Indian journal of clinical practice september 2014 by IJCP

Indexed with IndMED

ISSN 0971-0876

www.ijcpgroup.com

Volume 25, Number 4

September 2014, Pages 301â&#x20AC;&#x201C;400

Peer Reviewed Journal

American Family Physician

Cardiology

Community Medicine

Dentistry

Diabetology

ENT

Gastroenterology

Obstetrics and Gynecology

Orthopedics

Pediatrics

Respiratory Infections

Expert View

Medilaw

an i c i ys ians

Phly Physic y l mi ami

Fademy of F n ica Aca

er merican m A eA

ingurnal of th t a or d Jo

rp-reviewe o c In eer AP

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

Single Copy Rs. 300/-

Online Submission

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, Dr BC Roy National & DST National Science Communication Awardee

Dr KK Aggarwal Group Editor-in-Chief

Dr Veena Aggarwal MD, Group Executive Editor

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

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

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

Volume 25, Number 4, September 2014 from the desk of THE group editor-in-chief

305 Alternative Therapies Lower BP

KK Aggarwal

American Family Physician

309 Onychomycosis: Current Trends in Diagnosis and Treatment

Dyanne P Westerberg, Michael J Voyack

320 Practice Guidelines 322 Photo Quiz CARDIOLOGY

325 Status of HDL in Current Scenario

Geetha Subramaniyan, Dharmendra Jain, Balaji Lohiya, Neeraj Kumar

Community Medicine

333 Prevalence of Overweight and Obesity Among Students of a Medical College in South India: A Pilot Study

Jayaraj, PP Nair, Reny Napolean, Justin Stephen, Nishanth K, Suresh D

DENTiSTRY

338 Mandibular Molar Protraction with Orthodontic Temporary Anchorage Devices: A Case Report

Anurag Bhagat, Meenu Goel, Puneet Batra, Rajiv K Chugh

DIABETOLOGY

342 Prevalence of Gestational Diabetes Mellitus in a Medical College in South India: A Pilot Study

K Sreekanthan, A Belicita, K Rajendran, Anil Vijayakumar

348 Hypoglycemic Brain Injury: A Case Report

Monika Maheshwari, Rajesh Jain

ENT

352 Juvenile Nasopharyngeal Angiofibroma: A Tertiary Hospital-based Experience

Farooq A Itoo, Irfan Iqbal, Latief A Chiesti

356 Comparison of Finger Gloves Pack with BIPP Pack in Early Postoperative Period of Septal Surgery

Narmaya Thapa

Gastroenterology

360 A Case of Gastric Diverticulum (Solitary Fundal Diverticulum) â&#x20AC;&#x201C; Pictorial CME

Praveen Kumar, Kalpana Chandra

OBSTETRICS AND GYNECOLOGY

362 Progesterone and Prevention of Preterm Labor

Ruchika Garg, Urvashi Verma, Rajni Rawat, Somya Shrivastava, Renu Rajvanshi

364 Term Pregnancy in an Achondroplastic Dwarf: A Case Report

Rekha Rani, Shikha Singh, Saroj Singh, Urvashi Verma, Ruchika Garg, Hari Singh, Dibya Singh

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

367 Highly Aggressive Small-cell Neuroendocrine Carcinoma Cervix: A Rare Case Report

Taru Gupta, Sangeeta Gupta, Pushpa Bhatia, Sanjana Wadhwa, Nupur Gupta

ORTHOPEDICS

372 Atypical Fracture of Femur: Likely Related to Long-term

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

Bisphosphonate Use

Muhammed Zohaib Ghatala, Shriraam Mahadevan

Pediatrics

374 A Prevalence Study on Myopia Among School Going Children

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.

in a Rural Area of South India

K Rajendran, Mohammed Haneef, Kailas Chandrabhanu, Krishnamoorthy, Manil Muhammed, Ratheesh T Pillai

Respiratory Infections

381 Respiratory Problems Among Smokers in a Rural Area in

Editorial Policies

South India: A Pilot Study

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.

Anil Vijayakumar, K Sreekanthan, A Belicita, Rajendra

Around the Globe

385 News and Views EXPERT VIEW

389 Is there any Role of Other Systems of Medicines in Managing High Blood Pressure?

KK Aggarwal

mediLAW

392 Real Consent and not Informed Consent Applicable in India

KK Aggarwal

INSPIRATIONAL Story

395 The Three Races lighter reading

396 Lighter Side of Medicine

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.

IJCPâ&#x20AC;&#x2122;s Editorial & Business Offices Delhi

Mumbai

Kolkata

Bangalore

Chennai

Hyderabad

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

Mr. Nilesh Aggarwal 9818421222 Mr. Pravin Dhakne 8655611025, 24452066

Ritu Saigal Sr. BM 9831363901

H Chandrashekar GM Sales & Marketing 9845232974

Chitra Mohan Sr. BM 9841213823 40A, Ganapathypuram Main Road Radhanagar Chromepet Chennai - 600 044 Cont.: 22650144 chitra@ijcp.com

Venugopal GM Sales & Marketing 9849083558

Unit No: 210, 2nd Floor, Shreepal Complex Suren Road, Near Cine Magic Cinema Andheri (East)

7E, Merlin Jabakusum 28A, SN Roy Road Kolkata - 700 038 Cont.: 24452066 ritu@ijcp.com

Mumbai - 400 093 nilesh.ijcp@gmail.com

Sr.: Senior; BM: Business Manager; GM: General Manager

Arora Business Centre, 111/1 & 111/2, Dickenson Road (Near Manipal Centre) Bangalore - 560 042 Cont.: 25586337 chandra@ijcp.com

H. No. 16-2-751/A/70 First Floor Karan Bagh Gaddiannaram Dil Sukh Nagar Hyderabad 500 059 Cont.: 65454254 venu@ijcp.com

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

Padma Shri, Dr BC Roy National & DST National Science Communication Awardee Sr. Physician and Cardiologist, Moolchand Medcity President, Heart Care Foundation of India Group Editor-in-Chief, IJCP Group and eMedinewS National Senior Vice President, IMA Member, Ethics Committee, MCI Chairman, Ethics Committee, Delhi Medical Council 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)

Alternative Therapies Lower BP

group of experts has reviewed all the existing studies and concluded that indeed there are alternative treatments for lowering blood pressure – with aerobic exercise leading the pack as far as strong evidence goes.

Other alternative treatments – namely isometric handgrip and dynamic resistance exercises and guided breathing – also got high grades when it came to reducing high blood pressure in some patients, according to a scientific statement from the American Heart Association published online in the journal Hypertension. "The evidence is not as strong for transcendental meditation and acupuncture, but they may help as well," said co-senior author Sanjay Rajagopalan, MD, Professor of Cardiovascular Medicine at Ohio State University School of Medicine in Columbus. For the report, an expert panel headed by the University of Michigan’s Robert D. Brook, MD, reviewed 1,000 studies published from 2006 to 2011. They divided the studies into three major classes of alternative treatments: Behavioral therapies, noninvasive procedures and devices, and exercise. The panel did not review dietary and herbal treatments. Based on the level of evidence, they gave each an "A," "B," or "C" recommendation – with "A" being the highest – for implementation into clinical practice. The panel found:

ÂÂ Exercise-based regimens did the best overall, with dynamic aerobic exercises getting an "A" class of

recommendation, with a level of evidence of I, the highest possible.

ÂÂ Dynamic resistance exercises got a "B" and isometric handgrip exercises got a "C" grade, with levels of evidence

of IIA and IIB, respectively.

ÂÂ Still, 4 weeks of isometric hand grip exercises resulted in some of the most impressive improvements in several

studies – a 10% drop in systolic and diastolic blood pressure. However, isometric exercise should be avoided among people with severely uncontrolled hypertension (180/110 mmHg or higher).

ÂÂ As for noninvasive procedures or devices, device-guided breathing got a "B" with a level of evidence of II.

Device-guided slow breathing proved most effective in lowering blood pressure when performed for 15-minute sessions three to four times a week.

ÂÂ Acupuncture also got a "B," but its level of evidence was III, meaning no benefit. ÂÂ Among behavioral techniques, transcendental meditation and biofeedback both received "B" grades, with

IIBs for levels of evidence. Yoga got a C, with level of evidence of III, or no benefit, as did other meditation techniques.

ÂÂ The alternative approaches that work reduce systolic blood pressure by only 2-10 mmHg; whereas standard

doses of a blood pressure-lowering drug reduce systolic blood pressure by about 10-15 mmHg.

ÂÂ Alternative approaches are best for patients with blood pressure levels over 120/80 mmHg who can’t tolerate

or don’t respond well to standard medications.

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

305

MCI UPDATE

Amendment to the Indian Medical Council (Professional Conduct, Etiquette and Ethics) Regulations, 2002

his Bill/Notification, pending since 2010, has been recently approved by the General Body of the Medical Council of India (MCI) and is likely to get notified soon. MEDICAL COUNCIL OF INDIA NOTIFICATION New Delhi, the–May 2010 No.MCI-211(1)/2010(Ethics)/– In exercise of the powers conferred by Section 33 of the Indian Medical Council Act, 1956 (102 of 1956), the Medical Council of India with the previous sanction of the Central Government, hereby makes the following Regulations to amend the “Indian Medical Council (Professional Conduct, Etiquette and Ethics) Regulations, 2002:– (i)

(ii)

These Regulations may be called the "Indian Medical Council (Professional Conduct, Etiquette and Ethics) (Amendment) Regulations 2010" They shall come into force from the date of their publication in the Official Gazette."

1. In the "Indian Medical Council (Professional Conduct, Etiquette and Ethics) Regulations, 2002", the following additions/modifications/deletions/substitutions, shall be, as indicated therein:3.(i) The title of Section 6.8, as amended vide notification dated 10.12.2009, shall be further amended by deleting the words " and professional association of doctors" as under:– "6.8 Code of conduct for doctors in their relationship with pharmaceutical and allied health sector industry". (ii) Section 6.8.1(b); as amended vide notification dated 10/12/2009, shall be substituted as under: (b) Travel Facilities: A medical practitioner shall not accept any travel facility inside the country or outside; including rail, road, air, ship, cruise tickets, paid vacation; etc. from any pharmaceutical or allied healthcare industry or their representatives for self and family members for vacation or for attending conferences, seminars, workshops, CME Programme; etc. as a delegate. (iii) Action to be taken by the Council for violation of Section 6.8, as amended vide notification

306

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

dated 10/12/2009, shall be prescribed by further amending the Section 6.8.1 as under:– Section 6.8.1 In dealing with pharmaceutical and allied health sector industry, a medical practitioner shall follow and adheres to the stipulations given below: a) Gifts: A medical practitioner shall not receive any gift from any pharmaceutical or allied health care industry and their sales people or representatives Action ÂÂ Gifts more than Rs. 1,000/- upto Rs. 5,000/– Censure. ÂÂ Gifts more than Rs. 5,000/– up to Rs. 10,000/–

Removal from Indian Medical Register or State Medical Register for 3 (three) months.

ÂÂ Gifts more than Rs. 10,000/– to Rs. 50,000/– Removal

from Indian Medical Register or State Medical Register for 6 months.

ÂÂ Gifts more than Rs. 50,000/– to Rs. 1,00,000/–

Removal from Indian Medical Register or State Medical Register for 1 Year Gifts more than Rs. 1,00,000/– “Removal for a period of more than 1 year from Indian Medical Register or State Medical Register/".

b) Travel facilities: A medical practitioner shall not accept any travel facility inside the country or outside, including rail, road, air, ship, cruise tickets, paid vacations etc. from any pharmaceutical or allied healthcare industry or their representatives for self and family members for vacation or for attending conferences, seminars, workshops, CME programme etc as a delegate. Action ÂÂ Expenses for travel facilities more than Rs. 1,000/-

upto Rs. 5, 000/–: Censure.

ÂÂ Expenses for travel facilities more than Rs. 5,000/-

up to Rs. 10,000/–: Removal from Indian Medical Register or State Medical Register for 3 (three) months.

