are yellow to white in color, and can be found attached to the base of body hairs.

Clinical Presentation Persons with pediculosis typically present with pruritus. Pruritus associated with lice is a delayed hypersensitivity reaction. It may take two to six weeks to develop after the first exposure, with future episodes resulting in pruritus within one to two days of exposure.3 Intense itching leads to scratching, with subsequent excoriations and secondary cellulitis. In longstanding infestation, the skin may become lichenified and hyperpigmented, particularly on the trunk. Finding pubic lice should prompt an evaluation for other sexually transmitted infections.

Pediculosis Lice are obligate, blood-sucking parasites that can infest the head (Pediculus humanus var capitis), body (Pediculus humanus var corporis), and pubic region (Phthirus pubis).1 Body and scalp lice are approximately 1 to 3 mm long, or about the size of a sesame seed, and are KAREN GUNNING, PharmD, is an associate professor of pharmacotherapy at the University of Utah College of Pharmacy in Salt Lake City, and an associate professor in the Department of Family and Preventive Medicine at the University of Utah School of Medicine in Salt Lake City. Dr. Gunning also is a clinical pharmacist at Sugar House Health Center in Salt Lake City. KARLY PIPPITT, MD, is a clinical instructor in the Department of Family and Preventive Medicine at the University of Utah School of Medicine. BERNADETTE KIRALY, MD, is an assistant professor in the Department of Family and Preventive Medicine at the University of Utah School of Medicine. MORGAN SAYLER, PharmD, is an assistant professor in the Department of Pharmacy Practice & Science at the University of Iowa College of Pharmacy in Iowa City, and is a clinical pharmacist faculty member at the Iowa Lutheran Family Medicine Residency Program in Des Moines. At the time the article was submitted, Dr. Sayler was assistant professor of pharmacotherapy at the University of Utah College of Pharmacy.

Diagnosis Head lice infestation is diagnosed definitively by finding at least one live louse on visual inspection (Figure 14). Visualization can be improved by the use of a bright light, a magnifying lens, and combing the hair with a “lice comb” (fine-toothed comb) and examining the comb teeth.5 Lice are commonly found behind the ears and on the back of the neck.6

Source: Adapted from Am Fam Physician. 2012;86(6):535-541.

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American Family Physician

Figure 1. Pediculus humanus capitis (head louse). The adult female has a slightly larger abdomen than the male. The human body louse is similar in appearance to the head louse. Reprinted from Flinders DC, De Schweinitz P. Pediculosis and scabies. Am Fam Physician. 2004;69(2):341.

Figure 2. Adult female Phthirus pubis. An egg can be seen within the body cavity. Reprinted from the Centers for Disease Control and Prevention’s Laboratory Identification of Parasites of Public Health Concern.

Misdiagnosis is common. Finding only nits (louse eggs that may or may not be viable) on examination is not enough to indicate current infestation. Diagnosis requires observation of live lice. Additionally, nits can be confused with dandruff, hair spray debris, or dirt particles. Nits may remain on the hair for months after successful treatment. For all of these reasons, school- or day care-based “no nit” polices are not recommended by the American Academy of Pediatrics, and are thought to be harmful because they can result in significant absence from school.7 When lice are found in one family member, the entire family should be examined and treated if live lice are found on the head. Fomite transmission of lice is controversial, but lice have been found on clothing, towels, and sheets. Washing these items in water that is at least 122°F (50°C) provides effective lice eradication. Sprays, carpet treatments, and other chemical environmental decontamination measures are not necessary and can be harmful.3 Pubic lice infestation is diagnosed by finding lice on the pubic hair (Figure 2). Body lice should be suspected in patients with pruritus living in conditions of crowding and poor hygiene. Diagnosis is confirmed by identification of body lice in the seams of clothing.

results in paralysis of the louse and suffocation via “coating” the louse. Most clinical trials use substances that work via neurotoxicity through topical products like lindane 1% shampoo, permethrin 1% lotion, pyrethrins 0.3%/piperonyl butoxide 4% shampoo or mousse, and malathion 0.5% lotion (Table 17). Permethrin is recommended as first-line treatment for pediculosis.7 A key to formulating an effective treatment regimen is recognizing that available treatments destroy lice, but do not reliably destroy eggs. Repeat treatment typically is required for complete eradication, timed on the life cycle of the louse.8 The initial treatment followed by a second treatment seven to 10 days later should be sufficient to eradicate most nonresistant lice. Trials that use single-dose treatment may not fully evaluate the true effectiveness of the drugs. Resistance to permethrin and pyrethrins/piperonyl butoxide can be significant in various communities, necessitating the use of malathion, which has maintained relatively low resistance because of limited use in the United States. In the United Kingdom, malathion is used often and resistance is common.7 Although lindane still is available by prescription in most of the United States, the U.S. Food and Drug Administration (FDA) has cautioned against its use because of neurotoxicity concerns. It is not available in

Pharmacologic Treatment (Head Lice) Pharmacologic treatment of head lice infestation is focused on two general mechanisms: neurotoxicity that

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American Family Physician Table 1. Pharmacologic Treatments for Head Lice Treatment Benzyl alcohol 5% lotion Ovicidal No Directions Apply to dry hair, leave on for 10 minutes, then rinse; repeat in seven days (per package insert) Cost* $63 (227-g bottle) Comments Can be costly for long hair (dosed by hair length) Must be used in conjunction with nit combing Approved for children six months and older; can be used in pregnant and lactating women Ivermectin (not FDAapproved for treatment of pediculosis) Partial 200 to 400 mcg per kg, given $5 to $10 per 3-mg on day 1 and day 8 (total of tablet (total cost two doses) dependent on weight) Should not be used in children weighing less than 33 lb (15 kg) or in pregnant or breastfeeding women Common adverse effects include dizziness and pruritus Malathion 0.5% lotion Partial Apply to dry hair enough to sufficiently wet the hair and scalp; allow to dry naturally Shampoo eight to 12 hours later, rinse, and use lice comb Repeat after seven to nine days if live lice still are present Permethrin 1% lotion No Apply to damp hair and leave $20 for two 59-mL on for 10 minutes, then rinse; bottles repeat in seven days (per package insert) Apply to dry hair and leave on for 10 minutes, then rinse Apply to dry hair, leave on for 10 minutes, then rinse; repeat in seven days only if live lice are seen (per package insert) $20 for 236 mL First-choice treatment per guidelines7 $185 (59-mL bottle) Flammable; do not use hair dryer, cigarettes, or open flame while hair is wet

Pyrethrins 0.3%/piperonyl No butoxide 4% shampoo or mousse Spinosad 0.9% topical suspension Yes

Piperonyl butoxide is thought to prolong activity of pyrethrins; avoid in patients with chrysanthemum allergy Safe for use in children four years and older; may be used without nit combing, although best results occur with nit combing Do not use in infants younger than six months because of benzyl alcohol content

$263 (4-oz bottle)

FDA = U.S. Food and Drug Administration. *Estimated retail price based on information obtained at http://www.drugstore.com (accessed December 5, 2011) or from a national retail chain. Information from reference 7.

California or in the United Kingdom. Lindane may be used as a second-line agent in adults, but should not be used in children, older persons, or adults weighing less than 110 lb (50 kg). It should not be used unless all other agents are contraindicated or ineffective. It should not be reapplied in any situation.9 In 2009, the first prescription suffocation treatment, a nonovicidal benzyl alcohol 5% lotion, was approved by the FDA. This product prevents lice from closing

their respiratory spiracles, which causes permanent obstruction and results in death.10 Benzyl alcohol appears to be comparable in effectiveness to pyrethrins/ piperonyl butoxide.11 In early 2011, the FDA approved a pediculicidal topical suspension agent, spinosad 0.9%, which provokes hyperexcitation and eventual death by paralysis.12 In two comparative trials, spinosad was found to have approximately twice the eradication rate of permethrin

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American Family Physician at 14 days (85 and 84 percent, compared with 45 and 43 percent).13 Spinosad has shown effectiveness (without nit combing) after a single treatment (93 percent eradication versus 62 percent eradication with permethrin); it may be beneficial in patients not adherent to other therapies.13 Ivermectin is an oral antiparasitic that has demonstrated effectiveness in clinical trials, but is not FDA-approved for the treatment of pediculosis. A trial of 812 patients older than two years compared ivermectin (400 mcg per kg) with malathion 0.5% lotion in patients with lice that are resistant to malathion or pyrethroid-based products. The results showed that 95 percent of patients taking ivermectin were lice-free at day 15, compared with 85 percent of patients using malathion. The authors suggest that ivermectin may be an appropriate secondline therapy when resistance to topical treatments is documented.14 No difference in adverse effects was noted between the groups. 0.3%/piperonyl butoxide 4% as first-line agents, and alternative regimens of malathion 0.5% lotion or oral ivermectin at 250 mcg per kg, repeated in two weeks.18 The mainstay of treatment for body lice is laundering clothing and bedding in hot water, and regular bathing. A pediculicide is not always necessary.19 Scabies Scabies is a common public health problem, affecting approximately 300 million persons worldwide.20 It is caused by the mite Sarcoptes scabiei var hominis. The arthropod is an ovoid organism. The female is approximately 0.4 mm in size and the male is one-half this size. After mating on the skin surface, the male mite dies and the female mite begins to burrow under the skin, where she lays eggs for four to six weeks.21 Egg production occurs at a rate of one to three eggs per day; eggs hatch after three to four days, and then the new mites cut through the burrow to the skin surface to multiply.22 Female mites can travel up to 2.5 cm per minute,21 but they do not jump or fly. After exposure, mites can penetrate the epidermis within 30 minutes.23 Transmission occurs via direct skin-to-skin contact. A person with conventional scabies needs about 15 to 20 minutes of close contact to transfer the mite to another person.24 Fomite transmission is rare, so general contact precautions should be sufficient to prevent transmission.25,26 Although scabies is more common in young children, other predisposing factors include overcrowding, poor hygiene, poor nutritional status, homelessness, dementia, and sexual contact.27

Nonpharmacologic Treatment (Head Lice) Wet combing involves moistening the hair with commercially available leave-in conditioner and systematically combing the hair from root to tip with a lice comb. Wet combing alone for treating pediculosis does not have adverse effects, and often is preferred by parents wanting to avoid a chemical treatment; however, it can be time consuming depending on hair length and thickness. Combing should be done every three days for two weeks. Cure rates vary considerably (47 to 75 percent), but may be improved by increasing the duration of combing to 24 days.15 Delivery of hot air to kill lice by desiccation has been attempted by numerous investigators with mixed results. Research is ongoing on this minimally invasive treatment option.16 Cetaphil Gentle Skin Cleanser has been studied as a dry-on, suffocation-based pediculicide lotion with a demonstrated eradication rate of 95 percent, although there is question about the design and rigor of the study.17 The recommended protocol involves applying the lotion to the scalp thoroughly and waiting two minutes before combing out all lotion, drying the hair with a hand-held hair dryer, and waiting a minimum of eight hours before shampooing with regular shampoo.

Clinical Presentation Persons with scabies typically present with an intense and generalized pruritic rash that is worse at night, with the face and neck unaffected. The primary skin lesions are inflammatory pruritic papules, pustules, vesicles, and nodules. The pathognomonic finding is a burrow, which may not always be evident. These are most commonly found on the hands and feet or in the finger webs, and appear as short, wavy, scaly gray lines on the skin surface.21 Nonspecific secondary skin findings may be excoriations, eczematization, and pyoderma. The characteristic body distribution of lesions in adults is illustrated in Figure 3.4 Infants may present with pustules on the palms and soles of the feet, and vesicles or lesions on the neck and face28 (Figure 4). Crusted scabies (also called Norwegian scabies) is an extremely contagious atypical form of scabies

Pharmacologic Treatment (Body and Pubic Lice) Treatment of pubic lice is similar to that of head lice. The 2010 guidelines from the Centers for Disease Control and Prevention (CDC) on sexually transmitted diseases recommend permethrin 1% or pyrethrins

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Figure 4. Typical erythematous papules and burrows at wrists.

Figure 3. Characteristic distribution of lesions in adults with classic scabies. Burrows are more common on hands and wrists, whereas papular or nodular lesions generally are present elsewhere. Reprinted from Flinders DC, De Schweinitz P. Pediculosis and scabies. Am Fam Physician. 2004;69(2):345.

occurring primarily in patients who are older, immunocompromised, or living in close quarters. Patients may present with thick, crusted lesions on the hands and feet, nail abnormalities, generalized erythematous scaling eruptions, and scalp involvement. Because pruritus is mild or absent in this form, scabies is often misdiagnosed, leading to large nosocomial outbreaks.28 In a typical case of scabies, 10 to 15 mites may be present. In crusted scabies, thousands of mites may be present, and the risk of transfer is greater.

Figure 5. Sarcoptes scabiei, or scabies mite. Reprinted with permission from the University of Iowa College of Medicine, Department of Dermatology.

Treatment In contrast to lice, there are fewer randomized controlled trials of products to treat scabies. Most studies were conducted using lindane as the comparator. There is no clear evidence of resistance to permethrin 5% cream for classic scabies, despite heavy use over the previous two decades, and it remains the first-line treatment.18 Physicians should educate patients on correct application of permethrin cream, reminding them that the cream should be applied to all areas of the body from the neck down, kept on overnight or for eight to 14 hours, washed off, and reapplied in one week. Patients should be educated that they may continue to have itching for up to two weeks, even after appropriate and effective treatment. There is evidence for empiric treatment if a patient presents with pruritus and lesions typical of scabies in at least two body sites, or if there are others in the patient’s household with pruritus.29,30 A single dose of oral ivermectin at

Diagnosis Scabies may be diagnosed with a history of pruritus, rash in the typical distribution, and history of itching in close contacts. Finding mites, eggs, or fecal pellets provides definitive diagnosis. The most common method of examination for mites is skin scraping. Scrapings should be taken from nonexcoriated burrows, papules, or vesicles by applying a drop of mineral oil to the skin, scraping laterally across the lesion using a scalpel, and transferring the oil and skin scraping to a slide. A positive test result reveals mites, eggs, or fecal pellets (Figure 5).

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American Family Physician 200 mcg per kg and repeated at day 14 also is considered an option for first-line treatment of classic scabies by the CDC, although cost and availability often relegate it to second-line therapy if treatment with topical permethrin is unsuccessful.18 Environmental control measures for scabies include washing sheets and clothing at 140°F (60°C) and drying in a hot dryer. For items that cannot be machine washed, isolation in a plastic bag for at least 72 hours is sufficient. Other environmental measures such as pesticide sprays or powders are not recommended. Vacuuming may be helpful, although there is little direct evidence of benefit. Crusted scabies represents a treatment challenge. It often is longstanding because of misdiagnosis. Clinical trials are limited. The CDC recommends dual therapy with ivermectin at 200 mcg per kg orally on days 1, 2, 8, 9, and 15, plus permethrin 5% cream full-body application daily for seven days, then twice weekly until demonstrated cure.18,30 Environmental control measures in affected institutions include patient isolation until dual therapy is completed, barrier precautions with gloves, and screening and treatment of infected caregivers and close contacts. REFERENCES 1. Orion E, Marcos B, Davidovici B, Wolf R. Itch and scratch: scabies and pediculosis. Clin Dermatol. 2006;24(3):168-175. 2. Maunder JW. Lice and scabies. Myths and reality. Dermatol Clin. 1998;16(4):843-845. 3. Tebruegge M, Pantazidou A, Curtis N. What’s bugging you? An update on the treatment of head lice infestation. Arch Dis Child Educ Pract Ed. 2011;96(1):2-8. 4. Flinders DC, De Schweinitz P. Pediculosis and scabies. Am Fam Physician. 2004;69(2):341-348. 5. Jahnke C, Bauer E, Hengge UR, Feldmeier H. Accuracy of diagnosis of pediculosis capitis: visual inspection vs wet combing. Arch Dermatol. 2009;145(3):309-313. 6. Nash B. Treating head lice. BMJ. 2003;326(7401):1256-1257. 7. Frankowski BL, Bocchini JA Jr; Council on School Health and Committee on Infectious Diseases. Head lice. Pediatrics. 2010;126(2):392-403. 8. Lebwohl M, Clark L, Levitt J. Therapy for head lice based on life cycle, resistance, and safety considerations. Pediatrics. 2007;119(5):965-974. 9. U.S. Food and Drug Administration. Lindane shampoo and lindane lotion. 2009. http://www.fda.gov/Drugs/DrugSafety/ PostmarketDrugSafetyInformationfor PatientsandProviders/ ucm110452.htm. Accessed December 29, 2011. 10. Burkhart CG, Burkhart CN. Asphyxiation of lice with topical agents, not a reality... yet. J Am Acad Dermatol. 2006;54(4): 721-722. 11. Meinking TL, et al. The clinical trials supporting benzyl alcohol lotion 5% (Ulesfia): a safe and effective topical 19. treatment for head lice (Pediculosis humanus capitis). Pediatr Dermatol. 2010;27(1):19-24. Natroba topical suspension, Spinosad 0.9% topical suspension [product information]. Magnolia, Tex.: ParaPRO and/or Pernix Therapeutics, Inc.; 2011. http://www.natroba.com/Full%20 Prescribing%20Information.pdf. Accessed January 31, 2012. Stough D, Shellabarger S, Quiring J, Gabrielsen AA Jr. Efficacy and safety of spinosad and permethrin creme rinses for pediculosis capitis (head lice). Pediatrics. 2009; 124(3):e389-e395. Chosidow O, et al. Oral ivermectin versus malathion lotion for difficult-to-treat head lice [published correction appears in N Engl J Med. 2010;362(17):1647]. N Engl J Med. 2010;362(10):896-905. Tebruegge M, Runnacles J. Is wet combing effective in children with pediculosis capitis infestation? Arch Dis Child. 2007;92(9):818-820. Bush SE, Rock AN, Jones SL, Malenke JR, Clayton DH. Efficacy of the LouseBuster, a new medical device for treating head lice (Anoplura:Pediculidae). J Med Entomol. 2011;48(1):67-72. Pearlman DL. A simple treatment for head lice: dry-on, suffocation-based pediculicide. Pediatrics. 2004;114(3): e275-e279. Workowski KA, Berman S; Centers for Disease Control and Prevention (CDC). Sexually transmitted diseases treatment guidelines, 2010 [published correction appears in MMWR Recomm Rep. 2011;60(1):18]. MMWR Recomm Rep. 2010;59(RR-12):1-110. Centers for Disease Control and Prevention. Parasites—lice— body lice. Resources for health professionals. 2010. http:// www.cdc.gov/parasites/lice/body/health_professionals/ index.html. Accessed December 29, 2011. Strong M, Johnstone P. Interventions for treating scabies. Cochrane Database Syst Rev. 2007;(3):CD000320. Johnston G, Sladden M. Scabies: diagnosis and treatment. BMJ. 2005;331(7517):619-622. Chosidow O. Clinical practices. Scabies. N Engl J Med. 2006;354(16):1718-1727. Mellanby K. Scabies in 1976. R Soc Health J. 1977;97(1): 32-36, 40. Service MW. Medical Entomology for Students. 4th ed. Cambridge, United Kingdom: Cambridge University Press; 2008. Mellanby K. Mites in relation to scabies. Abstr Int Congr Trop Med Malar. 1948;56(4th Congr):135. Arlian LG, et al. Prevalence of Sarcoptes scabiei in the homes and nursing homes of scabietic patients. J Am Acad Dermatol. 1988;19(5 pt 1):806-811. Hicks MI, Elston DM. Scabies. Dermatol Ther. 2009;22(4): 279-292. Chouela E, et al. Diagnosis and treatment of scabies: a practical guide. Am J Clin Dermatol. 2002;3(1):9-18. Page TL, et al. Clinical inquiries. When should you treat scabies empirically? J Fam Pract. 2007;56(7):570-572. Wolf R, Davidovici B. Treatment of scabies and pediculosis: facts and controversies. Clin Dermatol. 2010;28(5): 511-518.

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20. 21. 22. 23. 24.

25. 26.

27. 28. 29. 30.

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Practice Guidelines American Urological Association Approach to the Diagnosis and Management of IC/BPS The American Urological Association has published recommendations aimed at guiding physicians in recognizing interstitial cystitis/bladder pain syndrome (IC/BPS), conducting a valid diagnostic process, and treating patients by maximizing symptom control and minimizing adverse effects. The guideline defines IC/BPS as an unpleasant sensation perceived to be related to the urinary bladder that is associated with lower urinary tract symptoms of more than six weeks’ duration, in the absence of infection or other unidentifiable causes. Diagnosis The basic assessment should include a history, physical examination, and laboratory analysis to document symptoms and signs of IC/BPS or that might rule out other disorders. The history should include duration of symptoms; number of daily voids; sensation of urgency to void; and characteristics of pain, pressure, or discomfort. Men should be asked about dyspareunia, dysuria, and ejaculatory pain, and women should be asked about pain related to menstruation. Abdominal and pelvic examinations should be performed to detect masses, tenderness, and hernias. A focused physical examination is important to rule out infection or other possible causes of pain, such as vaginitis, urethritis, tender prostate, or urethral diverticulum. The pelvic floor muscles and pelvic support for the bladder, urethra, vagina, and rectum also should be evaluated. All patients should receive a brief neurologic examination to rule out an occult neurologic problem, as well as an evaluation for incomplete bladder emptying to rule out occult retention. A trial of antibiotics may be initiated if infection is suspected. The basic laboratory evaluation includes urinalysis and urine culture. However, cytology may be considered in smokers or in those with untreated microhematuria because of the high risk of bladder cancer in smokers. Voiding symptoms and pain levels should be obtained at baseline to help measure subsequent treatment effects. A voiding log should be maintained for at least one day to be used to establish the characteristic lowvolume frequency voiding pattern of IC/BPS. Selfreport questionnaires also may be used to document baseline symptoms, although they are not sufficient for diagnosis. The isolated pain component focuses on the location, intensity and characteristics of the pain or discomfort, as well as any factors that alleviate or exacerbate it. Several tools can be used to document pain, including symptom checklists, visual analog scales, and body maps. Other tests may support the diagnosis of IC/BPS, but have low specificity for the condition. In general, additional testing should be performed only if the results may affect treatment. Cystoscopy and/or urodynamic testing should be considered when the diagnosis is in doubt, but the tests are not necessary to confirm an IC/BPS diagnosis in uncomplicated cases. The roll of cystoscopy is to exclude conditions that may mimic IC/BPS and to identify a Hunner ulcer. Cystoscopy can be used to identify bladder cancer, vesical stones, urethral diverticula, and intravesical foreign bodies. Urodynamic evaluation may be indicated if there is suspicion of outlet obstruction, possible poor detrusor contractility, or other conditions that may make initial first-line therapy ineffective. There are no agreed-upon cystoscopy or urodynamic testing findings that are diagnostic of IC/BPS. Treatment More conservative treatment strategies should be used first, with less conservative strategies initiated if there is inadequate symptom control or irreversibility. Surgical treatments (other than fulguration of Hunner ulcers) usually are indicated only after all other treatment options have been ineffective or if a rare end-stage, small, fibrotic bladder is confirmed and the benefits of surgery outweigh the risks. There are various treatments for IC/BPS. The choice depends on invasiveness; probability, duration, severity, and reversibility of adverse effects; and reversibility of the treatments themselves. However, the treatment strategy generally should proceed from more to less conservative.

Source: Adapted from Am Fam Physician. 2012;86(1):97-103

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American Family Physician Initial treatment choice and timing depend on symptom severity, physician judgment, and patient preference. It is important to educate patients about what to expect from treatment. Tailoring IC/BPS treatment to symptom type and severity and making sure patients have reasonable expectations of treatment are necessary for effective management. Concurrent treatments may be considered if it is in the best interest of the patient, although baseline assessments are essential to measure effectiveness. Some patients may benefit from concurrent treatments and this approach may be necessary to improve quality of life. Baseline symptom assessments are important for identifying ineffective treatments so that they can be discontinued. Ineffective treatments should be discontinued after a clinically meaningful interval has elapsed. Any treatment that is ineffective after a clinically meaningful period should be discontinued and alternative therapies considered. Pain management should be continually assessed for effectiveness because of its importance to quality of life. Inadequate pain management should prompt consideration of multidisciplinary treatment and referral. The underlying pathophysiology of IC/BPS is unclear; therefore, treatment focuses on symptom management. Optimizing quality of life, particularly through pain management, may require a multidisciplinary approach. The IC/BPS diagnosis should be reconsidered if no improvement occurs after multiple treatment approaches. If clinically meaningful trials of multiple treatments are ineffective, the diagnosis should be revisited including additional workup and possible referral. Clinical experience and limited evidence suggest that modifying certain behaviors can improve IC/BPS symptoms in some patients. These modifications may include altering the concentration and/or volume of urine (with fluid restriction or additional hydration); application of local heat or cold over the bladder or perineum; avoiding common irritants (e.g., coffee, citrus products); using an elimination diet to determine which foods or drinks may contribute to symptoms; over-the-counter products (e.g., nutraceuticals, calcium glycerophosphates, phenazopyridine); techniques applied to trigger points and areas of hypersensitivity (e.g., application of heat or cold); strategies to manage flare-ups (e.g., meditation, pelvic floor muscle relaxation, bladder training). Multidisciplinary assistance may be considered as appropriate to manage factors that appear to precipitate or exacerbate symptoms, such as irritable bowel syndrome, endometriosis, recurrent vaginitis or vestibulitis, flare-ups coinciding with menstrual cycle, panic attacks, and depression.

Second-line Therapies Appropriate manual physical therapy techniques should be offered if appropriately trained professionals are available to perform them. Pelvic floor strengthening exercises should be avoided. Tenderness and/or banding of the pelvic floor musculature is common with IC/BPS. Clinical experience and limited evidence suggest that manual physical therapy can relieve these symptoms; however, there is no evidence that pelvic floor strengthening (e.g., Kegel exercises) improves symptoms, and it may worsen the condition. Appropriate manual physical therapy techniques include maneuvers that resolve pelvic, abdominal, or hip muscular trigger points, lengthen muscle contractures, and release painful scars and other connective tissue restriction. No quality studies have assessed massage or other relaxation techniques for IC/BPS, although these techniques have been effective for other forms of chronic pain and can be recommended for IC/BPS. Multimodal pain management approaches (e.g., pharmacologic therapy, stress management, manual therapy) should be initiated. Pain management is an integral part of IC/BPS treatment and should be assessed at each clinical encounter. Although little is known about effective pharmacologic treatment for chronic pain in IC/BPS, the approach should be similar to that for other chronic pain conditions. A multimodal approach in which agents are combined with other therapies is most likely to

First-line Therapies First-line treatment of IC/BPS should include patient education. Patients should be educated about normal bladder function, that IC/BPS is not fully understood, about the benefits and risks of treatments, that no single treatment has been shown to be effective for most patients, and that acceptable symptom control may require trials of multiple treatment approaches before the optimal effect is achieved. The typical course of IC/BPS is chronic and includes symptom exacerbations and remissions. Self-care practices and behavior modifications that can improve symptoms should be discussed and implemented as feasible.

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American Family Physician be effective, and patients should be aware that several regimens may need to be attempted before optimal pain control is achieved. Flare-ups may require a flexible pain treatment protocol. The goal of pharmacotherapy is to find a medication or combination of medications that provides significant pain relief with minimal adverse effects. Decisions regarding a multidisciplinary approach and referral should be made individually. Pain management does not constitute sufficient treatment of IC/BPS, and underlying bladder-related symptoms also should be treated. Amitriptyline, cimetidine, hydroxyzine, or pentosan may be considered as second-line oral medications. Data show that amitriptyline significantly improves symptoms over placebo, although the drug has a substantial potential for adverse effects. Beginning at a low dose of amitriptyline (e.g., 25 mg) and titrating to 75 to 100 mg is an acceptable approach. Cimetidine has also been shown to significantly improve symptoms compared with placebo, without adverse effects. However, there is a lack of long-term follow-up data on a sufficient number of patients, and cimetidine has the potential for drug interactions. The balance between benefits and risks of hydroxyzine is unclear; however, it has been effective in a subset of patients, and there are no serious adverse effects. Pentosan is the most studied oral medication for IC/BPS. Although high-quality studies show inconsistent results, there is some certainty that pentosan may benefit a subset of patients with IC/BPS. Dimethyl sulfoxide, heparin, or lidocaine may be considered as second-line intravesical medications. Although studies of dimethyl sulfoxide garnered a wide range of effectiveness and adverse effect rates, the therapy is an option for IC/BPS. Physicians should be aware that dimethyl sulfoxide potentially enhances absorption of other substances, and no study has assessed the safety of combining the therapy with other therapies versus using it alone. It appears that heparin, in combination with other therapies or used alone, may benefit a subset of patients with IC/BPS, and adverse effects are minimal. Without placebocontrolled trials, the balance between benefits and risks is unclear. Lidocaine appears to provide short-term relief, and adverse effects typically are not serious, but the procedure itself may be associated with pain.

Treatments not Recommended for Use Treatments with a lack of effectiveness and/or unacceptable adverse effects include long-term oral antibiotics; intravesical bacille Calmette-Guérin; intravesical resiniferatoxin; high-pressure, long-duration hydrodistention; and long-term oral glucocorticoids.

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Photo Quiz

Painless, Red Nodule on the Finger of a Veterinary Student A 27-year-old otherwise healthy veterinary student presented with a slow-growing, painless, red mass on his finger that first appeared three weeks earlier. Weeping occurred without provocation, and it bled lightly with minimal trauma. It did not respond to an over-the-counter antibiotic ointment. The patient reported a minor skin break in the same area and that he had intubated a goat without wearing gloves about one month before the development of the lesion. He had no other local symptoms or history of an insect bite, fever, or malaise. Physical examination revealed a 1-cm, wellcircumscribed, erythematous nodule located on the dorsolateral aspect of the distal third finger (see accompanying figure). The lesion was firm and nontender to palpation. There was scant overlying exudate, but no surrounding erythema, edema, regional lymphadenopathy, or lymphangitis. Question Based on the patient’s history and physical examination findings, which one of the following is the most likely diagnosis?

A. Anthrax. B. Milker’s nodule. C. Orf. D. Pyogenic granuloma. E. Tularemia.

See the following page for discussion.

Source: Adapted from Am Fam Physician. 2012;86(1):77-79.

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American Family Physician Summary Table Condition Anthrax Transmission Bacillus anthracis infection from direct contact with spores originating on hoofed animals, their hides, or surrounding soil Parapoxvirus infection from direct contact with cattle Characteristics Rapidly enlarging, painless, red papule that ulcerates and forms a black eschar; extensive local edema, regional lymphadenopathy, and lymphadenitis usually are present Self-limited, painless, red papule that evolves through six stages; presentation and course essentially identical to orf

Milker’s nodule

Orf Pyogenic granuloma Tularemia

Parapoxvirus infection from direct contact with sheep Self-limited, painless, red papule that evolves or goats through six stages Noninfectious capillary proliferation secondary to minor skin insult Francisella tularensis infection from rabbits and rodents via arthropod vectors Rapidly enlarging, soft, red papule that bleeds easily Single rapidly enlarging, painful, red papule; ulcerates and forms a black eschar; fever and regional lymphadenopathy usually present

Discussion The answer is C: Orf, or contagious ecthyma, is a cutaneous zoonosis caused by a DNA virus of the Parapoxvirus genus that is endemic in sheep and goats. Transmission to humans usually occurs through direct contact with an infected animal (facilitated by a break in the skin), and less commonly by contacting contaminated meat, hides, or fomites.1 Orf is a common occupational disease, typically affecting the dorsum of the hands and fingers of farmers, butchers, and veterinarians. The diagnosis of orf is clinical, based on a classic history and physical examination. Following a threeto seven-day incubation period, the typically painless lesion progresses through six well-described, oneweek stages.1 This may be accompanied by lowgrade fever and regional lymphadenopathy. The first (maculopapular) stage begins with a red macule at the inoculation site that progresses into a papule, which changes in appearance during subsequent stages. The second (targetoid) stage is characterized by an inner white ring with an outer red halo. The third (active) stage involves expansion and weeping, which is depicted in the accompanying figure. In the fourth (regenerative) stage, the papule is dry with a thin crust of black dots. In the fifth (papillomatous) stage, the surface becomes verrucous. The sixth (regressive) stage ends with thick crusting and spontaneous resolution, usually without scarring. The treatment of orf is generally supportive (e.g., nonsteroidal anti-inflammatory drugs, moist dressings, immobilization) because the lesions resolve

spontaneously after about six weeks. Cryotherapy may hasten recovery but typically is not indicated. Case reports show some improvement with topical antivirals, although this is not the current standard of care.1-3 Secondary bacterial infections should be treated if present. Anthrax is a rare zoonosis caused by Bacillus anthracis, a gram-positive bacillus found in many wild and domesticated hoofed animals. Cutaneous disease is the most common and least serious form of anthrax. Transmission occurs by subcutaneous inoculation with spores originating on infected animals, their hides, or surrounding soil. Following a seven-day incubation period, a rapidly enlarging, painless, red papule emerges and progresses into a necrotic ulcer with black eschar. Extensive local edema, regional lymphadenopathy, and lymphangitis usually are present.4 Mortality drops from 20 percent to less than 1 percent with treatment.5 Milker’s nodule is a cutaneous zoonosis caused by a Parapoxvirus species endemic to cattle. Other than a different exposure history, the presentation, course, and treatment of milker’s nodule are essentially identical to orf. Definitive differentiation is unnecessary, but can be accomplished through viral culture, polymerase chain reaction, or histopathologic examination. Pyogenic granuloma is a noninfectious capillary proliferation secondary to a minor skin insult. It presents as a rapidly enlarging, soft, red papule that bleeds easily and occasionally profusely.4 This is the most common misdiagnosis in a patient with orf. Tularemia is a relatively rare cutaneous zoonosis caused by Francisella tularensis, a highly virulent, gram-negative coccobacillus found in rabbits and rodents. Transmission usually occurs through an

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American Family Physician arthropod vector rather than direct animal contact. A ulceroglandular presentation is most common and is characterized by a single rapidly enlarging, painful, red papule that develops a central necrotic ulcer and black eschar. Fever and regional lymphadenopathy usually are present.4,6 REFERENCES 1. Georgiades G, Katsarou A, Dimitroglou K. Human orf (ecthyma contagiosum). J Hand Surg Br. 2005;30(4):409-411. 2. Groves RW, Wilson-Jones E, MacDonald DM. Human orf and milker’s nodule: a clinicopathologic study. J Am Acad Dermatol. 1991;25(4):706-711. 3. Pether S, Guerrier CJ, Jones SM, Adam AE, Kingsbury WN. Giant orf in a normal individual. Br J Dermatol. 1986;115(4):497-499. 4. Fitzpatrick TB, Wolff K. Fitzpatrick’s Dermatology in General Medicine. 7th ed. New York, NY: McGraw-Hill; 2008. 5. Freedman A, Afonja O, Chang MW, et al. Cutaneous anthrax associated with microangiopathic hemolytic anemia and coagulopathy in a 7-month-old infant. JAMA. 2002;287(7):869-874. 6. Sjöstedt A. Tularemia: history, epidemiology, pathogen physiology, and clinical manifestations. Ann N Y Acad Sci. 2007;1105:1-29.