MCI UPDATE ÂÂ Expenses for travel facilities more than Rs. 10,000

ÂÂ Cash or monetary grants more than Rs. 50,000/–

ÂÂ Expenses for travel facilities more that Rs. 50,000/–

ÂÂ Cash or monetary grants more than Rs. 1,00,000/–:

ÂÂ Expenses

e) Medical Research: A medical practitioner may carry out, participate in, work in research projects funded by pharmaceutical and allied healthcare industries. A medical practitioner is obliged to know that the fulfillment of the following items (i) to (vii) will be an imperative for undertaking any research assignment; project funded by industry- for being proper and ethical. Thus in accepting such a position a medical practitioner shall:-

to Rs. 50,000/–: Removal from Indian Medical Register or State Medical Register for 6 months. to Rs. 1,00,000/–: Removal from Indian Medical Register or State Medical Register for 1 year. for travel facilities more than Rs. 1,00,000/–: Removal for a period of more than 1 year from Indian Medical Register or State Medical Register.

c) Hospitality: A medical practitioner shall not accept individually any hospitality like hotel accommodation for self and family members under any pretext. Action ÂÂ Expenses for Hospitality more than Rs. 1,000/- up

to Rs. 5,000/–: Censure.

ÂÂ Expenses for Hospitality more than Rs. 5, 000/–

up to Rs. 10,000/–: Removal from Indian Medical Register or State Medical Register for 3 (three) months.

ÂÂ Expenses for Hospitality more than Rs. 10,000/– to

Rs. 50,000/–: Removal from Indian Medical Register or State Medical Register for 6 months.

ÂÂ Expenses for Hospitality more than Rs. 50,000/–

to Rs. 1,00,000/–: Removal from Indian Medical Register or State Medical Register for 1 year.

ÂÂ Expenses for Hospitality more than Rs. 1,00,000/:

Removal for a period of more than 1 year from Indian Medical Register or State Medical Register.

d) Cash or monetary grants: A medical practitioner shall not receive any cash or monetary grants from any pharmaceutical and allied healthcare industry for individual purpose in individual capacity under any pretext. Funding for medical research, study etc. can only be received through approved institutions by modalities laid down by law/rules/guidelines adopted by such approved institutions, in a transparent manner. It shall always be fully disclosed. Action ÂÂ Cash or monetary grants more than Rs. 1,000/– up

to Rs. 5,000/– Censure.

to Rs. 1,00,000/–: Removal from Indian Medical Register for State Medical Register for 1 year. Removal for a period of more than 1 year from Indian Medical Register or State Medical Register.

(i) Ensure that the particular research proposal(s) has the due permission from the competent concerned authorities (ii)

Ensure that such a research project(s) has the clearance of national/state/institutional ethics committees/bodies

(iii) Ensure that requirements research

it fulfils all the legal prescribed for medical

(iv) Ensure that the Source and amount of funding is publicity disclosed at the beginning itself (v) Ensure that proper care and facilities are provided to human volunteers, if they are necessary for the research projects(s) (vi) Ensure that undue animal experimentations are not done and when these are necessary they are done in a scientific and a humane way (vii) Ensure that while accepting such an assignment a medical practitioner shall have the freedom to publish the results of the research in the greater interest of the society by inserting such a clause in the MoU or any other document/agreement for any such assignment. Action

ÂÂ Cash or monetary grants more than Rs. 5,000/–

ÂÂ First time censure, and thereafter removal of name

ÂÂ Cash or monetary grants more than Rs. 10,000/– to

f) Maintaining Professional Autonomy: In dealing with pharmaceutical and allied healthcare industry a medical practitioner shall always ensure that there

up to Rs. 10,000/–: Removal from Indian Medical Register or State Medical Register for 3 (three months). Rs. 50,000/–: Removal from Indian Medical Register or State Medical Register for 6 months.

from Indian Medical Register or State Medical Register for a period depending upon the violation of the clause.

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

307

MCI UPDATE shall never by any compromise either with his/her own professional autonomy and/or with the autonomy and freedom of the medical institution Action ÂÂ First time censure, and thereafter removal of name

from Indian Medical Register or State Medical Register.

g) Affiliation: A medical practitioner may work for pharmaceutical and allied healthcare industries in advisory capacities, as consultants, as researchers as treating doctors or in any other professional capacity. In doing so, a medical practitioner shall always: (i)

Ensure that his professional integrity and freedom are maintained

(ii)

Ensure that patient’s interests are not compromised in any way

(iii) Ensure that such affiliations are within the law

(iv) Ensure that such affiliations/employments are fully transparent and disclosed. Action First time censure, and thereafter removal of name from Indian Medical Register or State Medical Register for a period depending upon the violation of the clause. h) Endorsement: A medical practitioner shall not endorse any drug or product of the industry publicity. Any study conducted on the efficacy or otherwise of such products shall be presented to and or through appropriate scientific bodies or published in appropriate scientific journals in a proper way". Action ÂÂ First Time censure; and thereafter removal of name

from Indian Medical Register or State Medical Register. (Lt Col (Retd) Dr ARN Setalvad) Secretary Medical Council of India

Foot Note: The Principal Regulations, namely; "Indian Medical Council (Professional Conduct, Etiquette and Ethics) Regulations, 2002" were published in Part –III, Section (4) of the Gazette of India on the 6th April, 2002, and amended vide MCI notification dated 22/02/2003, 26/05/2004 & 10/12/2009.

Beware of patients who want to get admitted only for Mediclaim reimbursement I got a call yesterday, 14th August, from a patient who wanted a consultation with me. I told him to come to my clinic. He told me he wanted to see me early morning at Moolchand so that he could get admitted right away, if required, to get investigated. He came the next morning when I was busy with my Echo schedule. I told my assistant to ask them to get my consultation card made. He refused to pay for my consultation fee and instead asked me to admit him first and then see. I said, "How can I admit you without seeing a need for it". He said that he wanted reimbursement and would not pay for the pre admission consultation fee. Then I said, “What if you do not need an admission”. He asked me to send him to the emergency room and admit him first. I said even in ER the charges would be there and he will have to bear admission charges. He then brought one person who said that pre hospital bills are not admissible in insurance which was not correct as bills one month prior to admission are reimbursable. Any way I did not succumb to his request and he walked away. Lesson: Every day we get a request that someone wants to get admitted in the hospital so that he or she could be investigated fully and get reimbursement from Mediclaim. This is cheating the insurance company and amounts to violation of MCI Code of Medical Ethics Regulations and may attract a suspension of license to practice. No individual should be admitted to a hospital, unless there is an emergency and admission can be justified. A situation may arise when the same patient may later get admitted through emergency, then it is our duty not to fill the Mediclaim form if the admission was not justified.

308

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

Onychomycosis: Current Trends in Diagnosis and Treatment DYANNE P WESTERBERG, MICHAEL J VOYACK

Abstract Onychomycosis is a fungal infection of the nails that causes discoloration, thickening, and separation from the nail bed. Onychomycosis occurs in 10% of the general population, 20% of persons older than 60 years, and 50% of those older than 70 years. It is caused by a variety of organisms, but most cases are caused by dermatophytes. Accurate diagnosis involves physical and microscopic examination and culture. Histologic evaluation using periodic acidâ&#x20AC;&#x201C;Schiff staining increases sensitivity for detecting infection. Treatment is aimed at eradication of the causative organism and return to a normal appearance of the nail. Systemic antifungals are the most effective treatment, with meta-analyses showing mycotic cure rates of 76% for terbinafine, 63% for itraconazole with pulse dosing, 59% for itraconazole with continuous dosing, and 48% for fluconazole. Concomitant nail debridement further increases cure rates. Topical therapy with ciclopirox is less effective; it has a failure rate exceeding 60%. Several nonprescription treatments have also been evaluated. Laser and photodynamic therapies show promise based on in-vitro evaluation, but more clinical studies are needed. Despite treatment, the recurrence rate of onychomycosis is 10% to 50% as a result of reinfection or lack of mycotic cure.

Keywords: Onychomycosis, dermatophytes, systemic antifungals, concomitant nail debridement, recurrence

nychomycosis is a fungal infection of the fingernails or toenails that causes discoloration, thickening, and separation from the nail bed. Onychomycosis occurs in 10% of the general population but is more common in older adults; the prevalence is 20% in those older than 60 years and 50% in those older than 70 years.1 The increased prevalence in older adults is related to peripheral vascular disease, immunologic disorders, and diabetes mellitus. The risk of onychomycosis is 1.9 to 2.8 times higher in persons with diabetes compared with the general population.2 In patients with human immunodeficiency virus infection, the prevalence ranges from 15% to 40%.3 Onychomycosis affects toenails more often than fingernails because of their slower growth, reduced blood supply, and frequent confinement in dark, moist environments. It may occur in patients with distorted nails, a history of nail trauma, genetic predisposition, hyperhidrosis, concurrent fungal infections, and

DYANNE P. WESTERBERG, DO, FAAFP, is the founding chair of Family and Community Medicine at Cooper Medical School of Rowan University, and chief of Family and Community Medicine at Cooper University Hospital, both in Camden, N.J. At the time this article was written, she was chief of Family and Community Medicine at Cooper University Hospital, and vice chair of Family Medicine and Community Health at Robert Wood Johnson Medical School in Camden. MICHAEL J. VOYACK, DO, is an attending physician at Cooper University Hospital and a clinical instructor of family and community medicine at Cooper Medical School of Rowan University. Source: Adapted from Am Fam Physician. 2013;88(11):762-770.

psoriasis. It is also more common in smokers and in those who use occlusive footwear and shared bathing facilities.1,4 Microbiology Onychomycosis is caused by various organisms, most often dermatophytes of the genus Trichophyton. Other organisms include Candida, which is more common in fingernail infections (eFigure A) and in patients with chronic mucocutaneous candidiasis.1 Nondermatophyte molds are a less common cause in the general population. Recent studies, however, have demonstrated that they are the predominant organisms in patients with onychomycosis and human immunodeficiency virus infection3 (eTable A). Classification Onychomycosis is divided into several classes based on morphologic patterns and mode of invasion of the nail (Table 1).5 Classification provides a framework for diagnosis and expected response to treatment, and can help predict the prognosis. The classes include distal and lateral subungual onychomycosis (Figures 1 and 2), proximal subungual onychomycosis (Figure 3), superficial onychomycosis (Figure 4), and total dystrophic onychomycosis (Figure 5). A fifth class, endonyx subungual onychomycosis, is rare. Some nails have features from a combination of classes.

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

309

American Family Physician Table 1. Classification of Onychomycosis Onychomycosis class

Clinical features

Causative organism*

Mode of infection

Comments

Distal and lateral subungual

Begins distally at the hyponychium and spreads to the nail plate and bed; hyperkeratotic debris accumulates and results in onycholysis; nails thicken, chip, become dystrophic, and turn yellow-white or brown-black; infection can progress proximally, causing linear channels or â&#x20AC;&#x153;spikesâ&#x20AC;? that can make treatment difficult; associated with paronychia

Epidermophyton floccosum

Fungal invasion through break in the skin at the lateral or distal undersurface of the nail

Most common form

Nail develops a milky white appearance, indentations, and lamellar splitting; no hyperkeratosis or onycholysis

Trichophyton soudanense

Fungus invades the full thickness of the nail from directly under the skin without infecting the nail bed

Rare; considered a subtype of distal and lateral subungual onychomycosis

Debris accumulates under the proximal portion of the nail, causing onycholysis and a white color that spreads distally

T. rubrum

Fungus invades the proximal nail fold and cuticle; may also develop secondary to paronychia

Suggests an immunosuppressive condition (e.g., human immunodeficiency virus infection)

Nail appears to have powder-like patches of transverse striae on the surface

T. mentagrophytes

Previously known as superficial white onychomycosis, but some organisms produce black debris

Scytalidium species

May appear on the superficial nail plate or emerge from under the nail fold; may be deep penetration of the superficial infection

Can result from any of the other classes, although it is most often from severe distal and lateral subungual onychomycosis

Endonyx subungual

Proximal subungual

Superficial

Total dystrophic

Complete destruction of the nail from long-standing infection; nail thickens, and nail structure is lost

Trichophyton mentagrophytes Trichophyton rubrum Fusarium species Scopulariopsis brevicaulis Scytalidium specie Candida albicans

Trichophyton violaceum

Aspergillus species Fusarium species C. albicans T. rubrum Acremonium species Fusarium species

Note: Candidal onychomycosis was previously considered a class of onychomycosis. This condition, which more commonly involves the fingernails, has recently been excluded as a separate type because it was inconsistent to base a class on the organism alone. *Dermatophytes are listed first, followed by nondermatophyte molds and yeast. Information from reference 5.

Diagnosis Accurate diagnosis is crucial for successful treatment and requires identification of physical changes and positive laboratory analysis. Only 50% of nail problems are caused by onychomycosis,6 and clinical diagnosis by physical examination alone can be inaccurate. Psoriasis, chronic nail trauma, and other causes must also be considered. The differential diagnosis of onychomycosis is presented in Table 2,7 and an algorithm outlining a suggested diagnostic approach is shown in Figure 6.

310

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

Laboratory analysis involves evaluation of nail clippings and subungual debris from the involved portion of the nail. Samples should be collected after cleansing the area with 70% isopropyl alcohol to prevent contamination. Clippings should be obtained with a sterile nail clipper or curette, and subungual debris using a No. 15 surgical blade or a 2-mm curette. To improve accuracy, eight to 10 nail shards should be collected.8 Diagnostic precision is enhanced if the sample is collected with a nail drill9 and if it is taken from a more proximal

American Family Physician

Figure 1. Distal and lateral subungual onychomycosis.

Figure 4. Superficial onychomycosis.

Figure 2. Distal and lateral subungual onychomycosis with spike deformity.

Figure 5. Total dystrophic onychomycosis.

location on the nail in patients with suspected distal and lateral onychomycosis.10 In those with suspected proximal subungual onychomycosis, the upper nail plate of the proximal nail is debrided, and underlying debris is collected. In those with suspected superficial onychomycosis, the superficial aspect of the nail is scraped.

Figure 3. Proximal subungual onychomycosis.

Once the specimen has been obtained, office microscopy can be performed by preparing the samples with potassium hydroxide (KOH) 10% to 20% solution. The KOH will dissolve keratin, leaving the fungal cell intact. The specimen should be placed on a slide with a drop of KOH solution, then set aside at room temperature for five to 30 minutes; heating the slide or adding a dimethyl sulfide 40% solution will enhance keratin

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

311

American Family Physician Table 2. Common Conditions that can Mimic Onychomycosis Condition

Features

Infections Chronic paronychia

Viral warts

Chronic inflammation of the proximal paronychium; cross-striations of the nail; Streptococcus, Staphylococcus, or Candida found on smear and culture; common in children Localized in nail folds and subungual tissue; longitudinal depressed grooves in the nail plate

Diagnosis of Onychomycosis Nail is discolored, deformed, hypertrophic, or hyperkeratotic, or has subungual debris; onychomycosis is suspected Clean area with 70% isopropyl alcohol and obtain several samples of nail clippings and subungual debris Office microscopy using KOH or KOH/dimethyl sulfoxide, or laboratory microscopy using KOH or KOH/calcofluor white stain

Negative

Skin disorders Chronic dermatitis

Subungual dermatitis, hyperkeratosis, Beau lines, and pitting; thickened nail with corrugated surface

Lichen planus

Longitudinal grooves and fissures; usually affects fingernails

Psoriasis

Nail pitting, splinter hemorrhages, “oil staining,” yellow-gray or silvery white nails (eFigure B)

Twenty-nail dystrophy

Dystrophy of all 20 nails; usually resolves in childhood; associated with the lesions of lichen planus (eFigure C)

Trauma Footwear

Oncholysis, ingrown toenails, subungual keratosis, nail plate discoloration and irregularities; caused by friction against the shoe

Manipulation (e.g., manicures, pedicures, rubbing)

Horizontal parallel nail plate grooves, inflammation from Staphylococcus aureus or Pseudomonas infection (eFigure D)

Positive Begin treatment; consider studies to identify causative organism

Obtain culture and/or histologic evaluations with periodic acid–Schiff staining

Negative

Positive

Consider other nail disorders

Begin treatment

Figure 6. Algorithm for the diagnosis and treatment of onychomycosis. (KOH = potassium hydroxide.)

Tumors Bowen disease

Squamous cell carcinoma; bleeding, pain, nail deformity, and nail discoloration

Fibroma

Oval or spherical, white or yellow nodule; causes tunnel-like melanonychia; fibrous dermatofibroma or periungual fibroma

Melanoma

Brown-yellow nail with dark pigment extending into the periungual skin folds; poor prognosis

Information from reference 7.

dissolution.11 Commercial laboratories may use KOH with calcofluor white stain, which binds to cellulose and enhances the fungal components in fluorescent microscopy.11 Identification of hyphae, pseudohyphae, or spores confirms infection but does not identify the organism. To identify the organism, culture can be performed in a laboratory.12 Samples should be sent in a sterile

312

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

eFigure A. Candidal subungual onychomycosis.

container, and results are usually available in four to six weeks. Histologic evaluation can also be helpful for identification of the organism, and it can provide results within 24 hours. Periodic acid–Schiff (PAS)

American Family Physician eTable A. Common Pathogens in Onychomycosis Dermatophytes (80% to 90%) Epidermophyton floccosum Microsporum species Trichophyton interdigitale Trichophyton mentagrophytes Trichophyton rubrum Trichophyton tonsurans Nondermatophyte molds (2% to 10%)* Acremonium species Alternaria species Aspergillus species

eFigure B. Nail pitting in a patient with psoriasis. The pits are enhanced by the presence of grease.

Cladosporium carrionii Fusarium species Geotrichum candidum

eTable B. Risk Factors for Poor Response or Nonresponse to Treatment for Onychomycosis

Lasiodiplodia theobromae

Risk factor

Example

Onychocola species

Diagnostic problem

Another cause of nail dystrophy; mixed disease (e.g., onychomycosis and psoriasis)

Fungal problem

Infection with drug-resistant or multiple organisms

Nail condition that is difficult to treat

Dermatophytoma (i.e., a mass of hyphae and necrotic keratin below the nail plate); involvement of lateral aspect of the nail; more than 50% of nail affected; “spikes” extending from distal to proximal nail; subungual hyperkeratosis greater than 2 mm

Patient characteristic or condition

Older age; diabetes mellitus; immunosuppression; impaired peripheral circulation

Problem with medication adherence

Early termination of therapy; incorrect dosing; missed doses

Scopulariopsis species Scytalidium species Yeast (2% to 11%) Candida albicans Candida guilliermondii Candida parapsilosis *Nondermatophyte molds are the predominant organism in patients with human immunodeficiency virus infection. Information from: Alberhasky RC. Laboratory diagnosis of onychomycosis. Clin Podiatr Med Surg. 2004;21(4):565-578, vi. Kaur R, Kashyap B, Bhalla P. Onychomycosis—epidemiology, diagnosis and management. Indian J Med Microbiol. 2008;26(2):108-116. Surjushe A, Kamath R, Oberai C, et al. A clinical and mycological study of onychomycosis in HIV infection. Indian J Dermatol Venereol Leprol. 2007;73(6):397-401. Welsh O, Vera-Cabrera L, Welsh E. Onychomycosis. Clin Dermatol. 2010;28(2):151-159.

staining and methenamine silver stains are used. PAS staining is less expensive,13 and in a study of 1,146 nail clippings comparing PAS histologic examination with KOH light microscopy and culture, PAS staining was the most sensitive test (82% sensitivity, compared with 53% for culture and 48% for KOH microscopy).14 Combining PAS staining with culture increased sensitivity to 96%. In a review of cases in which treatment was initiated before specimens were obtained, PAS staining had the highest sensitivity, and culture had the least.14 Polymerase chain reaction testing has been shown to be more accurate than culture, and results can be

Information from: Scher RK, Baran R. Onychomycosis in clinical practice: factors contributing to recurrence. Br J Dermatol. 2003;149(suppl 65):5-9.

available in three days. However, it is not yet widely available.15,16 Treatment Onychomycosis is widely believed to be only a cosmetic problem, but it can be uncomfortable and can lead to cellulitis in older adults17 and foot ulcers in patients with diabetes.18 Eradication of the infection is key to improving appearance and avoiding these complications, but it is not easily accomplished because nails are made of keratin, which is nonvascular and

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

313

American Family Physician Table 3. Commonly Prescribed Medications for Treatment of Onychomycosis in Adults Medication

Dosing

Cure rates (%) Clinical 921

Organisms targeted

Potential adverse effects

29 to 3621 (77 when used in combination with debridement)22

Candida species, dermatophytes

Periungual erythema, erythema of the proximal nail fold, burning sensation, nail shape changes, ingrown toenails, nail discoloration

Mycotic

Ciclopirox 8% solution (nail lacquer)

Apply once daily to affected nails and to the underside of the nail

6 to

Fluconazole

100 to 300 mg orally every week for three to six months (fingernails) or six to 12 months (toenails)

4123

4823

Candida species

Nausea, vomiting, abdominal pain, diarrhea, headache, rash

Itraconazole

Pulse dosing: 200 mg orally two times per day for one week per month, for two months (fingernails) or three months (toenails) Continuous dosing: 200 mg orally once per day for six weeks (fingernails) or 12 weeks (toenails)

7023

63 (pulse dosing)

Candida species, dermatophytes, nondermatophyte molds, Aspergillus species

Nausea, vomiting, hypokalemia, elevated transaminase and triglyceride levels, rash

250 mg orally once per day for six weeks (fingernails) or 12 weeks (toenails)

6623

Some yeasts, dermatophytes, nondermatophyte molds

Gastrointestinal upset, rash, headache

Terbinafine

69 (continuous dosing)23

7623

FDA = U.S. Food and Drug Administration. *Not all possible drug interactions are listed; see package insert before prescribing. â&#x20AC; Estimated

retail price based on information obtained at http://www.goodrx.com (accessed March 4, 2013).

Information from references 21 through 27.

eFigure D. Median nail dystrophy caused by repetitive trauma to the nail from habitual rubbing. eFigure C. Twenty-nail dystrophy (also called sandpaper nails) is characterized by longitudinal ridges on all 20 nails. The nails may become discolored.

314

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

impermeable to many agents.19 Because of poor drug delivery to nails, results of treatment may not be apparent for a year.

American Family Physician

Potential drug interactions*

FDA pregnancy category

Estimated monthly costâ&#x20AC;

Comments

$11 for 3.3-mL bottle

Indicated for use in immunocompetent patients with mild to moderate onychomycosis without lunular involvement; patients should not bathe for eight hours after applying nail lacquer; lacquer should be removed once per week, and as much of the damaged nail as possible should be removed using scissors, nail clippers, or a nail file

Benzodiazepines, calcium channel blockers, statins

$13 for 30 100Not FDA approved for treatment of onychomycosis in children or mg tablets ($492 adults; prescribing guidelines recommend periodic monitoring of liver brand) function, renal function, and potassium levels; use with caution in breastfeeding women and in patients with hepatic or renal disease or porphyria

Benzodiazepines, calcium channel blockers, proton pump inhibitors, statins, warfarin, zolpidem

$195 for 30 100mg capsules ($523 brand)

Antiarrhythmic agents, beta blockers, selective serotonin reuptake inhibitors, tricyclic antidepressants, warfarin

$4 for 30 250Liver transaminase levels should be checked before therapy is mg tablets ($607 started; if treatment continues beyond six weeks, complete blood brand) count and liver function testing should be performed; use with caution in breastfeeding women and in patients with hepatic or renal disease, psoriasis, or porphyria

Treatment varies depending on the severity of nail changes, the organism involved, and concerns about adverse effects and drug interactions. Treatments also have varying effectiveness, based on cure parameters that are defined differently among studies. Mycotic cure denotes that no organism is identified on microscopy and culture. Clinical cure refers to improvement in the appearance of the nail, often defined as a normal appearance in 80% to 100% of the nail. It is a subjective measure that is difficult to compare across studies.20 Complete cure indicates that mycotic and clinical cure have been achieved.