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ANESTHESIOLOGY

Dexmedetomidine and Anesthesia Sudivya Sharma*, Prashast Jain**

Abstract The α2-adrenoceptors (ARs) by virtue of their sedative, analgesic, sympatholytic, anesthetic-sparing and hemodynamicstabilizing properties, have been used as an adjunct to local anesthetics for prolongation of effect. Dexmedetomidine a stereoisomer of medetomidine a highly selective α2-adrenergic receptor (AR) agonist with a relatively high ratio of α2/ α1-activity (1620:1 as compared to 220:1 for clonidine). It has recently been introduced in anesthesia practice. It is currently being

used for continuous intravenous sedation in the intensive care setting and procedural sedation in nonintubated patients. Keywords: Dexmedetomidine, α2-2 adrenergic receptor agonist, adjuvant, analgesic

D

exmedetomidine is a stereoisomer of medetomidine, with chemical formula 4-[(1S)1-(2, 3-dimethylphenyl) ethyl]-1H-imidazole. It is a highly selective α2-adrenergic receptor (AR) agonist with a relatively high ratio of α2/ α1-activity (1620:1 as compared to 220:1 for clonidine).1

CH H N O N H H

CH CH

Pharmacokinetics Dexmedetomidine undergoes almost complete hydroxylation through direct glucuronidation and cytochrome P450 metabolism in liver. Metabolites are excreted in the urine (about 95%) and feces (4%). The elimination half-life is approximately two hours. The average protein binding is 94%. Effects of dexmedetomidine can be antagonized easily by administering the α2-AR antagonist atipamezole. Uses The α2-adrenoceptors (ARs) by virtue of their sedative, analgesic, sympatholytic, anesthetic-sparing and hemodynamic-stabilizing properties, have been used as an adjunct to local anesthetics for prolongation of

Figure 1. Chemical formula of dexmedetomidine.

effect. Clonidine, an α2-AR agonists has been used with local anesthetics in peripheral nerve block, though the results have been somewhat less impressive.2,3 Dexmedetomidine, a highly selective α2-AR agonist has recently been introduced in anesthesia practice. It is currently being used for continuous intravenous sedation in the intensive care setting and procedural sedation in nonintubated patients. Its potential benefit as an adjuvant to local anesthetics in peripheral nerve blocks has been emphasized in few experimental studies.1 Mechanism There have been four proposed mechanisms of action of α2-AR agonists in peripheral nerve blocks. These mechanisms include: ÂÂ

Direct action on the peripheral nerve Centrally mediated analgesia α-2B-AR2 mediated vasoconstrictive effects Attenuation of the inflammatory response.4

*PGIMS, Rohtak **Dept. of Anesthesia PGIMS, Rohtak, Haryana Address for correspondence Dr Sudivya Sharma Flat No-77, B-Wing, Mahavir Krupa Building TJ Road, Sewari (W), Mumbai - 400 015 E-mail: drsudivyasharma@gmail.com

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Despite the fact that there is no α2-AR representation on peripheral nerves, there is prolongation of action by perineural administration of α2-AR agonist as

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ANESTHESIOLOGY an adjuvant to local anesthetics. They prolong the duration of analgesia by blocking the so-called hyperpolarization-activated cation current (Ih current). This is the most well-defined mechanism of α2-AR agonists. After an action potential (AP) has occurred, the nerve will have to repolarize to be able to produce new APs. The early repolarization phase will result in a hyperpolarized state that will make the generation of new APs virtually impossible, and the nerve is, during this period, judged to be refractory to stimulation. Thus, blocking the Ih current will result in prolonged hyperpolarization of the nerve, which in turn will result in an analgesic action. Blocking the Ih current may also have the potential to produce a selective sensory effect as this effect appears to be more pronounced in C fibers (pain) than in A alpha fibers (motor). Dexmedetomidine has more pronounced effect on inhibition of nerve fiber action potentials as compared to clonidine.5 Centrally, α2-AR agonists cause analgesia and sedation by inhibition of substance P release in the nociceptive pathway at the level of the dorsal root neuron and by activation of α2-AR in the locus coeruleus. Suppression of activity in the descending noradrenergic pathway, which modulates nociceptive neurotransmission, terminates propagation of pain signals leading to analgesia.1 Apart from above mechanisms, clonidine may reduce systemic uptake of the perineurally deposited local anesthetic-clonidine mixture by means of a1-receptormediated vasoconstriction. As dexmedetomidine has a very limited effect on a1-ARs, it is unlikely that a nerve block by a local anesthetic-dexmedetomidine mixture may prolong the block duration by this mechanism, despite being able to cause time limited vasoconstriction by stimulation of α2-ARs.5 The upcoming anti-inflammatory effects of α2-AR agonists has been highlighted by a series of animal studies by Brummett and colleagues who reported that large doses of dexmedetomidine or clonidine prolonged the duration of sciatic nerve block when added to local anesthetics like bupivacaine or ropivacaine in rats. In addition, histopathological examinations of sciatic nerves at 24 hours and 14 days showed that the nerve axon and myelin were unaffected after perineural application of dexmedetomidine. There was decrease in proinflammatory products from immune cells recruited to the site of injury and an increase in antiinflammatory cytokines. Hence, there was decrease in perineural inflammation as compared to sole use of local anesthetic. These findings reinforce the neuroprotective role of dexmedetomidine. Because of the safety profile of dexmedetomidine, it is now being used intrathecally without apparent toxicity.4,6 Other useful effects of activation of α2-ARs include decreased salivation, increased glomerular filtration, decreased intraocular pressure and increased seizure threshold.1 Adjuvant Dexmedetomidine exhibits synergism with local anesthetics, prolonging their duration of action. So far, the clinical evidence for the use of dexmedetomidine as an adjuvant to local anesthetic for peripheral nerve blocks is limited to few animal studies and three human studies.3,4,6-8 In the spinal cord, activation of both a-2C and a2ARs, situated in the neurons of superficial dorsal horn especially lamina II, directly reduces pain transmission by reducing the release of pronociceptive transmitter, substance P and glutamate from primary afferent terminals and by hyperpolarizing spinal interneurons via G-protein-mediated activation of potassium channels. Postsynaptic activation of central a2-ARs results in sympatholytic effect leading to hypotension and bradycardia, an effect judiciously used to attenuate the stress response of surgery.9-13 The greater a2-ARs selectivity of dexmedetomidine enhances the therapeutic window of dexmedetomidine in the treatment of pain. Its opiate sparing effect has important implications for the management of acute postoperative pain and chronic pain states, including disorders involving spasticity or myofascial pain, neuropathic pain, sympathetically maintained pain such as complex regional pain syndrome (CRPS) and chronic daily headaches. It is evolving as an adjuvant analgesic, both as intravenous and intrathecal infusion, in cancer pain refractory to multiple treatment modalities.14-16 Conclusion Dexmedetomidine has evolved as a panacea for various applications/procedures with multiple promising delivery routes. Its clinical applications in adults and children include premedication, as part of multimodal anesthetic regimen, regional anesthesia, sedation monitored anesthesia care, procedural sedation, prevention/treatment of emergence delirium, alcohol withdrawal and shivering, and the list continues to grow.

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ANESTHESIOLOGY References 1. Grewal A. Dexmedetomidine: New avenues. Anaesthesiol Clin Pharmacol 2011;27(3):297-302. J ropivacaine prolongs peripheral nerve block: a volunteer study. Br J Anaesth 2013 ;110(3):438-42. 9. I shii H, Kohno T, Yamakura T, Ikoma M, Baba H. Action of dexmedetomidine on the substantia gelatinosa neurons of the rat spinal cord. Eur J Neurosci 2008;27(12):3182-90. 10. R oudet C, Mouchet P, Feuerstein C, Savasta M. Normal distribution of alpha 2-adrenoceptors in the rat spinal cord and its modification after noradrenergic denervation: a quantitative autoradiographic study. J Neurosci Res 1994;39(3):319-29. 11. S tone LS, Broberger C, Vulchanova L, Wilcox GL, Hökfelt T, Riedl MS, et al. Differential distribution of alpha2A and alpha2C adrenergic receptor immunoreactivity in the rat spinal cord. J Neurosci 1998;18(15):5928-37. 12. A rain SR, Ebert TJ. The efficacy, side effects, and recovery characteristics of dexmedetomidine versus propofol when used for intraoperative sedation. Anesth Analg 2002;95(2):461-6, table of contents. 13. C andiotti KA, Bergese SD, Bokesch PM, Feldman MA, Wisemandle W, Bekker AY; MAC Study Group. Monitored anesthesia care with dexmedetomidine: a prospective, randomized, double-blind, multicenter trial. Anesth Analg 2010;110(1):47-56. 14. G rosu I, Lavand’homme P. Use of dexmedetomidine for pain control. F1000 Med Rep 2010;2:90. 15. R oberts SB, Wozencraft CP, Coyne PJ, Smith TJ. Dexmedetomidine as an adjuvant analgesic for intractable cancer pain. J Palliat Med 2011;14(3):371-3. 16. Ugur F, Gulcu N, Boyaci A. Intrathecal infusion therapy with dexmedetomidine-supplemented morphine in cancer pain. Acta Anaesthesiol Scand 2007;51(3):388.

2. H ickey R, Blanchard J, Hoffman J, Sjovall J, Ramamurthy S. Plasma concentrations of ropivacaine given with or without epinephrine for brachial plexus block. Can J Anaesth 1990;37(8):878-82. 3. E smaoglu A, Yegenoglu F, Akin A, Turk CY. Dexmedetomidine added to levobupivacaine prolongs axillary brachial plexus block. Anesth Analg 2010;111(6):1548-51. 4. B rummett CM, Padda AK, Amodeo FS, Welch KB, Lydic R. Perineural dexmedetomidine added to ropivacaine causes a dose-dependent increase in the duration of thermal antinociception in sciatic nerve block in rat. Anesthesiology 2009;111(5):1111-9. 5. L önnqvist PA. Alpha-2 adrenoceptor agonists as adjuncts to Peripheral Nerve Blocks in Children - is there a mechanism of action and should we use them? Paediatr Anaesth 2012;22(5):421-4. 6. B rummett CM, Norat MA, Palmisano JM, Lydic R. Perineural administration of dexmedetomidine in combination with bupivacaine enhances sensory and motor blockade in sciatic nerve block without inducing neurotoxicity in rat. Anesthesiology 2008;109(3):502-11. 7. O bayah GM, Refaie A, Aboushanab O, Ibraheem N, Abdelazees M. Addition of dexmedetomidine to bupivacaine for greater palatine nerve block prolongs postoperative analgesia after cleft palate repair. Eur J Anaesthesiol 2010;27(3):280-4. 8. M arhofer D, Kettner SC, Marhofer P, Pils S, Weber M, Zeitlinger M. Dexmedetomidine as an adjuvant to

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Cardiac Surgery Success Hinges on Teamwork Better communication is the key to improving patient outcomes after cardiac surgery, according to a new scientific statement from the American Heart Association. A wide-ranging review of evidence, led by Joyce Wahr, MD, of the University of Michigan Ann Arbor, called for such things as checklists, preoperative and postoperative briefings, and team training in communication skills. But the review, published online in Circulation, also cautioned that “research in this area is nascent but informative.” The investigators noted that cardiac surgical operating rooms form ‘a complex environment’ that includes many highly trained people working together and using sophisticated equipment to treat people with severe disease. “Preventable errors are often not related to failure of technical skill, training or knowledge,” they wrote, “but represent cognitive, system or teamwork failures.” Key to improvement of patient safety, they argued, are the “nontechnical skills” of communication, cooperation, coordination and leadership.

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CARDIOLOGY

Glucose Tolerance in Nondiabetic Patients after First Attack of Acute Myocardial Infarction and its Outcome Ajay S Dabhi*, M Vadivelan*, SR Rathava*

Abstract Aims: To find out the incidence of impaired glucose tolerance (IGT) and frank diabetes mellitus (DM) in patients of acute myocardial infarction (AMI) and to study the natural history of IGT in relation to AMI. Study Design: A crosssectional study was done in 60 patients of AMI in whom oral glucose tolerance test (OGTT) was performed after admission. Those with normal glucose tolerance on admission and till discharge were included in the study. Material and Methods: The study was conducted at the intensive coronary care unit (ICCU) of Shri Sayajirao General (SSG) Hospital, Vadodara, Gujarat. The study was done over a period of seven months in 60 patients of AMI. Results: The present study revealed that cardiovascular complications related to AMI were more common in patients with abnormal glucose tolerance. Conclusion: Glucometabolic abnormalities in nondiabetic patients with acute coronary event have an influence on in-hospital and short-term cardiovascular morbidity as well as mortality.

Keywords: Impaired glucose tolerance, acute myocardial infarction

D

espite impressive strides in the diagnosis and management of myocardial infarction, it still continues to be a major public health problem worldwide. Cardiovascular disease is a major cause of death in diabetic patients.1

factors. In patients with IGT, cardiovascular risk is equal and in some cases, even higher than in those diagnosed to have diabetes.4 AIMS OF STUDY ÂÂ

Although diabetes mellitus (DM) has emerged as a major risk factor for coronary artery disease (CAD)related morbidity and mortality, recently it has been suggested that impaired glucose tolerance (IGT) is also an independent risk factor.2 IGT is a dysglycemic state, which is the intermediate state between normal glycemic state and DM.3 Asymptomatic hyperglycemia is a significant public health problem and confers an increased cardiovascular risk, independent of other classical cardiovascular risk

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To find out the incidence of IGT and frank DM in patients of acute myocardial infarction (AMI) in three months follow-up period who, after first attack of AMI, were normoglycemic on admission and till discharge. To evaluate the relationship between plasma glucose level on admission and its outcome (in-hospital and short-term) in patients with AMI without previously known DM. To evaluate IGT as an independent cardiovascular risk factor in AMI. To study the natural history of IGT in relation to AMI and to compare the outcome in patients after three months follow-up.

*Assistant Professor Dept. of Medicine Medical College and SSG Hospital, Vadodara, Gujarat Address for correspondence Dr Ajay S Dabhi 38, Alkanagar, Near Priyalaxmi Mill, Old Alembic Road Vadodara - 390 003, Gujarat E-mail: dr_ajay_44@yahoo.co.in

MATERIAL AND METHODS In this prospective, cross-sectional study, 60 patients presenting with clinical features of AMI admitted to the intensive coronary care unit (ICCU) of Shri Sayajirao General (SSG) Hospital, Vadodara, Gujarat were taken as the study group.

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CARDIOLOGY Oral glucose tolerance test (OGTT) was performed in all patients and those with normal glucose tolerance on admission and till discharge were included in the study group.

Table 1. Age and Sex Distribution of Patients with Myocardial Infarction Age (years) Male (%) 35-45 46-55 56-65 Total 5 (8%) 9 (15%) 26 (44%) 40 (67%) Sex Female (%) 1 (2%) 6 (10%) 13 (21%) 20 (33%) 6 (10%) 15 (25%) 39 (65%) 60 (100%) Total (%)

Inclusion Criteria Adults below the age of 65 years who presented within 24 hours of AMI for the first time and with random blood sugar (RBS) level <180 mg/dl were included in the study sample.

Exclusion Criteria Patients with DM, systemic arterial hypertension, ischemic heart disease and those with history of gestational diabetes mellitus, cerebrovascular accident, peripheral vascular disease, structural heart disease, chronic liver and kidney disease were excluded from the study. RBS was estimated on admission and fasting blood sugar (FBS) was estimated on the second day after admission and on discharge. OGTT was carried out according to WHO guidelines under controlled conditions after an overnight fast. Impaired fasting glucose (IFG) was defined as venous plasma glucose level in the range of 110-125 mg/dl, while IGT was defined as venous plasma glucose level in the range of 140-199 mg/dl (2 hours after glucose load). Each patient was evaluated with OGTT (FBS and PG2BS), electrocardiogram (ECG) and echocardiogram at three months follow-up. RESULTS Sixty indoor patients admitted to ICCU with AMI and satisfying the inclusion criteria were selected for the study. The age of patients ranged from 35 to 65 years. Majority of patients were in the age group of 56-65 years (65%) indicating higher prevalence of AMI in elderly people. Out of 60 patients in the study group, 40 were males (67%) and 20 were females (33%) (Table 1). The AMI patients were further divided into subgroups on the basis of ECG findings. ST elevation-MI (STEMI) was seen in 52 (87%) patients and non-STEMI was seen in eight (13%) patients. In cases of STEMI, 35 (59%) patients had anterior wall MI (Table 2). Table 3 shows that glucose tolerance in all patients of study sample was normal till discharge. At the end of three months follow-up, 40 patients (67%) in Group A had normal glucose tolerance, while 14 patients (23%) in Group B1 had IGT and six patients (10%) in Group B2 had frank DM (Table 4). Table 5 shows segment motion abnormality in AMI on 2-D Echo done at the time of admission and on follow-up. Worsening of involved segment was noticed more in Group B as compared to Group A on 2-D Echo. Table 6

Table 2. ECG Findings in Study Sample Patients (%) STEMI Anterior wall MI Inferior wall MI Right ventricle MI Total NSTEMI Subendocardial MI ST-segment depression Fresh left bundle branch block (LBBB) Total 2 (3%) 4 (7%) 2 (3%) 8 (13%) 35 (59%) 14 (23%) 3 (5%) 52 (87%)

Table 3. RBS and OGTT Results in Study Sample Variable On admission RBS (mg/dl) On second day of admission FBS (mg/dl) PG2BS (mg/dl) On discharge FBS (mg/dl) PG2BS (mg/dl) In study, cut-off value of RBS <180 mg/dl.

Values 121 ± 57 97 ± 8 117 ± 18 93 ± 12 104 ± 8

Table 4. Division of Study Sample-based on Glucose Tolerance at the End of 3-month Follow-up Group A B1 B2 Total NGT = Normal glucose tolerance.

Patients (%) 40 (67%) 14 (23%) 6 (10%) 60 (100%)

Result NGT IGT Frank DM

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CARDIOLOGY Table 5. Comparison of Segment Motion Abnormality in Both Groups Segment motion abnormality On admission Normokinesia Hypokinesia Akinesia Paradoxical movement On follow-up Normokinesia Hypokinesia Akinesia Paradoxical movement 6 (15%) 15 (38%) 10 (25%) 9 (22%) 1 (5%) 8 (40%) 5 (25%) 6 (30%) 7 (12%) 15 (25%) 15 (25%) Percentage of involved patients

Percentage of involved patients

60 50 40 30 20 10 0

On admission

Group A (%)

Group B (%)

Total (%)

10 (25%) 21 (53%) 5 (12%) 4 (10%)

6 (30%) 8 (40%) 3 (15%) 3 (15%)

16 (27%) 29 (48%) 8 (13%) 7 (12%)

Group A Group B

>50% 41-50% 31-40% <30% LVEF (%) On follow-up

23 (38%)

40 35 30 25 20 15 10 5 0 >50% 41-50% 31-40% <30% LVEF (%) Group A Group B

Table 6. Comparison of Left Ventricle Ejection Fraction in Both Groups LVEF (%) On admission >50 (normal) 41-50 31-40 <30 On follow-up >50 (normal) 41-50 31-40 <30 6 (15%) 15 (38%) 10 (25%) 9 (22%) 1 (5%) 8 (40%) 5 (25%) 6 (30%) 7 (12%) 23 (38%) 15 (25%) 15 (25%) 10 (25%) 21 (53%) 5 (12%) 4 (10%) 6 (30%) 8 (40%) 3 (15%) 3 (15%) 16 (27%) 29 (48%) 8 (13%) 7 (12%) Group A (%) Group B (%) Total (%)

Figure 1. Comparison of left ventricle ejection fraction in both groups.

Table 7. Comparison of Both Groups for Complicated MI Acute MI Complicated Uncomplicated Total Group A (%) 17 (43%) 23 (57%) 40 (100%) Group B (%) 19 (95%) 1 (5%) 20 (100%) Total (%) 36 (60%) 24 (40%) 60 (100%)

shows progression to poor cardiac pump function in Group B as compared to Group A on 2-D Echo at three months follow-up. Out of 36 patients who developed cardiovascular complications related to AMI, 95% patients had abnormal glucose tolerance (IGT and frank DM). Among complications, patients developed congestive heart failure (CHF), cardiogenic shock and arrhythmias (Fig. 1 and Table 7). Table 8 shows that death due to cardiac cause was more in Group B than Group A. Cause of death was CHF in all patients. DISCUSSION Acute myocardial infarction is the commonest cause of cardiovascular disability in developed countries and the leading cause of morbidity and mortality in developing countries.5 Cardiovascular relative risk increases 2-4 folds in patients with diabetes as compared to the nondiabetic population.6 Stress hyperglycemia is usually associated with AMI and quite a large number of patients developed IGT or frank DM in due course after AMI.7 The risk of CHF is also increased in patients

Table 8. Comparison of Both Groups for MI-related Mortality Acute MI Alive Death Total Group A (%) 39 (98%) 1 (2%) 40 (100%) Group B (%) 16 (80%) 4 (20%) 20 (100%) Total (%) 55 (91%) 5 (9%) 60 (100%)

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CARDIOLOGY with stress hyperglycemia. Elevated glycosylated hemoglobin (HbA1C) in nondiabetic patients is a risk factor for one year mortality after AMI. Hyperglycemia in AMI is a transient phenomenon that is induced by acute stress, which increases the levels of cortisol and catecholamines in blood. HbA1C is the most powerful indicator of high blood glucose on admission. It is a marker of acute stress and also reflects the prevailing disturbed glucometabolic state.8 Patients with AMI with IGT and frank DM are at increased risk of in-hospital and short-term morbidity as well as mortality. Few possible mechanisms may explain this observation.9 ÂÂ

to exclude influence of stress hyperglycemia in glucometabolic abnormalities, which was not done in our study. CONCLUSION Patients with AMI who were found to have IGT and frank DM on screening with OGTT on follow-up had a high incidence of cardiovascular morbidity especially dyskinesia of involved segment, pump failure, arrhythmias and recurrent cardiac events as well as mortality. Thus, glucometabolic abnormalities in nondiabetic patients with acute coronary event have an influence on cardiovascular morbidity (in-hospital and short-term) as well as mortality. IGT confers an increased cardiovascular risk in acute ischemic event, even in the absence of other classic coronary risk factors. Hence, OGTT should be included in the armamentarium in patients with AMI to detect at high cardiovascular risk individuals. REFERENCES 1. Jovon GE. Cause of death in 1144 patients with diabetes mellitus. CMAJ 1986;134(7):754-64. 2. Capes SE, Hunt D, Malmberg K, Gerstein HC. Stress hyperglycemia and increased risk of death after myocardial infarction in patients with and without diabetes: a systematic review. Lancet 2000;355(9206):773-8. 3. American Diabetes Association. Consensus Development Conference on Insulin Resistance. 5-6 November 1997. Diabetes Care 1998;21(2):310-4. 4. Norhammar AM, Rydèn L, Malmberg K. Admission plasma glucose. Independent risk factor for long-term prognosis after myocardial infarction, even in nondiabetic patients. Diabetes Care 1999;22(11):1827-31. 5. Stubbs PJ, Allghband-Zadeh J, Laycock JF, Collinson PO, Carter GD, Noble MI. Significance of an index of insulin resistance on admission in non-diabetic patients with acute coronary syndromes. Heart 1999;82(4):443-7. 6. Antman EM, Braunwald E. Acute myocardial infarction. Braunwald’s Heart Disease. 8th edition, P. Libby et al (Eds.), Saunders, Philadelphia, 2008. 7. Mizock BA. Alteration in carbohydrate metabolism during stress: a review of the literature. Am J Med 1995;98(1):75-84. 8. Oswald GA, Smith CC, Betteridge DJ, Yudkin JS. Determinants and importance of stress hyperglycemia in non-diabetic patients with myocardial infarction. Br Med J (Clin Res Ed) 1986;293(6552):917-22. 9. Fuller JH, Shipley MJ, Rose G, Jarrett RJ, Keen H. Coronaryheart-disease risk and impaired glucose tolerance. The Whitehall study. Lancet 1980;1(8183):1373-6. 10. Tavani A, Bertuzzi M, Gallus S, Negri E, La Vecchia C. Diabetes mellitus as a contributor to risk of acute myocardial infarction. J Clin Epidemiol 2002;55(11):1082-7.

Hyperglycemia is a reflection of relative insulin deficiency which is associated with increased lipolysis and excess circulating free fatty acids. This effect is exaggerated in cases of acute stress such as MI. Free-fatty acids are toxic to ischemic myocardium and may lead to damaged cardiac cell membranes, calcium overload and arrhythmias. High concentration of free-fatty acids during myocardial ischemia increases myocardial contractility. Insulin deficiency also limits the ability of cardiac muscle to take up glucose for anerobic metabolism. Hyperglycemia may precipitate an osmotic diuresis, resulting in volume depletion that may interfere with Frank-Starling mechanism which is an important compensatory mechanism, for the failing left ventricle. Reflex adaptation to hemodynamic stress secondary to infarction may be impaired by autonomic dysfunction which is common in diabetics. Also, diabetics have extensive CAD that limits the availability of collateral blood flow to the infarct zone.10 IGT may be a marker of more extensive cardiac damage in AMI, which may lead to greater rise in stress hormones (promoting glycogenolysis and hyperglycemia) and may also increase the risk of CHF and mortality.

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LIMITATIONS ÂÂ

This cross-sectional, comparative study was conducted with only 60 patients of AMI and hence, information regarding boundaries of abnormal glucose tolerance could not be derived. Larger samples are needed to decide the cut-off values of abnormal glucose tolerance. In our study, three months follow-up was done, but long-term follow-up studies are needed to find out future development of overt DM in patients with IGT as well as long-term prognosis. Measurement of stress markers like circulating catecholamines and cortisol would be needed

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Dermatology

Cutaneous Drug Eruption Caused by Amoxicillin: A Case Report SWAPNIL C Jaykare*, VM Motghare**, SL Padwal†, JR Patil*, HN Pise*

Abstract Amoxicillin is a commonly used antimicrobial agent to combat various infections. Penicillin group of drugs are known to cause cutaneous drug eruptions especially in pediatric population. Most of the time, these eruptions are mild in nature, however, sometimes they represent the early manifestation of rare, severe drug-induced cutaneous reactions, such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Here, we report a case of maculopapular, erythematous rash induced by amoxicillin in an 18-year-old male patient. The case is being reported to emphasize the need for efficient pharmacovigilance in order to motivate adverse drug reaction reporting so as to gather more and more data regarding adverse drug reactions.

Keywords: Amoxicillin, drug eruption, maculopapular rash

A

moxicillin is a broad-spectrum, bactericidal antibiotic, which belongs to the group of β-lactam antibiotics. These β-lactam group of antibiotics are commonly used to treat bacterial infections caused by susceptible microorganisms. They are frequently used to treat common infections such as upper respiratory tract infections (URTIs) and lower respiratory tract infections (LRTIs) in both adult as well as pediatric population. Amoxicillin is usually the drug of choice within the class because it is better absorbed, following oral administration, compared to other β-lactam antibiotics. Amoxicillin is known to induce maculopapular or morbilliform type of rash in pediatric population, also known as ‘amoxicillin-induced morbilliform rash’.1 Here, we report a case of maculopapular, erythematous rash induced by amoxicillin.

Case Report An 18-year-old male patient presented to medical OPD three days back with complaints of cough with expectoration since few days. Patient was prescribed capsule amoxicillin for the same along with nonsteroidal anti-inflammatory drugs (NSAIDs). After consumption of a single capsule, within half an hour , the patient developed itching and maculopapular rashes over body. Rashes initially appeared over face, which spread rapidly to the neck, chest, back and the abdomen within few hours of appearance. Patient again visited casualty and was treated with injection chlorpheniramine and injection hydrocortisone to which he responded. On the next day, patient again consumed capsule amoxicillin after which the rashes reappeared, this time more severe in appearance following which he was admitted to hospital. On examination, patient was conscious, oriented and stable with pulse rate of 90/minute. Rash was typically maculopapular, erythematous in nature any associated with itching. Rashes remained localized to face, neck, chest and back. There was no involvement of mucosal areas sparing eyes, buccal mucosa and tongue. Systemic examination, otherwise, did not reveal any other significant findings. Laboratory finding did not reveal any significant abnormality. Considering the history, clinical examination and laboratory findings, patient was diagnosed as a case of allergic exanthematous adverse reaction to amoxicillin. Patient was managed

*Junior Resident II **Professor and Head †Associate Professor Dept. of Pharmacology Swami Ramanand Teerth Rural Medical College, Ambajogai, Beed, Maharashtra Address for correspondence Dr Swapnil C Jaykare Junior Resident III Dept. of Pharmacology Third Floor, College Building, Swami Ramanand Teerth Rural Medical College Ambajogai - 431 517, Beed, Maharashtra E-mail: swapniljaykare@gmail.com

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Dermatology

(a)

(b)

Figure 1. Erythematous maculopapular eruptions on face (a) and erythematous papular eruptions on chest (b).

consist of macules (distinct flat areas) and papules (raised lesions). They may or may not be associated with itching, but are commonly erythematous in nature. Manifestation may be localized or they may spread all over the body causing generalized eruptions. Amoxicillin is known to cause cutaneous drug eruptions in the form of maculopapular rashes. These reactions are common in pediatric population but occur in adults too. Seven cases of amoxicillininduced flare in patients with DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) induced by other drugs were reported by Mardivirin et al.3 A maculopapular exanthema caused by amoxicillin is one of the most common cutaneous adverse drug reactions in children. Most of the time, these manifestations are mild in nature and self-limiting, however, sometimes these reactions also represent the early manifestation of rare, severe drug-induced cutaneous reactions, such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), which result in epidermal detachment and have high rates of morbidity and mortality.4 As already stated, many commonly used drugs are associated with maculopapular drug eruptions. Sulfonamides are quite commonly used antimicrobial agents associated with cutaneous drug reactions. They are often associated with eruptions like maculopapular

Figure 2. Fading rash after treatment.

aggressively with injection chlorpheniramine and injection, hydrocortisone. When Naranjo’s scale was applied to carry out causality assessment, score revealed the association as ‘definite’. Discussion Prescribed medicines often cause adverse drug reactions manifesting in different forms. Maculopapular eruption is one such manifestation, which had a fairly common occurrence. These maculopapular eruptions are basically immune-mediated hypersensitivity responses shown by host.2 Maculopapular rashes

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Dermatology eruptions, SJS and TEN ecrolysis.5 Anticonvulsant drugs are another class of drug associated with cutaneous eruptions. Around 20% of patients receiving anticonvulsant medication experience such eruptions especially with drugs like carbamazepine, phenytoin, and phenobarbital.6 Considering their current role in patient management, these drugs cannot be withdrawn for causing such eruptions as their incidence is quite low and benefits outweighs the risk. Conclusion Amoxicillin is a commonly used broad-spectrum bactericidal antimicrobial agent. Cutaneous drug eruptions are quite common with its use especially in pediatric population. These cutaneous drug eruptions range from mild-to-severe in nature, most of the cases being mild. Since, amoxicillin is a common drug used in microbial infections, which is a common problem in developing country like India where poverty and poor hygienic conditions leads to huge prevalence of infections. Upon occurrence of such events, patients may become noncompliant, ultimately causing therapeutic failure and increased antimicrobial resistance. Hence, reporting of such events is utmost necessary, efficient pharmacovigilance holds key in this regard. Upon occurrence, the suspected drug (s) should be stopped immediately and the patient should be managed symptomatically followed by necessary replacement therapy. References 1. Thomas EA, John M, Kanish B. Mucocutaneous manifestations of dengue fever. Indian J Dermatol 2010; 55(1):79-85. 2. Hashizume H. Recent progress of elucidating the mechanisms of drug hypersensitivity. Asia Pac Allergy 2012;2(3):203-9. 3. Mardivirin L, Valeyrie-Allanore L, Branlant-Redon E, Beneton N, Jidar K, Barbaud A, et al. Amoxicillin-induced flare in patients with DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms): report of seven cases and demonstration of a direct effect of amoxicillin on human herpes virus 6 replication in vitro. Eur J Dermatol 2010;20(1):68-73. 4. Ghislain PD, Roujeau JC. Treatment of severe drug reactions: Stevens-Johnson syndrome, toxic epidermal necrolysis and hypersensitivity syndrome. Dermatol Online J 2002; 8(1):5. 5. Warrington R, Silviu-Dan F. Drug Allergy. Allergy Asthma Clin Immunol 2011;7Suppl:S10. 6. Galindo PA, Borja J, Gomez E, Mur P, Gudin M, Garcia R, et al. Anticonvulsant drug hypersensitivity. J Investig Allergol Clin Immunol 2002;12(4):299-304.