Oral Azoles and Allylamines Antifungals from the azole and allylamine classes are the most widely used oral medications for the treatment of onychomycosis. The azole class includes itraconazole, fluconazole, and ketoconazole; however, ketoconazole is rarely prescribed because of drug interactions and hepatotoxicity. The allylamine class is represented by terbinafine. These medications and their dosing regimens are shown in Table 3.21-27 A meta-analysis of treatments for toenail onychomycosis

Liver function should be monitored in patients with preexisting hepatic dysfunction, and in all patients being treated for longer than one month; serum drug levels should be monitored because of erratic bioavailability with capsule formulation; renal function should be monitored; use with caution in breastfeeding women and in patients with hepatic or renal disease or porphyria; contraindicated in patients with ventricular dysfunction or congestive heart failure

determined that mycotic cure rates were 76% for terbinafine, 63% for itraconazole with pulse dosing, 59% for itraconazole with continuous dosing, and 48% for fluconazole.23 Clinical cure rates were 66% for terbinafine, 70% for itraconazole with pulse dosing, 70% for itraconazole with continuous dosing, and 41% for fluconazole. Common adverse effects included headache, gastrointestinal problems, and rash; these drugs also have been associated with Stevens-Johnson syndrome, prolonged QT interval, and ventricular dysfunction. The use of these agents is discouraged in patients with liver, renal, or heart disease, and in those receiving medications with which there may be significant drug-drug interactions.25 Liver function studies are recommended before beginning treatment and after one month of therapy.24 A metaanalysis concluded that the risk of asymptomatic elevation of transaminase levels in immunocompetent patients receiving oral antifungal agents was 2%, and that the risk of elevations requiring termination of therapy was 1%.28 Although these medications are not approved for use in children, they have been used in children with positive results.29

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

315

American Family Physician Table 4. Nonprescription Treatments for Onychomycosis Agent

Administration

Clinical cure rate (%)

Mycotic cure rate (%)

Comments

Ageratina pichinchensis (snakeroot) extract33

Apply every third day for the first month, twice per week for the second month, then once per week for the third month

Study of 110 patients; therapeutic effectiveness was similar to that in the control group, which used ciclopirox

Cyanoacrylate, undecylenic acid, and hydroquinone34

Soak and debride affected nails, then apply solution every two weeks for three to four visits; patients may also apply at home

50 to 65 (mild to moderate cases)

Study of 154 patients with cure rates reported after three months

Dual-wavelength near-infrared laser35

Treatment on days 1, 14, 42, and 120

Mild cases:

35 (severe cases)

Toenails were evaluated on day 180

65 (3 mm of nail clearance) 26 (4 mm of nail clearance) Moderate to severe cases: 63 (3 mm of nail clearance)

Melaleuca alternifolia (tea tree) oil36

Apply twice per day

Cochrane review found no evidence of benefit31

Mentholated ointment37

Apply small amount with cotton swab daily

Pilot study of 18 patients; 56% had artial clearance, and 17% had no clearance

Neodymium: yttriumaluminum- garnet laser38

One to three sessions four to six weeks apart

61 (complete cure) 19 (significant improvement)

Study of 37 toenails with onychomycosis

11 (moderate improvement) NA = not available. Information from references 31, and 33 through 38.

Topical Agents Several topical agents are used for the treatment of onychomycosis. These agents have few contraindications and no drug-drug interactions. Ciclopirox 8% solution is the only topical prescription medication available in the United States for the treatment of onychomycosis. It is a synthetic hydroxypyridine antifungal formulated as a nail lacquer. Adverse effects include burning, itching, and stinging at the application site.30 It may be used in patients who cannot take oral antifungals and in those with less than 50% of the distal nail affected and no lunular involvement.21 It has been used in children, although it is not approved for use in patients younger than 12 years.29 When used alone, ciclopirox has a mycotic cure rate of 29% to 36%, and a clinical cure rate of 6% to 9%.21 A Cochrane review

316

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

noted that the treatment failure rate was 61% to 64% after 48 weeks of use.31 Ciclopirox has also been used in combination with oral agents to improve effectiveness. In one comparative study, a combination of ciclopirox and oral terbinafine had a mycotic cure rate of 88% and a complete cure rate of 68%, whereas terbinafine alone had a mycotic cure rate of 65% and a complete cure rate of 50%.32 Nonprescription agents have also been used for treatment of onychomycosis (Table 4).31,33-38 These therapies have been evaluated in only a small number of studies involving few patients. Topical mentholated ointment (Vicks Vaporub) was used in a small study involving 18 patients.37 After 48 weeks, 28% had mycotic and clinical cure, 56% had partial clearance, and 17% had no improvement. Tea tree

American Family Physician oil (Melaleuca alternifolia) has been evaluated in two studies. Although one trial was favorable, combined data from both studies did not demonstrate significant benefit.29,36 Snakeroot extract (Ageratina pichinchensis) is an antifungal derived from plants of the sunflower family. It was studied in a randomized trial involving 96 patients who applied the extract or ciclopirox for six months to nails with confirmed infections.33 Mycotic cure occurred in 59% of patients receiving the extract and in 64% of those receiving ciclopirox. Clinical cure occurred in 71% and 81% of patients, respectively. Differences between the two treatments were not statistically significant. A small study showed that a combination of cyanoacrylate, undecylenic acid, and hydroquinone (marketed as Renewed Nail) demonstrated mycotic cure in 78 of 154 participants (50%).34

Physical Treatments Nail trimming and debridement are often performed concomitantly with other treatments and appear to offer benefit. Study groups that received nail debridement with oral terbinafine had higher clinical cure rates than those who received oral terbinafine alone.39 When debridement was performed with concurrent administration of ciclopirox, the mycotic cure rate was 77%, higher than that for ciclopirox alone.22 Improvement in nail appearance was reported, but clinical cure rates were not. Although they are expensive, laser and photodynamic therapies have become popular based on the success of in-vitro studies. Several neodymium:yttriumaluminum-garnet (Nd:YAG) laser therapies have been approved by the U.S. Food and Drug Administration for treatment of onychomycosis.40 The Pinpointe Footlaser, Cutera GenesisPlus laser, and Cooltouch Varia laser are short-pulse laser systems, whereas the Light Age Q-Clear laser is a Q-switched laser. However, there are only limited data about the use of these therapies in patients. In one study, Nd:YAG laser light was used to treat 37 nails, with one to three treatments given four to eight weeks apart. At 16 weeks, 61% were completely cured, 19% had significant improvement in the nail appearance, and 11% had moderate improvement in the nail appearance.38 Another laser treatment, the dual-wavelength nearinfrared laser, is approved for dermatologic use, but not specifically for treatment of onychomycosis.41 This treatment was used on 26 nails on days 1, 14, 42, and 120. After 180 days, 91% of nails with mild

infection showed clinical improvement (3 to 4 mm of the nail free of clinical infection); however, only 30% had mycotic cure.42 Photodynamic therapy using photosensitizing drugs and light to destroy fungal cells has shown some success in the treatment of onychomycosis, but further evaluation is needed.43 Treatment Failure Despite the number of available treatments, not all patients with onychomycosis are cured. Numerous factors have been cited to explain the lack of response to therapy, such as nonadherence to treatment, incorrect diagnosis, or advanced disease. Factors contributing to poor response or nonresponse to treatment are listed in eTable B. For those who appear to be cured, recurrent infection is a risk, with a number of factors increasing the chance of recurrence. Risk factors include concomitant disease, genetic factors, immunosuppression, incorrect dosing or duration of treatment, moisture, occlusive footwear, older age, poor hygiene, tinea pedis, and trauma.44 Recurrence can be caused by lack of mycotic cure or reinfection, and the reported rate of clinical recurrence of onychomycosis ranges from 10% to 53%, regardless of the treatment method used.45 Many patients tire of continued unsuccessful treatments or recurrences, and ultimately elect to undergo permanent nail removal. REFERENCES 1. Thomas J, Jacobson GA, Narkowicz CK, Peterson GM, Burnet H, Sharpe C. Toenail onychomycosis: an important global disease burden. J Clin Pharm Ther. 2010;35(5): 497-519. 2. Mayser P, Freund V, Budihardja D. Toenail onychomycosis in diabetic patients: issues and management. Am J Clin Dermatol. 2009;10(4):211-220. 3. Surjushe A, Kamath R, Oberai C, et al. A clinical and mycological study of onychomycosis in HIV infection. Indian J Dermatol Venereol Leprol. 2007;73(6):397-401. 4. Gupta AK, Gupta MA, Summerbell RC, et al. The epidemiology of onychomycosis: possible role of smoking and peripheral arterial disease. J Eur Acad Dermatol Venereol. 2000;14(6):466-469. 5. Hay RJ, Baran R. Onychomycosis: a proposed revision of the clinical classification. J Am Acad Dermatol. 2011;65(6):1219-1227. 6. Faergemann J, Baran R. Epidemiology, clinical presentation and diagnosis of onychomycosis. Br J Dermatol. 2003;149(suppl 65):1-4.

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

317

American Family Physician 7. Allevato MA. Diseases mimicking onychomycosis. Clin Dermatol. 2010;28(2):164-177.

treatment of pedal onychomycosis: a randomized, controlled trial. J Foot Ankle Surg. 2009;48(3):294-308.

8. Alberhasky RC. Laboratory diagnosis of onychomycosis. Clin Podiatr Med Surg. 2004;21(4):565-578.

23. Gupta AK, Ryder JE, Johnson AM. Cumulative metaanalysis of systemic antifungal agents for the treatment of onychomycosis. Br J Dermatol. 2004;150(3):537-544.

9. Shemer A, Davidovici B, Grunwald MH, Trau H, Amichai B. Comparative study of nail sampling techniques in onychomycosis. J Dermatol. 2009;36(7):410-414. 10. Shemer A, Trau H, Davidovici B, Grunwald MH, Amichai B. Nail sampling in onychomycosis: comparative study of curettage from three sites of the infected nail. J Dtsch Dermatol Ges. 2007;5(12):1108-1111. 11. Snyder JW, Atlas RM, LaRocco MT. Reagents, stains, and media: mycology. In: Versalovic J, Carroll KC, Funke G, Jorgensen JH, Landry ML, Warnock DW, eds. Manual of Clinical Microbiology. 10th ed. Washington, DC: ASM Press; 2011:1767. 12. Kaur R, Kashyap B, Bhalla P. Onychomycosis— epidemiology, diagnosis and management. Indian J Med Microbiol. 2008;26(2):108-116. 13. Barak O, Asarch A, Horn T. PAS is optimal for diagnosing onychomycosis. J Cutan Pathol. 2010;37(10):1038-1040. 14. Wilsmann-Theis D, Sareika F, Bieber T, Schmid-Wendtner MH, Wenzel J. New reasons for histopathological nailclipping examination in the diagnosis of onychomycosis. J Eur Acad Dermatol Venereol. 2011;25(2):235-237.

24. Lexi-Comp. http://online.lexi.com/crlsql/servlet/crlonline (subscription required). Accessed April 2, 2012. 25. Antifungal drugs. Treat Guidel Med Lett. 2009;7(88):95102. 26. Bennett JE. Antifungal agents. In: Brunton L, Chabner B, Knollman B, eds. Goodman & Gilman’s the Pharmacological Basis of Therapeutics. 12th ed. New York, NY: McGraw-Hill; 2011:1571-1592. 27. Sweetman S, ed. Martindale. The Complete Drug Reference. London, U.K.: Pharmaceutical Press. Electronic version, Greenwood Village, Colo.: Thompson Reuters (Healthcare) Inc. Updated periodically. 28. Chang CH, Young-Xu Y, Kurth T, Orav JE, Chan AK. The safety of oral antifungal treatments for superficial dermatophytosis and onychomycosis: a meta-analysis. Am J Med. 2007;120(9):791-798. 29. Gupta AK, Skinner AR. Onychomycosis in children: a brief overview with treatment strategies. Pediatr Dermatol. 2004;21(1):74-79.

15. Sato T, Takayanagi A, Nagao K, et al. Simple PCR-based DNA microarray system to identify human pathogenic fungi in skin. J Clin Microbiol. 2010;48(7):2357-2364.

30. Rotta I, Sanchez A, Gonçalves PR, Otuki MF, Correr CJ. Efficacy and safety of topical antifungals in the treatment of dermatomycosis: a systematic review. Br J Dermatol. 2012;166(5):927-933.

16. Litz CE, Cavagnolo RZ. Polymerase chain reaction in the diagnosis of onychomycosis: a large, single-institute study. Br J Dermatol. 2010;163(3):511-514.

31. Crawford F, Hollis S. Topical treatments for fungal infections of the skin and nails of the foot. Cochrane Database Syst Rev. 2007;(3):CD001434.

17. Roujeau JC, Sigurgeirsson B, Korting HC, Kerl H, Paul C. Chronic dermatomycoses of the foot as risk factors for acute bacterial cellulitis of the leg: a case-control study. Dermatology. 2004;209(4):301-307.

32. Avner S, Nir N, Henri T. Combination of oral terbinafine and topical ciclopirox compared to oral terbinafine for the treatment of onychomycosis. J Dermatolog Treat. 2005;16(5-6):327-330.

18. Boyko EJ, Ahroni JH, Cohen V, Nelson KM, Heagerty PJ. Prediction of diabetic foot ulcer occurrence using commonly available clinical information: the Seattle Diabetic Foot Study. Diabetes Care. 2006;29(6): 1202-1207.

33. Romero-Cerecero O, Zamilpa A, Jiménez-Ferrer JE, RojasBribiesca G, Román-Ramos R, Tortoriello J. Double-blind clinical trial for evaluating the effectiveness and tolerability of Ageratina pichinchensis extract on patients with mild to moderate onychomycosis. A comparative study with ciclopirox [published correction appears in Planta Med. 2008;74(14):1767]. Planta Med. 2008;74(12):1430-1435.

19. Baran R, Kaoukhov A. Topical antifungal drugs for the treatment of onychomycosis: an overview of current strategies for monotherapy and combination therapy. J Eur Acad Dermatol Venereol. 2005;19(1):21-29. 20. Scher RK, Tavakkol A, Sigurgeirsson B, et al. Onychomycosis: diagnosis and definition of cure. J Am Acad Dermatol. 2007;56(6):939-944. 21. Gupta AK, Fleckman P, Baran R. Ciclopirox nail lacquer topical solution 8% in the treatment of toenail onychomycosis. J Am Acad Dermatol. 2000;43(4 suppl):S70-S80. 22. Malay DS, Yi S, Borowsky P, Downey MS, Mlodzienski AJ. Efficacy of debridement alone versus debridement combined with topical antifungal nail lacquer for the

318

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

34. Rehder P, Nguyen TT. A new concept in the topical treatment of onychomycosis with cyanoacrylate, undecylenic acid, and hydroquinone. Foot Ankle Spec. 2008;1(2):93-96. 35. Landsman AS, Robbins AH, Angelini PF, et al. Treatment of mild, moderate, and severe onychomycosis using 870and 930-nm light exposure. J Am Podiatr Med Assoc. 2010;100(3):166-177. 36. Buck DS, Nidorf DM, Addino JG. Comparison of two topical preparations for the treatment of onychomycosis: Melaleuca alternifolia (tea tree) oil and clotrimazole. J Fam Pract. 1994;38(6):601-605.

American Family Physician 37. Derby R, Rohal P, Jackson C, Beutler A, Olsen C. Novel treatment of onychomycosis using over-the-counter mentholated ointment: a clinical case series. J Am Board Fam Med. 2011;24(1):69-74. 38. Kimura U, Takeuchi K, Kinoshita A, Takamori K, Hiruma M, Suga Y. Treating onychomycoses of the toenail: clinical efficacy of the sub-millisecond 1,064 nm Nd:YAG laser using a 5 mm spot diameter. J Drugs Dermatol. 2012;11(4):496-504. 39. Jennings MB, Pollak R, Harkless LB, Kianifard F, Tavakkol A. Treatment of toenail onychomycosis with oral terbinafine plus aggressive debridement: IRON-CLAD, a large, randomized, open-label, multicenter trial. J Am Podiatr Med Assoc. 2006;96(6):465-473. 40. Gupta AK, Simpson F. Newly approved laser systems for onychomycosis. J Am Podiatr Med Assoc. 2012;102(5): 428-430. 41. 510(k) summary: Noveon (Model LS1100-01-0968) dual wavelength laser instrument. http://www.accessdata.fda.

gov/cdrh_docs/pdf7/K071815.pdf. Accessed January 20, 2012. 42. Landsman AS, Robbins AH. Treatment of mild, moderate, and severe onychomycosis using 870- and 930-nm light exposure: some follow-up observations at 270 days. J Am Podiatr Med Assoc. 2012;102(2):169-171. 43. Sotiriou E, Koussidou-Eremonti T, Chaidemenos G, Apalla Z, Ioannides D. Photodynamic therapy for distal and lateral subungual toenail onychomycosis caused by Trichophyton rubrum: preliminary results of a singlecentre open trial. Acta Derm Venereol. 2010;90(2): 216-217. 44. Scher RK, Baran R. Onychomycosis in clinical practice: factors contributing to recurrence. Br J Dermatol. 2003;149(suppl 65):5-9. 45. Piraccini BM, Sisti A, Tosti A. Long-term follow-up of toenail onychomycosis caused by dermatophytes after successful treatment with systemic antifungal agents. J Am Acad Dermatol. 2010;62(3):411-414.

■■■■

Corrigendum In the August 2014 issue of IJCP, name of the principal author of the article "Significance of Peripheral Blood Smear in Diagnosis of Blood Parasitic Infection" was wrongly published as Gopal Rawal, Devang Patwari, D Kothari, P Joshi and M Pandya. It should read as Avni Shah, S Darji and K Shelat. The error is regretted.

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

319

American Family Physician

Practice Guidelines Management of Stable Ischemic Heart Disease: Recommendations from the ACP The American College of Physicians (ACP), in collaboration with the American College of Cardiology Foundation, American Heart Association, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, and Society of Thoracic Surgeons, has developed a guideline on the management of stable ischemic heart disease (IHD). This summary presents recommendations related to risk factor modification (including strategies of unproven benefit), medical therapies to prevent myocardial infarction and death and to relieve symptoms, and alternative therapies for relief of symptoms in patients with stable IHD. The full guideline contains additional recommendations related to patient education, revascularization to improve survival and symptoms, and patient follow-up.

Risk Factor Modification Lipid Management Lifestyle modifications are recommended for lipid management in all patients, including daily physical activity and weight management. The recommended dietary therapy for all patients should include reducing intake of saturated fats to less than 7% of total calories, reducing intake of trans-fatty acids to less than 1% of total calories, and reducing daily cholesterol intake to less than 200 mg. In addition, moderate- to high-dose statin therapy should be prescribed in the absence of contraindications or documented adverse effects. Hypertension Patients who have hypertension should receive counseling on the need for lifestyle modification. This includes maintaining a healthy weight, increasing physical activity, limiting intake of dietary sodium, moderating alcohol consumption, and increasing intake of fresh fruits, vegetables, and low-fat dairy products. In addition to following a trial of lifestyle modifications, patients with stable IHD and a blood pressure of 140/90 mm Hg or higher should be treated with antihypertensive drug therapy to achieve goal blood

Source: Adapted from Am Fam Physician. 2013;88(9):612-616.

320

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

pressure. Specific medications should be based on individual patient characteristics, and may include angiotensin-converting enzyme inhibitors and/or beta blockers, with other drugs such as thiazide diuretics or calcium channel blockers, if needed.

Diabetes Mellitus Rosiglitazone should not be initiated in patients with diabetes mellitus who have stable IHD. Physical Activity Risk assessment with a physical activity history is recommended to guide prognosis and prescription for all patients. When clinically indicated, an exercise test should be performed. Based on the results of this assessment, patients should be encouraged to engage in 30 to 60 minutes of moderate-intensity aerobic activity at least five days per week, and preferably seven days per week. Aerobic activity should be supplemented by an increase in daily activities, such as walking during breaks at work, gardening, or household activities, to improve cardiorespiratory fitness and motivate patients who are less fit, less active, and at increased risk. For patients considered at-risk at first diagnosis, medically supervised programs such as cardiac rehabilitation and physician-directed, home-based programs are recommended. Weight Management Patient body mass index or waist circumference should be assessed at every visit. Physicians should consistently encourage patients to maintain or reduce weight through an appropriate balance of lifestyle physical activity, structured exercise, caloric intake, and formal behavioral programs when indicated to help patients maintain or achieve a body mass index between 18.5 and 24.9 kg per m2, and a waist circumference less than 40 inches (102 cm) in men and less than 35 inches (89 cm) in women (less for certain racial groups). The initial goal of weight loss therapy should be to reduce body weight by approximately 5% to 10% from baseline; if successful, further weight loss can be attempted if indicated. Smoking Cessation Cessation of smoking, and avoidance of exposure to environmental tobacco smoke at work and at home, should be encouraged for all patients. A five-step

American Family Physician strategy for smoking cessation called the 5 A’s framework (ask, advise, assess, assist, arrange), patient follow-up, referral to special programs, and pharmacotherapy are also recommended.

systolic left ventricular dysfunction (ejection fraction 40% or less) with heart failure or previous myocardial infarction, metoprolol succinate, carvedilol, or bisoprolol should be used, unless contraindicated.

Reduction Strategies of Unproven Benefit

In all patients with stable IHD who also have hypertension, diabetes, left ventricular systolic dysfunction, or chronic kidney disease, angiotensinconverting enzyme inhibitors should be prescribed, unless contraindicated. Angiotensin receptor blockers are recommended for patients who have indications for, but are intolerant of, angiotensin-converting enzyme inhibitors.

Estrogen therapy should not be initiated in postmenopausal women with stable IHD for reducing cardiovascular risk or improving clinical outcomes. Elevated homocysteine levels should not be treated with folate or vitamins B6 and B12 to reduce cardiovascular risk or improve clinical outcomes. In addition, chelation therapy should not be used to improve symptoms or reduce cardiovascular risk. The following therapies should not be used to reduce cardiovascular risk or improve clinical outcomes: vitamin C, vitamin E, and beta carotene supplementation; garlic; coenzyme Q10; selenium; and chromium.

Medical Therapy to Prevent Myocardial Infarction and Death Aspirin (75 to 162 mg daily) should be continued indefinitely in the absence of contraindications. When aspirin is contraindicated, treatment with clopidogrel is a reasonable option. Dipyridamole should not be used as antiplatelet therapy. In all patients with normal left ventricular function following myocardial infarction or acute coronary syndromes, beta-blocker therapy should be initiated and continued for three years. For all patients with

Annual influenza vaccination is recommended for patients with stable IHD.

Medical Therapy for Symptom Relief Beta blockers should be prescribed as initial therapy for relief of symptoms. When beta blockers are contraindicated or cause unacceptable adverse effects, calcium channel blockers or long-acting nitrates should be prescribed. If initial beta-blocker therapy is unsuccessful, calcium channel blockers or long-acting nitrates should be prescribed in combination with beta blockers. Sublingual nitroglycerin or nitroglycerin spray should be used for immediate relief of angina in patients with stable IHD.

Alternative Therapies for Symptom Relief Acupuncture should not be used to improve symptoms or reduce cardiovascular risk.

■■■■

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

321

American Family Physician

Photo Quiz Facial Palsy in a 38-Year-Old Man A 38-year-old man presented with a painful rash on his right ear that had lasted for seven days. Over the previous four days, he developed ipsilateral tinnitus and progressive difficulty in closing his right eye and mouth. He had no notable medical history. On examination, he had multiple vesicles on an erythematous base on the concha of his right ear (Figure 1). Neurologic examination showed right-sided hearing impairment and lower motor neuron facial palsy with lagophthalmos, an inability to smile on the affected side, and loss of definition in the right nasolabial fold (Figure 2).

Figure 1.

Figure 2.

Question Based on the patientâ&#x20AC;&#x2122;s history and physical examination findings, which one of the following is the most likely diagnosis? A. Bell palsy. B. Neurosarcoidosis. C. Parry-Romberg syndrome. D. Ramsay Hunt syndrome.

Source: Adapted from Am Fam Physician. 2013;88(11):771-772.

322

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

SEE PAGE 324 FOR DISCUSSION.

American Family Physician Discussion

Summary Table

The answer is D: Ramsay Hunt syndrome, or herpes zoster oticus, is characterized by herpes zoster infection of the external ear or tympanic membrane with involvement of the facial and/or auditory nerves.1 The clinical manifestation includes unilateral peripheral facial palsy, with or without tinnitus, vertigo, or deafness.1,2 Ramsay Hunt syndrome can usually be diagnosed based on clinical findings.1 A Tzanck smear of the vesicular fluid can be performed to evaluate for multinucleated giant cells, which are indicative of varicella or herpes zoster infection.1,2 A viral culture is generally not required, but can differentiate between varicella and herpes simplex virus.1

Condition

Characteristics

Bell palsy

Unilateral facial weakness and drooping; difficulty closing an eye; loss of furrows in the brow; most cases resolve spontaneously

Neurosarcoidosis

Bilateral or unilateral seventh cranial nerve palsy; other cranial nerve palsies can also be associated; most resolve spontaneously but may recur

Parry-Romberg syndrome

Unilateral facial atrophy; includes degeneration of the soft tissue on one side of the face; autoimmune reaction; more common in women

Ramsay Hunt syndrome

Unilateral peripheral facial palsy; herpes zoster infection of the external ear or tympanic membrane with involvement of facial or auditory nerves; tinnitus, vertigo, or deafness may occur

Initiation of antiviral therapy within 72 hours of rash onset leads to the best outcomes in most adults.1,3-5 However, less than 50% of patients achieve complete neurologic recovery.1 Topical antiviral therapy is effective against cutaneous infection of herpes simplex virus but is not effective on the herpes zoster rash.1 The use of systemic corticosteroids is controversial, but may be considered for healthy older adults with severe pain and no contraindications.1 The pain of herpes zoster can be a significant problem, especially in older persons.1,3,5 Most patients experience pain during the acute phase that requires regular analgesics. Occlusive ointments and creams or lotions containing corticosteroids should be avoided.1 Postherpetic neuralgia is a common complication of herpes zoster infection and is defined as any pain occurring 90 to 120 days after rash onset.1,3 Postherpetic neuralgia has an overall incidence of 8% to 15%, but is most common in older persons.1 Bell palsy is a common cause of facial drooping. Patients present with unilateral facial weakness, difficulty closing an eye, and loss of furrows in the brow. Most cases are idiopathic and will resolve spontaneously.6 Neurosarcoidosis occurs in 5% to 10% of patients with sarcoidosis. The most common clinical manifestation of neurosarcoidosis is a bilateral or unilateral seventh cranial nerve palsy, although other cranial nerve palsies are possible. The condition usually resolves spontaneously but may recur, possibly years after the initial presentation.