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Ultrasound Patch Accelerates Tissue Repair A novel ultrasound applicator significantly accelerated tissue healing in patients with venous ulcers, according to findings from a small clinical study. Investigators with the National Institutes of Health treated chronic wounds in five patients using 15 minutes of 20 kHz ultrasound, 45 minutes of 20 kHz ultrasound, 15 minutes of 100 kHz ultrasound or 15 minutes of a placebo ultrasound. The group receiving 15 minutes of 20 kHz ultrasound showed the greatest improvement, researchers noted in a news release. All patients experienced complete healing by the fourth treatment. In vitro studies in which mouse fibroblasts were treated using 20 kHz ultrasound for 15 minutes corroborated investigators’ findings, according to the news release. On average, a 32% increase in cell metabolism and a 40% increase in cell proliferation was seen after 24 hours in the treated cells compared with control cells. Patients who received 45 minutes of treatment didn’t achieve the same benefits as those receiving 15 minutes of treatment, which may indicate a dose effect, researchers noted. Investigators are expanding the in vitro studies to examine the effects of low-frequency ultrasound on macrophages and collagen production to determine why it promotes healing. “In wound healing, there is the inflammation phase, the proliferation phase and the remodeling phase. We’re looking at the primary cell participants at each phase and examining the effects of ultrasound on each of these individually and then collectively,” said Joshua Samuels, Ph.D. candidate and lead author of the study. The ultrasound technology used was developed by researchers at Drexel University, Philadelphia, with funding from the National Institute of Biomedical Imaging and Bioengineering (NIBIB), part of the National Institutes of Health. Larger studies will need to be performed to confirm the safety and efficacy of the technology, researchers noted.

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A Study of Somatic Status and Complications Among Female Hospitalized and Non-hospitalized Diabetic Patients from Mysore Urban Area Prabhavathi SN*, Charlotte G Karunakaran**, Ashoka HGâ&#x20AC;

Abstract In recent years, India has undergone rapid urbanization and socioeconomic development. Changes in time trends have resulted in erratic lifestyle, characterized by physical inactivity, unhealthy eating habits and resultant increase in obesity and diabetes. Diabetes is a major cause of mortality and morbidity in India and its prevalence is increasing at an alarming rate. Chronic complications of diabetes, especially coronary artery diseases and chronic renal diseases results in frequent hospitalization. The main aim of the investigation was to study the somatic status and diabetic complications among the female hospitalized and nonhospitalized patients. A total of 80 female volunteers (40 hospitalized and 40 nonhospitalized) of a private hospital in Mysore, with known history of type 2 diabetes mellitus for more than two years, were recruited for the study. The tools were developed to collect information on personal history, demography, socioeconomic status, dietary habits, and anthropometric measurements. Suitable statistical analysis was applied to the data. The results projected that majority of the patients were hospitalized on an average of at least three times a year. More than 90% of the subjects exhibited blood sugar >300 mg on admission. The reason for high morbidity status included poor dietary habits and erratic lifestyle practices among the female hospitalized patients as compared to nonhospitalized patients. Adapting a healthy lifestyle and maintenance of normal blood sugar level can reduce the incidence of complications and hospitalization among the subjects.

Keywords: Urbanization, socioeconomic development, obesity, diabetes, somatic status, diabetic complications, hospitalized and nonhospitalized patients

D

iabetes is a multifactorial disease that combines hereditary and environmental factors. The prevalence of diabetes is increasing globally. Diabetes is pandemic in both developed and developing countries. In the year 2000 it was estimated that there are 175 million diabetics world wide and expected to increase to 354 million by the year 2030. Based on a compilation of studies from different parts of the world, World Health Organization (WHO) has projected that the maximum increase in diabetes would occur in India.1

Presently India is facing a major health care burden due to the high prevalence of type 2 diabetes as it is a major cause of mortality and morbidity in India, and is increasing at an alarming rate. Genetic predisposition superimposed by erratic lifestyle- physical inactivity, unhealthy eating habits is one of the major causes for increase of diabetes in India. The prevalence of type 2 diabetes is found to be 4-6 times higher in the urban areas as compared to rural areas. The onset of diabetes among Indians is about a decade earlier than their western counterparts and this has been noted in Asian Indians in several studies. Studies show that among urban Asian Indians even minor changes in body mass index BMI/central adiposity tilts the metabolic balance towards hyperglycemia/insulinemia. Asian Indians are said to have higher upper body adiposity measured as waist-hip-ratio (WHR). The cutoff values for normal waist circumference were 80 cm and 0.8 for WHR among women.2 The cardiometabolic risk associated with abdominal obesity is attributed to the presence of visceral adipose tissue (VAT), which promotes insulin resistance, dyslipidemia and

*Dept. of studies in Food Science and Nutrition Manasagangothri, Mysore **Clinical Nutritionist Aadithya Hospital, Mysore â&#x20AC; Assistant Professor Dept. of General Medicine JSS Medical College and Hospital, JSS University, Mysore Address for correspondence E-mail: pprabhavathisn@gmail.com

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diabetology hypertension.3-5 A national survey of diabetes in the year 2000 conducted in six major cities in India reported 54.1% of diabetes developed in most productive years of life and had higher risk of developing complications of diabetes.6, 7 Asian dyslipidemia is characterized by high serum levels of triglycerides (TG) and lipoprotein {Lp(a)}, borderline high levels of low-density lipoprotein (LDL), and low levels of high-density lipoprotein (HDL) cholesterol. Asian Indians have high ratio of total cholesterol (TC) to HDL, TG/HDL and apoB/apoA.8-10 These ratios are highly correlated with premature incidence and severity of CAD as well as acute myocardial infraction among Asian Indians. On an average, diabetic patients stay in the hospital 1-3 days longer than patients without diabetes. The prevalence of micro and macro vascular complications were more in Asians when compared to Europeans. Acute and chronic complications of diabetes, especially cardiovascular diseases, results in hospitalization of many patients with diabetes.11 The projections of the present study throw light on the Mysore female diabetic subjects and can be used to develop prevention strategies by consulting physicians. Methodology A total of 80 volunteers (40 NHP and 40 HP) with known history of type 2 diabetes mellitus for more than two years were recruited for the study. Volunteers willing to participate and belonging to the age group of 30-70 years with no history of hormonal therapy or hyperthyroidism were included as subjects. Anthropometric measurements like height, weight, mid-upper-arm-circumference (MUAC), triceps skin fold (TSF), were recorded using standard procedures.12 Indices viz. BMI, WHR were calculated as an index of obesity. Biochemical assessment included fasting blood sugar (FBS), post prandial blood sugar (PPBS) and lipid profile. The values were recorded from the medical record of the patients. A pretested questionnaire was applied to elicit information. Description of the methods applied to collect the data is given below. ANTHROPOMETRIC MEASUREMENTS Height (cm): was measured with the subject standing, back to a stadiometer in the base feet. Feet were kept parallel with the heels together. The moving arm of the stadio meter was lowered to touch the top of the head and height was measured to the nearest 1.0 mm. Weight (kg): was measured to the nearest 0.005 kg with a weighing machine, which was calibrated daily by using known 5 kg weights. MUAC (cm): was measured on the right arm at the point between the tip of olecranon, elbow bent at 90 degree. Skin fold thickness (mm) was measured according to the protocol described by Durmin and Womersley (1) using skin fold calipers (beta technology incorporated; USA). Triceps skinfold (mm): was measured at mid point of right arm elbow, bent at 90 degree on the lateral side. Waist circumference (cms): was measured midway between the lateral ribs and iliac crests. The subjects were asked not to tuck their stomach in, and the measurement was taken in gentle expiration. Their clothes were loosened around the waist area. Hip circumference (cms): was measured at the widest part over the trochanters with the feet kept 25-30 cm. apart. Statistical analysis: the collected data was compiled for obtaining mean ± SD. Student ‘t’ test was used for comparison of groups. All the analysis was done using windows-based SPSS statistical package (version 11.0). Significant figures used; 0.05 < P < 0.10* Moderately significant, 0.01 < P ≤ 0.05** Strongly significant P ≤ 0.01. Results The baseline characteristics of the subjects are shown in Table 1. From among the 80 subjects, 40 were hospitalized (HP) and the other 40 nonhospitalized (NHP). The mean age of the subjects was 57 (HP) and 60 (NHP) years. Majority of the subjects from both the groups (74%) reported to have family history of diabetes. It was observed that majority (32%) of HP subjects developed diabetes at an younger age (35-45 years), while among the nonhospitalized subjects the onset was after 45 years of age (37%). A considerably higher percentage of the subjects were found to have basic primary school education (40%) and 30% were illiterate. High majority (47%) of the subjects were found to be daily wagers and were economically backward and belonged to the among the HP group. Diet history showed that a high percentage (68%) of the subjects were nonvegetarians. It is noteworthy to mention that a significantly higher mean body weight (p = 0.031) and BMI (p = 0.005) was seen among the hospitalized subjects while, TSF (0.038) was significantly higher among the nonhospitalized subjects. Waist circumferences was above the normal cut-off level (> 80 cm) recommended for Asian Indians

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diabetology Table 1. Baseline Characteristics of the Subjects Hospitalized (n = 40) Age (years) ≥35-< 45 ≥45-< 55 ≥55-< 65 >65 ≥35-< 45 ≥45-< 55 ≥55-< 65 >65 Marital status Married Unmarried Education Illiterates 1-7th 8-10th PUC and above Yes No Income ≥5000 10-20,000 20-40,000 40-60,000 >60,000 Type of diet Vegetarians Non vegetarians 14 (35) 26 (65) 12 (30) 28 (70) 26 (32) 54 (68) 4 (10) 19 (47.5) 8 (20) 4 (10) 5 (12.5) 9 (22.5) 11 (27.5) 12 (30) 8 (20) 4 (5) 28 (35) 19 (23.8) 16 (20) 13 (16.2) 10 (25) 14 (35) 8 (20) 8 (20) 13 (32.5) 10 (25) 10 (25) 7 (17.5) 24 (30) 18 (22.5) 15 (18.7) 23 (28.8) Myocardial infarction COPD CKD 59 (74) 21 (26) 25 10 5 Complications n Duration of diabetes 8 5 >15 40 (100) 40 (100) 80 (100) 4 (10) 10 (26) 13 (32) 13 (32.5) 13 (32) 08 (20) 12 (30) 07 (18) 3 (7) 9 (23) 12 (30) 16 (40) 07 (18) 15 (37) 8 (20) 10 (25) 7 (8.7) 19 (23.7) 25 (31.3) 29 (36.3) 25 (20) 29 (23) 25 (20) 21 (17) Height (cm) Weight (kg) BMI (kg/m2) Waist (cm) WHR (cm) MUAC (cm) TSF (cm) Non hospitalized (n = 40) Total (n = 80) percentage

Table 2. Mean ± SD Anthropometric Measures and Indices Parameters n = 40 Hospitalized patients 157.4 ± 5.4 63.2 ± 10.1 25.9 ± 4.2 88.6 ± 10.5 0.83 ± 0.04 28.0 ± 3.7 19.6 ± 2.7 n = 40 Nonhospitalized patients 157.4 ± 5.8 58.8 ± 7.5 23.6 ± 2.9 85.8 ± 6.1 0.81 ± 0.03 26.8 ± 2.6 20.9 ± 2.8 1.000 0.031* 0.005** 0.219 0.204 0.093 0.038 p-value

Age of onset of diabetes

Table 6. Complications and Duration of Diabetes Hospitalized patients Nonhospitalized patients n 9 10 3 Duration of diabetes 12 8 >15

Family history of diabetes mellitus 30 (75) 10 (25) 29 (73) 11 27)

was longer, complication of myocardial infarction was found only in 22% of the subjects. Among the subjects, COPD appeared to be a common complication in both the groups. It was observed that subjects having diabetes for more than 15 years developed chronic kidney diseases, which accounted for 13% among HP and 7% in NHP subjects. The correlation of somatic measures with biochemical parameters are presented in table 4. Significant associations were observed in HP subjects against various body and biochemical parameters. Higher BMI showed significant association with total cholesterol and LDL. Hip circumference showed inversely significant relationship with LDL. BMI showed moderately significant association with FBS only in NHP subjects. Correlation between various biochemical parameters are shown in table 5. Significant association was found between FBS and triglycerides only among HP subjects. Those with high FBS also had high PPBS among the HP subjects. While among NHP subjects PPBS was highly significant with HDL. Triglycerides showed significant

in both the groups. Protein status as indicated through MUAC was within the normal range. Different co-morbidity conditions of the subjects are presented in table 3. Sixty two percent of the HP subjects had myocardial infarction as a major complication. The mean duration of diabetes among these subjects was found to be eight years. Among the NHP subjects, though the duration of diabetes

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diabetology Table 3. Mean Biochemical Parameters of the Subjects Biochemical parameters (mg) Total-cholesterol High-density lipoproteins Low-density lipoproteins Tryglycerides Fasting blood sugar Post-prandial blood sugar HP 199.5 ± 36.7 46.4 ± 13.2 119.6 ± 31.2 157.1 ± 59.9 176.7 ± 68.3 326.2 ± 99.8 NHP 198.0 ± 35.8 40.4 ± 7.4 112.7 ± 30.4 146.4 ± 35.8 158.0 ± 23.5 267.2 ± 62.7 t-value 0.179 2.57 1.00 0.98 1.63 3.16 p-value 0.858 0.012 0.315 0.331 0.107 0.002

Table 4. Correlation for Somatic Measures Parameters BMI T.Cho LDL FBS PPBS HIP WHR TSF LDL LDL LDL Hospitalized patients 0.016* 0.015* NS NS 0.018* 0.038* 0.042* Nonhospitalized patients NS NS 0.041* NS NS NS NS

Table 5. Correlation of Biochemical Parameters Parameters FBS PPBS Triglyceride TGL PPBS HDL T.Cho LDL NS NS Hospitalized patients 0.016** 0.0002** 0.004** 0.0001** 0.001** Non-hospitalized patients

*moderately significant, ** highly significant

*moderately significant, ** highly significant

population, could be one of the cause for early onset of diabetes among the subjects. The three urban diabetic surveys conducted in 1989, 1995 and 2000 in randomly collected areas in the city of Madras (now known as Chennai) reported no significant time-related change in the prevalence of obesity as measured by BMI.7,13 Analysis of these surveys showed, that among the diabetic women, a higher percentage had BMI of 23-24.9 kg/m.2,19 The normal cut-off values for Asian Indians are below 23 kg/m2. A BMI of ≥ 25 kg/m2 has been considered to indicate different grades of obesity. In the present study the HP patients had a mean BMI of 25.9 and 23.6 among the NHP subjects.7 A peculiar pattern was observed among the study population that, there was no significant association between BMI and PPBS in the HP subjects while, NHP subjects had significant association with only FBS. Studies show that the factors which influence the BMI and the WHR have also frequently lacked specificity with respect to women.7,13 Central obesity is common among Indians despite low rates of general obesity and this android pattern of body fat typified by more upper body adiposity measured as WHR was found to be a greater risk factor as compared to general obesity. The cut-off values for normal waist circumference are 80 cm and 0.8 for WHR in women.20-22 Asian Indians have higher upper body adiposity measured as WHR. This has been suggested

correlation with total cholesterol and LDL among only the NHP subjects. DISCUSSION Epidemiological studies conducted in southern India show a steady increase in the prevalence of diabetes in the urban population. The earlier reports from Chennai show a male preponderance in the prevalence of diabetes which in subsequent years had shifted slightly towards a female excess.6,7,13-16 In India nearly 75% of the type 2 diabetics have first degree family history of diabetes indicating a strong familial aggregation. Risk factors for developing type 2 diabetes, peculiar to the Indian population, are high familial aggregation, central obesity, insulin resistance and life style changes due to urbanization.17 Insulin resistance has been demonstrated to be a characteristic feature of Asian Indians. In the present study, the onset of diabetes was found to be between the age groups of 35-45 years and all the subjects reported family history of diabetes. The mean age of onset of diabetes was found to be 35 years. Several studies on the Asian population reveal that the onset of diabetes is seen before the age of 50 years and at the time of diagnosis of diabetes most of them had developed micro and macro vascular complications.18 Familial aggregation, a typical feature of the Indian

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diabetology to be a superior predictor of CVD risk because it includes a measurement of hip circumference, which is inversely associated with dysglycemia, dyslipidemia, diabetes, hypertension, CVD and death.23-27 The present study population also exhibited higher WHR as compared to the Asian standards. This could be one of the major causes for dyslipidemia exhibited by the subjects. Increasing evidence suggests that waist and hip circumferences have independent and opposite associations with glucose and lipid levels and risk of diabetes and cardiovascular disease.28-29 Study by Ramachandran et al17 has reported that Asian Indians require higher levels of plasma insulin to maintain normoglycemia; they also have other features of insulin resistance such as central obesity and high percentage of body fat in comparison to many other populations. Significant association was found between various lipid profile parameters and blood sugar levels in HP subjects, while for NHP subjects PPBS was strongly associated with HDL and triglycerides with total cholesterol and LDL. Based on the available published data there is a paucity of reliable data on diabetes related complications among people worldwide. A common complication of diabetes and the most common cause of mortality in people with diabetes is cardiovascular diseases.18 This was prominently seen among hospitalized subjects who had blood sugar levels of >300mg% on admission. The most common complications seen was myocardial infarction followed by COPD and CKD. Among the subjects majority were hospitalized on an average of at least 3 times a year. The reason for hospitalization included; MI, COPD and/or nephropathy. More than 90% of the subjects exhibited blood sugar >300 mg on admission despite being on oral hypoglycemic agents. Evaluation of elevated blood sugar revealed-poor dietary habits, irregular meal timings, festive occasions, physical inactivity and poor morbidity status. Conclusion The main findings of the study were that, majority of the subjects had onset of diabetes mellitus at the mean age of 35 years. This early onset of diabetes will result in higher diabetes related complications at an earlier age which can lead to increased mortality in the productive years of life. There is an urgent need to prevent diabetes and its complications rather than simply treat it once established. Patients should be educated for lifestyle changes such as weight control, increased physical exercise and smoking cessation, which are potentially beneficial in preventing diabetes mellitus and coronary artery disease. The limited data available on genderwise, region-wise diabetes complication rates highlight the need for nation-specific and population-specific studies. Furthermore, the morbidity and mortality caused by diabetes mellitus can be reduced by secondary prevention through regular screening, early detection and appropriate treatment of chronic complications. REFERENCES 1. Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 2004;27(5):1047-53. 2. Must A, Jacques PF, Dallal GE, Bajema CJ, Dietz WH. Long-term morbidity and mortality of overweight adolescents. A follow-up of the Harvard Growth Study of 1922 to 1935. N Engl J Med 1992;327(19):1350-5. 3. Tchernof A, Lamarche B, Prud’Homme D, Nadeau A, Moorjani S, Labrie F, et al. The dense LDL phenotype. Association with plasma lipoprotein levels, visceral obesity, and hyperinsulinemia in men. Diabetes Care 1996;19(6):629-37. 4. Pouliot MC, Després JP, Nadeau A, Moorjani S, Prud’Homme D, Lupien PJ, et al. Visceral obesity in men. Associations with glucose tolerance, plasma insulin, and lipoprotein levels. Diabetes 1992;41(7):826-34. 5. Després JP, Moorjani S, Lupien PJ, Tremblay A, Nadeau A, Bouchard C. Regional distribution of body fat, plasma lipoproteins, and cardiovascular disease. Arteriosclerosis 1990;10(4):497-511. 6. Ramaiya KL, Kodali VR, Alberti KG. Epidemiology of diabetes in Asians of the Indian subcontinent. Diabetes Metab Rev 1990;6(3):125-46. 7. Ramachandran A, Snehalatha C, Dharmaraj D, Viswanathan M. Prevalence of glucose intolerance in Asian Indians. Urban-rural difference and significance of upper body adiposity. Diabetes Care 1992;15(10):1348-55. 8. Enas EA. How to beat the heart disease epidemic among south Asians; a prevention and management guide for asian Indians and their doctors. Downers Grove IL; Advanced Heart Lipid Clinic USA; 2007. 9. Smith J, Cianflone K, Al-Amri M, Sniderman A. Body composition and the apoB/apoA-I ratio in migrant Asian Indians and white Caucasians in Canada. Clin Sci (Lond) 2006;111(3):201-7. 10. Sierra-Johnson J, Somers VK, Kuniyoshi FH, Garza CA, Isley WL, Gami AS, et al. Comparison of apolipoprotein-B/ apolipoprotein-AI in subjects with versus without the metabolic syndrome. Am J Cardiol 2006;98(10):1369-73. 11. Chowdhury TA, Lasker SS. Complications and cardiovascular risk factors in South Asians and Europeans with early-onset type 2 diabetes. QJM 2002;95(4):241-6. 12. Jelliffee DB. The Assessment of the Nutritional Status of the Community. WHO Monograph Series no. 53. Geneva: World Health Organization, 1966.

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diabetology 13. Ramachandran A, Snehalatha C, Latha E, Manoharan M, Vijay V. Impacts of urbanisation on the lifestyle and on the prevalence of diabetes in native Asian Indian population. Diabetes Res Clin Pract 1999;44(3):207-13. 14. Iyer R, Upasani S, Baitule MN. Diabetes mellitus in Dombivli – an urban population study. 17th International Diabetes Federation Congress. Mexico city. Diabetes Res Clin Pract. 2000; 50 (suppl 1). P 519. 15. Mohan V, Shanthirani S, Deepa R, Premalatha G, Sastry NG, Saroja R; Chennai Urban Population Study (CUPS No. 4). Intra-urban differences in the prevalence of the metabolic syndrome in southern India -- the Chennai Urban Population Study (CUPS No. 4). Diabet Med 2001;18(4):280-7. 16. V erma NPS, Madhu SV. Prevalence of known diabetes in urban east Delhi. Diabetes Res Clin Pract 2000;50 (suppl 1):121. 17. Davey G, Ramachandran A, Snehalatha C, Hitman GA, McKeigue PM. Familial aggregation of central obesity in Southern Indians. Int J Obes Relat Metab Disord 2000;24(11):1523-7. 18. Ramachandran A, Snehalatha C, Satyavani K, Sivasankari S, Vijay V. Metabolic syndrome in urban Asian Indian adults--a population study using modified ATP III criteria. Diabetes Res Clin Pract 2003;60(3):199-204. 19. Ramachandran A, Snehalatha C, Vijay V. Temporal changes in prevalence of type 2 diabetes and impaired glucose tolerance in urban southern India. Diabetes Res Clin Pract 2002;58(1):55-60. 20. Ramachandran A, Snehalatha C, Kapur A, Vijay V, Mohan V, Das AK, et al; Diabetes Epidemiology Study Group in India (DESI). High prevalence of diabetes and impaired glucose tolerance in India: National Urban Diabetes Survey. Diabetologia 2001;44(9):1094-101. 21. Pope SK, Sowers MF, Welch GW, Albrecht G. Functional limitations in women at midlife: the role of health conditions, behavioral and environmental Womens Health Issues 2001;11(6):494-502. factors.

22. Luke A, Durazo-Arvizu R, Rotimi C, Prewitt TE, Forrester T, Wilks R, et al. Relation between body mass index and body fat in black population samples from Nigeria, Jamaica, and the United States. Am J Epidemiol 1997;145(7):620-8. 23. Willett WC. Anthropometric measures and body composition. In: Nutritional Epidemiology. Oxford University Press: New York 1998p.244-72. 24. Seidell JC, Pérusse L, Després JP, Bouchard C. Waist and hip circumferences have independent and opposite effects on cardiovascular disease risk factors: the Quebec Family Study. Am J Clin Nutr 2001;74(3):315-21. 25. Okura T, Nakata Y, Yamabuki K, Tanaka K. Regional body composition changes exhibit opposing effects on coronary heart disease risk factors. Arterioscler Thromb Vasc Biol 2004;24(5):923-9. 26. Lissner L, Björkelund C, Heitmann BL, Seidell JC, Bengtsson C. Larger hip circumference independently predicts health and longevity in a Swedish female cohort. Obes Res 2001;9(10):644-6. 27. Heitmann BL, Frederiksen P, Lissner L. Hip circumference and cardiovascular morbidity and mortality in men and women. Obes Res 2004;12(3):482-7. 28. S nijder MB, Dekker JM, Visser M, Yudkin JS, Stehouwer CD, Bouter LM, et al. Larger thigh and hip circumferences are associated with better glucose tolerance: the Hoorn study. Obes Res 2003;11(1):104-11. 29. Snijder MB, Dekker JM, Visser M, Bouter LM, Stehouwer CD, Kostense PJ, et al. Associations of hip and thigh circumferences independent of waist circumference with the incidence of type 2 diabetes: the Hoorn Study. Am J Clin Nutr 2003;77(5):1192-7.

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Artificial Sweeteners can Cause Diabetes Consumption of non-caloric, artificially sweetened beverages is associated with an increased risk for obesity, type 2 diabetes, metabolic syndrome and cardiovascular disease. This counterintuitive result reflects negative consequences of interfering with learned relationships between sweet tastes and typical postingestive outcomes, which may result in impaired ability to compensate for energy provided when caloric sweeteners are consumed. The study by Dr Susan E Swithers at Purdue University, West Lafayette, IN published in July issue of Trends in Endocrinology & Metabolism found an elevated risk for weight gain and obesity, metabolic syndrome, type 2 diabetes, coronary heart disease, and hypertension in those who consumed ASBs. No decreased risk for weight gain or increased body fat percentage was associated with ASB intake.

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ENT

A Randomized, Open Label, Prospective, Comparative, Multicentric Study to Evaluate the Efficacy and Safety of Montelukast and Fexofenadine Fixed-dose Combination vs Montelukast and Levocetirizine Fixed-dose Combination in Allergic Rhinitis Prateek Nayak*, CV Srinivas**, MV Jagade†, S Chandrasekharan‡

Abstract Background: Allergic rhinitis (AR) has impact on the physical, psychological and social aspects of the patients’ life and work. Therefore, it is imperative to identify the treatment options for AR. Objective: This randomized, open label, prospective, two arm, comparative, multicentric study evaluated the efficacy and safety of montelukast 10 mg + fexofenadine 120 mg (MF) fixed dose combination (FDC) versus montelukast 10 mg + levocetirizine 5 mg (ML) FDC in subjects with AR. Materials and methods: The adult subjects were randomized to either treatment: ML (n = 62), MF (n = 56), administered once-daily for 14 days. The primary endpoint was the change in total symptom score (TSS) (the sum of total nasal symptom score [TNSS]) and total ocular symptom score (TOSS]) at the end of study as compared to baseline. The secondary endpoints were TNSS and TOSS: At the end of study as compared to baseline, physician’s and patient’s global assessment for efficacy and tolerability and adverse events. Results: Both groups were comparable with respect to demographic characters and vital parameters. In MF group, the reduction in TSS at the end of study was 93.86% as compared to 87.71% in ML. The changes in TNSS and TOSS at the end of study were 92.52% and 95.34% in MF group as compared to 85.58% and 92.23% in ML group. Global impression by investigator showed 53.23% subjects rated excellent to very good with MF as compared to 36.36% subjects with ML. Global impression by subjects showed excellent to very good rating for 50% subjects with MF and for 34.54% subjects with ML. Conclusions: Montelukast + fexofenadine showed better improvement in symptoms of AR and a better global impression by both investigators and subjects compared to montelukast + levocetirizine.

Keywords: Allergic rhinitis, montelukast + fexofenadine, montelukast + levocetirizine

R

hinitis is inflammation of the mucous membrane of the nose and is usually caused by the common cold or an allergy. Allergic rhinitis (AR) is caused by a reaction of the body’s immune system to an environmental trigger. It occurs when an allergen, such as pollen, dust or animal dander is inhaled by an individual with a sensitized immune system. This heterogeneous disorder is often undiagnosed despite its high prevalence. It is characterized by one or more symptoms including sneezing, itching, nasal

* Pace Clinical Research Center, Bangalore *Gowri Prasanna Diabetes and Heart Care Center, Bangalore †Grant Govt. Medical College and Sir JJ Hospitals, Mumbai ‡Public Health Center, Chennai

congestion and rhinorrhea.1 About 40 million people in the United States alone are affected by AR, and the incidence is increasing.2 The pathophysiology of AR is complex. A strong genetic component to the allergic response is driven through mucosal infiltration and action on plasma cells, mast cells and eosinophils. The allergic responses are described as the ‘early’ and ‘late’ phase responses. Early phase response occurs within minutes of exposure to the allergen and may result in sneezing, itching and clear rhinorrhea while late-phase response that occurs 4-8 hours after allergen exposure tends to cause congestion, fatigue, malaise, irritability and possibly neurocognitive deficits.1 In India, AR is not considered as a disease of significant importance,

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ENT although 75% of children and 80% of asthmatic adults were observed to have symptoms of rhinitis.3 Traditionally, AR has been categorized as seasonal or perennial, depending on whether an individual is sensitized to cyclic pollens or to year-round allergens.4 The Allergic Rhinitis and its Impact on Asthma (ARIA) workshop report proposed that patients be categorized as ‘intermittent’ and ‘persistent’ while severity was classified as ‘mild’ and ‘moderate-to severe’. The ARIA guidelines have another classification of the patients with AR depending on their predominant symptom, as ‘sneezers-runners’ and ‘blockers’. The ‘blockers’ had significantly higher sinusitis and had higher sensitization to fungi.3,4 According to the studies conducted in India, AR has proven to often restrict the patient’s quality-of-life (QoL). It has impact on the physical, psychological and social aspects of the patients’ life and also on their work. Additionally, sleep-related QoL is also adversely affected by AR.3 Meltzer et al5 have reported a study to affirm that the patients with AR had added effects on various aspects of their daily life. The patients complained of disturbed sleep in the night and fatigue and distraction during the day due to their symptoms. In most cases, nasal problems such as nasal congestion and rhinorrhea caused disturbances in breathing and sleep. The ARIA guidelines also have included sleep disturbances as a key factor in their definition of severity based on the impact of rhinitis on healthrelated QoL (HRQoL).5 The Nasal Allergy Survey Assessing Limitations (NASAL) measured the burden of disease of AR in the United States by comparing the health status of adults with current hay fever, AR or nasal allergies with a national sample of adults without nasal allergies. NASAL showed that the burden of disease of AR imposed a social and economic cost on the patient and on society through its impact on work performance. In addition to keeping them from working, their health limited them from doing well at work compared with other co-workers. Their estimated productivity reduced to 71% on days when their nasal symptoms were at their worst from an average of 89% on days when they did not have nasal symptoms.5 The studies have also identified a major effect on the QoL in Indian patients. However, AR is seldom given the importance it deserves.3 We need to identify the treatment options for AR. This study was planned to evaluate efficacy and safety of fixed-dose combination (FDC) of montelukast and fexofenadine. Materials and Methods This randomized, open label, prospective, two arm, comparative, multicentric, Phase IV trial was conducted with an objective to evaluate the efficacy and safety of montelukast and fexofenadine FDC versus montelukast and levocetirizine FDC in the management of subjects with AR. The total treatment period was 14 days. The study was conducted in keeping with the principles described in the Declaration of Helsinki and Indian GCP guidelines. The study protocol and the sites were approved by the Institutional and Independent Ethics Committee. The eligible subjects were randomized into 1:1 (MF: ML) using permuted block design. They were assigned to arm-1 or arm-2 as per predetermined randomization schedule as follows: ÂÂ

Arm-1 (MF): FDC of montelukast 10 mg + fexofenadine 120 mg tablet - One tablet once-daily for 14 days. Arm-2 (ML): FDC of montelukast 10 mg + levocetirizine 5 mg tablet - One tablet once-daily for 14 days.

ÂÂ

The study was conducted at four sites, i.e., Mumbai, Chennai, two sites at Bangalore. It was planned to screen 140 subjects to enrol 120 in order to get 100 completed subjects at the end of the study. The subjects of either gender between age groups of 18-75 were included after obtaining informed consent from them. Subjects diagnosed with AR (a total nasal symptom score [TNSS]; the sum of all the 4 individual nasal symptoms [nasal congestion, rhinorrhea, nasal itching and sneezing] scores of 6 or greater and/or a total ocular symptom score [TOSS]; the sum of all the three individual ocular symptom [itching/burning eyes, tearing/watering eyes and eye redness] scores of 4 or greater) were enrolled. Subjects were scrutinized for inclusion criteria having bronchial symptoms along with AR, signs and symptoms and willingness to regular follow-up. Subjects with severe asthma, upper respiratory tract infection or acute or chronic pulmonary disorder, were excluded from the study. Subjects with known hypersensitivity to montelukast or fexofenadine or other piperazine derivatives and pregnant or lactating women and females of child-bearing potential not practicing contraception were not enrolled in the study. Subjects on antihistamines, corticosteroids (in any dosage form), cromolyn sodium, nedocromil, inhaled cholinergics, oral or long-acting beta-agonists, theophylline and leukotriene modifiers were excluded from the study. Also subjects on nasal decongestants, anti-inflammatory drugs and AR rescue medications were not permitted during the course of the trial.

Study Procedures The subjects were enrolled in the study after ensuring the fulfilment of inclusion/exclusion criteria. They

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ENT were assigned to either of the two treatment arms as per predetermined randomization schedule. The enrolled subjects were followed-up for assessing signs and symptoms (efficacy parameters) of AR on Day 7 and Day 14. The safety parameters were assessed at screening, Day 7 and Day 14. Global assessment for efficacy and tolerability by investigator and subjects were assessed at Day 14. of study treatment (Day 10) was analyzed by using McNemer’s Chi-square test. For all statistical tests, the significance level was taken as p < 0.05. Results A total of 118 subjects were enrolled at four sites. Table 1 shows the demographic characters of the population. The number of male subjects (64.29%) was more than the number of female subjects (35.71%) in ML group. The subjects were evaluated for vital parameters like pulse rate and systolic and diastolic blood pressure. The baseline values were similar in the two treatment groups and there was no significant change in vital parameters throughout study. The other parameters like age, height and weight were comparable in both the groups. The symptoms of AR at the screening are presented in Table 2. In both the groups, most frequently reported symptoms were sneezing followed by running nose, watery eyes and red eyes. The baseline values and the values of TNSS throughout the study period are represented in Table 3. The baseline mean TNSS score in MF group was 7.89%. There was reduction in the mean TNSS value from Table 1. Demographic Characters MF (n = 62) N Male Female 33 29

Efficacy Endpoints The primary endpoints of this study included: ÂÂ

The change in total symptom score (TSS) (the sum of TNSS and TOSS) at the end of study as compared to baseline.

The secondary endpoints included: ÂÂ TNSS at the end of study as compared to baseline ÂÂ TOSS at the end of study as compared to baseline ÂÂ Individual parameters of TNSS at the end of the study as compared to baseline ÂÂ Investigator and subject’s global assessment for efficacy and tolerability ÂÂ To evaluate the safety by assessing the type, number, frequency and proportion of subjects with adverse events (AEs) during the study. The scores for TNSS and TOSS were graded on 4-point categoric scale: 0 = None/no symptoms 1 = Mild symptoms, but not affecting any activities during the day/sleep at night 2 = Moderate symptoms affecting at least one activity or disturbing sleep 3 = Severe symptoms affecting >2 daily activities or disturbing sleep all night or most of the night. The safety parameters and AEs during the study were assessed by monitoring AEs, vital signs and physical examination and assessment of blood chemistry during each visit.

ML (n = 56) N 36 20

% 53.23 46.77

% 64.29 35.71

Table 2. Present Symptoms Data of Patients Enrolled MF (n = 62) No Sneezing Running nose Watery eyes Redness of eye Nasal congestion Itching/burning eyes Nasal blockade Cough Fatiguability Nasal itching Headache Fever Breathlessness 51 25 22 22 17 13 4 3 3 2 1 1 1 % 82.26 40.32 35.48 35.48 27.42 20.97 6.45 4.84 4.84 3.23 1.61 1.61 1.61 ML (n = 56) No 51 29 26 22 16 11 5 0 1 1 1 1 1 % 91.07 51.79 46.43 39.29 28.57 19.64 8.93 0.00 1.79 1.79 1.79 1.79 1.79

Statistical Methods Analysis was done on intention-to-treat (ITT) population which included all subjects who had taken at least one dose of study medication and was used for the analysis of the primary efficacy endpoint and safety evaluation. Repeat measures analysis of variance (ANOVA) (parametric) and Friedman test (nonparametric repeat measures ANOVA) was applied for the change in efficacy variables from baseline over the course of study. The change in grade of global improvement or clinical success or response rate from baseline value till the end

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ENT Table 3. Percentage Change in TNSS from Baseline MF (n = 62) Mean Baseline Day 7 Day 14 Change from baseline Day 7 Day 14 7.89 3.16 0.59 Mean ch. -4.72 -7.30 SD 2.07 2.08 1.02 % ch. -59.88 -92.52 ML (n = 56) Mean 7.80 3.25 1.13 Mean ch. -4.55 -6.68 SD 1.99 2.30 1.24 % ch. -58.35 -85.58 Baseline Day 7 Day 14 Change from baseline Day 7 Day 14

Table 6. Percentage Change in TSS from Baseline MF (n = 62) Mean 11.60 4.64 0.77 Mean ch. -6.96 -10.83 SD 3.83 3.34 1.43 % ch. -59.99 -93.36 ML (n = 56) Mean 11.48 4.75 1.41 Mean ch. -6.73 -10.07 SD 3.35 3.69 1.66 % ch. -58.63 -87.71

Table 4. Scores for Individual TNSS MF (n = 62) Mean Nasal congestion Baseline Day 7 Day 14 Rhinorrhea Baseline Day 7 Day 14 Nasal itching Baseline Day 7 Day 14 Sneezing Baseline Day 7 Day 14 2.11 0.76 0.22 0.75 0.74 0.42 2.11 0.86 0.43 0.82 0.80 0.57 1.52 0.58 0.06 0.86 0.69 0.31 1.43 0.50 0.13 0.87 0.71 0.33 2.08 0.79 0.13 0.84 0.70 0.38 2.11 0.86 0.20 0.76 0.70 0.40 2.18 0.98 0.21 0.74 0.76 0.45 2.16 1.11 0.38 0.63 0.73 0.52 SD ML (n = 56) Mean SD

baseline by −4.72 (59.88%) on Day 7, by −7.30 (92.52%) on Day 14. Similarly, the baseline mean TNSS value in ML group was 7.8%. The reduction in the mean TNSS values from baseline was −4.55 (58.35%) on Day 7 and −6.68 (85.58%) on Day 14. The individual nasal scores for each parameter are presented in Table 4. At the end of study, the MF group showed better reduction from baseline in the mean scores for individual parameters as compared to ML group. Nasal congestion showed reduction of -1.97 (90.37%) for MF group and -1.79 (82.64%) for ML group. For rhinorrhea, the reduction was - 1.95 (93.8%) for MF group and -1.91 (90.68%) for ML group. Nasal itching showed reduction of -1.45 (95.74%) for MF group and -1.30 (91.25%) for ML group. For sneezing, the reduction was -1.90 (89.75%) and -1.68 (79.66%) for MF and ML groups, respectively. Table 5 depicts the baseline values and the values of TOSS at different visits. The mean TOSS at baseline in MF group was 3.87%. There was reduction in the mean TOSS value from baseline by -2.44 (63.16%) on Day 7, by -3.69 (95.34%) on Day 14. Similarly, the baseline mean TOSS value in ML group was 3.68%. There was reduction in the mean TOSS values from baseline by -2.18 (59.22%) on Day 7, by -3.39 (92.23%) on Day 14. The baseline values and the values of TSS at different visit periods are presented in Table 6. The mean baseline score of TSS in MF group was 11.60%. There was reduction in the mean TSS value from baseline by -6.96 (59.99%) on Day 7, by -10.83 (93.36%) on Day 14. The baseline mean TSS value in ML group was 11.48%. There was reduction in the mean TSS values from baseline by -6.73 (58.63%) on Day 7, by -10.07 (87.71%) on Day 14. Global impression for efficacy by investigator showed 53.23% subjects were rated excellent to very good with MF, whereas with ML it was only 36.36%. Similarly,

Table 5. Percentage Change in TOSS from Baseline MF (n = 62) Mean Baseline Day 7 Day 14 Change from baseline Day 7 Day 14 3.87 1.43 0.18 Mean ch. -2.44 -3.69 SD 2.57 1.42 0.47 % ch. -63.16 -95.34 ML (n = 56) Mean 3.68 1.50 0.29 Mean ch. -2.18 -3.39 SD 2.28 1.69 0.56 % ch. -59.22 -92.23

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ENT Global efficacy by Doctor (% of pts) 56.36 43.55 MF (n = 62) ML (n = 55) 27.42 25.45 25.81 Global efficacy by Doctor (% of pts) 56.36 43.55 30.65 25.45 19.35 9.09 6.45 Excellent Very Good Good 9.09 MF (n = 62) ML (n = 55)

60 50 40 30 20 10 0 Excellent

60 50 40 30 20

10.91 3.23 Very good Good

7.27

10 0

Satisfactory

Satisfactory

Figure 1. Global efficacy assessment.

Global tolerabillity by Doctor (% of pts) 83.64 74.19 MF (n = 62) ML (n = 55) Global tolerability by Doctor (% of pts) 87.27 MF (n = 62) ML (n = 55)

90 80 70 60 50 40 30 20 10 0

90 80 70 60 50 40 30

82.26

24.19 16.36 1.61 0.00 Good Moderate Poor

20 10 0 Good

17.74

12.73 0.00 0.00

Moderate

Poor

Figure 2. Global tolerability assessment.

global impression for efficacy by subjects showed that 50.00% had excellent to very good rating with MF compared to 34.54% in ML (Figs. 1 and 2). Figure 2 depicts the global assessment for tolerability by investigators and subjects in both groups. In global assessment for tolerability by investigators on Day 14 showed that 74.19% subjects in MF group had good response to therapy, whereas 83.64% subjects had good response to therapy in ML group. The global assessment for tolerability by subjects on Day 14 showed that 82.26% subjects in MF group had good response to therapy and 87.27% subjects in ML group had good response to therapy. In safety assessment, 98.39% subjects showed good to excellent safety with MF, while 96.37% subjects showed good to excellent safety with ML. There were no clinically significant changes observed in the vital parameters of pulse rate and blood pressure, and laboratory parameters. No serious AE occurred in any of the patient enrolled. There were total three mildto-moderate AEs, which were reported. Thus, MF administered for 14 days was safe for use and did not cause any AEs. The subjects were also observed for sedation. Though, the differences were not statistically

significant, it was observed that sedation was more common in ML (23.21%) group compared to MF (9.68%) group. The two treatments were compared at baseline with respect to the demography and baseline scores to test randomization success. Data of age, symptom scores and laboratory parameters were compared between the two treatment arms using one way ANOVA. Change from baseline in the symptom scores were calculated and were compared between the two treatments using one way ANOVA. Ordinal data of overall assessment (outcome) were compared between the two groups using Mann-Whitney â&#x20AC;&#x2DC;Uâ&#x20AC;&#x2122; test. Discrete data was compared between the two treatments using Chi-square test. All testing was done using 2-sided tests at 95% confidence intervals. Discussion Due to the impact of AR on HRQoL and QoL of patients, it becomes imperative to treat AR. Treatments available for AR include oral or topical antihistamines, oral leukotriene receptor antagonists, topical corticosteroids, mast cell stabilizers, decongestants and anticholinergic agents. Among immunomodulatory

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ENT treatments, immunotherapy is gaining widespread use, while antibody treatment is restricted mainly to resistant cases, nasal irrigation, saline sprays, nasal glucocorticoids, antihistamines and immunotherapy.6 Antihistamines like terfenadine and astemizole were being used since long time and had potential side effects. The newer antihistamines developed to replace these are loratadine, cetirizine and fexofenadine. Intranasal steroid sprays are more effective in patients with nasal stuffiness. The leukotriene receptor antagonists including zafirlukast and montelukast, when taken orally avoid the discomfort of nasal sprays and seem to have few side effects.7 Montelukast, an oral leukotriene receptor antagonist, is used for the treatment of asthma and AR. Fexofenadine is an antihistamine drug used in allergic symptoms. Antihistamine-decongestant combinations are used routinely for the treatment of seasonal AR. Recently, the combination of an antihistamine and a leukotriene receptor antagonist has been shown to be efficacious. This study evaluated efficacy and safety of FDC of montelukast and fexofenadine. The two treatment groups were similar with respect to the demographic characters, personal history, baseline data and all other relevant characteristics, implying success of randomization. The mean baseline TNSS in MF group was 7.89%. There was reduction in the mean TNSS value from baseline by -4.72 (59.88%) on Day 7, by -7.30 (92.52%) on Day 14. Similarly, the baseline mean TNSS value in ML group was 7.8%. There was reduction in the mean TNSS values from baseline by -4.55 (-58.35%) on Day 7, by -6.68 (-85.58%) on Day 14. Although, the change in mean TNSS was not significant in both groups, the subjects treated with MF showed better symptomatic improvement compared to subjects treated with ML. The individual nasal scores for each parameter (nasal congestion, sneezing, nasal itching and rhinorrhea) were also assessed. The MF group showed better reduction from baseline in the mean scores for individual parameters as compared to ML group. The percentage reduction in the mean TOSS value from baseline was -2.44 (63.16%) on Day 7 and -3.69 (95.34%) on Day 14 in the MF group; whereas the percentage reduction for ML group for the mean TOSS values from baseline was -2.18 (59.22%) on Day 7 and -3.39 (92.23%) on Day 14. Although, the percentage change in mean TOSS was not significant in both groups, the subjects treated with MF had a greater improvement in symptoms of AR compared to subjects treated with ML. TSS was sum of TNSS and TOSS. The reduction in the mean TSS values on Day 14 from baseline was 10.83 (93.36%) in MF group compared to 10.07 (87.71%) in ML group. Although, the change in mean TSS was not significant in both groups, the subjects in MF group had better symptomatic improvement compared to subjects treated with ML. It was observed at Day 14 that sedation was more commonly seen in ML (23.21%) group compared to MF (9.68%) group though the differences were not statistically significant. It is often seen that drowsiness or sedation affects QoL of AR patients.8 This may or may not be related to the medication. However, it is an important factor to be considered while treating AR. Conclusion In this study, montelukast + fexofenadine showed better improvement in symptoms of AR and less incidence of sedation as compared to montelukast + levocetirizine.

Acknowledgments Authors would like to thank Abbott Healthcare Pvt Ltd for funding and providing the study medications. We would also like to thank the medical affairs team (Dr Qayum Mukaddam, Dr Prashant Khandeparkar and Dr Ashwini Nayak) and clinical research team (Dr Manoj Naik and Mr Tushar Fegade) of Abbott Healthcare Pvt Ltd, Mumbai for successful management of the study. References 1. Skoner DP. Allergic rhinitis: definition, epidemiology, pathophysiology, detection, and diagnosis. J Allergy Clin Immunol 2001;108(1 Suppl): S2-8. 2. Asthma and Allergy Foundation of America. Allergy facts and figures. http://www.aafa.org/display.cfm?id=9 & sub=30. Accessed Jan 2013. 3. Shah A, Pawankar R. Allergic rhinitis and co-morbid asthma: perspective from India - ARIA Asia-Pacific Workshop report. Asian Pac J Allergy Immunol 2009;27(1):71-7. 4. Greiner AN. Allergic rhinitis: impact of the disease and considerations for management. Med Clin North Am 2006;90(1):17-38. 5. Meltzer EO, Gross GN, Katial R, Storms WW. Allergic rhinitis substantially impacts patient quality of life: findings from the Nasal Allergy Survey Assessing Limitations. J Fam Pract 2012;61(2 Suppl):S5-S10. 6. Mandhane SN, Shah JH, Thennati R. Allergic rhinitis: an update on disease, present treatments and future prospects. Int Immunopharmacol 2011;11(11):1646-62. 7. Tkachyk SJ. New treatments for allergic rhinitis. Can Fam Physician 1999;45:1255-60. 8. Sheikh J, Najib U. Allergic rhinitis clinical presentation. http://emedicine.medscape.com/article/134825-clinical. Accessed Feb 2013.

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HEMATOLOGY

Distribution of Blood Groups in and Around Bellary, Karnataka Gadwalkar Srikant R*, Sunil Kumar N**, Ravidhar**

Abstract Objective: A retrospective study was conducted at Vijayanagara Institute of Medical Sciences, Bellary, Karnataka and licensed private blood-banks in Bellary over a period of one year from 1st April 2012 to 31st March 2013 to determine and compare the frequency of ABO and Rh blood groups in and around Bellary. Results: The study showed that the ‘B’ blood group formed the most common with 35.48% followed by ‘O’ blood group with 34.33%. ‘AB’ blood group was the least common with 8.49%. This was in contrast to studies done in South Karnataka, which showed ‘O’ blood group as most common followed by ‘B’ blood group. Conclusion: The study depicts the frequency occurrence of different blood groups among the people in and around Bellary and helps to prepare a database for the blood banks and also to create awareness about which blood groups should be stored and given importance. So, it is advisable to do blood grouping studies in each region for drafting proper national transfusion policies and supplying blood to the needy patients during emergency.

Keywords: Blood banks, ABO and Rhesus, blood group system, database, national transfusion policies

U

p till now about 400 red cells antigens have been identified. The majority are inherited by Mendelian fashion. The ABO and Rhesus (Rh) blood group system are most important for blood transfusion purposes, parental testing, legal medicine and in population genetic study. All human populations share the same blood group systems; although they differ in the frequencies of specific types. The incidence of ABO and Rh groups varies markedly in different races, ethnic groups and socioeconomic groups in different part of the world. The frequencies of ABO and Rh blood groups vary from one population to another and time to time in the same region. The knowledge of distribution of ABO and Rh blood groups at local and regional levels are helpful in the effective management of blood banks and safe

blood transfusion services. Identification of Rh system is important to prevent erythroblastosis fetalis, which commonly arises when an Rh negative (Rh-ve) mother carries an Rh positive (Rh+ve) fetus. Knowledge of the distribution of ABO and Rh blood group is essential for effective management of blood banks inventory, be it a facility of a smaller local transfusion service or a regional or national transfusion service. It is, therefore imperative to have information on the distribution of these blood groups in any population. Knowledge of blood group distribution is also important for clinical studies, for reliable geographical information and it will help a lot in reducing the maternal mortality rate, as access to safe and sufficient supply of blood will help significantly in reducing the preventable deaths. Apart from their importance in blood transfusion practice, the ABO and Rh blood groups are useful in population genetic studies, researching population migration patterns as well as resolving certain medicolegal issues, particularly of disputed paternity cases. In modern medicine besides their importance in evolution, their relation to disease and environment is being increasingly important. It is, therefore imperative to have information on the distribution of these blood groups in any population group. This observational cross-sectional study was conducted to determine and compare the frequency of ABO and Rh

* Professor and Head **Postgraduate Student Dept. of General Medicine Vijayanagara Institute of Medical Sciences, Bellary, Karnataka Address for correspondence Dr Gadwalkar Srikant R Professor and Head

Dept. of General Medicine Vijayanagara Institute of Medical Sciences, Bellary, Karnataka E-mail: srikantbly@gmail.com

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HEMATOLOGY blood groups in blood donors and patients admitted in tertiary care teaching hospital at Vijayanagara Institute of Medical Sciences, Bellary, Karnataka as well as from licensed private blood banks in Bellary. Material and Methods A retrospective study was conducted at Dept. of Medicine by collecting data from blood bank of Vijayanagara Institute of Medical Sciences, Bellary, Karnataka and licensed private blood banks in Bellary over a period of one year from 1st April 2012 to 31st March 2013. Blood group of the blood donors and

A-21.68% B-35.48% AB-8.49% O-34.33%

Figure 1. Depicting percentage of blood groups.

Table 1. Distribution of ABO and Rh Blood Group Systems in Bellary Sex Blood groups A+ AB+ BAB+ ABO+ OBombay+ Total

Male Subject 2,135 141 3,558 171 876 27 3,511 162 1 10,582

Female Percentage (%) 20.17 01.33 33.62 01.64 08.27 00.25 33.18 01.53 00.009 100

Subject 1,158 57 1900 112 441 23 1,738 86 5,515

Percentage (%) 20.99 01.05 34.45 02.25 07.99 00.27 31.51 01.71 100

Table 2. Comparison Study on Frequency of ABO and Rh Phenotypes at Different Geographical Areas (in Percentage) Place of study Within India Shimoga-Malnad Davangere Eastern Ahmedabad Punjab Bangalore Chittoor Vellore Present study Outside India Pakistan Nepal Australia Britain USA 23.8 34 38 41.7 41 38 29 10 8.6 9 10 4 3 3 4 10 33 49 46.7 46 24.27 26.15 23.3 21.9 23.85 18.95 18.85 21.68 29.43 29.85 35.5 37.6 29.95 25.79 32.69 35.48 7.13 7.24 8.8 9.3 6.37 7.89 5.27 8.49 39.17 36.76 32.5 29.3 39.82 47.37 38.75 34.33 A B AB O

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HEMATOLOGY patients admitted in hospital was determined by commercially available standard monoclonal antisera by test tube agglutination technique. A total of 16,097 donor blood groups were studied. Observation and Results Table 1 shows the distribution of various blood groups in numbers as well as in percentage form. Males constituted 65.74% (10,582) and females constituted 34.26% (5,515) of this study. ‘B’ blood group formed the most common with 35.48% followed by ‘O’ blood group with 34.33%. ‘AB’ blood group was the least common with 8.49% (Fig. 1). A rare blood group of Bombay was also found in this study (0.0094%). Discussion In this study, the distribution of ABO and Rh blood groups are depicted in Table 1. The results of this study were comparable to the studies done at Eastern Ahmedabad,1 Punjab2 and Pakistan3 (Table 2). All these studies have described ‘B’ as the most frequent and ‘AB’ as the least common blood group. Studies at Shimoga-Malnad,4 Davangere,5 Bangalore,5 Chittoor7 and Vellore8 have described contrast findings with ‘O’ being the most common blood group followed by ‘B’, ‘A’ and ‘AB’ (Table 2). This shows that the distribution of blood groups is different in North Karnataka in contrast to South Karnataka. In Nepal,9 which is connected to western India, as well as Australia,10 Britain11 and USA,12 ‘O’ and ‘A’ are the common blood groups that are followed by ‘B’ and ‘AB’ (Table 2). While looking at Rh grouping 90-95% donors are detected as Rh+, which is comparable to all other studies. Conclusion The present study has a significant implication regarding the management of blood bank and transfusion services in the area. Knowledge of blood group distribution is also important for clinical studies, reliable geographical information and for forensic studies. The different types of information are useful for medical diagnosis, genetic information, genetic counseling and also for the general well-being of individuals. The study depicts the frequency occurrence of different blood groups among the people in and around Bellary and helps to prepare a database for the blood banks and also to create awareness as to which blood groups should be stored and given importance. So, it is advisable to do blood grouping studies in each region for drafting proper national transfusion policies and supplying blood to the needy patients during emergency. In short, generation of a simple database of blood groups, not only provides data about the availability of human blood in case of regional calamities, but also serves to give insight into possibilities of future burden of diseases. We thank blood bank officials, Medical Superintendent, Vijayanagara Institute of Medical Sciences, Bellary and Gopi blood bank, Bellary for allowing us to use the data. REFERENCES 1. Girish CJ, Chandrashekhar TN, Ramesh Babu K, Kantikar SM. ABO and Rhesus blood group distribution among Malnad region blood donors. Res Rev Biomed Biotechnol 2011;2(3):25-30. 2. Mallikarjuna SC, Basavaraj PB, Kavitha GU, Shashikala P. Prevalence of ABO and Rhesus blood groups among blood donors. Indian J Public Health Res Develop 2012;3(2):106-9. 3. Wadhwa MK, Patel SM, Kothari DC, Pandey M, Patel DD. Distribution of ABO and Rhesus blood groups in Gujarat, India: a hospital based study. Indian J Ped Oncol 1998;19(4):137-41. 4. Sidhu S. Distribution of the ABO blood groups and Rh(D) factor among the scheduled caste population of Punjab. Anthropologist 2003;5:203-5. 5. P eriyavan S, Sangeetha SK, Marimuthu P, Manjunath BK, Seema DM. Distribution of ABO and Rhesus-D blood groups in and around Bangalore. Asian J Transfus Sci 2010;4(1):41. 6. R eddy KSN, Sudha G. ABO amd Rh (D) blood groups among the Desuri Reddis of Chittoor District, Andhra Pradesh. Anthropologist 2009;11(3):237-8. 7. D as PK, Nair SC, Harris VK, Rose D, Mammen JJ, Bose YN, et al. Distribution of ABO and Rh-D blood groups among blood donors in a tertiary care centre in South India. Trop Doct 2001;31(1):47-8. 8. H ammed A, Hussain W, Ahmed J, Fazli-Rabbi, Qureshi QA. Prevalence of phenotypes and genes of ABO and Rhesus (Rh) blood groups in Faisalabad, Pakistan. Pak J Biol Sci 2002;5:722-4. 9. P ramanik T, Pramanik S. Distribution of ABO and Rh blood groups in Nepalese medical students: a report. East Mediterr Health J 2000;6(1):156-8. 10. A ustralian Red Cross society. All about blood. Available at/URL: www.donateblood.com.au/all-aboutblood/ blood-types. Accessed on:21st July 2013. 11. F rances TF. Blood groups (ABO groups). In: Common Laboratory and Diagnostic Tests. 3rd edition, Lippincott: Philadelphia 2002:p.19-5. 12. Mollison PL, Engelfriet CP, Conteras M. The Rh blood group system. In: Blood Transfusion in Clinical Medicine. 9th edition, Black well Scientific Publication: Oxford 1993:p.2008-9.

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MEDICINE

Clinical Profile of Multiorgan Involvement in Malaria P Ratan, KC Nayak, S Kumar, V Singh, BK Gupta, M Sisodiya, V Tundwal, V Kulkarni, A Vyas

Abstract Background and aims: In view of high incidence, increasing morbidity and mortality due to malaria in an endemic area like Bikaner, it was planned to study the clinical profile of multiorgan involvement in Plasmodium vivax, Plasmodium falciparum and mixed type of malaria. Material and methods: Prospective data were collected from 201 adult patients with multiorgan involvement, admitted in classified malaria ward and confirmed by asexual parasitemia in peripheral blood film. Results: Prevalence of renal failure was 57.7%, cerebral malaria 47.8%, jaundice 41.8%, severe anemia (hemoglobin [Hb] â&#x2030;¤5 g/dl) in 31.8%, severe thrombocytopenia, shock, septicemia in 19.9%, 12.4%, 8.96%, respectively. Out of this P. vivax was associated with renal failure in 10.4%, with cerebral malaria in 7.46%, with jaundice in 9.5% and with severe anemia in 3.5%. Multiorgan dysfunction was a major cause of death in 25.87% patients (18.4%, P. falciparum 6%, P. vivax 1.5%, mixed). Acute respiratory distress syndrome (ARDS) was found in 14 (7%) of patients out of which 13 expired. Conclusion: P. vivax which was previously considered to be benign, has now turned to be malignant. ARDS came out with the worst outcome. Early institution of dialysis and use of antimalarial drugs aggressively can result in better prognosis.

Keywords: P. falciparum, P. vivax, cerebral malaria, ARDS

M

alaria remains a major socioeconomic burden on community and accounts for 85% of global infectious disease burden.1 It is an important cause of morbidity and mortality irrespective of age group in subtropics and tropics. In the Southeastern Asian Region of World Health Organization (WHO) of â&#x2C6;ź1.4 billion people living in 11 countries (land area; 8,466,600 km2; i.e., 6% of global area), 1.2 billion are exposed to the risk of malaria, most of whom live in India.2 However, Southeast Asia contributed to only 2.5 million cases to the global burden of malaria. Of this, India alone contributed 76% of the total cases. Signs and symptoms of malaria are nonspecific but sometimes became fatal. The spectrum of disease has changed worldwide and there is increasing trend for multiple organ dysfunction attributed to Plasmodium vivax previously a nonlethal and benign entity which now has turned malignant.3-5 Burden of P. vivax malaria in world has been calculated at 71-80 million cases, of which Southeast Asia and Western pacific countries contributed 42 million cases.6 Bikaner district, a part of the Thar Desert is considered as a hypoendemic area for malaria due to its geoecological diversity. An assessment and analysis of local

malaria problems are a prerequisite before embarking on any control program. AIM AND OBJECTIVES To study clinical profile of multiorgan involvement in P. vivax and mixed type of malaria. MATERIAL AND METHODS Five hundred adult patients of both sexes infected with P. falciparum and mixed (P. falciparum and P. vivax) malaria were included in the study. It was planned to evaluate clinical profile of multiorgan involvement in P. falciparum and P. vivax malaria as per WHO guidelines 2006.

Inclusion Criteria Patients admitted in a classified malaria ward of a tertiary care PBM Hospital, Bikaner, Rajasthan during the year September 2006 to October 2008 with asexual form of Plasmodium in peripheral blood film (PBF).

Exclusion Criteria Patients, who were known cases of hypertension, diabetes mellitus, chronic renal failure, tuberculosis, nephrotic syndrome, chronic/acute viral hepatitis, alcoholic liver disease and patients on hepatotoxic and nephrotoxic drugs were excluded from the study.

Dept. of Medicine Sardar Patel Medical College, Bikaner, Rajasthan

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MEDICINE A thorough clinical examination and investigation including blood sugar, complete hemogram, bleeding time, clotting time, prothrombin time, hepatic and renal function tests, serum electrolytes, chest radiogram, ECG, urine analysis, USG (whole abdomen), Widal test, hepatitis B surface antigen (HbsAg). EEG, CSF, CT head were done in those patients having features of hepatic encephalopathy and neck rigidity. Daily progress of their clinical status along with their laboratory tests were monitored. ÂÂ

Patients were subjected to hemodialysis when oliguria persisted or deteriorated and there were signs of fluid overload.

RESULTS A total of 500 patients with malaria were admitted during the study period, of which 325 patients had P. falciparum and 74 patients had P. vivax malaria. Two hundred one adult patients with multiorgan involvment were included in this study with various outcomes. Prevalence of renal failure was found to be 116 (57.7%). P. vivax was associated with renal failure in 21 (10.4%) patients. Cerebral malaria was present in 96 (47.8%) and P. vivax was associated with 15 (7.46%) patients. Jaundice was present in 84 (41.8%) of cases out of which 19 (9.5%) patients were due to P. vivax. Severe anemia (Hb ≤5 g/dl) was present in 64 (31.8%) and P. vivax with severe anemia in seven (3.5%) patients. Severe thrombocytopenia, shock, septicemia was present in 40 (19.9%), 25 (12.4%) and 18 (8.96%) patients, respectively. Acute respiratory distress syndrome (ARDS) was present in 14 (7%) of patients, out of which 13 patients expired. ARDS was associated with worst outcome. Hemoglobinuria and hypoglycemia was present in three (1.5%) and three (1.5%) patientrespectively. A total no. of 32 patients of P. vivax had associated multiorgan dysfunction, out of which 12 (6%) expired.

Management Plan All patients were treated with intravenous (IV) quinine. ÂÂ

Quinine was administered as a loading dose of 20 mg/kg followed by 10 mg/kg IV till the patients were able to take orally. Hepatic encephalopathy was treated by administration of 25% glucose, lactulose and correction of the serum electrolytes. Renal failure patients were monitored by daily urine output. Fluids were given according to urine output plus 750 ml/day. Blood transfusions were given to patients with hemoglobin (Hb) ≤ 5 g/dl or those having bleeding manifestations.

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Table 1. Major Manifestations of Malaria Patients (n = 201) Manifestations PF No. Renal failure (S. creatinine >3 mg/dl) Cerebral malaria Jaundice (S. bilirubin >3 mg/dl) Severe anemia (Hb <5g/dl) Severe thrombocytopenia Shock (BP < 80 mmHg) Spontaneous bleeding Septicemia ARDS Hemoglobinuria Hypoglycemia (blood sugar <40) 71 65 57 44 26 22 13 13 10 3 1 % 35.3 32.34 28.4 21.9 12.9 10.9 6.47 6.5 5.0 1.5 0.5 0.15 0.15 0.17 0.17 0.45 0.01 0.22 0.02 0.27 0.09 0.13 P value No. 21 15 19 7 5 1 1 1 3 0 1 PV % 10.4 7.46 9.5 3.5 2.5 0.5 0.5 0.5 1.5 0.5 0.16 0.45 0.01 0.09 0.25 0.04 0.10 0.15 0.27 0.22 0.20 PBF P value PV + PF No. 24 16 8 13 9 2 4 1 1 0 1 % 11.9 7.96 4.0 6.5 4.5 1.0 2.0 0.5 0.5 0.5 0.37 0.13 0.00 0.46 0.32 0.05 0.39 0.09 0.10 0.00 0.27 P value No. 116 96 84 64 40 25 18 15 14 3 3 Total % 57.7 47.8 41.8 31.8 19.9 12.4 8.96 7.5 7.0 1.5 1.5

S. = Serum; PBF = Peripheral blood film; PF = Plasmodium falciparum; PV = Plasmodium vivax

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80 70 60 50 40 30 20 10 0 a Ren iu l fal re a enia emi ce aria mal Jaundi ytop e an l r a e r v boc e eb m r S o e r C th ere Sev Sho Spo ck e blee ous ding ticemia Sep S ia ria ARD cem binu ogly oglo Hyp Hem

PF PV PF + PV

ntan

Figure 1. Major manifestations of malaria patients (n = 201).

Table 2. Distribution of Cases According to Outcome in Relation to PBF Outcome PF No. Recovered Expired Total 92 37 129 % 45.8 18.4 64.2 No. 20 12 32 PV % 10.0 6.0 15.9 No. 37 3 40 PBF PV + PF % 18.4 1.5 19.9 No. 149 52 201 Total % 74.1 25.9 100

Table 1 and Figure 1 showing major manifestation of malaria in patients. Renal failure was the most common manifestation of severe malaria. Others included cerebral malaria, jaundice, severe anemia, severe thrombocytopenia. Table 2 showed the distribution of cases according to PBF. Total 52 (25.87%) patients expired out of which 37 (18.41%) cases of PF, 12 (5.97%) cases of PV and three (1.49%) cases were of PV and PF combination, out of these 17 (8.46%) dialyzed cases three (1.49%) cases expired in spite of dialysis. DISCUSSION The present study was carried out on 201 patients with mutiorgan involvement and majority of patients (56.7%) were between 21-40 years of age; this group is more mobile and actively engaged in agricultural activities in the rural areas. One hundred twenty-nine (64.2%) of the total cases were due to P. falciparum, 32 (15.9%) cases of P. vivax and 40 (19.9%) cases due to mixed infection. All patients were febrile at the time of admission and gave a history of fever for last 2-8 days and vomiting at the time of presentation. Jaundice was present in 84 (41.8%) patients out of which 57 (28.4%) were of PF, 19 (9.5%) were of PV and eight (4%) cases had mixed infection.