Parry-Romberg syndrome is a rare progressive unilateral facial atrophy. It is thought to be an autoimmune disease and is more common in women. Symptoms include degeneration of the soft tissue, typically on one side of the face. REFERENCES 1. Fitzpatrick TB, Wolff K, eds. Fitzpatrick’s Dermatology in General Medicine. 7th ed. New York, NY: McGraw-Hill; 2008. 2. McKee PH, Calonje E, Granter SR, eds. Pathology of the Skin: With Clinical Correlations. 3rd ed. Philadelphia, Pa.: Elsevier Mosby; 2005. 3. Uscategui T, Dorée C, Chamberlain IJ, Burton MJ. Antiviral therapy for Ramsay Hunt syndrome (herpes zoster oticus with facial palsy) in adults. Cochrane Database Syst Rev. 2008;(4):CD006851. 4. Whitley RJ. A 70-year-old woman with shingles: review of herpes zoster [published corrections appear in JAMA. 2010;303(8):734, and JAMA. 2009;302(17):1864]. JAMA. 2009;302(1):73-80. 5. Sampathkumar P, Drage LA, Martin DP. Herpes zoster (shingles) and postherpetic neuralgia. Mayo Clin Proc.

2009;84(3):274-280.

6. Gronseth GS, Paduga R. Evidence-based guideline update: steroids and antivirals for Bell palsy: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2012;79(22):22092213.

■■■■

324

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

CARDIOLOGY

Status of HDL in Current Scenario GEETHA SUBRAMANIYAN*, DHARMENDRA JAIN†, BALAJI LOHIYA‡, NEERAJ KUMAR‡

Abstract Cardiovascular disease is a leading cause of death worldwide. Coronary heart disease (CHD) caused by atherosclerosis is the most common cause of morbidity and mortality. Prevention, stabilization and regression of atherosclerotic plaques may have a major impact on reducing the risk of acute coronary events. Low-density lipoprotein-cholesterol (LDL-C) lowering agents, primarily the statins, are the current mainstay in the pharmacologic management of dyslipidemia. Epidemiologic and observational studies have shown that high-density lipoprotein-cholesterol (HDL-C) is also a strong independent predictor of CHD, suggesting that raising HDL-C levels might afford clinical benefit in the reduction of cardiovascular risk. HDL particles have key atheroprotective functions—including the capacity to efflux cellular cholesterol—in addition to having antioxidative, anti-inflammatory, antiapoptotic, antithrombotic and vasodilatory actions. Therapeutic approaches to raise HDL-C levels can target one or more of several mechanisms, including the production of apolipoprotein A-I (apoA-I) or modification of intravascular remodeling of HDL particles. However, the landscape of HDL-raising therapies is now littered with failed therapies, including niacin and the negative results with the cholesteryl ester transfer protein (CETP) inhibitors. This is attributed to potential adverse effects of CETP inhibition such as the generation of HDL particles that have deficient biological activities and a deleterious impact on reverse cholesterol transport and steroid metabolism. Normalization of both defective HDL function and diminished HDL levels should, therefore, be the focus of pharmacological HDL-raising in future studies.

Keywords: Cardiovascular disease, low-density lipoprotein-cholesterol, statins, high-density lipoproteincholesterol, niacin, CETP inhibitors

ardiovascular disease is a leading cause of death worldwide. Among cardiovascular disorders, coronary heart disease (CHD) caused by atherosclerosis is the most common cause of morbidity and mortality. Prevention, stabilization and regression of atherosclerotic plaques may have a major impact on reducing the risk of acute coronary events. Lowdensity lipoprotein-cholesterol (LDL-C) lowering agents, primarily the statins, are the current mainstay in the pharmacologic management of dyslipidemia. However, even with statin use, residual CHD risk from dyslipidemia remains. Epidemiologic and observational studies have shown that high-density lipoproteincholesterol (HDL-C) is also a strong independent predictor of CHD, suggesting that raising HDL-C levels might afford clinical benefit in the reduction of cardiovascular risk.

*Emeritus Professor DRMGR Medical University †Assistant Professor Dept. of Cardiology ‡DM Fellow Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh Address for correspondence Dr Dharmendra Jain Assistant Professor, Dept. of Cardiology Institute of Medical Sciences, Banaras Hindu University Varanasi, Uttar Pradesh - 221 005 E-mail: djaincardio@gmail.com

Chasing HDL: Insights Approaches that target HDL remodeling can either increase the number of circulating HDL particles, or increase the duration for which apolipoprotein A-I (apoA-I) circulates by increasing its lipidation with the formation of cholesteryl ester-rich HDL or both. Mechanistic strategies to achieve these goals include the following: Inhibition of cholesteryl ester transfer protein (CETP); enhanced lipidation of apoA-I; enhanced efflux of cholesterol and phospholipids from peripheral cells to either mature spherical HDL or lipid poor apoA-I, mediated by ATP-binding cassette transporters A1 and G1 (ABCA1 and ABCG1) or scavenger receptor BI (SR-BI, also known as SCARB1) and inhibition of the uptake of HDL holoparticles or HDL-cholesteryl ester by the liver.1 Therapeutic approaches to raise HDL-C levels can target one or more of several mechanisms, including the production of apoA-I—the principal protein component of HDL—or modification of intravascular remodeling of HDL particles. ApoA-I-based therapies potentially increase the number of circulating HDL particles and primarily involve stimulation of apoA-I production by the liver, intestine or both. Fibrates, statins and glitazones are the best known examples of agents able to raise de novo apoA-I synthesis in hepatocytes.2 Other approaches center on infusion of recombinant

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

325

CARDIOLOGY apoA-I, reconstituted HDL, partially-delipidated HDL or apoA-I mimetic peptides. In terms of physicochemical properties and biological activity, circulating HDL particles are highly heterogeneous, reflecting their dynamic and complex intravascular metabolism. Each class of HDL-raising agent tends to produce a specific profile of HDL particles.1 Although different HDL-raising agents increase absolute HDL-C levels by differing degrees, elevated amounts of large, cholesterylester-rich HDL are commonly observed upon treatment with CETP inhibitors and niacin and to a lesser degree with statins. Interestingly, similar qualitative changes in HDL profile occur as a result of regular physical exercise or moderate alcohol consumption. By contrast, reconstituted HDL and apoA-I mimetics do not provide sustained elevations of HDL-C, but transiently increase circulating levels of HDL that are small, lipid-poor and protein-rich. HDL particles have key atheroprotective functions— including the capacity to efflux cellular cholesterol—in addition to having antioxidative, anti-inflammatory, antiapoptotic, antithrombotic and vasodilatory actions. Small, protein-rich HDL are notable because of their potent antiatherogenic properties.1,3 Consistent with these findings, both reconstituted HDL and apoA-I mimetics could enhance antiatherogenic functions of HDL.4 Despite considerable research, the therapeutic value of such agents remains unclear.5,6 Large randomized studies have previously shown that lowering LDL-C by 40 mg/dL (1 mmol/L) for 4-5 years with statin therapy cuts the risks of heart attacks and strokes by about a quarter, and recent studies suggest that more intensive LDL-lowering can produce extra benefits. But, despite the use of statins, the risk of heart attacks, strokes and other vascular complications among people who have vascular disease remains high. Subnormal levels of HDL-C constitute a major cardiovascular risk factor. Low levels of HDL-C constitute a strong, independent and inverse predictor of the risk of premature development of atherosclerosis and cardiovascular disease (CVD).7 Clinical studies have shown that increasing HDL-C is an effective therapeutic strategy to slow progression of atherosclerotic disease and induce regression of coronary atherosclerosis. The antiatherogenic effects of HDL are primarily mediated by cholesterol efflux from foam cells in atherosclerotic lesions via reverse cholesterol transport. Impairment of HDL functionality has been observed within certain populations, such as patients with metabolic syndrome or type 2 diabetes. Low plasma concentrations of

326

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

HDL-C are frequently a characteristic of type 2 diabetes as well as mixed or combined dyslipidemia, renal and hepatic insufficiency states and autoimmune diseases. In addition to low HDL-C, these disease states feature a moderate or marked degree of HTG. The intravascular metabolism of triglyceride (TG)-rich lipoproteins (principally very LDL [VLDL]) is intimately linked to that of HDL. Drug-induced raising of HDL-C may lead to beneficial reduction in the cholesterol content of both VLDL and LDL; the magnitude of reduction in VLDL-cholesterol (VLDL-C) and LDL-C under these circumstances tends to differ markedly as a function of the specific mechanism of action of the pharmacological agent concerned, as well as the dose employed and the baseline lipid phenotype. Furthermore, the percentage increase in HDL-C following treatment tends to be greater in subjects with the lowest baseline levels.8 The available options for elevating low HDL-C levels are relatively few. While HDL-C levels may be increased by up to ≈10% by implementing therapeutic lifestyle changes, including weight reduction, exercise, smoking cessation and moderate alcohol consumption, many patients will also require pharmacological intervention if target levels should be set. However, there is until now no clear direct evidence that raising HDL-C really results in CVD prevention. The landscape of HDL-raising therapies is now littered with failed therapies, including niacin and the negative results with the CETP inhibitors. These trials show just how difficult it is to provide additional benefit when patients are well-treated with statins. Observational studies have shown that raising HDL-C with exercise, eating a lower saturated-fat diet, losing weight, stopping smoking and drinking small amounts of alcohol raises HDL-C and lowers cardiovascular risk. Now one always thought that was causative, that HDL going up caused the lower cardiovascular events, but it’s more appropriate to see how the HDL went up that lowered cardiovascular events. Different available drug types that raise HDL-C, like niacin and the CETP inhibitors, have all crashed and burned when we study them. After AIM-HIGH and HPS-2 THRIVE study: where does niacin stand?

AIM-HIGH–First Flop of Niacin: A Critical Review The AIM-HIGH (Atherothombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health Outcomes) study9 has generated much debate, even leading some

CARDIOLOGY to question the role of niacin in the management of cardiometabolic disease.10 The study had planned to investigate whether adding niacin (extended-release [ER] formulation) to simvastatin therapy reduced cardiovascular events in high-risk patients with controlled LDL-C levels (74 [59-87] mg/dL) and low HDL-C (35 [31-39] mg/dL; <1.03 mmol/L in men and <1.29 mmol/L in women) and elevated TGs (162 [128-218] mg/dL). The previous European Atherosclerosis Society (EAS) Consensus Panel statement has highlighted the high-risk associated with this dyslipidemic profile despite achievement of LDL-C goal.11 Patients with a history of CVD were randomly allocated to either high-dose ER niacin (titrated to 1.5-2 g/day, n = 1,718) or placebo treatment (n = 1,696), against a background of simvastatin therapy. This event-driven trial was designed to have an 85% power to detect a 25% reduction in cardiovascular events. It was planned that a sample size of 3,400 participants followed for 2.5-7 years would generate the required 800 primary events. However, the study was terminated 18 months earlier than planned due to futility, with no statistically significant differences between the groups for any of the key outcomes. Further Analysis Revealed Several Reasons for the AIM-HIGH Trial’s Failings ÂÂ First, the planned event rates for this trial were

overly ambitious for the study population. While treatment with niacin increased HDL-C levels by 25-42 mg/dL, there was also a substantial increase in HDL-C in the placebo group (by 12-38 mg/dL). Based on population studies, the difference between the two groups - 4 mg/dL – would have predicted at most a 10% difference in cardiovascular events, less than half the predicted 25% reduction on which the power calculations were based.

ÂÂ Second, the vast majority (ca. 90%) of patients

had already been treated with statin therapy for more than 1 year before the study. In addition, ca. 20% of patients had previously received niacin (treatment was discontinued for 30 days before entry to the study).

ÂÂ Third, the placebo was supplemented with a low-

dose of immediate-release niacin (50 mg/0.5 or 1.0 g niacin tablet) to maintain study blinding. This may have impacted the study findings given uncertainties regarding the dose-benefit curve for niacin.

ÂÂ Fourth, there was considerable use of additional

lipid-modifying therapy in the placebo group. Seventy-five percent of patients in this group were receiving simvastatin doses of 40 mg/day or higher, and 21% were also receiving add-in ezetimibe.

Thus, AIM-HIGH was not powered to test the potential benefits of adding niacin to statin-treated patients.

HPS-2 THRIVE – A Second Major Setback of Niacin: A Critical Review The Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events (HPS-2 THRIVE) study, a secondary-prevention trial testing the addition of extended-release niacin to statin therapy, has missed its primary endpoint and shown no clinical benefit for extended-release niacin. After nearly 4 years of follow-up, the combination of niacin with the antiflushing agent laropiprant did not significantly reduce the risk of the combination of coronary deaths, nonfatal myocardial infarction (MI), strokes or coronary revascularizations compared with statin therapy, according to Merck, the sponsor of the HPS-2 THRIVE trial. In a press release on 20 December 2012 announcing the results, Merck said the combination significantly increased the risk of nonfatal but serious side effects.12 One day after the Merck announcement, the European Medicines Agency announced that it would be starting a review of the safety and efficacy of Tredaptive, given the results of the HPS-2 THRIVE study.13 It will make a recommendation to the Committee on Medicinal Products for Human Use (CHMP), and an opinion on any required regulatory action is expected in January 2013. Trial Design of HPS-2 THRIVE Might have Influenced Results The HPS-2-THRIVE was an all-comers secondaryprevention study and did not preselect patients with very low LDL-C levels. The epidemiologic relationship with HDL-C and cardiac events is inverse, but it’s inverse curvilinear, meaning that when HDL gets <40 mg/dL for men and 50 mg/dL and women, there is a signal of increased risk. But, the risk really gets steep when you get an HDL <35 or 30 mg/dL. With an all-comers design where baseline HDL-C levels were 50 mg/dL, for the sake of argument, a 20% increase in HDL with niacin would increase levels to 60 mg/dL, but this is the flat part of the event curve. Although powered for clinical events, the improvement in HDL would likely be insufficient to result in a significant reduction in cardiovascular events.

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

327

CARDIOLOGY Could there have been some sort of interaction between the laropiprant component of the niacin/laropiprant combination? Laropiprant works by blocking DP1 receptors on vascular cells to prevent flushing, but the DP1 receptors are elsewhere in body, including platelets, neurons and respiratory tissue. It remains unknown if the lack of benefit was the result of ineffectiveness when niacin was added to simvastatin or whether the benefit was canceled out as a result of an off-target effect caused by laropiprant.

the TG content of HDL particles. TG-rich HDL are then subject to hydrolysis by hepatic lipase, with subsequent structural destabilization involving shedding of apoA-I and elimination from the circulation by the kidney. As a result, apoA-I turnover is accelerated.16 As small TG enriched HDL are deficient in atheroprotective activities,1 CETP inhibitors could theoretically correct not only the core lipid composition of HDL (cholesteryl ester TG ratio) but also HDL functional defects seen in patients with metabolic disease.

This is the second major setback for physicians hoping that niacin, a drug that raises HDL-C levels, might be used clinically to reduce the risk of cardiovascular events. In May 2011, the National Heart, Lung and Blood Institute (NHLBI)-sponsored AIM-HIGH study, was halted early after showing no benefit of niacin when given in addition to statin therapy.

ILLUMINATE – First Flop Trial of CETP Inhibitors Torcetrapib: A Critical Review

A Meta-analysis of 11 Niacin Trials: Still Hope for Niacin Coincidentally, a systematic review and meta-analysis by Drs Paul Lavigne and Richard Karas (Tufts Medical Center, Boston, MA) evaluated 11 studies including 9,959 subjects, primarily secondary-prevention studies, treated with niacin.14 The studies included ARBITER-2 and ARBITER-6, as well as the AIM-HIGH study. In the meta-analysis, which is published online December 19, 2012 in the Journal of the American College of Cardiology, treatment with niacin was associated with a significant 34% reduction in the composite endpoint of any CVD event and a significant 25% reduction in CHD events.

After ILLUMINATE and Dal–OUTCOME: Where does CETP Inhibitors Stand? CETP inhibitors are presently the most potent HDLraising agents available, resulting in dose-dependent HDL-C elevation of up to 100%.15 This HDLraising effect constitutes the basis for the concept of pharmacological CETP inhibition for reduction of the residual cardiovascular risk after statin therapy. Consistent with the traditional view that cholesterol efflux capacity represents a central atheroprotective activity of HDL, enhanced reverse cholesterol transport from peripheral tissues to the liver before HDL level elevation has long been envisaged as the major antiatherogenic corollary of CETP inhibition. Of note, it is important to remember that high CETP activity, typical of metabolic diseases such as type 2 diabetes mellitus and the metabolic syndrome, enriches

328

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

Torcetrapib was the first CETP inhibitor to enter a largescale, prospective, placebo-controlled interventional trial, the Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events (ILLUMINATE), which was prematurely terminated in December 2006, because of excess cardiovascular and noncardiovascular mortality in the active treatment group. Therapy with torcetrapib was associated with considerable increases in aldosterone level and blood pressure and changes in serum electrolytes indicative of mineralocorticoid excess.17 These findings indicate that torcetrapib has off-target toxic effects unrelated to HDLraising that involve the activation of mineralocorticoid receptors by aldosterone and result in the induction of hypertension. In contrast with torcetrapib, other CETP inhibitors such as JTT-705 and MK-825 (anacetrapib) do not increase blood pressure in humans,18 an observation which discounts a class effect.

Dal-OUTCOMES – Second Set back Trial of CETP Inhibitors – Dalcetrapib: A Critical Review The dal-OUTCOMES trial evaluated the efficacy and safety profile of dalcetrapib when added to existing standard of care in patients with stable CHD following an acute coronary syndrome (ACS).19 Roche announced that following the results of the second interim analysis of the dal-OUTCOMES Phase III trial, the independent Data and Safety Monitoring Board (DSMB) has recommended stopping the trial due to a lack of clinically meaningful efficacy.20 No safety signals relating to the dal-OUTCOMES trial were reported from the DSMB. The dal-HEART is a global development program involving six clinical trials: dal-OUTCOMES, dal-OUTCOMES 2, dal-PLAQUE 2, dal-ACUTE, dal-PLAQUE (completed) and dal-VESSEL (completed). Roche has decided to terminate the dal-OUTCOMES trial and all the studies in the dal-HEART program. Researchers hoped

CARDIOLOGY dalcetrapib was a CETP inhibitor that could succeed where torcetrapib failed. Torcetrapib was abandoned when studies showed it appeared to increase the risk of cardiovascular events despite substantially increasing HDL-C levels.

There is Still Hope That the More Potent CETP Inhibitors can Improve Outcomes The failure of dalcetrapib shouldn’t be that much of a surprise. The likelihood of dalcetrapib succeeding was always very low. It’s a weak CETP inhibitor. The degree of HDL increase with the drug is very modest and it doesn’t lower LDL, and the concern all along had been that it just wouldn’t be effective enough to reduce morbidity and mortality. Earlier studies showed that dalcetrapib increases HDL by about 30%, while evacetrapib and anacetrapib (Merck, Whitehouse Station, NJ) increase HDL by more than 100% and reduce LDL by 35-40%, so there is still hope that the more potent CETP inhibitors can improve outcomes in ACS patients. It’s important to see this through to completion. The researchers should not lose their nerve. There’s going to be a lot of debate that the CETP hypothesis is wrong, but one don’t know that yet. One will need to be careful not to jump to conclusions and carry out these experiments.

Anacetrapib – A Potent CETP Inhibitor – The REVEAL HPS-3 TIMI-55 Trial: A Ray of Hope Anacetrapib has been found to produce substantial reductions in blood levels of ‘bad’ LDL-C in addition to those achieved with statin drugs, and it more than doubles ‘good’ HDL-C levels. The REVEAL HPS-3 TIMI-55 trial (Randomized EValuation of the Effects of Anacetrapib through Lipid-modification) is a large, randomized placebo-controlled trial assessing the clinical effects of anacetrapib (a potent CETP inhibitor) among patients with pre-existing vascular disease. When used either as monotherapy or in combination with a statin, the CETP inhibitor anacetrapib increases HDL-C and apoA-I concentrations by about 140% and 45%, respectively and reduces LDL-C and apoB concentrations by about 30-40%. Anacetrapib has been well-tolerated in early phase studies and, importantly, has no effects on blood pressure or aldosterone levels. In the REVEAL trial, all patients receive effective LDL-lowering treatment with atorvastatin. The primary aim of REVEAL is to assess the effect of anacetrapib on the composite outcome of Major Coronary Event, defined as coronary death, myocardial infarction or coronary revascularization. The REVEAL

trial is investigating whether a drug anacetrapib can drive down the risks of coronary deaths, heart attacks, strokes and other vascular complications. The study will involve 30,000 people who have some form of heart or other vascular disease. Till August 2012, over 20,000 people have been recruited into REVEAL, including over 5,000 in Europe, 6,000 in North America and 8,000 in China. It is anticipated that the recruitment of 30,000 patients will be completed during 2013, follow-up is anticipated to continue until 2016 and that the study results will become available in 2017.

Evacetrapib – A Potent CETP Inhibitor – ACCELERATE Study: Another Ray of Hope The phase III Study of Evacetrapib started in October 2012, ACCELERATE study (Assessment of Clinical Effects of Cholesteryl Ester Transfer Protein Inhibition with Evacetrapib in Patients at a High-Risk for Vascular Outcomes) will involve 11,000 people with high-risk vascular disease (HRVD). The purpose of the ACCELERATE study is to evaluate the efficacy and safety of evacetrapib in participants with HRVD. The primary objective of this study is to test the hypothesis that evacetrapib 130 mg daily, in comparison to placebo, reduces the incidence of the composite endpoint of cardiovascular death, MI, stroke, coronary revascularization or hospitalization for unstable angina in HRVD patients. The estimated primary completion date (Final data collection date for primary outcome measure) is September 2015. Chasing HDL: Current Status and Future Perspectives

Current Guidelines The European Society of Cardiology (ESC) 2011 Recommendations if drug treatment of low HDL-C is considered are Class IIa for Niacin and Class IIb for Statins and Fibrates. Presently, only niacin is approved by the Food and Drug Administration (FDA) for HDL-C elevation and can raise HDL-C levels by 20-30%. However, its use can be limited by a high incidence of flushing and, less commonly, by elevation of blood glucose and potential hepatic toxicity. Assessment of HDL functionality may be more relevant, given emerging experimental evidence of the pleiotropic potentially atheroprotective functions of HDL. Apart from its role in cholesterol efflux and lipid homeostasis, the HDL particle has been shown to exhibit a wide range of activities which include antithrombogenic, anti-inflammatory, anti-oxidative, antiplatelet and

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

329

CARDIOLOGY vasodilatory functions.21 A recent study (reviewed in EAS Newsletter January 2011) showed that cholesterol efflux capacity had a strong inverse association with carotid intima-media thickness and the risk of angiographic coronary artery disease, irrespective of plasma lipid levels.22 There are also emerging data for a number of innovative HDL-raising therapies targeted to the acute management of high-risk patients. The findings from these studies will help in resolving whether HDL is indeed a target for therapy. The available data do not, however, exclude potential adverse effects of CETP inhibition such as the generation of HDL particles that have deficient biological activities and a deleterious impact on reverse cholesterol transport and steroid metabolism. Normalization of both defective HDL function and diminished HDL levels should, therefore, be the focus of pharmacological HDL-raising in future studies. The unexpected failure of torcetrapib highlights unresolved questions in the HDL field. Thus, the mechanistic relevance of a simple measurement of HDL-C remains controversial.4 Given the functional heterogeneity of HDL particles, whether HDL-C quantification reflects the quantity (number) or the quality (function) of HDL particles still remains to be determined. Indeed, the clinical value of measuring plasma apoA-I levels, which reflect numbers of HDL particles rather than their cholesterol load, is hotly debated.23-25 Whether our primary target should be raising HDL-C levels, normalizing HDL functionality or whether it should encompass both aspects is unknown. This uncertainty is further corroborated by the paucity of data on the influence of HDL-raising agents on HDL functionality. There is proposal that measurement of HDL-C should be combined with the evaluation of HDL function when assessing the benefit of HDL-targeted therapies. In vitro assays that focus on â&#x20AC;&#x2DC;surrogate markers of HDL functionality in vivoâ&#x20AC;&#x2122; need to be developed and applied in studies of the therapeutic efficacy of CETP inhibitors. Such assays may involve measurements of the capacity of HDL to induce cellular cholesterol efflux through the ABCA1, ABCG1 and SR-BI pathways, together with determinations of lecithin: Cholesterol acyltransferase (LCAT) activity and of anti-inflammatory activities, such as the capacity to inhibit LDL oxidation and to decrease cellular expression of adhesion molecules. Such an integrated approach should be adopted for evaluation of new and promising HDL-raising agents as a prerequisite to large clinical trials assessing morbidity and mortality.