Severe complications caused by P. vivax have been reported from Bikaner, Rajasthan, India.5,15 It was observed that 72 of 440 patients with microscopically and polymerase chain reaction (PCR) confirmed monoinfection of P. vivax had severe manifestations and these were jaundice 33 (45.8%) severe anemia, 11 (15.3%), respiratory distress with acidosis, eight (11.1%), acute renal failure, seven (9.7%), cerebral dysfunction with convulsions, six (8.6%) and abnormal bleeding, six (8.6%). Our observations showed 32 of 201 patients infected with P. vivax had renal failure 21 (10.4%) had jaundice, 19 (9.5%) had cerebral dysfunction with convulsions, 15 (7.46%) had severe anemia, seven (3.5%) had abnormal bleeding and anemia (.5%).5 Few reports were observed from elsewhere in recent years.7-9 Major manifestations of 1994 epidemic were cerebral malaria (25.75%), severe anemia (5.83%), renal failure (2.07%), jaundice (11.47%) and multiorgan dysfunction (9.59%). Our study revealed that cerebral malaria was present in 96 (47.8%), anemia was present in 64 (31.8%), jaundice in 84 (41.8%) and renal failure in 116 (57.7%).10 Thus, prevalence of severe anemia, jaundice, renal failure and multiorgan dysfunction has significantly increased in last decade. This could be attributed to change in the environment due to various causes and possibility of changes in the antigenic and pathogenic

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MEDICINE characteristics of the parasite cannot be ruled out. We found that 71 (35.3%) of the cases having renal failure were due to P. falciparum, 21 (10.4%) due to P. REFERENCES 1. Murray CJ, Lopez AD. Evidence-based health policy lessons from the Global Burden of Disease Study. Science 1996;274(5288):740-3. 2. Kondrashin AV. Malaria in the WHO Southeast Asia region. Indian J Malariol 1992;29(3):129-60. 3. Kumar A, Valecha N, Jain T, Dash AP. Burden of malaria in India: retrospective and prospective view. Am J Trop Med Hyg 2007;77(6 Suppl):69-78. 4. Ozen M, Gungor S, Atambay M, Daldal N. Cerebral malaria owing to Plasmodium vivax: case report. Ann Trop Paediatr 2006;26(2):141-4. 5. Kochar DK, Saxena V, Singh N, Kochar SK, Kumar SV, Das A. Plasmodium vivax malaria. Emerg Infect Dis 2005;11(1):132-4. 6. Mendis K, Sina BJ, Marchesini P, Carter R. The neglected burden of Plasmodium vivax malaria. Am J Trop Med Hyg 2001;64(1-2 Suppl):97-106. 7. Beg MA, Khan R, Baig SM, Gulzar Z, Hussain R, Smego RA Jr. Cerebral involvement in benign tertian malaria. Am J Trop Med Hyg 2002;67(3):230-2. 8. Valecha N, Bagga A, Chandra J, Sharma D. Cerebral symptoms with P. vivax malaria. Indian Pediatr 1992;29(9):1176-8. 9. Patial RK, Kapoor D, Mokta JK. Cerebral dysfunction in vivax malaria: a case report. Indian J Med Sci 1998;52(4):159-60. 10. Kochar DK, Kumawat BL, Bajiya HN, Chauhan S, Kochar SK, Agrawal RP. Prophylactic role of single dose phenobarbitone in preventing convulsions in cerebral malaria. J Assoc Physicians India 1997;45(2):123-4. 11. Sharatkumar N, Indraprasit S, Pchanugol C, et al. Renal function in malaria. J Trop Med Gyg 2000;69:242. 12. Kochar DK, Pakalapati D, Kochar SK, Sirohi P, Khatri MP, Kochar A, et al. An unexpected cause of fever and seizures. Lancet 2007;370(9590):908. 13. Nautiyal A, Singh S, Parmeswaran G, DiSalle M. Hepatic dysfunction in a patient with Plasmodium vivax infection. MedGenMed 2005;7(1):8. 14. Oh MD, Shin H, Shin D, Kim U, Lee S, Kim N, et al. Clinical features of vivax malaria. Am J Trop Med Hyg 2001;65(2):143-6. 15. Kaur D, Wasir V, Gulati S, Bagga A. Unusual presentation of Plasmodium vivax malaria with severe thrombocytopenia and acute renal failure. J Trop Pediatr 2007;53(3):210-2. 16. Mehta KS, Halankar AR, Makwana PD, Torane PP, Satija PS, Shah VB. Severe acute renal failure in malaria. J Postgrad Med 2001;47(1):24-6. 17. Prakash J, Singh AK, Kumar NS, Saxena RK. Acute renal failure in Plasmodium vivax malaria. J Assoc Physicians India 2003;51:265-7. 18. Kochar DK, Das A, Kochar SK, Saxena V, Sirohi P, Garg S, et al. Severe Plasmodium vivax malaria: a report on serial cases from Bikaner in northwestern India. Am J Trop Med Hyg 2009;80(2):194-8. 19. Rogerson SJ, Carter R. Severe vivax malaria: newly recognised or rediscovered. PLoS Med 2008;5(6):e136.

vivax and 24 (11.9%) cases had mixed infection with P. vivax and P. falciparum. P. falciparum was responsible for 80.9% cases of renal failure in malaria; where as, P. vivax was responsible for 11.7%.11 Severe manifestations with P. vivax monoinfection are similar to those of severe P. falciparum infection and include cerebral malaria with generalized convulsions and status epilepticus,4,5,7,12 severe anemia,5 hepatic dysfunction and jaundice,5,13 acute lung injury, ARDS and pulmonary edema,5 shock, splenic rupture,14 acute renal failure,5,15,16 and severe thrombocytopenia with or without bleeding from different parts of the body.5,14,15,17 Complications like hepatic dysfunction and jaundice were observed in 23 (57.5%) patients, renal failure in 18 (45%) patients, severe anemia in 13 (32.5%) patients, cerebral malaria in five patients (12.5%), ARDS in four patients (10%), shock in three

patients (7.5%), hypoglycemia in one (2.5%) patient, thrombocytopenia in five (12.5%) patients, and multiorgan dysfunction was detected in 19 (47.5%) patients in an another prospective study during 2003-05.18 There is also an urgent need to re-examine the clinical spectrum and burden of P. vivax malaria for adequate control measures against this emerging but neglected disease. The observation that a significant proportion of severe malaria morbidity is also caused by P. vivax would have tremendous implications for control of the infection especially as P. vivax invariably increases relative to P. falciparum under effective transmission reduction.19 CONCLUSION

Malaria burden is higher in low socioeconomic society in developing countries, which has adverse impact on economy of the world. Bikaner has always been regarded as hypoendemic area for malaria with an upsurge in the incidence of multiple organ involvement. Multiorgan dysfunction is the major cause of death in 25.87%.ARDS was associated with worst outcome. P. vivax, which was previously considered to be nonlethal and benign entity now has turned as malignant as P. falciparum causing severe complicated malaria. P. vivax positive malarial patients should be observed meticulously for developing complications. So, an early diagnosis, initiation of specific and supportive modalities of treatment in patients having multiorgan involvement will reduce morbidity and mortality.

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obstetrics and gynecology

Double-headed Monster Delivered Vaginally N Singh*, S Barya**, K Pandey†, P Dubey‡, D Kumar¶

Abstract Double-headed monster is a rare and interesting variety of twin pregnancy. In this report, we describe a case of 26-year-old gravida 3 para 2 + 0 who was referred to our center with delivered head since one hour and failure to deliver rest of the body. Here, rest of the body with second head was delivered vaginally using McRobert’s maneuver with only few vaginal lacerations to mother.

Keywords: Conjoint twins, double-headed monster, monozygotic twin

O

ne of the most interesting and rare anomaly of multiple pregnancies is conjoint twins and double-headed monster is one of them. This disorder affects 1:200 of monozygotic twin pregnancies, 1:900 of twin pregnancies and 1:25,000 to 1:1,00,000 of births. Conjoint twins result from incomplete fission of inner cell mass in early gestation, after development of embryonic plate and before second week of fertilization. Conjoint twins are classified according to the site of union i.e., ventral (87%) and dorsal (13%). Ventral union includes thoracopagus (19%), omphalopagus (18%), ischiopagus (11%) and craniopagus (11%), dorsal union includes craniopagus (5%), pyopagus (6%) and rachipagus (2%). Antepartum diagnosis is usually missed and if it could be made, helps in management as decision of termination or continuation of pregnancy can be taken and if pregnancy is continued, safe place and mode of delivery can be decided. Case report A 26-year-old gravida 3 para 2 + 0 who was referred to our center with delivered head since one hour and

Dept. of Obstetrics and Gynecology GSVM Medical College, Kanpur, Uttar Pradesh ¶Lecturer CSM Medical University, Lucknow, Uttar Pradesh Address of correspondence Dr N Singh D-20, GSVM Medical College Campus, Kanpur, Uttar Pradesh E-mail: smitabgoy@gmail.com, drneetusingh.73@gmail.com

*Lecturer **Senior Resident †Professor and Head ‡Professor

failure to deliver rest of the body. She was an unbooked case and admitted to our center with chief complaints of labor pains for four hours and leaking per vaginum for 12 hours following term pregnancy for which she went to nearby Primary Health Center (PHC), where her vaginal delivery was tried. There, head of the baby was delivered normally but rest of the body could not be delivered for half an hour inspite of all their efforts, for which she was referred to our side for further management. At the time of admission her general condition was fair, pulse rate 124/min, blood pressure (BP), 106/70 mmHg, mild pallor and mild dehydration were present. Systemic examination revealed no abnormality. On abdominal examination uterus size corresponding to 36 weeks of pregnancy and it was tonically contracted, fetal heart sounds could not be detected and delivered head was deeply congested. She was diagnosed as a case of full-term pregnancy with intrauterine fetal death with shoulder dystocia. She was prepared for delivery under general anesthesia or cesarean section if required. Intravenous (IV) fluid and IV antibiotics were started. Under general anesthesia, McRobert’s maneuver was tried and with one effort of gentle traction on head second head was delivered and rest of the twisted trunk delivered normally. The delivered fetus had two heads, 2 upper limbs two lower limbs, single trunk of unusual shape (as division of trunk had started but was incomplete) and a tail like structure. Her inflicted cervical and vaginal tears were stitched, intravaginal packing was done for vaginal lacerations and Folley’s catheter was put. Her postnatal period was uneventful and she was discharged on 7th postnatal day in satisfactory condition. Follow-up period was uneventful.

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obstetrics and gynecology Discussion Dicephalic fused twins or double-headed monster is a variety of conjoint twins with fused thorax and abdomen. The incidence of dicephalic fused twins is not well-established as it is rare for such type of twins to survive. The classic examples being Scotish brothers who attained 28 years age, Rita-Christina born in Sardina in 1829 and Tocci brothers born in Italy in 1877. Goel and Goel, also reported a twin delivered by cesarean section having two heads, two arms, a single body and two lower limbs. Nagaria (Raipur) also reported a case of dicephalic twin with three upper limbs, the central one having 2 palms, single body and 2 lower limbs. Post delivery X-ray, ultrasonography (USG), computed tomography (CT) scan of the fetus was also done in this case. This type of conjoint twins is a rare anomaly. As this case was unbooked and there was no antenatal check-up, safer mode and place of delivery could not be planned. With the help of early diagnosis, early termination of pregnancy is an option to reduce maternal morbidity and mortality. As reviewed by van den Brand and associates (1994), the diagnosis of conjoint twins can frequently be made at midpregnancy using USG, which allows parents to decide between termination or continuation of pregnancy. It is possible if an effort is made to rule out this condition in all monozygotic twin gestations. A comprehensive USG between 18-22 weeks may be useful to determine to anatomy of the shared organs and to detect associated malformations. Twins facing each other, the heads at the same level and plane, the thoracic cages in unusual proximity, both fetal heads hyperextended and no change in the relative position of the fetuses with movement, manipulation or in repeat examination obtained hours or days later, are the USG findings increasing the probability of conjoint twins. Cardiac connections between the twins can be diagnosed by repeated 2D and 3D and 3D USG, CT and magnetic resonance imaging (MRI) scanning. Parents should be counseled after proper evaluation of point of connection between twins. Termination of pregnancy is better considered when vital organs like heart or brain are shared. Surgical separation of nearly completely joined twins may be successful when organs essential for life are not shared and when it can be performed on a planned as opposed to emergency basis (Spitz and Kiely 2003). SUGGESTED READING 1. Spencer R. Anatomic description of conjoined twins: a plea for standardized terminology. J Pediatr Surg 1996;31(7):941-4. 2. Kerrâ&#x20AC;&#x2122;s M. Operative Obstetrics. 10th edition, KM Verghese Co: Bombay 1982:p.117. 3. Goel S, Goel M. Asian J Obstet Gynecol Practice 1999;3:34-5. 4. Nagaria T. Conjoint twins delivered vaginally. J Obstet Gynecol India 2006;56(4):348-9. 5. van den Brand SF, Nijhuis JG, van Dongen PW. Prenatal ultrasound diagnosis of conjoined twins. Obstet Gynecol Surv 1994;49(9):656-62. 6. Fernando A. Practical Guide to High Risk Pregnancy and Delivery. 3rd edition, Arias Daftary and Bhide Multiple gestation 2007:p.306:307. 7. Spitz L, Kiely EM. 2003;289(10):1307-10. Conjoined twins. JAMA

Paternal Age and Fertility Older men can be reassured that any excess risk of disease in their offspring related to paternal age is very small, but not zero. Advanced paternal age is associated with an increase in new autosomal dominant mutations. The best estimate of risk of autosomal dominant disease in progeny is = 0.5 percent. Spontaneous germ line mutations in X-linked genes may be more common with advancing paternal age. These mutations would be transmitted from carrier daughters to affected grandsons. Women are generally aware of the reproductive issues related to advanced maternal age, typically defined as 35 years of age or older on the estimated date of confinement. These issues include higher risks of infertility, fetal aneuploidy, gestational diabetes, preeclampsia, and still birth.

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Effectiveness of Music Therapy on Anxiety and Depression Among High-risk Pregnant Women Kalaivani G*, Jesinda*, Nalini Jeyavanthsantha**

Abstract This study was intended to evaluate the effectiveness of music therapy on anxiety and depression, among high-risk pregnant women. The conceptual framework for this study was based on JW Kenny’s open system model. The research design for this study was pre-test, post-test, nonequivalent control group quasi experimental design. Setting of the study was selected by using convenient sampling technique. Samples were selected randomly for experimental and control group. Each group consisted of 30 samples. The tool used for assessing the anxiety and depression was hospital anxiety and depression scale. Content validity of the tool was outlined by seven experts in the field of psychiatric and obstetrics. Split half technique was used to assess the reliability of the tool. A pilot study was done among six subjects to check the feasibility of conducting the study. Data collection period was six weeks. Both descriptive and inferential statistics were used for this study. The music therapy was given to experimental group for 30 minutes a day for four weeks. The post-test was done using same tool after the intervention. The following were the findings of the study. The mean post-test level of anxiety in experimental group (13.23) is lesser than mean post-test level of anxiety in the control group (16.5). The obtained ‘t’ value is (3.99). The mean post-test level of depression in the experimental group (13.6) is lesser than mean post-test level of depression in the control group (14.96). The obtained ‘t’ value is (1.78). There was a significant reduction in post-test level of anxiety and depression in the experimental group. The study findings implies that the music therapy is effective in reducing the anxiety and depression among high-risk pregnant women.

Keywords: High-risk pregnant women, anxiety and depression, music therapy

A

nxiety and depression in pregnancy are risk factors for adverse outcomes for mothers and children. Anxiety in pregnancy is associated with shorter gestation and has adverse implications for fetal neurodevelopment and child outcomes. Anxiety about a particular pregnancy is especially potent. Chronic strain, exposure to racism and depressive symptoms in mothers during pregnancy are associated with lower birth weight infants with adverse consequences for infant development. These distinguishable risk factors and related pathways to distinct birth outcomes merit further investigation. High-risk pregnancy is one of the common gestational complications with a reported incidence ranging between 5-10%. In India, the incidence of pre-eclampsia is reported to be 8-10% of the pregnancies. Women with pregnancy complications, including hypertension, tend

to have higher anxiety than those women who are healthy during their pregnancy. Association between stress and significant blood pressure elevations were documented in hypertensive pregnancies. There is evidence that foetal exposure to high levels of stress hormones may contribute to low birth weight babies and pre-term birth. Therefore, there is need for interventions to lower blood pressure through decreases in stress responses in pregnant hypertensive women. Simple relaxation techniques can be used to relieve the stress and anxiety during pregnancy. Music therapy is one of the effective relaxation techniques for anxiety and stress relief during pregnancy. OBJECTIVES OF THE STUDY Evaluate the effectiveness of music therapy among high-risk pregnant women with anxiety and depression.

Research Approach Experimental approach *Associate Professor ** Principal Sacred Heart College of Nursing, Madurai, Tamil Nadu

Research Design: Pre-test, post-test, nonequivalent control group quasi experimental design was used for this study.

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obstetrics and gynecology Variables ÂÂ ÂÂ

Dependent variable - Anxiety and depression Independent variable - Music therapy

Setting of the Study This study was conducted at selected hospitals of Madurai.

Among 36 samples, 30 samples were selected for the experimental group randomly. Fifty-two samples were screened to identify the anxiety and depression in the control group. Among 52 samples, 41 samples had anxiety and depression (using hospital anxiety and depression scale). Among the 41 samples, 30 samples were selected for the control group randomly. RESULTS Effectiveness of music therapy on high-risk pregnant women with anxiety and depression ÂÂ

Population The target population of the study was high-risk pregnant women in the selected hospitals, Madurai.

Sample Samples were the high-risk pregnant women who had mild, moderate or severe anxiety and depression and those who were admitted in antenatal ward in selected hospitals at Madurai, and those who fulfilled the inclusion criteria. MATERIAL AND METHODS Forty-five samples were screened to identify the anxiety and depression in the experimental group. Among 45 samples, 36 samples had anxiety and depression (using hospital anxiety and depression scale). ÂÂ

Table 1 shows the mean post-test level of anxiety in experimental group (13.23) is lesser than mean post-test level of anxiety score in the control group (16.5). The obtained ‘t’ value (3.99) was statistically significant at 0.05 level. Table 2 portrays, that the mean post-test level of depression in the experimental group (13.6) is lesser than mean post-test level of depression in the control group (14.96). The obtained ‘t’ value (1.78) was statistically significant at 0.05 level. Table 3 portrays, that the mean score of anxiety (13.23), and mean score of depression (13.57) of high-risk pregnant women have a significant high positive relationship since the ‘r’ value is 0.87.

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Table 1. Comparison of Mean Post-test Level of Anxiety in Experimental Group and Control Group (n = 60) Variables Experimental group Control group N 30 30 Mean 13.23 3.27 16.5 2.9 MD SD 3.14 3.99* 0.05 t value p value

Table 2. Comparison of Mean Post-test Level of Depression in Experimental Group and Control Group (n = 60) Variables Experimental group Control group N 30 30 Mean 13.6 1.36 14.96 2.5 MD SD 3.33 1.78* 0.05 t value p value

Table 3. Relationship between Anxiety and Depression of High-risk Pregnant Women in the Experimental Group (n = 30) Variables Anxiety Depression Mean 13.23 13.57 SD 3.14 0.87 3.47 r value

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obstetrics and gynecology DISCUSSION The following conclusions were drawn from the present study. ÂÂ

Most of the high-risk pregnant women in the experimental and control group suffered from severe depression and severe anxiety. Music therapy was effective in reducing the level of depression and anxiety among high-risk pregnant women. zz

ÂÂ

The mean post-test level of anxiety in the experimental group (13.23) was lesser than the mean pre-test level of anxiety in the experimental group (15.8). The obtained ‘t’ value (18.5) was statistically highly significant at 0.05 level. This illustrates the mean difference of (2.6) was a true difference and has not occurred by chance. This may be due to the effect of music therapy. The mean post-test level of depression (13.57) in the experimental group was lesser than the mean pre-test level of depression (15.06) in the experimental group. The obtained ‘t’ value (7.5) was statistically highly significant at 0.05 level. This illustrates the mean difference of (1.5) was a true difference and had not occurred by chance. This may also be due to the effect of music therapy. The mean post-test level of anxiety in experimental group (13.23) is lesser than mean post-test level of anxiety score in the control group (16.5). The obtained ‘t’ value (3.99) was statistically significant at 0.05 level at 58 d.f. This, illustrate the difference (3.27) was a true difference and had not occurred by chance. This may be due to the effect of music therapy. The mean post-test level of depression in the experimental group (13.6) is lesser than mean post-test level of depression in the control group (14.96). The obtained ‘t’ value (1.78) was statistically significant at 0.05 level at 58 d.f. This, illustrate the difference (1.36) was a true difference and had not occurred by chance. This may be due to the effect of music therapy. There is a statistically significant association between post-test level of anxiety and selected

demographic variable like educational status (X2-14.02) at 0.05 level of significance. The educational status of high-risk pregnant women has some effect on music therapy. Therefore, the researcher rejects null hypothesis and accepts research hypothesis. There is no significant association between the post-test level of anxiety and selected demographic variables such as age, age at marriage, occupation, type of family, area of residence, religion, family support, gestational age, type of illness, time of diagnosis, number of conception, number of delivery, number of abortion and number of still birth. zz

zz

There is no significant association between post-test level of depression and selected demographic variables such as age, age at marriage, education, occupation, area of residence, religion, type of family, family support, gestational age, type of illness, time of diagnosis, number of conception, number of delivery, number of abortion and number of stillbirth.

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The study findings revealed that music therapy can be administered to all the high-risk pregnant women in reducing anxiety and depression.

SUGGESTED READING 1. Borton C. Depression in pregnancy. Patient UK. 2010. Retrieved from www.patient.co.uk. Accessed October 2011. 2. Bauer CL, Victorson D, Rosenbloom S, Barocas J, Silver RK. Alleviating distress during antepartum hospitalization: a randomized controlled trial of music and recreation therapy. J Womens Health (Larchmt) 2010;19(3):523-31. 3. Correia LL, Linhares MB. Maternal anxiety in the preand postnatal period: a literature review. Rev Lati Ame Enfermagem 2007;15(4):677-83. 4. Couto ER, Couto E, Vian B, Gregoria Z, Nomera ML, Zaccaria R, et al. Quality of life, depression and anxiety among pregnant women with previous adverse pregnancy outcomes. Sao Paulo Med J 2009;127(4):185-9. 5. Yang M, Li L, Zhu H, Alexander IM, Liu S, Zhou W, et al. Music therapy to relieve anxiety in pregnant women on bedrest: a randomized, controlled trial. MCN Am J Matern Child Nurs 2009;34(5):316-23.

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obstetrics and gynecology

A Study to Evaluate the Efficacy of Actim Partus (A Rapid Bedside Test) in the Prediction of Preterm Labor SHIKHA SINGH*, SAROJ SINGH**, MUKESH CHANDRA†, REKHA RANI‡, SUCHIT VERMA¶

Abstract Objective: The objective of the study was to evaluate the efficacy of bedside test kits (Actim partus kit) based on detection of phosphorylated insulin-like growth factor binding protein-1(PIGFBP-1) in cervical secretions in predicting preterm delivery. Material and methods: Patients presenting with symptoms of preterm labor between 28 and 36 weeks of gestation were recruited. PIGFBP-1 bedside tests (Actim partus test) were performed. Managing obstetricians and patients were blinded to the PIGFBP-1 results. Tocolysis and steroid therapy were administered to all the recruited patients. Outcome data were collected after delivery. Results: Fifty patients were recruited into the study, the median [± standard deviation [SD] gestational age at delivery was 34.12 weeks (± 2.1 weeks) and 37.14 weeks (± 2.8 weeks), patient testing positive and negative for Actim partus test, respectively. A positive result was associated with significantly reduced admission-to-delivery interval. The median admission-to-delivery interval was 3.25 days in the group with positive PIGFBP-1 results while 6.97 days with a PIGFBP-1 result (p < 0.001). Sensitivity, specificity, positive predictive value and negative predictive value of Actim partus test is 72.22%, 90.6% 81.25% and 85.29%, respectively. Conclusion: Actim partus (IGFBP-1) tests are effective adjuvant bedside test kits for the prediction of preterm delivery in patients presenting with signs or symptoms of preterm labor. High negative predictive values have great value in avoiding unnecessary interventions.

Keywords: Bedside test kits (Actim partus kit), preterm delivery, preterm labor

M

odern obstetrics aim at providing every child born an optimum chance for complete mental and physical development. This can be achieved by ensuring delivery of the fetus, as near term as possible, thus allowing optimal development of the fetus in utero before coming out to face the rigors of extrauterine life. Diagnosis of preterm labor poses a problem. A test to predict better who are most likely to deliver preterm would allow us to direct the therapy more appropriately. The latest modality to diagnose preterm labor is detection of phosphorylated insulin-

like growth factor binding protein-1 (PIGFBP-1) in cervical secretions. Insulin-like growth factor binding protein-1 (IGFBP-1) belongs to super family of insulin-like binding protein. Out of six subtypes, a highly phosphorylated isoform is found in the decidual tissues. Amniotic fluid contains nonphsophorylated and lesser phosphorylated isoform. Because of difference in the origin of IGFBP-1, decidual or amniotic fluid can be identified through the use of monoclonal antibodies. The process of labor is hypothesized to disrupt the choriodecidual interface, releasing PIGFBP-1 in the cervical secretions. Developments in biomedical engineering have allowed the development of a commercial bedside test kit (Actim partus kit) for the qualitative detection of PIGFBP-1 above the level of 10 µg/l. This prospective study was planned to evaluate the efficacy of readily available bedside test kit (Actim partus kit) based on detection of PIGFBP-1 in predicting the preterm labor and thus timely starting the necessary intervention for its prevention and ensuring optimal chances for survival of baby.

*Assistant Professor **Professor and Head †Professor ‡Lecturer ¶Junior Resident-III Dept. of Obstetrics and Gynecology SN Medical College, Agra, Uttar Pradesh Address for correspondence

Prabhu Lal Verma C-364, Avas Vikas Colony, Indira Nagar, Raebareli, Uttar Pradesh E-mail: suchitaverma186@gmail.com

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obstetrics and gynecology AIMS and OBJECTIVES ÂÂ

To assess the sensitivity of Actim partus (a rapid bed test) for prediction of preterm labor. To assess the specificity of Actim partus (a rapid bed test) for prediction of preterm labor.

sample and was held until the liquid front entered the result area. Dipstick was removed from the solution and placed in horizontal position. Result was available in 5 minutes.

ÂÂ

Reading the Result ÂÂ ÂÂ

MATERIAL and METHODS The present study was conducted in the Dept. of Obstetrics and Gynecology, SN Medical College and Hospital, Agra, Uttar Pradesh over a period of July 2010 to September 2012. This was a prospective cohort study, which included pregnant females with 28-36 weeks of gestation selected from Indoor ward and Obstetrics OPD. Fifty cases were included in study.

Positive: When two blue lines were visible. Negative: When only control line was visible.

All patients were followed upto delivery. Following delivery data collection on gestational age at the time of delivery, admission to delivery interval was completed. RESULT In the present study, cases with gestational age 28-36 weeks were included. In the study Actim partus test was positive in 16 cases (32%) and negative in 34 cases (68%) (Table 1). In patients testing positive for Actim partus test, mean gestational age was 33.12 ± 1.9 weeks while in patients testing negative for Actim partus test gestational age were 30.17 ± 1.7 weeks (p < 0.05) (Table 2). Mean gestational age at delivery in patients testing positive for Actim partus was 34.12 ± 2.1 weeks and in patients testing negative for Actim partus test was 37.14 ± 2.8 (p < 0.01) (Table 3). Admission to delivery internal in positive Actim partus test was 3.25 ± 1.58 days and in negative Actim Table 1. Distribution of Cases According to Result of Actim Partus at Admission Actim partus test Positive Negative Total No. of cases 16 34 50 Percentage (%) 32 68 100

Inclusion Criteria ÂÂ ÂÂ ÂÂ ÂÂ

Gestational age between 28-36 weeks Regular uterine contractions Intact membranes Cervical dilatation 1 to < 3 cm

Exclusion Criteria ÂÂ ÂÂ ÂÂ ÂÂ ÂÂ

Pregnancy before 28 and after 37 weeks Premature rupture of membranes Bleeding per vagina Heart disease Diabetes

Detailed history of all patients were taken. Gestational age was calculated based on the last menstrual period and confirmed by first or early second trimester ultrasonography and when discrepancy of more than 10 days occurred, gestational age was set only by first trimester ultrasonographic examination. A detailed general systemic and obstetric examination including digital cervical assessment was done in all cases.

Performing the Test ÂÂ

Specimen collection: Sterile dacron swab was applied over cervical os and was left approximately for 10-15 seconds to absorb cervical specimen. Extraction of specimen: The specimen was extracted from the swab by swirling the latter vigorously in the tube containing specimen extraction solution. Dipping: Aluminium foil pouch containing dipstick was opened out. Identifying marks was written on the upper purple part of dipstick. Yellow testing dip area of stick was placed into tube containing

Table 2. Correlation of Gestation Age at Admission with Actim Partus Test Result Period of gestation in weeks 28-30 31-33 34-36 Total Mean ± SD Positive Actim partus No. 2 2 12 16 % 4 4 24 100 Negative Actim partus No. 16 11 7 34 % 47 32.3 20.58 100

ÂÂ

ÂÂ

33.12 ± 1.9

30.17 ± 1.7

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obstetrics and gynecology Table 3. Correlation of Gestation Age at Delivery with Actim Partus Test Result Gestational age at time of delivery (in weeks) 28-30 31-33 34-36 37-38 39-40 Total Mean ± SD p value Positive Actim partus test No. 4 6 3 2 1 16 % 25 37 18.75 12.5 6.25 100 < 0.01 Negative Actim partus test No. 1 2 2 17 12 34 % 2.9 5.88 5.88 50 35.29 100

was 36.2 ± 2.4 weeks (p value 0.001). In study of Kwek et al,1 a total of 47 women were recruited for the study. The average maternal age was 28 years and the range of gestational age was between 23 and 33 weeks. Eighteen women (38.3%) tested positive for PIGFBP-1, while 29 women (61.7%) tested negative. The women who tested negative for IGFBP-1 had a significantly shorter stay in the delivery suite, as well as a reduced requirement for tocolysis and a shorter hospitalization. Less than a quarter of the women who tested negative delivered before 36 weeks, compared to more than 75% of the women who tested positive. This result was statistically significant. The result shows that the beside test for PIGFBP-1 has a sensitivity of 87.37% and a specificity of 82.6% for the prediction of preterm delivery before 36 weeks. The positive predictive value of the test is 77.8% and the negative predictive value is 79.2%. A Lembet et al,3 carried out a prospective study on 36 women between 20 and 36 weeks of gestation with regular contractions. Eighteen patients had a positive. Actim partus test and 18 had a negative test. Among the 18 patients with a positive test, only one delivered at term and the other 17 patients delivered preterm (<37 weeks). Among the 18 women with a negative test, only two delivered preterm (p < 0.05). Sensitivity, specificity, positive and negative predictive values of the rapid PIGFBP-1 test for preterm delivery were 89.5%, 94.1%, 94.4% and 88.9%, respectively. In study of Ting et al,4 108 patients were recruited into the study. Among those with negative PIGFBP-1, the median (± standard deviation [SD]) gestational age delivery was 37.4 weeks (± 1.8 weeks) and in positive PIGFBP-1 the median gestational age at delivery was 32.9 weeks (± 4.0 weeks). The p value was <0.001. Based on this discussion it can be concluded that results are comparable for Actim partus test. This test has very reasonable accuracy and easy to use. The test result were all readable within five minutes of sampling. The women who tested negative for Actim partus experienced a reduced need for hospitalization and tocolysis, as well as a substantial prolongation of pregnancy, compared to women who tested positive. CONCLUSION Actim partus test kit is a rapid bedside immunoenzymatic test kit shows promising results and is clinically useful in the diagnosis and exclusion of premature labor and delivery in symptomatic women. It is a simple,

34.12 ± 2.1

37.14 ± 2.8

Table 4. Admission to Delivery Interval Admission to delivery interval in days < 2 (48 hours) 2-7 >7 Total Mean ± SD p Value Positive Actim partus No. 10 3 3 16 % 62.5 18.75 18.75 100 Negative active partus No. 6 7 21 34 < 0.01 % 77.6 20.58 61.76 100

3.25 ± 1.58

6.97 ± 2.24

partus test was 6.97 ± 2.24 days (p < 0.001) (Table 4). Sensitivity of Actim partus test (72.22%), specificity of Actim partus test (90.6%), positive predictive value of Actim partus test (81.25%), negative predictive value of Actim partus test (85.29%). DISCUSSION Mean gestational age at delivery in patients testing positive for Actim partus was 34.12 ± 2.1 weeks and in patients testing negative for Actim partus test was 37.14 ± 2.8 (p < 0.01). In studies of Kwek et al,1 median gestation age at delivery in patients testing positive for Actim partus test was 33 weeks while in patients testing negative for Actim partus test was 37 weeks (p < 0.05). In studies of Elizur, et al,2 mean gestational age at delivery in patients testing positive for Actim partus

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obstetrics and gynecology convenient reliable test and results are available within few minutes, so important decision on patient care can be made immediately. This saves both time and resources. REFERENCES 1. Kwek K, Khi C, Ting HS, Yeo GS. Evaluation of a bedside test for phosphorylated insulin-like growth factor binding protein-1 in preterm labour. Ann Acad Med Singapore 2004;33(6):780-3. 2. Elizur SE, Yinon Y, Seidman DS, Schiff E, Sivan E. Insulin-like growth factor binding protein-1 detection in preterm labor: evaluation of a bedside test. Am J Perinatol 2005;22(6):305-9. 3. Lembet A, Eroglu D, Ergin T, Kuscu E, Zeyneloglu H, Batioglu S, et al. New rapid bed-side test to predict preterm delivery: phosphorylated insulin-like growth factor binding protein-1 in cervical secretions. Acta Obstet Gynecol Scand 2002;81(8):706-12. 4. Ting HS, Chin PS, Yeo GS, Kwek K. Comparison of bedside test kits for prediction of preterm delivery: phosphorylated insulin-like growth factor binding protein-1 (pIGFBP-1) test and fetal fibronectin test. Ann Acad Med Singapore 2007;36(6):399-402.

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How does Contraception Work?

Contraceptive agents are usually divided into those that are either hormonal or nonhormonal. Most of the hormonal contraceptives work by changing a woman’s hormone levels to mimic a pregnancy, therefore preventing eggs from being able to be released from the ovary. In contrast, nonhormonal contraceptive agents or devices work by preventing a man’s sperm from joining a woman’s egg.

Which Surgery is Recommended for Infertility?

Laparoscopic treatment of minimal and mild endometriosis has been associated with a small but significant improvement in pregnancy rates. In a study, 29% of women who had their endometriosis treated conceived over nine months, in contrast to only 17% of women whose endometriosis was diagnosed, but not treated during laparoscopy. Treatment of moderate and severe endometriosis by laparoscopy and/or laparotomy increases pregnancy rates for women in whom no other causes of infertility have been found. (Dr Kaberi Banerjee, IVF expert, New Delhi)

What are the Psychological Effects of a Multiple Pregnancy on a Family?

Many women with a multiple pregnancy do well; their families may experience significant stress. Even if medical problems are overcome and the infants survive without disability, the effect of multiple births on family life is profound and life-altering. The impact of a multiple birth clearly affects the parents, but also the babies, other siblings, and the extended family. Financial stresses may be overwhelming. Obvious additional costs include feeding, clothing, housing and caring for multiple children.

What is ICSI? Before a man’s sperm can fertilize a woman’s egg, the head of the sperm has to attach to the outside of the egg. Then it pushes through the outer layer of the egg to the inside of the egg (cytoplasm). Sometimes the sperm cannot penetrate the outer layer. A procedure called intracytoplasmic sperm injection (ICSI) can help fertilize the egg by injecting the sperm directly into the egg.

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obstetrics and gynecology

A Case-control Study of Pelvic Inflammatory Disease and Its Association with Multiparity among Patients Attending SSG Hospital, Vadodara, Gujarat SV Patel*, RK Baxi**, PV Kotecha†, VS Mazumdar**, HN Bakshi‡, KG Mehta¶

Abstract Objective: To know the association between pelvic inflammatory disease (PID) and multiparity. Study design: Case control study. Setting: Shree Sayaji General (SSG) Hospital, Government Medical College, Vadodara. Participants: Women attending Gynec Clinics and Curative Practice and General Practice (CPGP) OPD. Sample size: One hundred fifty cases and 150 controls. Statistical analysis: Chi-square test. Results: The odds ratio (OR) for PID with multiparity as risk factor was 0.69 with 95% confidence interval (CI) being 0.42-1.09. Among 143 cases multiparity was present in 63 cases (44.05), while in 150 controls it was in 80 (53.33%). The difference was not statistically significant (p = 0.141). But, the OR with untrained person as a risk factor for PID was 2.41 with 95% CI being 1.78-3.27. This suggests etiological fraction of 58.5% (CI 43.9-69.4%) among untrained persons. The delivery by untrained person was significantly higher in cases than in controls (p 0.00001). Conclusions: Present study did not show multiparity as risk factor but delivery conducted by untrained persons emerged as a risk factor.

Keywords: Pelvic inflammatory disease, multiparity, case-control study

P

elvic inflammatory disease (PID) is one of the most serious infections faced by women today. It is a common problem encountered in gynecologic infertility, family planning, legal abortions, postnatal and sterilization clinics in India and abroad.1 PID as described by the Centers for Disease Control, is a general term that refers to infection of the uterus, fallopian tubes and other reproductive organs. It is a common and serious complication of some sexuallytransmitted diseases (STDs), especially chlamydia and

gonorrhea. PID can damage the fallopian tubes and tissues in and near the uterus and ovaries. Untreated PID can lead to serious consequences, including infertility, ectopic pregnancy, abscess formation and chronic pelvic pain.2 PID is one or the most widespread and debilitating disease affecting women today. Present case-control study was undertaken to know the association between PID and multiparity. Objective To know the association between PID and multiparity.

*Associate Professor **Professor Dept. of PSM Government Medical College, Vadodara, Gujarat †Country Representative Academy for Educational Development, A2Z The USAID Micronutrient Project India ‡Tutor Dept. of PSM ¶Junior Lecturer Government Medical College, Vadodara, Gujarat Address for correspondence Dr Sangita Patel Associate Professor Dept. of Community Medicine Government Medical College, Vadodara - 390 00,1 Gujarat E-mail: sangita_psm@yahoo.co.in

Methodology This study was conducted at Shree Sayaji General (SSG) Hospital, which as a regional referral hospital attached to Government Medical College, Vadodara. Selection of cases and sources of cases The Dept. of Obstetric and Gynecology of SSG Hospital has daily outpatients service. Average daily outpatient at this OPD is 100 gynecological cases per day, of which 8-10% have PID. In the present study, 150 patients of PID who attended gynec OPD of SSG Hospital over

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obstetrics and gynecology a period of one year were selected with uniformly accepted criteria for PID as given under: ÂÂ ÂÂ ÂÂ

Table 1. Compare Age Group in Both Cases and Control Age group (years) 16-20 21-25 26-30 31-35 36-40 >40

Complaint of lower abdominal pain Vaginal discharge Adnexal tenderness leading to pain.

Cases 02 28 38 42 21 19

Control 06 24 41 38 20 21

All cases meeting with the above diagnostic criteria were labeled as clinical cases of PID.

Exclusion Criteria Those who had extramarital history were excluded from both cases and controls. After taking consent, we obtained information by conducting in-depth interviews for 2-3 sessions with each patient.

Table 2. Association between Multiparity and PID Cases Multiparity + Multiparity 63 (44.05%) 80 (55.94%) 143 Controls 80 (53.33%) 70 (46.66%) 150 Total 143 150 293

Selection of Controls and Sources of Controls For each case, a control was selected from women attending SSG Hospital outdoor for any complaint, health problems other than obstetrics and gynecology. One hundred fifty controls were selected from Curative, Preventive and General Practice (CPGP) unit of SSG Hospital. CPGP has adequately comfortable offices, which provided necessary privacy for interviews of the control group. For the purpose of present study definition of the term multiparity was considered from available literature. Multiparity Those women who have more than three living children born were labeled as multiparous women. In order to evaluate the role of multiparity as risk factor, which might influence the pathogenesis of PID, each patient was matched with a patient in the concurrent group with a patient with respect to age (by 5 years age group). The mean age in cases was 32.56 ± 7.31 and in controls was mean 32.58 ± 8.05. The difference was statistically not significant.

Table 3. Comparison of Delivery Assistance in Total No. of Deliveries in Both Groups Total Total deliveries deliveries among controls among cases Trained persons Untrained persons Total 193 (52.34%) 175 (47.56%) 368 282 (72.69%) 106 (27.31%) 385

Total

475 281 756

Table 4. Comparison of Place of Delivery in Total No. of Deliveries in Both the Groups Total Total deliveries deliveries among controls among cases Hospital deliveries Home deliveries Total 165 (45.96%) 194 (54.04%) 359 254 (64.96%) 137 (35.04%) 391

Total

419 331 750

Data Processing and Statistical Analysis The entire information from the questionnaire of cases and controls was coded and data fed into computer by using statistical software EPI-Info. Data was analyzed by Epi-Info.3 Significance of difference in the prevalence of PID patients (cases) and controls due to multiparity was analyzed by using Chi-square. Results Among 143 cases, multiparity was present in 63 cases (44.05%) while in 150 controls it was in 80 (53.33%). The difference was not statistically significant (p = 0.141) The odds ratio for PID with multiparity as a risk factor was

0.69 with 95% confidence interval (CI) being 0.42-1.09 (Table 2). Delivery in itself is not a risk factor for PID but delivery by untrained person is a risk factor. The OR with untrained person as a risk factor for PID was 2.41 with 95% CI being 1.78-3.27. This suggests etiological fraction of 58.5% (CI 43.9-69.4%) among untrained persons. The delivery by untrained persons was significantly higher in cases than in controls (p 0.00001) (Table 3).

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obstetrics and gynecology Discussion A standard proforma was used to collect delivery history. The present study is a hospital-based study. The cases as well as controls were drawn from hospitals so other factors like occupation, income, socioeconomic status, personal hygiene, etc. were similar because both cases and controls represented the same group of patients presenting to the hospital. In seven cases, information on multiparity was not available. Multiparity initially was thought to be a risk factor because: ÂÂ ÂÂ

the data between hospital delivery and home delivery is separated, the importance of conduction of delivery by trained person can not be ignored. So, we analyzed the data comparing delivery by trained and untrained persons. The OR with untrained person as a risk factor for PID was 2.41 with 95% CI being 1.78-3.27. This suggests etiological fraction of 58.5% (CI 43.9-69.4%) among untrained persons. The delivery by untrained person was significantly higher in cases than in controls (p 0.00001). Conclusions Present study did not show multiparity as a risk factor but delivery conducted by untrained persons emerged as a risk factor for PID. Recommendation Training of dais is important. The Government of India has already started training program for dais in aseptic techniques, which should be strengthened to ensure aseptic delivery. References 1. Pachauri S. Defining a reproductive health package for India: A proposed framework. Regional Working Paper No 4. 1995. 2. Tolu Oyelowo DC. Pelvic Inflammatory Disease. In: Mosby’s Guide to Women’s Health. 2007:p.68-71. 3. Epi_Info VdAwp, Database, and Statistical Programme for Public Health on IBM-compatible Microcomputers. Centers for Disease Control and Prevention. Atlanta, Georgia, USA Developed by Dean AG, Coulombier D, Brendel KA, Smith DC, Burton AG, Dicker RC, et al. 2001. 4. Duncan ME, Tibaux G, Pelzer A, Reimann K, Peutherer JF, Simmonds P, et al. First coitus before menarche and risk of sexually transmitted disease. Lancet 1990;335(8685):338-40. 5. Eschenbach DA. Prospective study of Pelvic inflammatory-disease by clinical criteria. Obstetrics Gynecology 1950;55:1485-525. 6. Lee NC, Rubin GL, Grimes DA. Measures of sexual behavior and the risk of pelvic inflammatory disease. Obstet Gynecol 1991;77(3):425-30. 7. Sweet RL, Draper DL, Hadley WK. Etiology of acute salpingitis: influence of episode number and duration of symptoms. Obstet Gynecol 1981;58(1):62-8. 8. Beerthuizen RJ. Pelvic inflammatory disease in intrauterine device users. Eur J Contracept Reprod Health Care 1996;1(3):237-43. 9. Wright EA, Aisien AO. Pelvic inflammatory disease and the intrauterine contraceptive device. Int J Gynaecol Obstet 1989;28(2):133-6.

Repeated births cause infection in the birth passage. Patient’s general immunity is decreased due to repeated delivery, so increasing chances of infection Repeated blood loss due to repeated deliveries, lead to anemia and chances of infections are much more in anemic women

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The OR for PID with multiparity as a risk factor was 0.69 with 95% CI being 0.42-1.09. Among 143 cases multiparity was present in 63 cases (44.05%) while in 150 controls it was in 80 (53.33%). The difference was not statistically significant (p = 0.141). The possible explanation for the same could be: ÂÂ

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High estrogen and progesterone hormones levels like in pregnant state give protective effect against PID; similar to protective effect observed due to oral contraceptive use. The frequency of sexual intercourse is decreased during pregnancy and sexual intercourse acts as a risk factor for PID. So, less chances of PID in multiparity.4-6 Repeated deliveries mean repeated contacts with doctors, if infection was present then it would have been treated. PID in the fallopian tubes (salpingitis) can cause adhesions or complete tubal obstruction. Thus ectopic pregnancy or infertility may occur even after only one episode. For example in a Swedish study of 415 women with a history of salpingitis 21% were infertile compared with 3% in a comparison group with no history of salpingitis.7

One study conducted by Beerthuizen found that nulliparous women with stable monogamous relationships are not at higher risk of PID than parous women.8 One longitudinal study done by Wright demonstrated that there was no relationship between the parity of the patients and the development of PID.9 Delivery in itself is not a risk factor for PID but delivery by untrained person is a risk factor. Although,

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ORTHOPEDICS

An Update on Bisphosphonate-related Osteonecrosis of the Jaw Jacob Kurien*, E Anuradha Sunil*, Archana Mukunda†, Sunitha Raj Philip‡

Abstract Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a condition found in patients who have received intravenous and oral forms of bisphosphonate therapy for various bone-related conditions. BRONJ, manifests as exposed, nonvital bone involving the maxillofacial structures. The mandible is more commonly affected than the maxilla (2:1), and 60% of cases are preceded by a dental surgical procedure. The signs and symptoms that may occur before the appearance of clinically evident osteonecrosis include changes in the health of periodontal tissues, nonhealing mucosal ulcers, loose teeth and unexplained soft-tissue infection. Although, the definitive role of bisphosphonates remains to be elucidated, alteration in bone metabolism with surgical insult or prosthetic trauma appears to be key factors in the development of BRONJ. The significant benefits that bisphosphonates offer to patients clearly outbalance the risk of potential side effects; however, any patient for whom prolonged bisphosphonate therapy is indicated, should be provided with preventive dental care in order to minimize the risk of developing this severe condition. This article provides a review of current developments about the pathogenetic, clinical, management and preventive aspects of BRONJ.

Keywords: Bisphosphonates, osteonecrosis of jaw, bisphosphonate related osteonecrosis of jaw

B

isphosphonate-related osteonecrosis of the jaw (BRONJ) is an area of uncovered bone in the maxillofacial region, which does not heal within eight weeks, occurring in patients receiving bisphosphonates without previous radiation therapy to the craniofacial region.1 BRONJ was first reported by Marx (2003) as a complication in patients who were on intravenous (IV) or oral bisphosphonate.2 It adversely affects the quality- of-life and produces significant morbidity in afflicted patients.3 Interestingly, BRONJ was described over 100 years ago in the British Medical Journal. Phossy Jaw was a deadly occupational hazard of white (or yellow) phosphorous workers in the ‘strike-

anywhere match’ industry from 1840-1910.4 The vapor inhaled by workers caused deposition of phosphorous in the bones and the jaws were most often affected. Workers developed toothaches, gingivitis, abscesses, bone loss, disfigurement, a foul smelling discharge and finally cerebral complications. Some would actually glow a greenish white color in the dark. Epidemiology It is noted that almost 94% of people using bisphosphonate develop BRONJ. However, it is IV use of bisphosphonate that is more associated with BRONJ than oral administration. Patients with more than three years of oral administration of bisphosphonates are at a high-risk of BRONJ, whereas cumulative doses of IV bisphosphonate increases the risk of BRONJ. There is no variation in occurrence of BRONJ and sex, ethnicity or any known risk factors such as diabetes, alcoholism, cigarette smoking and obesity. It is noted mostly in old age with prolonged use of bisphosphonate. BRONJ occurs after tooth extraction or minor surgical procedure to jaw bones in almost 60% of cases. However, in 40% of cases, it spontaneously occurs in edentulous jaw bones. It is noted most commonly in mandible than maxilla and may at times affect both jaw bones.5 The jaw bones are more commonly affected than other bones as the bone remodel at a faster rate than other

*Professor and Head Dept. of Oral and Maxillofacial Pathology St. Gregorios Dental College (KUHS), Chelad, Kerala **Professor and Head †Reader Dept. of Oral and Maxillofacial Pathology Royal Dental College (KUHS), Chalissery, Kerala ‡Senior Lecturer Dept. of Oral Medicine and Radiology St. Gregorios Dental College (KUHS), Chelad, Kerala Address for correspondence

Dr Anuradha Sunil Professor and Head Dept. of Oral and Maxillofacial Pathology Royal Dental College (KUHS), Chalissery, Kerala E-mail: anuradhasunil@hotmail.com

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ORTHOPEDICS bones like tibia (>10 times). The alveolar bone is mostly susceptible to infection as it is present in close relation to teeth, which are prone for infections. The infection from teeth and gums can easily spread to the alveolar bone and jaw bone as there is decreased vasculature and altered osteoclastic bone resorption and remodeling here than in any other bone, resulting in BRONJ.6 Bisphosphonates Bisphosphonates are stable analogs of pyrophosphates, which are naturally occurring modulators of bone metabolism.7 The chemical structure of bisphosphonates includes a P-C-P backbone that bestows a strong affinity for hydroxyapatite crystal on bony surfaces and provides potent inhibition of bone turnover both in vivo and in vitro.8 They are potent inhibitors of osteoclast-mediated bone resorption and have cytotoxic effects on mature osteoclasts and inhibit the formation of osteoclasts from precursors.9 Hence, they are used as antiresorptive medicines to maintain or increase bone density and strength in diseases like osteoporosis, hypercalcemia, Paget’s diseases, bone metastasis, multiple myeloma, primary hyperparathyroidism, osteogenesis imperfecta and numerous other conditions that feature bone fragility. Bisphosphonate can be given by oral or IV administration. It is noted that IV bisphosphonates are used extensively to treat osteolytic bone lesions related to multiple myeloma and bone metastasis of solid cancers, breast cancer or prostate cancer. An increased risk of osteonecrosis in the jaw bones is noted since 2003, causing large and therapy resistant bone exposures of the maxilla and the mandible in patients with a history of bisphosphonates administration orally or by IV route. Marked inhibition of bone resorption is seen, particularly when administered by IV infusion.2,9,10 Pathophysiology The exact origin of BRONJ is not known but many hypotheses seem to explain the pathogenesis under the following headings: ÂÂ ÂÂ

Healthy osteocytes have canaliculi by which they communicate with adjacent osteocytes as well as exchange nutrients through blood supply. So, once the osteocytes die the nutrition is also cut-off leading to necrosis of bone. It is also noted that BP attached to the bone act as cytotoxic agents to the osteocytes thereby leading to their death and later their necrosis. On antiangiogenesis: It is experimentally proved that bisphosphonate have antiangiogenic property as they suppress capillary regeneration, epithelial growth factor and angiogenesis. The normal healing mechanism in jaw bone following extraction or invasive dental treatments is disturbed as the blood clot will not form due to angiosuppression by bisphosphonate. In addition to this, bone remodeling is inhibited as osteoclasts are suppressed by bisphosphonates leading to delay in wound healing process and BRONJ ultimately.11

Adverse effects and Risks of bisphosphonate therapy Generally, the side effects seen are hypocalcemia, skeletal bone and joint pain, constipation or diarrhea, tiredness, etc. Oral bisphosphonates can cause upset stomach causing inflammation and erosions of the esophagus. IV infusion can give rise to fever and flu like symptoms after first infusion but the greatest risk is that of development of BRONJ.12 Risk factors for the development of BRONJ can be grouped as: Drugrelated; local risk factors; demographic/systemic factors.

Drug-related Risk Factors ÂÂ

IV route of administration results in a greater drug exposure than the oral route. Long duration of therapy appears to be associated with increased risk.12

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Local Risk Factors ÂÂ

On bone remodeling: It is noted that bisphosphonate causes bone remodeling suppression. The jaw bones have high rate of remodeling than other bones hence rapid bone remodeling of jaw and suppression of remodeling leads to osteonecrosis. On osteocytes: In normal bone osteocytes at the end of their life cycle are removed and replaced with new ones. This process will be absent when bone remodeling is suppressed by bisphosphonate. The lacunae, where osteocyte resided will now be empty and can be demonstrated by fuchsin dye.

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Dentoalveolar surgeries like extractions, dental implant placement, periapical and periodontal surgery involving osseous injury. Patients receiving IV bisphosphonates and undergoing dentoalveolar surgery are more likely to develop BRONJ than patients who are not having dentoalveolar surgery. Local anatomy: It has been observed that lesions are found more commonly in the mandible than the maxilla (2:1) and more commonly, areas with thin mucosa overlying bony prominences such as tori, bony exostoses and the mylohyoid ridge are

ÂÂ

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ORTHOPEDICS frequently traumatized.13 ÂÂ

Concomitant oral disease: Patients with a history of inflammatory dental disease, e.g., periodontal and dental abscesses are at a 7-fold increased risk for developing BRONJ.12

Table 1. As Suggested by Ruggiero et al at AAOMS in 2009, Clinical Staging of BROJ is Given Below At risk No apparent necrotic bone in patients who category have been treated with either oral or IV bisphosphonates Stage 0 Stage 1 Stage 2 No clinical evidence of necrotic bone but nonspecific clinical findings and symptoms. Exposed/Necrotic bone in patients who are asymptomatic and have no evidence of infection. Exposed/Necrotic bone associated with infection as evidenced by pain and erythema in the region of the exposed bone with or without purulent drainage. Exposed/Necrotic bone in patients with pain, infection and one or more of the following: Pathologic fracture, extraoral fistula or osteolysis extending to the inferior border.

Demographic and Systemic Factors ÂÂ

Age, sex, race, cancer diagnosis with or without osteoporosis were reported as risk factors of BRONJ. There are no racial and sexual factors as risk for development of BRONJ. Increasing age is associated with increased risk in development of BRONJ. Systemic factors like renal dialysis, low hemoglobin, obesity and diabetes were variably reported to increase the risk of BRONJ. Type of malignancy cannot be considered a risk factor but malignancies, which metastasize were at an increased risk of BRONJ.

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Stage 3

Genetic Factors It is noted that single nucleotide polymorphisms, in the cytochrome P450-2C gene (CYP2C8) were associated with an increased risk of BRONJ among multiple myeloma patients treated with IV bisphosphonates.12,14

Table 2. Treatment Strategy of BRONJ as per the Recommendation of AAOMS in 2009 is Given Below At risk No special treatment required; possibility of category BRONJ and symptoms should be explained to patient Stage 0 Antibiotics should be administered if needed. Conservative treatment should be used for patient with dental caries and periodontal problems. 0.12% chlorhexidine gluconate is effective in treatment at this stage. Surgery is not required. Oral antibiotics and chlorhexidine mouthwash are used. Usually penicillin is preferred, but if patient is allergic to it then quinolones, metronidazole, clindamycin, doxycycline and erythromycin can be administrated. Combination of oral and intravenous antibiotics may be required. Necrotic tissue is removed superficially without disturbing the underlying soft tissue. Necrotized bone is removed. Systemic antibiotics have to be given along with anti-inflammatory drugs. Oral antiseptic mouth washes are recommended.

Other Factors Some of the other associated risk factors of BRONJ include corticosteroid therapy, diabetes, alcohol use, smoking, chemotherapeutic drugs and poor oral hygiene.11,12 BRONJ Case Definition Patients with BRONJ present with localized pain, neuropathy, halitosis, exposed bone, erythema, gingivitis, mobility of teeth with suppuration and pus discharge.6 In order to standardize the criteria for BRONJ the American Association of Oral and Maxillofacial Surgeons (AAOMS) in 2007 has come-up with the three following criteria:16 ÂÂ

Stage 1

Stage 2

Stage 3

Current or previous bisphosphonate

treatment

with

a

Prevention of BRONJ Since treatment for BRONJ is limited, prevention remains imperative. That is because even if patients discontinue uptake of BPs, the effect of discontinuation is subtle due to the characteristics of bisphosphonates in that it remains in the bone for several years. In patients taking or considering bisphosphonates therapy, the approach to preventing BRONJ is largely determined by the type of bisphosphonates therapy. Given the apparently low-risk of BRONJ among patients receiving oral bisphosphonates for osteoporosis, maintenance of

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Exposed, necrotic bone in the maxillofacial region that has persisted for more than eight weeks No history of radiation therapy to the jaws.11,12

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Ruggiero et al Suggested the following clinical staging of BRONJ at AAOMS in 2009 (Table 1)11-13,16 Treatment strategy of BRONJ As Per the recommendation of AAOMS in 2009 (Table 2).11-13 Hyperbaric oxygen is of no help in the treatment of BRONJ.

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ORTHOPEDICS good oral hygiene and the same level of dental care as for the general population needs to be implemented and followed by patients of BRONJ. For the prevention of BRONJ, the following patient education measures are recommended: ÂÂ

References 1. Vescovi P, Nammour S. Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ) therapy. A critical review. Minerva Stomatol 2010;59(4):181-203, 204-13. 2. Bagan J, Scully C, Sabater V, Jimenez Y. Osteonecrosis of the jaws in patients treated with intravenous bisphosphonates (BRONJ): A concise update. Oral Oncol 2009;45(7):551-4. 3. AAOMS position paper on bisphosphonate-related osteonecrosis of the Jaws. J Oral Maxillofac Surg 2007;65:369-76. 4. Hellstein JW, Marek CL. Bisphosphonate osteochemonecrosis (bis-phossy jaw): is this phossy jaw of the 21st century? J Oral Maxillofac Surg 2005;63(5):682-9. 5. Helsloot RS, van den Berg T, Frank MH, Everts V. Bisphosphonate related osteonecrosis of the jaw; a literature review and a new hypothesis. Intern Oral Res 2011;2:e3. 6. Ruggiero SL, Fantasia J, Carlson E. Bisphosphonate-related osteonecrosis of the jaw: background and guidelines for diagnosis, staging and management. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006 ;102(4):433-41. 7. Russell RG. Bisphosphonates: from bench to bedside. Ann N Y Acad Sci 2006;1068:367-401. 8. Nancollas GH, Tang R, Phipps RJ, Henneman Z, Gulde S, Wu W, et al. Novel insights into actions of bisphosphonates on bone: differences in interactions with hydroxyapatite. Bone 2006;38(5):617-27. 9. Marx RE, Sawatari Y, Fortin M, Broumand V. Bisphosphonate-induced exposed bone (osteonecrosis/ osteopetrosis) of the jaws: risk factors, recognition, prevention, and treatment. J Oral Maxillofac Surg 2005;63(11):1567-75. 10. Migliorati CA, Schubert MM, Peterson DE, Seneda LM. Bisphosphonate-associated osteonecrosis of mandibular and maxillary bone: an emerging oral complication of supportive cancer therapy. Cancer 2005;104(1):83-93. 11. Kim YG, Lee YD, Kwon YD, Suh JH, Jeen SM. Study on bisphosphonates-related osteonecrosis of the jaw (BRONJ): Case report and literature review. J Korean Assoc Oral Maxillofac Surg 2010;36:291-302. 12. Ruggiero SL, Dodson TB, Assael LA, Landesberg R, Marx RE, Mehrotra B; American Association of Oral and Maxillofacial Surgeons. American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonaterelated osteonecrosis of the jaws - 2009 update. J Oral Maxillofac Surg 2009;67(5 Suppl):2-12. 13. Rizzolo D, Sedrak M. Managing the adverse effects of bisphosphonate therapy on the jaw. JAAPA 2009;22(11):48-52. 14. Ruggiero SL, Mehrotra B, Rosenberg TJ, Engroff SL. Osteonecrosis of the jaws associated with the use of bisphosphonates: a review of 63 cases. J Oral Maxillofac Surg 2004;62(5):527-34. 15. Badros A, Weikel D, Salama A, Goloubeva O, Schneider A, Rapoport A, et al. Osteonecrosis of the jaw in multiple myeloma patients: clinical features and risk factors. J Clin Oncol 2006;24(6):945-52. 16. Ikebe T. Pathophysiology of BRONJ: Drug-related osteoclastic disease of the jaw. Oral Science International. 2013;10(1):1-8.

When dental treatment is needed, patients need to notify dental clinicians of their bisphosphonate uptake. Prior to the BPs treatment, patients to be told of advantages of BPs and possibility of developing BRONJ as a rare complication. Patients need to maintain good oral hygiene. Patient needs to notify clinicians when patient has risk factors or symptoms of BRONJ. Patient to notify clinicians when patient has edema, pain or exposed bone. Prior to treatment with bisphosphonates, any unsalvaged teeth should be removed, all invasive dental procedures should be complete and optimal oral health should be achieved. Patient with established BRONJ should be treated by skilful dental specialists, and the purpose of treatment should be to release pain and infection of soft tissue and bone, and minimize osteonecrosis of the jaw. Chlorhexidine mouthwash, an antiseptic agent, is an effective treatment method for infection, and if there is any evidence of infection, systemic antibiotics are recommended. The conservative treatment should be the first choice because there is a possibility that periodontal surgery makes the surgical site to re-necrotize, thus it should be delayed as long as possible.

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Conclusion ÂÂ

Although, the definitive role of bisphosphonates remains to be elucidated, the alteration in bone metabolism together with surgical insult or prosthetic trauma appear to be key factors in the development of osteonecrosis. The dental practitioner must understand the consequence of altering or halting bisphosphonate therapy for a relatively small incidence of BRONJ. That is, to recommend a patient to stop taking bisphosphonate because of the fear of a low incidence of necrotic bone ulcers may be a poor decision. These patients can suffer from debilitating vertebral bone fractures whose consequence far outweighs the problems created by jawbone ulcers. Conversely, medical practitioners must seriously consider the longstanding use of prolonged oral bisphosphonate use after bone saturation levels are reached.

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Pediatrics

Exclusive Breast-feeding: Is Motivation the Only Issue?

M Girish*, N Mujawar**, V Dandge**, P Pazare†, K Gaikwad‡

Abstract Objectives: The aim of the study was: (1) To know the frequency of suboptimal infant breastfeeding behavior (SIBB), delayed onset of lactation (DOL) and excess neonatal weight loss (EWL) in mother-infant pairs with a high motivation to breastfeed; (2) to see if SIBB influenced lactational problems represented by: a] DOL, b] EWL; (3) in addition, we have tried to assess the risk factors for SIBB and other risk factors for DOL and EWL. Material and methods: A longitudinal hospital-based observational study. Infant breastfeeding behavior was assessed by IBFAT score, DOL was measured by maternal perception of breast fullness and maternal motivation by an initial interview based on breastfeeding self-efficacy scale. Results: Frequency of SIBB was 13.3% on Day 0, 6.6% on Day 3 and 2.9% on Day 7. DOL occurred in 11.8% of mothers and excess weight loss in 17.7% of infants. Prolonged labor, medications given during labor, inadequacy of sleep during peripartum and use of supplementary feeds were found to be significantly associated with SIBB. Infants with SIBB on Day 0 were 17 times more likely to have SIBB on Day 3 and they were also four times more likely to have excess weight loss. Failure of exclusive breastfeeding (EBF) occurred in 8.1% and showed a significant association with SIBB, but at two weeks all were breastfeeding exclusively. Conclusion: Infant behavior plays an important role in the success of early breastfeeding and if suboptimal, contributes to failure of EBF. Both infant behavior and onset of lactation constitute significant predictors of excessive weight loss and short-term failure of exclusive breastfeeding and help in determining the need for intensive lactation counseling in high-risk cases.

Keywords: Suboptimal infant breastfeeding behavior, exclusive breastfeeding, neonatal weight loss, onset of lactation

T

he mother-baby symbiotic dyad can be considered to last for 15 months, connected by the umbilical cord for the first nine months and by breastfeeding for the next six months. The infant’s health is imperiled not just if the first period of nine months is shortened but also if the second period is pruned. Exclusive breastfeeding (EBF) remains uncommon in most countries (both developed and developing), even in countries with high rates of breastfeeding initiation.1,2

*Associate †Lecturer

**Professor ‡Assistant

Professor

Studies investigating failure of EBF3,4 have put the spotlight on the mother or the environmental influences acting on the mother (lack of support for breastfeeding by social workers and healthcare providers, emotional stress in mothers and their perception of not having enough breast milk, and pressure from close relatives to introduce other liquid foods, unsupportive hospital practices that delay early initiation of breastfeeding and maternal employment). While psychosocial and cultural barriers are reported as important contributing factors, there have been instances where mothers were highly motivated to breastfeed but were discouraged within the first few weeks due to insufficient milk and suboptimal breastfeeding behaviors among newborns leading to excessive weight loss and other medical complications, even death.5,9 Based on the hypothesis that even highly motivated mothers can face problems in breastfeeding including problems with infant behavior we decided to study the phenomenon of suboptimal infant breastfeeding behavior (SIBB) and other lactation problems in this group of mothers.

Lecturer Dept. of Pediatrics NKP Salve Institute of Medical Sciences and Research Center Nagpur, Maharashtra Address for correspondence Dr Kiran Gaikwad 28, Karim Layout, Gopal Nagar, Nagpur, Maharashtra - 440 022 E-mail: ksgaikwad@hotmail.com

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Pediatrics aims and objectives The aim of the study was: (1) To know the frequency of SIBB, delayed onset of lactation (DOL) and excess neonatal weight loss (EWL) in mother-infant pairs with a high motivation to breastfeed; (2) to see if SIBB influenced lactational problems represented by: a) DOL, b) EWL; (3) in addition, we have tried to assess the risk factors for SIBB and other risk factors for DOL and EWL. Material and Methods This observational longitudinal study was conducted in a tertiary care hospital in Nagpur, Maharashtra after taking approval from the Institutional Ethics Committee. A pilot study was done and the prevalence of SIBB was found to be 11%. In the absence of Indian data, 11% prevalence at 95% confidence interval (CI) and 80% power was considered to calculate the sample size. All mothers who delivered their babies during the period between April and September 2009, were interviewed and included if: (1) They delivered term appropriate for age babies with no perinatal morbidities; (2) they were motivated to breastfeeding exclusively (based on a shortened version of the breastfeeding selfefficacy scale) and (3) they resided near the hospital area and were willing to participate in the study. Infant’s behavior was assessed using the Infant Breastfeeding Assessment Tool (IBFAT), which includes ratings for arousal, rooting, time to latch and feed well, sucking effectiveness. Each point is worth 0-3 with a total maximum score of 12. A score of <10 was considered SIBB. Onset of lactation (OL) was determined by maternal report of breast fullness changes; DOL was defined as breast fullness perceived after 72 hours. EWL was defined as loss of weight ≥10% of birthweight by Day 3. At the time of delivery, information was collected from the medical record concerning the duration of Stage I and II labor (from onset of regular contractions to cervical dilation of 10 cm and from full dilation to the delivery of the infant, respectively), mode of delivery, labor medications, infant resuscitation, gravida, parity and infant birth weight. Breastfeeding guidance was given by the first author within 24 hours of delivery and then at every opportunity, emphasizing correct positioning and latching on to the breast and the importance of demand feeding and avoidance of supplements. The mother was interviewed for following information: ÂÂ ÂÂ

The interval without sleep before delivery. Infant feeding pattern since birth (when first put to breast since the time of birth; infant interest in nursing in the form of smacking or licking lips, opening and closing mouth, sucking on lips, tongue, hands, fingers, increased alertness and movements of arms and legs, number of breastfeeds; use of supplemental fluids/feeds). Family support during delivery. Previous experience of breastfeeding. Her confidence in her ability to exclusively breastfeed her infant for six months (on a scale of 1 = no confidence, to 5 = very confident).

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Breastfeeding observation was done by a research assistant who worked exclusively on this project for six months. Data regarding nipple type (flat/inverted/ normal), maternal and infant positioning, suckling behavior and mother’s report of pain during feeding was recorded. IBFAT score was recorded on Days 0, 3, 7 (counting the day of birth as 0) and lactation guidance was continued. The guidance provided was as per the ILCA (International Lactation Consultant Association) guidelines. On Day 3 additional information collected were: a) Frequency of feeding; b) level of breast fullness (on a scale of 1-5; with 1 = no change and 5 = uncomfortably full); c) the approximate time postpartum when breast fullness first reached 3; d) supplemental feeds given; e) the level of support received from other family members (1 = most not supportive, 2 = some supportive, 3 = a lot of support) and f) any pain or discomfort encountered during feeding. Infant’s weight was taken on an electronic weighing scale. Any baby who had excess weight loss was given appropriate management (either close observation or neonatal intensive care unit [NICU] admission). Maternal body mass index (BMI) was measured on Day 14. Statistical Analysis Bivariate associations between five outcome variables, namely, SIBB on Days 0, 3, 7, DOL, excessive weight loss and 13 independent variables were examined using χ2 tests or Fisher’s test. Multiple logistic regression analysis was used to control for associations among the independent variables. Stepwise selection was used to construct the preliminary models (p level for inclusion or removal = 0.05). The independent variables for each

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Pediatrics preliminary model were chosen based on whether: a) There was a theoretical basis for an association between the independent variable and the outcome; b) the independent variable preceded the outcome variable in occurrence, potential interaction with parity and mode of delivery were examined, wherever there was a significant outcome for a given independent variable in the bivariate analyses. In preliminary analyses, potential interactions with parity and delivery mode were also examined, but these were not included in the regression models because there was little evidence that the association of the outcomes with any of the independent variables differed in mothers with vaginal versus cesarean section delivery or in primipara versus multipara. Bivariate associations among the five outcome variables were also examined. Results One hundred thirty-five mother-infant pairs were included for the final analysis. Attitude towards breastfeeding were strongly positive with 84.4% mothers confident about breastfeeding exclusively for six months and 93.3% reporting full family support for same. About 8.1% babies received supplementation in the form of cow’s milk, water or glucose supplementation. The mean maternal age was 22.4 years and 50% were primiparous. Majority of mothers were educated upto middle school (63.7%). About 32.2% mothers underwent cesarean section, 80% of which was performed on primipara. The duration of labor was longer in primipara, analgesics during labor were given to only 14% and 12.5% received oxytocin, all in primipara. Early breastfeeding (within half an hour after normal delivery and 4 hours after cesarean section) was influenced more by the mode of delivery (delayed in 36% of cesarean) than by the parity. Average breastfeeding frequency was 8 ± 2 on Day 0. Frequency of SIBB was 13.3% on Day 0, 6.6% on Day 3 and 2.9% on Day 7. SIBB was significantly associated with prolonged labor (SIBB Day 0), medications given during labor especially oxytocin and maternal analgesics (SIBB Day 0), inadequacy of sleep in the mother during the peripartum period (SIBB Days 0 and 3), use of supplementary feeds (SIBB Days 3 and 7). DOL occurred in 11.8% of mothers. There was significant association with the use of supplementary feeds in the babies and the type of family (nuclear/joint). Excess weight loss occurred in 23.7% of infants and was also significantly associated with use of supplementary feeds and type of family (more common in nuclear family). Infants with SIBB on Day 0 were 17 times more likely to have SIBB on Day 3 (p < 0.002, lower CL 2.6 and upper CL 125.7, Fisher exact test) and they were also nearly four times more likely to have excess weight loss. No significant association was found between SIBB on Day 0 and SIBB on Day 7 as well as DOL in the mother. At two weeks, all the babies were on exclusive breastfeeding. Discussion The results indicate that lactation difficulties are not uncommon during first few days postpartum even among mothers who were highly motivated to breastfeed exclusively, though the incidence of SIBB reported in our study (13.3% on Day 0, 6.6% on Day 3 and 2.9% on Day 7) population is much lower than that observed in a similar study done in California, USA.10 But, the incidence of excess weight loss is much higher in our study (21.7%) as compared to western data.11 Significant association between SIBB on Day 0 and the risk of excess weight loss and SIBB on Days 3 and 7 with the use of supplementary feeds indicates that infant breastfeeding behavior assessment would help in identifying babies at high-risk for breastfeeding complications. In our study, all the babies with a low SIBB score were given repeated and intensive lactation counseling and this may explain the fact that the incidence of SIBB decreased progressively by Day 7, SIBB on Day 0 improved and weight gain occurred by Day 7 and more importantly, the fact that all the mothers were giving exclusive breastfeeding at two weeks. DOL occurred in 11.8% but we found no significant association with suboptimal infant behavior either on Day 0 or Day 3. DOL was significantly associated with the use of supplementary feeds in the first 48 hours and this finding has been corroborated by several other studies.12-15 The vicious cycle of supplementary feeding and lactational problems have been highlighted and emphasized in the past. Early supplementary feeds lead to DOL resulting in further supplementation thereby perpetuating the cycle. This may also prime future decisions to supplement, leading to an earlier introduction of top feeds. Exclusive breastfeeding indicates that the baby will receive only breast milk and no prelacteals or supplementary feeds with the exception of drops or syrups consisting of vitamins, mineral supplements or medicines.16 By this definition, all the babies who received supplementary

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Pediatrics feeds in our study (8.1%) represent failure of exclusive breastfeeding and towards this end, both SIBB (on Days 0 and 3) and DOL contributed towards temporary failure in exclusive breastfeeding but the trend was reversed successfully through timely intervention. There have been conflicting reports on association of labor medications and infant suckling behavior.17-20 We studied induction of labor with oxytocin and IV analgesics during labor and found that they significantly affected breastfeeding behavior on first day of life. Two other factors found to be associated with a greater risk of SIBB on Day 0 were prolonged labor (total duration >12 hours) and adequacy of sleep before labor pains in the mother. We presume that the longer duration of labor and inadequate sleep could increase stress in the mother during the postpartum period and this may affect mother infant bonding. These findings imply that modification of the labor and delivery experience should improve early lactation success, a recommendation often made in various studies.21-23 The role of joint family system on the success of exclusive breastfeeding is controversial. While administration of prelacteals and supplementary feeds is usually attributed to family pressures in a joint family system, we found that supplementary feeds were more often used and delayed lactation occurred more commonly in mothers belonging to nuclear families thus reinforcing the need for the traditional joint family system; of course lactation guidance should be given to the entire family! Conclusion In the list of factors conducive for exclusive breastfeeding in healthy neonates the thrust so far has been on maternal factors. In this study, we have tried to turn the spotlight also on infant behavior as an important variable, which deserves attention. Infant behavior plays an important role in the success of early breastfeeding and if suboptimal, contributes to failure of EBF. Evaluation of infant breastfeeding behavior as well as onset of lactation in the early days could predict excessive weight loss and possibility of supplementary feeding in the neonate. Suboptimal infant breastfeeding behavior is amenable to intervention (lactation management counseling, avoidance of supplementary feeds, modifications in use of labor medications). All women with breastfeeding problems initially can eventually establish an adequate milk supply but the phenomenon should be taken seriously and every opportunity should be taken to address all the issues responsible for this including infant behavior, not only because it can lead to poor breastfeeding outcome in the short-term but it is known to lead to shorter duration of exclusive breastfeeding.7 References 1. Dimond HJ, Ashworth A. Infant feeding practices in Kenya, Mexico and Malaysia. The rarity of the exclusively breast-fed infant. Hum Nutr Appl Nutr 1987;41(1):51-64. 2. Perez-Escamilla R. Breastfeeding in Africa and the Latin American and Caribbean region: the potential role of urbanization. J Trop Pediatr 1994;40(3):137-43. 3. Froozani MD, Permehzadeh K, Motlagh AR, Golestan B. Effect of breastfeeding education on the feeding pattern and health of infants in their first 4 months in the Islamic Republic of Iran. Bull World Health Organ 1999;77(5):381-5. 4. Imdad A, Yakoob MY, Bhutta ZA. Effect of breastfeeding promotion interventions on breastfeeding rates, with special focus on developing countries. BMC Public Health 2011;11 Suppl 3:S24. 5. Banapurmath CR, Nagaraj MC, Banapurmath S, Kesaree N. Breastfeeding practices in villages of central Karnataka. Indian Pediatr 1996;33(6):477-9. 6. Hall RT, Mercer AM, Teasley SL, McPherson DM, Simon SD, Santos SR, et al. A breast-feeding assessment score to evaluate the risk for cessation of breast-feeding by 7 to 10 days of age. J Pediatr 2002;141(5):659-64. 7. McLeod D, Pullon S, Cookson T. Factors influencing continuation of breastfeeding in a cohort of women. J Hum Lact 2002;18(4):335-43. 8. Mathur GP, Chitranshi S, Mathur S, Singh SB, Bhalla M. Lactation failure. Indian Pediatr 1992;29(12):1541-4. 9. Neifert MR. Prevention of breastfeeding tragedies. In: The Pediatric Clinics of North America, Breastfeeding 2001, Part II: The Management of Breastfeeding. Volume 48. Schanler RJ (Ed.), WB Saunders: Philadelphia, PA 2001:p.273-98. 10. Chapman DJ, Pérez-Escamilla R. Identification of risk factors for delayed onset of lactation. J Am Diet Assoc 1999 ;99(4):450-4; quiz 455-6. 11. Dewey KG, Nommsen-Rivers LA, Heinig MJ, Cohen RJ. Risk factors for suboptimal infant breastfeeding behavior, delayed onset of lactation, and excess neonatal weight loss. Pediatrics 2003;112(3 Pt 1):607-19. 12. Manganaro R, Mamì C, Marrone T, Marseglia L, Gemelli M. Incidence of dehydration and hypernatremia in exclusively breast-fed infants. J Pediatr 2001;139(5):673-5. 13. Ransjö-Arvidson AB, Matthiesen AS, Lilja G, Nissen E, Widström AM, Uvnäs-Moberg K. Maternal analgesia during labor disturbs newborn behavior: effects on breastfeeding, temperature, and crying. Birth 2001; 28(1):5-12.

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Pediatrics 14. Kramer MS, Barr RG, Dagenais S, Yang H, Jones P, Ciofani L, et al. Pacifier use, early weaning, and cry/fuss behavior: a randomized controlled trial. JAMA 2001;286(3):322-6. 15. ABM Clinical Protocol #3. Hospital Guidelines for the Use of Supplementary Feedings in the Healthy Term Breastfed Neonate, Revised 2009. The Academy of Breast Feeding Medicine Protocol Committee. Breast Feeding Medicine 2009:4(3):175-82. 16. WHO Geneva. Indicators for assessing breastfeeding practices. WHO Geneva Switzerland: WHO Document WHO/CDD/SER1991;9:14. 17. Crowell MK, Hill PD, Humenick SS. Relationship between obstetric analgesia and time of effective breast feeding. J Nurse Midwifery 1994;39(3):150-6. 18. Riordan J, Gross A, Angeron J, Krumwiede B, Melin J. The effect of labor pain relief medication on neonatal suckling and breastfeeding duration. J Hum Lact 2000;16(1):7-12. 19. MacMullen NJ, Dulski LA. Factors related to sucking ability in healthy newborns. J Obstet Gynecol Neonatal Nurs 2000;29(4):390-6. 20. Halpern SH, Levine T, Wilson DB, MacDonell J, Katsiris SE, Leighton BL. Effect of labor analgesia on breastfeeding success. Birth 1999;26(2):83-8. 21. Radzyminski S. The effect of ultra low dose epidural analgesia on newborn breastfeeding behaviors. J Obstet Gynecol Neonatal Nurs 2003;32(3):322-31. 22. Ounsted MK, Hendrick AM, Mutch LM, Calder AA, Good FJ. Induction of labour by different methods in primiparous women. I Some perinatal and postnatal problems. Early Hum Dev 1978;2(3):227-39. 23. Zuppa AA, Vignetti M, Romagnoli C, Tortorolo G. Assistance procedures in the perinatal period that condition breast feeding at the time of discharge from the hospital. Pediatr Med Chir 1984;6(3):367-72.

Nearly half of parents who visited the emergency department with a child who had suffered a head injury knew that computed tomography (CT) imaging was associated with an increased lifetime cancer risk, and 90.7% of parents wanted to know about such risk potential before CT use, according to a prospective cross-sectional study. (Source: Medscape) Close to half of 2-month-old have “positional plagiocephaly” - a flat spot on the back of their heads - and changes in parents’ habits may be a cause. Although not thought to be medically dangerous, the flattened head shape can become permanent, which can have psychological implications for kids as they grow up, Canadian authors suggest. (Source: Medscape) Newborn screening for critical congenital heart disease (CCHD) in the United States could be reasonably costeffective, according to the first US cost-effectiveness analysis of such screening, published online August 5 in Pediatrics. According to Cora Peterson, PhD, from the National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia, and colleagues, clinical evidence indicates newborn (CCHD) screening through pulse oximetry is lifesaving. In 2011, CCHD was added to the US Recommended Uniform Screening Panel for newborns. (Source: Medscape) For newborn babies, taking ethnicity into account may help determine how small is too small. Canadian researchers have found that birth-weight standards based on population averages did not predict which babies born at or near term were likely to suffer problems associated with being small for gestational age. Gillian Hanley of the School of Population and Public Health at the University of British Columbia in Vancouver said that based on her results, adjusting the standards may be necessary. (Source: Medscape) Providers often prescribe antibiotics for outpatient pediatric urinary tract infections (UTIs) without obtaining urine tests according to a new study published online August 5th in the journal Pediatrics. According to Dr. Hillary L. Copp from University of California, San Francisco, children presenting with UTI symptoms that are treated for a UTI with and without urine testing should be prospectively evaluate to determine the implications of these different treatment approaches. (Source: Medscape)

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PEDIATRICS

Vitamin E Level in Normal Indian Children Geeta Gathwala, Subrika Yadav, Ojawanai, G Lal

Abstract Objective/Background: The study was conducted a aim to determine vitamin E levels in normal Indian children. Vitamin E has positive effect on cardiovascular health through its ability to influence signaling process in platelets and also has significant role in neurodegenerative disorders. Vitamin C and vitamin E supplementation retards the progression of coronary arteriosclerosis during early stage following cardiac transplantation. It also mediates the generation and availability of superoxide and nitric oxide and is beneficial in preventing prostate cancer or delaying disease progression. Material and methods: Study included 30 healthy children of either sex, they were divided into three groups each of 10 children i.e., Group I (2-4 years) mean age 3.42 years, Group II (4-6 years) mean age 5.35 years and Group III (6-10 years) mean age 8 years. Vitamin E levels were measured in their serum fluorometric micro methods for serum tocopherol as described by Hansen and Warwick. Result: In Group I, the mean ± SEM value of vitamin E was 2.74 ± 1.10 µgm/ml, in Group II it was 2.82 ± 1.11 µgm/ml and in Group III it was 2.93 ± 1.12 µgm/ml. Conclusion: Serum vitamin E levels in healthy Indian children is 2.82 ± 1.11µg/ml and there is no sex predilection.

Keywords: Vitamin E, healthy Indian children

V

itamin E was discovered by Even and Bishop. Vitamin E is indispensable for reproduction and prevents diseases associated with oxidative stress, such as cardiovascular disease, cancer, chronic inflammation and neurologic disorders.1-3 Vitamin E and ω-3 fatty acids are positive effectors of cardiovascular health through their ability to influence signaling process in platelets. Vitamin E has significant role in neurodegenerative disorders.4,5 Vitamin C and vitamin E supplementation retards progression of coronary arteriosclerosis during early stage following cardiac transplantation.6-8 Vitamin E may mediate the generation and availability of superoxide and nitric oxide.9 Vitamin E may be beneficial in preventing prostate cancer or delaying disease progression.10 At transcriptional level, several genes (CD36, tocopherol transfer protein [a-TTP], a-topomyosin and collagenase) are modulated by

a-tocopherol. These effects result in inhabitation of smooth muscle cell proliferation, platelet aggregation and monocyte adhesion and thus protect atherosclerosis.11 Vitamin E has an additional positive effect on autoimmune disease by decreasing proinflammatory cytokines, lipid mediators and has important role in rheumatoid arthritis patients.12 Prolonged vitamin E deficiency leads to peripheral neuropathy, muscle weakness and ophthalmoplegia, which are irreversible. Fifty to 70% of children with chronic cholestasis are vitamin E deficient, even when consuming standard supplements of vitamin E.7 a-tocopherol is the most bioactive form of vitamin E followed in order by b, g and d tocopherol. The most commonly used pharmacologic form of a-tocopherol is a totally synthetic product and has both D and L stereoisomers now designated as racemic a-tocopherol. This synthetic form has considerably less bioactivity (approximately 75%) than the pure naturally occurring form. Vitamin E is absorbed into intestinal mucosa by nonsaturable, noncarrier-mediated passive diffusion process and absorption is maximal in median small intestine and none is absorbed in large intestine. Human body stores 40 mg/kg vitamin E, 77% of which is in adipose tissue, 20% in muscle and only 1% in liver. Since, there is paucity of Indian data, the study was planned to assess the serum vitamin E levels in normal Indian children.

Dept. of Pediatrics Biochemistry Pt. BD Sharma Postgraduate Institute of Medical Sciences, Rohtak, Haryana Maulana Azad Medical College, New Delhi Address for correspondence Dr Geeta Gathwala Professor and Head, Dept. of Pediatrics 6J/8, Postgraduate Institute of Medical Sciences, Rohtak E-mail: g_gathwala@hotmail.com

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Pediatrics MATERIAL AND METHODS This study was conducted in 30 healthy children of either sex, whowere divided into three groups each of 10 children i.e., Group I (2-4 years) mean age 3.42 years, Group II (4-6 years) mean age 5.35 years and Group III (6-10 years) mean age eight years. Vitamin E levels were measured in their serum by fluorometric micro method for serum tocopherol as described by Hansen and Warwick.13 RESULT In Group I, the mean ± SEM (standard error of mean) value of vitamin E was 2.74 ± 1.10 ± µg/ml, in Group II it was 2.82 ± 1.11 ± µg/ml while in Group III it was 2.93 ±1.12 ± µg/ml. (Table 1) On inter group comparison, using students t test the difference in values amongst the three groups was found to be nonsignificant. Since, there was no significant difference in serum vitamin E levels in different age groups of children and there no specific gender predilection, we assumed the 60 children belonging to one group to report the serum vitamin E level in normal Indian children to be 2.82 ± 1.11µg/ml. DISCUSSION Among the nutritional factors contributing to maintain health during aging, fat-soluble vitamins are crucial to protect against free radical generated degenerative processes or impaired efficiency of immune system.14,15 Antioxidant activity is provided by a number of naturally occurring substances including a-tocopherol (vitamin E) and b-carotene, whose effects are mediated by their capacity to quench ringlet oxygen, scavenge free radicals and prevent the formation of free radicals and is used to prevent ultraviolet-induced skin damage.16,17 Inadequate, intake of several vitamins is linked to chronic diseases, including coronary heart disease, cancer and osteoporosis.18 Enterally, fed premature infants are supplemented fat soluble vitamins.19 The normal serum vitamin E levels in Table 1 Effect of Age on Vitamin E levels Group Age (years) 2-4 4-6 6-10

children and adults range from 5 to 20 µg/ml and are slightly lower in infants and young children i,e, 3-10µgm/ ml. In our study also, vitamin E levels were found to increase with age i.e., (mean ± SEM was 2.74 ± 1.10, 2.82 ± 1.11, 2.93 ± 1.12 in Groups I, II and III, respectively (Table 1). Though, this increment in vitamin E levels was not found to be significant, which may be due to the minor differences in age of different groups. A ratio of < 0.6 mg in children under 12 years and less than 0.8 mg total tocopherol per gram of lipid in older children and adults, represents vitamin E deficiency.1 conclusion In conclusion serum vitamin E levels in healthy Indian children is 2.82 ± 1.11µ and there is no sex predilection. REFERENCES 1. Brigelius-Flohé R, Kelly FJ, Salonen JT, Neuzil J, Zingg JM, Azzi A. The European perspective on vitamin E: current knowledge and future research. Am J Clin Nutr 2002;76(4):703-16. 2. Marchioli R, Schweiger C, Levantesi G, Tavazzi L, Valagussa F. Antioxidant vitamins and prevention of cardiovascular disease: epidemiological and clinical trial data. Lipids 2001;36 Suppl:S53-63. 3. Ricciarelli R, Zingg JM, Azzi A. Vitamin E: protective role of a Janus molecule. FASEB J 2001;15(13):2314-25. 4. Butterfield DA, Castegna A, Drake J, Scapagnini G, Calabrese V. Vitamin E and neurodegenerative disorders associated with oxidative stress. Nutr Neurosci 2002;5(4):229-39. 5. Martin A, Youdim K, Szprengiel A, Shukitt-Hale B, Joseph J. Roles of vitamins E and C on neurodegenerative diseases and cognitive performance. Nutr Rev 2002;60(10 Pt 1):308-26. 6. Liu L, Meydani M. Combined vitamin C and E supplementation retards early progression of arteriosclerosis in heart transplant patients. Nutr Rev 2002;60(11):368-71. 7. Praticò D. Vitamin E: murine studies versus clinical trials. Ital Heart J 2001;2(12):878-81. 8. Soares KV, McGrath JJ. Vitamin E for neurolepticinduced tardive dyskinesia. Cochrane Database Syst Rev 2001;(4):CD000209. 9. Chow CK, Hong CB. Dietary vitamin E and selenium and toxicity of nitrite and nitrate. Toxicology 2002;180(2):195-207. 10. Fleshner NE. Vitamin E and prostate cancer. Urol Clin North Am 2002;29(1):107-13, ix.

Mean Age (years) 3.42 5.35 8.00

Vitamin (Mean ± SEM) 2.74 ± 1.10 2.82 ± 1.11 2.93 ± 1.12

P value NS NS NS

I II III

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Pediatrics 11. Ricciarelli R, Zingg JM, Azzi A. Vitamin E 80th anniversary: a double life, not only fighting radicals. IUBMB Life 2001;52(1-2):71-6. 12. Tidow-Kebritchi S, Mobarhan S. Effects of diets containing fish oil and vitamin E on rheumatoid arthritis. Nutr Rev 2001;59(10):335-8. 13. Hansen LG, Warwick WJ. A fluorometric micro method for serum tocopherol. Tech Bull Regist Med Technol 1966;36(6):131-6. 14. Sorg O, Tran C, Saurat JH. Cutaneous vitamins A and E in the context of ultraviolet- or chemically-induced oxidative stress. Skin Pharmacol Appl Skin Physiol 2001;14(6):363-72. 15. Rock E, Winklhofer-Roob BM, Ribalta J, Scotter M, Vasson MP, Brtko J, et al. Vitamin A, vitamin E and carotenoid status and metabolism during ageing: functional and nutritional consequences (VITAGE PROJECT). Nutr Metab Cardiovasc Dis 2001;11(4 Suppl):70-3 16. Anstey AV. Systemic photoprotection with alphatocopherol (vitamin E) and beta-carotene. Clin Exp Dermatol 2002;27(3):170-6. 17. Podhaisky HP, Wohlrab W. Is the photoprotective effect of vitamin E based on its antioxidative capacity? J Dermatol Sci 2002;28(1):84-6. 18. F airfield KM, Fletcher RH. Vitamins for chronic disease prevention in adults: scientific review. JAMA 2002;287(23):3116-26. 19. Greer FR. Fat-soluble vitamin supplements for enterally fed preterm infants. Neonatal Netw 2001;20(5):7-11.

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Repair Aortic Coarctation Early and Follow for Life: 60-year Study Babies born with a narrowing of the aorta should be followed for cardiac issues throughout their lives, say the authors of a six-decade review of cases at the Mayo Clinic in Rochester, Minnesota. (Source: Medscape)

Presence of Eczema may Affect Infant Food Allergies Infants with atopic dermatitis (AD), also known as atopic eczema, may be more likely than infants without AD to be sensitized to commonly allergenic foods, according to an article published online July 18 in the Journal of Investigative Dermatology. (Source: Medscape)

Less Sleep, More Behavioral Problems in Kids Children who have relatively short nighttime sleep duration are at high risk for several externalizing behavioral problems. A cohort study of almost 9000 preschool-aged children showed that those who averaged fewer than 9 hours of sleep per night were significantly more likely to show impulsivity, anger, and overactivity and to have tantrums than their peers who averaged more nightly sleep. The children with less sleep were also 80% more likely to show aggression. (Source: Medscape)

Finland Bucks the Trend: Type 1 Diabetes in Kids Flattens An analysis of data from the Finnish National Institute for Health and Welfare on type 1 diabetes diagnosed in children aged 0 to 14 years during 2006–2011 is published July 23 in a research letter in JAMA shows that the incidence of type 1 diabetes appears to be leveling off in the country. Finland has the highest incidence of T1D in the world, and its T1D registry is one of the longest-running. (Source: Medpage Today)

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PEIDATRICS

An Interesting Case of Meckel-Gruber Syndrome Sangeeta Arya*, K Pandey**, A Verma†, RK Singh‡, S Chauhan¶

Abstract Meckel-Gruber syndrome, also known as ‘Dysencephalia splanchnocystica’, is a rare lethal autosomal recessive disorder consisting of central nervous system malformation- mainly posterior encephalocele (80%), multicystic kidneys (95%) and polydactyly (75%). Besides the classic triad of neural tube defects, polydactyly and cystic dysplasia of the kidneys, other abnormalities can occur in association with the syndrome, which may be detected sonographically include micrognathia, cardiac abnormalities, syndactyly, clinodactyly and clubbed foot. We report a case of a 26-year-old woman with previous LSCS referred from a private practitioner with abnormal ultrasonographic findings. She was diagnosed to have Meckel-Gruber syndrome. Woman and her husband were counseled regarding this lethal condition incompatible with life and after proper consent and information, pregnancy was terminated.

Keywords: : Prenatal diagnosis, Meckel-Gruber syndrome, trisomy 13, encephalocele

M

eckel-Gruber syndrome, also known as ‘Dysencephalia splanchnocystica’, is a rare lethal autosomal recessive disorder consisting of central nervous system malformation- mainly posterior encephalocele (80%), multicystic kidneys (95%) and polydactyly (75%). In some cases-hepatic developmental defects also occur along with pulmonary hypoplasia due to oligohydramnios.

fetus corresponding to around 26 weeks with mild oligohydramnios amniotic fluid index (AFI) = 7, placenta post-Grade I maturity, post part of skull showing gap of around 2.2 cm with herniation of brain

Case report A 26-year-old woman G3P1L1A1 with previous lowersegment cesarean section (LSCS) two years back (indication-severe pre-eclamptic toxemia [PET] with fetal distress) was referred from a private practitioner as her USG done at 26 weeks showed single live

*Lecturer **Head of the Dept. Dept. of Obstetrics and Gynecology †Assistant Professor Dept. of Anesthesiology ‡Assistant Professor Dept. of Surgery ¶Junior Resident Dept. of Obstetrics and Gynecology GSVM Medical College, Uttar Pradesh Address for correspondence Dr Sangeeta Arya New Type IV/8, (Near CSA Gate), GSVM Medical College Campus Kanpur, Uttar Pradesh E-mail: sangeetanilverma@gmail.com

Figure 1. Baby showing syndactyly with postaxial polydactyly.

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PEDIATRICS cysts. Histopathology of placenta showed thick walled blood vessels, large areas of fibrinoid necrosis with signs of acute chorioamnionitis. Umbilical cord showed normal, three vessels. DISCUSSION Besides the classic triad of neural tube defects, polydactyly, and cystic dysplasia of the kidneys, other abnormalities can occur in association with the syndrome, which may be detected sonographically include micrognathia, cardiac abnormalities, syndactyly, clinodactyly and clubbed foot.1 Recurrence risk of a neural tube defect may be between 1% and 3% in a given family, whereas recurrence of MeckelGruber syndrome is as high as 25%, due to its autosomal recessive inheritance pattern. So, in a fetus with neural tube defect, other anamolies associated with Meckel-Gruber syndrome should be carefully sought for.1,2 It is estimated that Meckel-Gruber syndrome accounts for 5% of all neural tube defects.3,4 The most likely syndrome to be confused with MeckelGruber syndrome is trisomy 13, since 30% of fetuses with trisomy 13 will have enlarged, cystic kidneys and many of them will also have polydactyly and neural tube defects.2,3 Ideally, a karyotype should be done in fetuses with this constellation of physical findings. Fetal prognosis is same whether the fetus has, trisomy 13 or Meckel-Gruber syndrome but the rate of recurrence is indeed very different, trisomy 13 is mostly a sporadic event with a lower recurrence rate than Meckel-Gruber syndrome. References 1. Nyberg DA, Hallesy D, Mahony BS, Hirsch JH, Luthy DA, Hickok D. Meckel-Gruber syndrome. Importance of prenatal diagnosis. J Ultrasound Med 1990;9(12):691-6. 2. Karjalainen O, Aula P, Seppala M, Hartikainen-Sorri AL, Ryynanen M. Prenatal diagnosis of the Meckel syndrome. Obstet Gynecol 1981;57(6 Suppl):13S-5S. 3. Pardes JG, Engel IA, Blomquist K, Magid MS, Kazam E. Ultrasonography of intrauterine Meckels syndrome. J Ultrasound Med 1984;3(1):33-5. 4. Ahdab-Barmada M, Claasen D. A distinctive triad of malformations of the central nervous system in the Meckel-Gruber Syndrome. J Neuropathol Exp Neurol 1990;49(6):610-20.

Figure 2. Baby with large encephalocele.

tissue through it. Her fundal height corresponded to 24 weeks, liquor seemed to be clinically reduced. We repeated her ultrasound which showed - gestational age corresponding to 24 wks, (BPD 21 weeks 5 days, HC 20 weeks 4 days, AC 24 weeks 5 days, FL 25 weeks 6 days), hypotelorism present, large occipital encephalocele present, normal anatomy of cervicovertebral junction, liquor reduced, with bilateral multicystic kidneys, polydactyly could not be seen due to oligohydramnios with no cystic lesions in lungs or liver. In presence of these findings, most probable diagnosis of MeckelGruber syndrome was made. Woman and her husband were counseled regarding this lethal condition incompatible with life. They wanted termination of pregnancy. After proper consent and information, pregnancy was terminated. She delivered a dead born female baby who had large occipital encephalocele with hypotelorism with postaxial polydactyly in both hands. Lower limbs had normal number of toes. Fetal kidney biopsies were taken, which showed multiple

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PHARMACOLOGY

To Assess the Attitude, Knowledge and Practices of Medical Professionals About Adverse Drug Reactions and Their Reporting in a Teaching Hospital Manoj Goyal*, Monika Bansal**, Shailesh Yadav†, Varnika Grover‡, Preetkanwal‡

Abstract Adverse drug reactions (ADRs) are one of the leading causes of morbidity and represent a substantial burden on healthcare resources. It has been reported that 2.4-6.5% of the total admissions in the hospitals are due to the adverse reactions, many of which are preventable. Voluntary ADR reporting is fundamental to medical drug safety surveillance; however, substantial underreporting is the main limitation of the system. It is estimated that only 6-10% of all ADRs are reported. Therefore, the present study has been designed to assess the knowledge, attitude and practices of the medical professionals towards the ADRs and their reporting in our Institute. Aim and objectives: This study is aimed at investigating the knowledge and attitude and practices of medical professionals in a teaching hospital. Material and methods: The present study was a questionnaire based study. A structured validated questionnaire was used consisting of open ended and closed ended questions to collect the information after approval from the Institutional Ethics Committee (IEC). The study population consisted of all the medical teachers of the institute. Results: The response rate was 85%. Eighty percent of the respondents identified ADR as one of the major causes for mortality and morbidity in patients. ADR reporting was considered important by 87.5% respondents. More than 85% wrote that they did not have enough knowledge about how to report an ADR. One hundred percent of the participants believed that there should be a system of ADRs reporting and monitoring in the institute. Interestingly, all the respondents believed that if the teachers from allied streams (dental, nursing, physiotherapy, pharmacy) are sensitized, it can be useful. Conclusion: There are gaps between knowledge and ADRs reporting among doctors working in a teaching hospital. These gaps need to be filled by improved training and awareness in pharmacovigilance at various levels of healthcare system.

Keywords: Adverse drug reactions, attitude, knowledge and practices of medical professionals

A

dverse drug reactions (ADRs) are one of the leading causes of morbidity and represent a substantial economic burden on healthcare resources.1 It has been reported that 2.4-6.5% of the total admissions in the hospitals are due to the adverse reactions, many of which are preventable.2 The incidence of serious ADRs is 6.7% in India.3

‡MBBS Student Maharishi Markandeshwar Institute of Medical Sciences and Research Mullana, Ambala, Haryana,133 207 Address for correspondence Dr Manoj Goyal Associate Professor Dept. of Pharmacology Maharishi Markandeshwar Institute of Medical Sciences and Research Mullana, Ambala, Haryana -133207 E-mail: dr_manojgoyal@yahoo.co.in

*Associate Professor Dept. of Pharmacology **Associate Professor Dept. of Physiology †Professor Dept. of Pharmacology

Spontaneous ADR reporting is fundamental to medical drug safety surveillance. Though, this system is inexpensive and easy to operate and encompasses all drugs and patient populations, including special groups but substantial under-reporting and inability to calculate the incidence of ADRs are the inherent disadvantages of this system.3,4 Under-reporting can lead to long delays between marketing and detection/ regulatory action of an adverse reaction. Almost seven million patients were exposed to fenfluramine before the association with valvular heart disease led to its withdrawal from the market.5 In one of the studies, 72% of surgical specialists and 81% of medical specialists had diagnosed an ADR but did not report, due to multiple reasons.6 It is estimated that only 6-10% of all ADRs are reported.7 Therefore, the present study was contemplated and done to assess the knowledge, attitude and practices of the medical professionals working in a teaching hospital in North India regarding ADRs and reporting to get an insight into

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PHARMACOLOGY the reasons for nonreporting and to suggest possible ways of improving spontaneous reporting based on our findings. Material and methods The present survey was carried out at Maharishi Markandeshwar Institute of Medical Sciences and Research (MMIMSR), Mullana, Ambala, Haryana, a teaching postgraduate medical institute in North India. The study participants comprised of the medical teachers working in various preclinical, paraclinical and clinical specialties of the institute involved in imparting medical education to the undergraduate and postgraduate students. A structured validated questionnaire was used to collect the information from the study participants (n = 150) after approval from the Institutional Ethics Committee (IEC) using a Paper-and-pencil questionnaire administration mode.8 A verbal consent was taken and objective of the survey was clearly explained to them before administering the questionnaire. Results and observations The filled up questionnaires were collected and analyzed. The response rate was 85%. Eighty percent of the respondents said that ADR is one of the major causes for mortality and morbidity in patients. ADR reporting was considered important by 87.5% respondents. Morbidity can be decreased, will help in identifying and banning the drug, and will increase awareness about particular ADRs, were some of the reasons quoted by the participants for the importance of reporting. 27.5% said all types of ADRs should be reported; whereas, 50% believed that only severe ADRs should be reported. 28.5% were aware about the country’s Pharmacovigilance program and 22% of the respondents wrote that ADRs can be reported using ADR reporting forms of which only 10% had reported an ADR to an ADR reporting and monitoring center. 67.5%, 95% and 100% had written that natural health products, medical devices and equipment and vaccines, respectively can also produce ADRs. No one could write the four essential components of an ADR report, whereas 30% mentioned atleast one component of an ADR report. Majority believed that it is the seriousness, certainty and unusual nature of an ADR, which influences them to report an ADR (Table 1). More than 85% wrote that they did not have enough knowledge about how to report an ADR (Table 2). Others reasons; reporting forms not available, ADR Table 1. Factors which would Influence them to Report ADRs Factors Seriousness of an ADR Certainty of ADR due to drug Unusual ADR Serious + Unusual ADR Serious + Certain Unusual + Certain Serious + Certain + Unusual Percentage (%) 17.5 2.5 2.5 7.5 2.5 2.5 65

Table 2. Factors Influencing the Respondents not to report an ADR Factors 1 2 3 1&2 1&3 1, 2 & 3 1, 2, 3 & 4 Percentage of respondents 42.5% 5% 7.5% 10% 5% 7.5% 22.5%

1. Not enough knowledge, 2. Reporting forms not available, 3. ADR already well known, 4.others; no time to report, no incentive for reporting etc

already well-known, no incentive is given for reporting, no time to report, were also answered by few of the respondents (Table 2). One hundred percent of the participants believed that there should be a system of ADRs reporting and monitoring in their institute and all of them opined that this kind of system would be useful for their patients and for them to be better healthcare professionals. Pharmacologists’ and clinical pharmacists’ assistance will be useful in detection, reporting and management of ADRs was agreed upon by 87.55 and 57.5%, respectively. Interestingly, all the respondents believed that if the teachers from allied streams (dental, nursing, physiotherapy, pharmacy) are sensitized, can be useful. All of them said were of the view point that if the medical students and the students from the allied fields are sensitized and trained, may prove useful. Discussion During the developmental phase of a drug a good deal is known about its therapeutic activity but rather less about its safety because the clinical trials are conducted in a controlled environment in a lesser number of

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PHARMACOLOGY patients and subjects. Once a drug gains entry into the market it will be prescribed by hundreds of doctors to thousands of patients belonging to different age groups. The scenario is complicated when there are ethnic variations, presence of co-morbid conditions and concomitant medications. During this phase only unusual and rare ADRs are encountered. So, if we have a system which can help us determine any new information available in relation to their safety profile can be critically useful. And since there are considerable social and economic consequences of ADRs, there is a need to engage healthcare professionals, in a well structured program to build synergies for monitoring ADRs. As ADR reporting is of prime importance in the success of any pharmacovigilance program, so the present survey was conducted with the intention of assessing the outlook of prescribers towards this. Studies identify ADRs as important factors leading to hospital admissions.9 Our respondents felt that ADRs contribute to excessive healthcare costs through increased patient morbidity and mortality. It has been reported that the ADRs come as 4th-6th largest cause for mortality in the USA, including one million deaths and 2.2 million hospitalizations.10 16% of hospital admissions in UK are due to ADRs.11 Some countries spend upto 15-20% of their hospital budget dealing with drug complications.12 Majority of our respondents felt that ADR reporting was important for the reason that it will bring down the mortality and morbidity and will decrease the healthcare cost. In one of the studies it was reported that 49.3% of ADRs leading to hospital admissions are avoidable13 and direct cost of managing drug-related morbidity and mortality in ambulatory setting was exorbitant at USD 76.6 billion/year.14 There is a considerable degree of under-reporting, which might partly be explained by lack of knowledge and misconceptions about spontaneous reporting of ADRs. More than 85% of the respondents in our survey admitted not having enough information on how to report ADRs as one of the reasons for not reporting, along with other reasons. Similar observations are made in other studies as well.15 Ignorance was admitted as a reason for not reporting ADRs in one of the studies by the respondents.16 Almost everyone admitted that if there is such kind of system in place then it would be useful for patients and them as well. The reasons for under-reporting of ADRs have been summarized by Inman17 as the â&#x20AC;&#x2DC;seven deadly sinsâ&#x20AC;&#x2122;. This includes financial incentives (rewards for reporting), legal aspects (fear of litigation), complacency (belief that the serious ADRs are already documented when a drug is introduced in the market), diffidence (belief that reporting should be done when there is certainty that the reaction is caused by the use of a particular drug), indifference (belief that a single report would make no difference), ignorance (that only serious ADRs are to be reported), lethargy (excuses about lack of time or disinterestedness). In our study, a major reason observed was ignorance about the reporting system, while the financial and other aspects were given less importance. This suggests that an intervention to generate awareness on how to report ADRs may be necessary. Available data indicate that the introduction of nurse and pharmacist reporting is proving to be very useful.18-20 Our respondents have also suggested sensitizing the members of allied streams including the paramedical staff about this issue. Continuous medical education (CME), training and workshops were the most cited means of improving ADR reporting in the suggestions. This certainly shows that the doctors are willing to improve their knowledge of ADR reporting and increase their participation in the pharmacovigilance program of the country if education and awareness on the reporting scheme is instituted in the hospital. The objective of this study was to evaluate the attitudes and knowledge of doctors in our teaching hospital to spontaneous ADR reporting. It would be logical to extend this study to other teaching hospitals, private practitioners, members of allied fields, students of medical and associated streams to enable us generalize our findings. Conclusion There are gaps between knowledge and ADRs reporting among doctors working in a teaching hospital. These gaps need to be filled by improved training and awareness in pharmacovigilance at various levels of healthcare system. Attitudinal changes would be critical for a long-term improvement of ADR reporting. This may have important implications in terms of public health, if knowledge and attitudes are viewed as potentially modifiable factors.

Possible Interventions and Suggestions by the Authors Regular CMEs and workshops for all levels of healthcare system at institutional level and in the private sector. Faculty from the allied fields should be incorporated in the program to strengthen the

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PHARMACOLOGY system and improve the reporting culture. Students of medical, dental, nursing and physiotherapy should also be sensitized in order to spread the awareness about it. Increased educational efforts are needed to up-skill undergraduates and postgraduates in drug safety and pharmacovigilance. Mass media including the social media can be brought into use to spread the awareness about ADRs. ADR reporting is critical for drug safety monitoring and should be considered more of a professional responsibility by all the stakeholders in healthcare system in order to contribute optimally to the well-being of the society. References 1. Kohn LT, Corrigan JM, Donaldson MS. To err is Human: Building a Safer Health System. Institute of Medicine: Washington DC; 2000. 2. Carrasco-Garrido P, de Andrés LA, Barrera VH, Ángel de Miguel G, Jiménez-García R. Trends of adverse drug reactions related-hospitalizations in Spain (2001-2006). BMC Health Services Research 2010;10:28. 3. Desai CK, Iyer G, Panchal J, Shah S, Dikshit RK. An evaluation of knowledge, attitude, and practice of adverse drug reaction reporting among prescribers at a tertiary care hospital. Perspect Clin Res 2011;2(4):129-36. 4. Herdeiro MT, Figueiras A, Polónia J, Gestal-Otero JJ. Physicians’ attitudes and adverse drug reaction reporting : a case-control study in Portugal. Drug Saf 2005;28(9):825-33. 5. Pillans PI. Clinical perspectives in drug safety and adverse drug reactions. Expert Revof Clinical Pharmacol2008;1(5):695-705. 6. Eland IA, Belton KJ, van Grootheest AC, Meiners AP, Rawlins MD, Stricker BH. Attitudinal survey of voluntary reporting of adverse drug reactions. Br J Clin Pharmacol 1999;48(4):623-7. 7. Oshikoya KA, Awobusuyi JO. Perceptions of Doctors to Adverse Drug Reaction Reporting in a Teaching Hospital in Lagos, Nigeria. BMC Clin Pharmacol 2009;9:15. 8. Mellenbergh GJ.Tests and Questionnaires: Construction and administration. In: Advising on Research Methods: A Consultant’s Companion. Adèr HJ, Mellenbergh GJ (Eds.) Johannes van Kessel Publishing: Huizen, The Netherlands 2008p.211-36. 9. Rehan HS, Vasudev K, Tripathi CD. Adverse drug reaction monitoring: knowledge, attitude and practices of medical students and prescribers. Natl Med J India 2002;15(1):24-6. 10. Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA 1998;279(15):1200-5. 11. Moore N, Lecointre D, Noblet C, Mabille M.. Frequency and cost of serious adverse drug reactions in a department of general medicine. Br J Clin Pharmacol 1998;45(3):301-8. 12. White TJ, Arakelian A, Rho JP. Counting the costs of drug-related adverse events. Pharmacoeconomics 1999;15(5):445-58. 13. Nelson KM, Talbert RL. Drug-related hospital admissions. Pharmacotherapy 1996 ;16(4):701-7. 14. Lassetter JH, Warnick ML. Medical errors, drug-related problems, and medication errors: a literature review on quality of care and cost issues. J Nurs Care Qual 2003;18(3):175-81; quiz 182-3. 15. Lopez-Gonzalez E, Herdeiro MT, Figueiras A. Determinants of under-reporting of adverse drug reactions: a systematic review. Drug Saf 2009;32(1):19-31. 16. Inman WH. Attitudes to adverse drug-reaction reporting. Br J Clin Pharmacol 1996;41:433-5. 17. van Grootheest K, Olsson S, Couper M, de Jong-van den Berg L. Pharmacists’ role in reporting adverse drug reactions in an international perspective. Pharmacoepidemiol Drug Saf 2004;13(7):457-64.

Personalized Vaccine Targets Leukemia A new personalized cancer vaccine that was deployed soon after bone marrow stem cell transplantation saw 13 of 18 chronic lymphocytic leukemia patients live a median of almost three years in complete remission. Six patients in the phase I trial that received the maximum vaccine doses produced CLL–specific CD8+ T cells. The results suggest that the new regimen could enhance anti–tumor response post transplantation, said Catherine J. Wu, MD, medical oncologist and researcher at Dana–Farber Cancer Institute. They reported the results of the new approach in the Journal of Clinical Investigation. Wu and her colleagues injected the vaccines once a week with three doses and then three more every other week. Median follow–up was 2.9 (range, 1 to 4) years and showed an estimated 2–year progression–free survival rate for vaccinated patients at 82%. Overall survival rate was 88%. The investigators extracted whole tumor cells from each patient and irradiated the cells for the vaccine formulation. Their goal was to trigger an immunogenic response that would target personalized antigens. In tandem with the irradiated tumor cells, the researchers also injected cells engineered to secrete GM–CSF, as a cytokine adjuvant.

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mediLAW

When can Hospitals be Liable for Medical Negligence Deaths?

KK Aggarwal

I

f a patient dies due to medical negligence in a hospital then its management cannot be prosecuted and it is only the doctors who should be penalized, the Delhi High Court has ruled. However, the court held that the management of the hospital would be liable in case of administrative negligence and failure to provide basic infrastructure to patients. Justice SN Dhingra passed the order on a petition filed by Indraprastha Medical Corporation Limited challenging a metropolitan magistrate’s order for registration of a first information report against it for alleged medical negligence resulting in the death of a patient in 2007. Setting aside the trial court order, Justice Dhingra said: “The hospital or company cannot be held liable for the personal negligence of the doctor in giving wrong treatment.” “If there is an administrative negligence or a negligence of not providing basic infrastructure, which results into some harm to an aggrieved person or such negligence which is impersonal, the hospital can be held liable”. The court, said that it is the doctor who treats the patients and hospitals should not be punished due to error on part of its medical staff. “The offence of medical criminal negligence cannot be fastened on the company since the company can neither treat nor operate a patient of its own.” “It is the doctor working in the hospital who treats and performs operations. It is the doctors who examine the patients and prescribe medicines. If there is a deliberate or negligent act of the doctor working in the hospital, it is the liability of the doctor and not of the hospitals for criminal negligence,” the court said. In the present case, the company contended that the hospital could not be held responsible as the patient was being treated by three doctors from the Department of Cardiology a few years back.

Judgment: Present petition has been filed by the petitioner for quashing of order dated 19th December, 2007, passed by learned Metropolitan Magistrate in a complaint case under section 336/337/471 read with section 34 IPC qua the petitioner. It is submitted that petitioner Indraprastha Medical Corporation Limited was a company incorporated under Companies Act and the company being only a juristic person was incapable of committing a crime of medical negligence, because it involved personal negligent act. A complaint was filed before the learned M.M. against the petitioner company and the Doctors involved in the treatment of deceased wherein it was alleged that deceased died due to gross medical negligence of the Doctors. It is also submitted that Doctors involved in treatment advised wrong/superfluous treatments in order to extract extra money. The petitioner’s counsel stated that petitioner is not assailing the order as against Doctors but is assailing it so far as company was concerned on the ground that the company running the hospital, could not have acted in the manner in which it is assailed by the complainant. In Standard Chartered Bank vs. Directorate of Enforcement, 2005 SCC (Cri.) 961, SC made following observations regarding criminal liability of the Corporation: “6. There is no dispute that a company is liable to be prosecuted and punished for criminal offences. Although there are earlier authorities to the effect that corporations cannot commit a crime, the generally accepted modern rule is that except for such crimes as a corporation is held incapable of committing by reason of the fact that they involve personal malicious intent, a corporation may be subject to indictment or other criminal process, although the criminal act is committed through its agents. 8. In asmuch as all criminal and quasi-criminal offences are creatures of statute, the amenability of the corporation to prosecution necessarily depends upon the terminology employed in the statute. In the case of strict liability, the terminology employed by the legislature is such as to reveal an intent that guilt shall not be predicated upon the automatic breach of the statute but on the establishment of the actus reus, subject to the defence of due diligence. The

Padma Shri and Dr BC Roy National Awardee President Heart Care Foundation of India Chairman Legal Cell Indian Academy of Echocardiography Editor - eMedinewS E-mail: emedinews@gmail.com

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mediLAW law is primarily based on the terms of the statutes. In the case of absolute liability where the legislature by the clearest intendment establishes an offence where liability arises instantly upon the breach of the statutory prohibition, no particular state of mind is a prerequisite to guilt. Corporations and individual persons stand on the same footing in the face of such a statutory offence. It is a case of automatic primary responsibility. It is only in a case requiring mens rea, a question arises whether a corporation could be attributed with requisite mens rea to prove the guilt. But as we are not concerned with this question in these proceedings, we do not express any opinion on that issue.” In Kalpnath Rai Vs. State, 1998 AIR (SC) 201, SC made following observations: “The company is not a natural person. We are aware that in many recent penal statutes, companies or corporations are deemed to be offenders on the strength of the acts committed by persons responsible for the management of affairs of such company or corporations e.g. Essential Commodities Act, Prevention of Food Adulteration Act etc. But there is no such provision in TADA which makes the company liable for the acts of its officers. Hence, there is no scope whatsoever to prosecute a company for the offence under Section 3 (4) of TADA. The corollary is that the conviction passed against A-12 is liable to be set aside.” In Standard Chartered Bank Vs. Vinay Kumar Sood and Ors, 2009 (1) JCC 756, this court had observed as under: “Undisputedly, the petitioner is a bank incorporated in England with limited liability by Royal Charter, 1853 and, therefore, is a corporation/company. A company cannot be in any case held to have committed an offence under Section 500 IPC because; most essential ingredient of the said offence i.e. ‘mens rea’ would be missing as a company is a juristic entity or an artificial person, whereas a Director is not a company. The company may be made liable for offences, however, if there is anything in the definition or context of a particular Section or a particular statute which would prevent the application of the said section to a limited company, the limited company cannot be proceeded against. There are number of provisions of law in which it would be physically impossible by a limited company to commit the offence. A limited company, therefore, cannot generally be tried for offences where mens rea is essential. Similarly, a company cannot face the punishment of imprisonment for obvious reasons that company cannot be sent to prison by way of a sentence.” 5. The offence of criminal negligence requires a specific state of mind in respect of the person committing the offence. The offence of medical criminal negligence cannot be fastened on the company since the company can neither treat nor operate a patient of its own. It is the Doctor working in the company who treats and performs operations. It is the Doctor who examines the patients and prescribes medicines. If there is a deliberate or negligent act of the Doctor working in the Corporation/Hospital, it is the liability of the Doctor and not of the Corporation for criminal negligence despite the fact that due to the act of the Doctor of treating patients the Corporation was getting some revenue. These days, all Doctors with big hospitals, are on panels where they have fixed fee for examination of patients and for conducting operations. Out of this fee, a percentage is paid to the hospital. The hospital/ company cannot be held liable for the personal negligence of the Doctor in giving wrong treatment. However, if there is an administrative negligence, or a negligence of not providing basic infrastructure, which results into some harm to an aggrieved person or such negligence which is impersonal, the hospital can be held liable. But, in the case of medical negligence, which is personal to the Doctor who gave treatment, the Corporation would not be liable and it is the Doctor who can be indicted for medical criminal negligence. 6. I therefore, allow this petition in respect of the petitioner. The order passed by learned M.M. qua the petitioner is hereby quashed. Comments ÂÂ This is an important judgment. ÂÂ Needs to be read in totality. ÂÂ It is applicable mainly for the criminal act and not for compensation purposes. ÂÂ A criminal negligence on the part of a resident will be the responsibility of the resident and not the hospital. ÂÂ But a fault of a resident where compensation is awarded will have to be paid by the hospital as he is the full time salaried staff of that hospital. ÂÂ The judgment lines “However, if there is an administrative negligence, or a negligence of not providing basic infrastructure, which results into some harm to an aggrieved person or such negligence which is impersonal, the hospital can be held liable” Covers a lot of situations. A mistake by the nurse, resident, pathology services, radiology services etc. will come under the “providing basic infrastructure services”.

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medifinance

Retirement

R

etirement tends to be the part of life that most people look toward after their working days are over. Not everyone is cut out to become an investment or money expert, nor do they need to be. In fact, many retirees use the pursuit of investment knowledge as a replacement for the jobs they retired from rather than to enhance the quality of their retirement life. This portion of the financial plan deals with the sources of income after a doctor retires. It is seen that the longer he works and the longer his funds can accumulate the more income that will be available.

ÂÂ One will spend less on home, clothing, savings, etc. However, remember that most will probably spend more on healthcare and travel after retirement. There will be more time to travel and unfortunately, the aging process will probably increase medical outlay. Once having decided how he/she wants to live and having determined roughly how much it will cost, compare that with a projected income: ÂÂ Company and other pension payments ÂÂ Insurance or mutual funds to annuitize for income ÂÂ Calculate after-tax profit from home sale ÂÂ If one plans to sell his home, the proceeds could generate additional income. However, he should consider the rent required for the type of home that would meet his post-retirement needs - as well as the location. Remember, however, that there are no ceilings on rent increase. ÂÂ Other liquid assets to produce additional cash. ÂÂ All investments can produce income to supplement retirement. However, one must retain some liquidity and keep a portion of the funds invested to offset inflation. How to Achieve One’s Goal Determine how much one will need to save each year between now and retirement in order to finance needs. For this, it is wisest to consult with a financial planning specialist since there are many factors to be considered. The best way to reach goals is to maximize income during peak earning years and develop disciplined saving and investment habits. Traps to avoid: ÂÂ Giving too much of the money to the government in taxes ÂÂ Failing to put enough money into appreciating assets, (these include financial investments, art, and the right real estate) ÂÂ Giving too much money to creditors in interest payments ÂÂ Spending too much on intangible expenses, (this might include rent, utilities, entertainment and travel) ÂÂ Spending too much on depreciating assets (these might include furniture, clothing, boats and cars).

Retirement Income Analysis The Retirement Income Analysis estimates all the sources of income upon retirement. Income tax is then calculated on that amount. Once the after-tax retirement income is calculated, it is then compared to the after-tax retirement income goal. To make the report even more realistic, the desired after-tax retirement income should be inflated to reflect the desired income in inflated rupees that provide the same purchasing power as today’s rupees. Retirement Tax Suggestions Some people retire by choice. Others do so involuntarily due to events like corporate restructuring. Even if a person does not intend to retire early, or is only in their twenties, planning for retirement should begin now. The sooner it is initiated, the easier it will be, regardless of whom decides when it is time to retire. If someone known has just retired, consider how they will live the rest of their life. Where and how will they live? This exercise will help to determine how to achieve dreams and desires. Although it is difficult to determine exactly how much money will be needed in 30 or more years, estimate how much this lifestyle will cost. One way to do this is to base it on current spending and the lifestyle, and adjusting for long-term inflation. The less money that is needed to live on, the easier it will be to retire early. Do not make plans so ambitious that they will never be achievable. Use the following guidelines: ÂÂ Most people manage on 65-80% of pre-retirement income

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forthcoming conferences

International Conferences European Society of Cardiology Congress 2013 Date: 31 Aug 2013 - 04 Sep 2013 Venue: Congress centre, Amsterdam RAI The Netherlands Website: www.escardio.org/ESC2013

International Stroke Conference Date: 12-14 February 2014 Venue: San Diego Convention Center, San Diego, Website: www.strokeconference.org/

International Cardiometabolic Syndrome Eastern Mediterranean Congress Date: 27 February-02 Mar 2014 Venue: Acapulco Hotel Resort and Convention Center, North Cyperus Website: www.cardiometabolicsyndrome2014.org/

Acute Cardiac Care Congress 2013 Date: 12-14 October 2013 Venue: Convention Center, Madrid, Spain Website: www.escardio.org/congresses/acute-cardiac-care-2013/ Pages/welcome-address.aspx

AMERICAN COLLEGE OF CARDIOLOGY 2014 WASHINGTON Date: 30 Mar - 01 Apr 2014 Venue: D C Convention Center, Washington Website: www.acc.org/

TRANSCATHETER CARDIOVASCULAR THERAPEUTICS 2013 Date: 27 Oct-01 Nov 2013 Venue: MOSCONE Convention Center San Francisco, CA Website: www.tctconference.com/

Euro Heart Care 2014 Date: 04-05 April 2014 Venue: Stavanger-Norway Website: www.escardio.org

11th Annual World Congress on Insulin Resistance, Diabetes and Cardiovascular Disease Date: 7-9th November, 2013 Venue: Hilton Universal City Hotel, Los Angeles, CA Website: www.wcir.org/

HEART RHYTHM/NASPE 2014 SAN FRANCISCO Date: 7-10 May 2014 Venue: Moscone Convention Center, San Francisco Website: www.eventsinamerica.com

AMERICAN HEART ASSOCIATION 2013 DALLAS Date: 16-20 November 2013 Venue: Dallas Convention Center, TX â&#x20AC;&#x201C; Cabana Website: www.cabanatrial.org/

AMERICAN THORACIC SOCIETY 2014 SAN DIEGO Date: 18-21 May 2014 Venue: San Diego Convention Center, San Diego Website: http://conference.thoracic.org/2013/attendees/futureconferences/

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emedinews inspiration

Dakshinayana is the Start of Negative State of Mind The uttarayana and dakshinayana are not only time periods mentioned in the Vedic literature but also the state of minds. Uttarayana means a period for a positive state of mind and Dakshinayana a period for relatively negative state of mind. Dakshinayana is the southern transit of the Sun. The Uttarayana and Dakshinayana period is calculated differently in South and North India. Bhagwad Geeta talks about Moksha and liberation. Those who believe in the philosophy of rebirth know that once a soul is liberated at death, a person is not reborn. Those who believe that hell and heaven are in this birth only for them liberation means dying peacefully and without sufferings. The theory of rebirth is well described in Bhagwad Geeta in Chapter 8. The gist of Lord Krishna’s teaching is: ÂÂ Whatever you think throughout your life will be your thought at the time of death. ÂÂ Whatever is the state of mind at the time of death will be the atmosphere you will get in the rebirth. For example if your state of mind is in cruelty at the time of death, you will be born in a cruel family. If you are relaxed, thinking of God or Chanting AUM at the time of death, there are chances your soul will be liberated. ÂÂ Fire, illumination, daytime, fortnight before the full moon and uttarayana are the paths for liberation. It means these are the periods / ways for spontaneous positive thinking. And the reverse is for dakshinayana From mental health point of view, this knowledge can be converted into medical prescription. Uttarayana means satwa, healthy state of mind and dakshinayana means a depressed negative state of mind. Performing and attending to Yagna, sitting in well illuminated lights or exposing oneself to the day sunlight can be an adjunct to depression treatment. During the first fortnight of full moon and during uttarayana, the psychotherapy and counseling invariable will work better and the requirement of drugs may get reduced. The reverse will happen in dakshinayana. In chakra language, from mooladhara chakra to anahata chakra is the dakshinayana path and from anahata chakra to ajna chakra is the uttarayana path. Those who travel on the uttarayana path travel from anahata chakra. Those who travel on the dakshinayana path start from mooladhara. The Chatur Mas or Four holy months in Hinduism falls during the period of Dakshinayana. Chaturmas begins on July 11 and ends on November 6. It begins on the Ekadasi day in Shukla Paksha in the month of Ashada and ends on the Ekadasi in the Shukla Paksha in the month of Kartik. It occurs during monsoon season and most important festivals take place during this period. It’s a four month period for observing fast, rituals, pujas and festivals. Chaturmas has following months 1st Shravan month is dedicated to Lord Shiva, especially the Mondays. Is a month or Vata or air imbalance. The classical song” Savan ka mahina Pavan kare shor” explains the air imbalance in this month. The vata function in the mind is related to emotional imbalance. 2nd Bhadrapad is the month of festivals including the Ganesh Chaturthi and Janmaasthmi. The month is again related to Vata or air imbalance. The classical Bollywood song “tere naina savan bhado phir bhi mera man payasa” explains the state of the mind in savan and bhado months. The state of the mind is negative with chances of more non fulfillment of desires. 3rd Ashwin month include, Durga Puja, Navratri, Diwali etc. 4th Kartik and Diwali celebrations end in this month. It’s a saying to avoid green leafy vegetables in Shravan month, Curd in Bhadrapad, milk in Ashwin and pulses, the split variety in Kartik month. No marriages or important functions take place in chaturmas for many reasons ÂÂ Firstly it is a period of negative state of mind and hence more chances of divorce ÂÂ For the same reason more chances of infertility ÂÂ Due to rainy seasons more chances of worms on the surface and infesting the leafy vegetables ÂÂ Due to Vata (movement) predominance, leafy vegetables will not be health friendly ÂÂ Due to pitaa (metabolism) suppression the digestive fire will be weak ÂÂ Many people avoid garlic and onion as it can stimulate unnecessary excitements, cause indigestion and distract devotee from pujas and prayers.

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eMedi Quiz

Quiz Time Q1. Immunoassays detect all except A. Lupus anticoagulant B. Anti-b2-glycoprotein 1 antibodies B. C. Fluid overload Cardiac arrhythmias

D. Pulmonary emboli Q4. A male client with acute pyelonephritis receives a prescription for co-trimoxazole P.O. twice daily for 10 days. Which finding best demonstrates that the client has followed the prescribed regimen? A. Urine output increases to 2,000 ml/day B. Flank and abdominal discomfort decrease C. Bacteria are absent on urine culture D. The red blood cell (RBC) count is normal Q5. The most common manifestation of cutaneous adverse reaction to food is A. Acute urticaria B. Pruritus C. Flare of atopic dermatitis D. Contact urticaria

C. Antibodies against phospholipids other than cadiolipins D. Antibodies against plasma protein phospholipids binding

Q2. Dilute Russel viper venom test is used to diagnose A. Anticardiolipin B. C. Antibiotic against prothrombin Lupus anticoagulant

D. Anti-B2-glycoprotein 1 antibodies Q3. Nurse Ted is administering I.V. fluids to an infant. Infants receiving I.V. therapy are particularly vulnerable to: A. Hypotension

Answers to eMedi Quiz Published in July 2013 Issue Q1. (c) Cerebral hyperemia Q2. (a) 1 minute Q3. (b) Omega-3 > omega-6 fatty acids Q4. (d) HIB, DTP, HepB; and IPV Q5. (a) Hepatomegaly

Send your answers to the Editor-Indian Journal of Clinical Practice. E-mail: editorial@ijcp.com The correct answers will be published in the next issue of IJCP.

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lighter reading

Lighter Side of Medicine During Medical Practice A foreigner with a single loose stool developed sepsis.

Quote

Make Sure

“Happy is the man who can do only one thing; in doing it, he fulfills his destiny” —Joseph Joubert

Oh my God! Why were antibiotics not started in time?

Mind Trivia 1. What is this word? c o n 2. Below are incomplete words. Place three (3) letters in each bracket so that you can complete the word on the left and begin the word on the right. Good luck. ©IJCP Academy

unf (_ _ _ ) est to (_ _ _) tures hic (_ _ _) ful eit (_ _ _) etic

Make sure that all foreigners are diagnosed to be suffering from Traveler’s diarrhea even if there is one single loose motion.

KK Aggarwal

Dr. Good & Dr. Bad Situation: A pregnant lady with a liver problem wanted

to have her CT scan done.

Get ct sacan done

your liver condition is not serious, we can have the ct scan done later

Lesson: In the first trimester of pregnancy getting a

CT scan done may not be safe. Like X-ray, CT scan also exposes the fetus to radiation.

Dr KK Aggarwal

©IJCP Academy

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Ans. (1) Condescending (2) unfold - oldest, topic - pictures, hiccup - cupful, either - heretic.

ILLUSION

293

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

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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.

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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,

Results –

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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. Books Stansfield AG. Lymph Node Biopsy Interpretation Churchill Livingstone, New York 1985. Articles in Books Strong MS. Recurrent respiratory papillomatosis. In: Scott Brown’s Otolaryngology. Paediatric Otolaryngology Evans JNG (Ed.), Butterworths, London 1987;6:466-470. Tables – These should be typed double spaced on separate sheets with the table number (in Roman Arabic numerals) and title above the table and explanatory notes below the table.

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 ___________________________ 5. Special requests _____________________________ 6. Suggestions for reviewers (name and postal address) Indian 1.____________Foreign 1._ _______________ 2.____________ 3.____________ 4.____________ 2._ _______________ 3._ _______________ 4._ _______________

7. All authors’ signatures________________________ 8. Corresponding author’s name, current postal and e-mail address and telephone and fax numbers __________________________________________

Legends – These should be typed double spaces on a separate sheet and figure numbers (in Arabic numerals) corresponding with the order in which the figures are presented in the text. – The legend must include enough information to permit interpretation of the figure without reference to the text.

Online Submission Also e- Issue @ www.ijcpgroup.com For Editorial Correspondence Group Editor-in-Chief Indian Journal of Clinical Practice E-219, Greater Kailash, Part-1 New Delhi - 110 048. Tel: 40587513 E-mail: editorial@ijcp.com Website: www.ijcpgroup.com

Dr KK Aggarwal

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R.N.I. No. 50798/90 Date of Publication 13th of Same Month Date of Posting 13-14 Same Month

DL (S)-01/3200/2012-2014 Posted in N.D. PSO New Delhi