330

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

CONCLUSION Normalization of both defective biological HDL function and low HDL levels should, therefore, be the focus of pharmacological HDL-raising strategies.1,26 Influence of major HDL-raising pharmacological agents on HDL functionality should be assessed in humans, especially in the setting of hypertriglyceridemia seen in those with insulin resistance.27 Such agents include extendedrelease niacin (alone or in combination with an inhibitor of the prostaglandin D receptor),28 niacin-receptor agonists,29 fibrates, statins and other HDL-raising agents. It is encouraging that such data are now appearing in press.30,31 With such an approach, pharmacologicallyinduced HDL-C elevation can be anticipated to finally translate into diminished cardiovascular risk and clinical benefit. References 1. Kontush A, Chapman MJ. Functionally defective high-density lipoprotein: a new therapeutic target at the crossroads of dyslipidemia, inflammation, and atherosclerosis. Pharmacol Rev 2006;58(3):342-74. 2. Dullens SP, Plat J, Mensink RP. Increasing apoA-I production as a target for CHD risk reduction. Nutr Metab Cardiovasc Dis 2007;17(8):616-28. 3. Kontush A, Chapman MJ. Antiatherogenic small, dense HDL - guardian angel of the arterial wall? Nat Clin Pract Cardiovasc Med 2006;3(3):144-53. 4. Ansell BJ, Fonarow GC, Fogelman AM. The paradox of dysfunctional high-density lipoprotein. Curr Opin Lipidol 2007;18(4):427-34. 5. Navab M, Anantharamaiah GM, Reddy ST, Van Lenten BJ, Datta G, Garber D, et al. Potential clinical utility of highdensity lipoprotein-mimetic peptides. Curr Opin Lipidol 2006;17(4):440-4. 6. Shah PK. High-density lipoprotein mimetics: focus on synthetic high-density lipoprotein. Am J Cardiol 2007;100(11 A):S62-7. 7. Cooney MT, Dudina A, De Bacquer D, Wilhelmsen L, Sans S, Menotti A, et al; SCORE investigators. HDL cholesterol protects against cardiovascular disease in both genders, at all ages and at all levels of risk. Atherosclerosis 2009;206(2):611-6. 8. Poulter N. The impact of micronized fenofibrate on lipid subfractions and on reaching HDL-target levels in 7,098 patients with dyslipidaemia. Br J Cardiol 1999;6:682-5. 9. The AIM-HIGH Investigators, Boden WE, Probstfield JL, Anderson T, Chaitman BR, Desvignes-Nickens P, Koprowicz K, et al. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med 2011;365(24):2255-67.

CARDIOLOGY 10. Giugliano RP. Niacin at 56 years of age - time for an early retirement? N Engl J Med 2011;365(24):2318-20. 11. Chapman MJ, Ginsberg HN, Amarenco P, Andreotti F, Borén J, Catapano AL, et al; European Atherosclerosis Society Consensus Panel. Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management. Eur Heart J 2011;32(11):1345-61. 12. Merck. Merck announces HPS2-THRIVE study of Tredaptive (extended-release niacin/laropiprant) did not achieve primary endpoint (press release). December 20, 2012. 13. European Medicines Agency. European Medicines Agency starts review of Tredaptive, Pelzont and Trevaclyn (press release). December 21, 2012. 14. Lavigne PM, Karas RH. The current state of niacin in cardiovascular disease prevention: a systematic review and meta-regression. J Am Coll Cardiol 2013;61(4):440-6. 15. Barter PJ, Kastelein JJ. Targeting cholesteryl ester transfer protein for the prevention and management of cardiovascular disease. J Am Coll Cardiol 2006;47(3): 492-9. 16. Lewis GF, Rader DJ. New insights into the regulation of HDL metabolism and reverse cholesterol transport. Circ Res 2005;96(12):1221-32. 17. Barter PJ, Caulfield M, Eriksson M, Grundy SM, Kastelein JJ, Komajda M, et al; ILLUMINATE Investigators. Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med 2007;357(21):2109-22. 18. Chapman MJ. Therapeutic elevation of HDL-cholesterol to prevent atherosclerosis and coronary heart disease. Pharmacol Ther 2006;111(3):893-908. 19. Schwartz GG, Olsson AG, Ballantyne CM, Barter PJ, Holme IM, Kallend D, et al; dal-OUTCOMES Committees and Investigators. Rationale and design of the dalOUTCOMES trial: efficacy and safety of dalcetrapib in patients with recent acute coronary syndrome. Am Heart J 2009;158(6):896-901.e3. 20. Schwartz GG, Olsson AG, Abt M, Ballantyne CM, Barter PJ, Brumm J, et al; dal-OUTCOMES Investigators. Effects of dalcetrapib in patients with a recent acute coronary syndrome. N Engl J Med 2012;367(22):2089-99.

21. Rye KA, Bursill CA, Lambert G, Tabet F, Barter PJ. The metabolism and anti-atherogenic properties of HDL. J Lipid Res 2009;50 Suppl:S195-200. 22. Khera AV, Cuchel M, de la Llera-Moya M, Rodrigues A, Burke MF, Jafri K, et al. Cholesterol efflux capacity, highdensity lipoprotein function, and atherosclerosis. N Engl J Med 2011;364(2):127-35. 23. van der Steeg WA, Boekholdt SM, Stein EA, El-Harchaoui K, Stroes ES, Sandhu MS, et al. Role of the apolipoprotein B-apolipoprotein A-I ratio in cardiovascular risk assessment: a case-control analysis in EPIC-Norfolk. Ann Intern Med 2007;146(9):640-8. 24. Walldius G, Jungner I. Apolipoprotein A-I versus HDL cholesterol in the prediction of risk for myocardial infarction and stroke. Curr Opin Cardiol 2007;22(4): 359-67. 25. Ingelsson E, Schaefer EJ, Contois JH, McNamara JR, Sullivan L, Keyes MJ, et al. Clinical utility of different lipid measures for prediction of coronary heart disease in men and women. JAMA 2007;298(7):776-85. 26. Watson KE, Ansell BJ, Watson AD, Fonarow GC. HDL function as a target of lipid-modifying therapy. Rev Cardiovasc Med 2007;8(1):1-8. 27. Kontush A, Chapman MJ. Why is HDL functionally deficient in type 2 diabetes? Curr Diab Rep 2008;8(1):51-9. 28. Lai E, De Lepeleire I, Crumley TM, Liu F, Wenning LA, Michiels N, et al. Suppression of niacin-induced vasodilation with an antagonist to prostaglandin D2 receptor subtype 1. Clin Pharmacol Ther 2007;81(6): 849-57. 29. Kamanna VS, Kashyap ML. Nicotinic acid (niacin) receptor agonists: will they be useful therapeutic agents? Am J Cardiol 2007;100(11 A):S53-61. 30. Sviridov D, Hoang A, Ooi E, Watts G, Barrett PH, Nestel P. Indices of reverse cholesterol transport in subjects with metabolic syndrome after treatment with rosuvastatin. Atherosclerosis 2008;197(2):732-9. 31. Charles-Schoeman C, Khanna D, Furst DE, McMahon M, Reddy ST, Fogelman AM, et al. Effects of high-dose atorvastatin on anti-inflammatory properties of high density lipoprotein in patients with rheumatoid arthritis: a pilot study. J Rheumatol 2007;34(7):1459-64.

■■■■

ÂÂ There has been a significant improvement in the 1-year mortality rates of elderly individuals admitted to

the hospital for acute MI over the past 15 years, and this could be attributed to improved medical therapy and access to PCI, suggests a new analysis presented at the European Society of Cardiology 2014 Congress.

ÂÂ The use of an algorithm with a highly sensitive assay for cardiac troponin T (hs-cTnT) allows physicians

treating patients with chest pain in the emergency department to safely and effectively rule out acute MI within 1 hour, suggested the results of the High-Sensitivity Cardiac Troponin T Assay for Rapid Rule Out of Acute Myocardial Infarction (TRAPID-AMI) study. The results were presented recently at the European Society of Cardiology 2014 Congress.

332

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

Community Medicine

Prevalence of Overweight and Obesity Among Students of a Medical College in South India: A Pilot Study Jayaraj*, PP Nair†, Reny Napolean*, Justin Stephen‡, Nishanth K$, Suresh D#

Abstract Background: Obesity is emerging as a serious problem throughout the world, not only among adults but also children, teenagers and young adults. Of the factors contributing to obesity, stress seems to be particularly important as stressful condition leads to irregularity in diet, lack of exercise and addiction, each being considered an independent factor leading to obesity. Medical education is stressful throughout the whole course of training. The amount of material to be absorbed, social isolation, pressure of examination, discrepancies between expectation and reality all can be anticipated to bring psychological stress. Hence, this study was undertaken to find out the prevalence of overweight and obesity among undergraduate medical students. Aims and objectives: To assess the prevalence of overweight and obesity among medical students in Azeezia Medical College and also to find the relationship of the following risk factors with obesity; a) Physical inactivity, b) sleeping habits, c) diet, d) stress and e) association with other diseases (thyroid disorders, menstrual disorders). Study design: A cross-sectional study was conducted in selected sample of 89 subjects. Settings: The study setting was in a rural area in Kollam district of Kerala. Material and methods: Anthropometric measurements including height and weight were taken as per WHO criteria. Body mass index were calculated and classified accordingly as normal, overweight and obese. Details of factors influencing were obtained using a pretested questionnaire in a pilot study. Results and conclusion: The study revealed overall a high prevalence of overweight (44%) and obesity (10%). In males 35% were overweight and 11% were obese, while in females 49% were overweight and 9% were obese. Relation with increased frequency of meals (p = 0.007), increased sleep duration (p = 0.003) and regular exercise (p = 0.047) were found to be significant. Increased prevalence of overweight among females and obesity among males in rural area were observed. The importance of regular physical activity and certain aspects of healthy aging need to be emphasized in the elderly population. Growing old is not an end to everything but an opening for challenges and approach.

Keywords: Obesity, overweight, geriatric, obese, pre-obese

besity is a complex multifactorial chronic disease that develops from an interaction of social, behavioral, culture, psychological, metabolic and genetic factors. The condition of obesity is chronic, relapsing and neurochemical and involves interaction between host and environment and the need for permanent lifestyle changes supersedes the person`s desire for quick weight loss. Genetics account

*Professor †Professor and Head ‡Assistant Professor Dept. of Surgery #Assistant Professor $Associate Professor Dept. of Medicine Azeezia Institute of Medical Sciences and Research Center Meeyannoor, Kollam, Kerala Address for correspondence Azeezia Institute of Medical Sciences and Research Center Meeyannoor, Kollam - 37, Kerala E-mail: medicalcollge@azeezia.com

for about 30-40% of the variations in weight between the individuals. Environmental causes of obesity are often related to overconsumption of high fat foods, decrease in activity and smoking cessation. Obesity is an increase in body weight as the result of excessive accumulation of body fat and occurs when the calorie value of food intake exceeds energy output. Overweight and obesity is one of the preventable causes of death. Morbidity associated with overweight and obesity is also enormous. The social implication of obesity and overweight is a major problem that is often neglected. Obesity is emerging as a serious problem throughout the world, not only among adults but also children, teenagers and young adults. Of the factors contributing to obesity, stress seems to be particularly important as stressful conditions lead to irregularity in diet, lack of exercise and addiction, each being considered an independent factor leading to obesity and the prevalence of obesity

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

333

Community Medicine is increasing rapidly worldwide.1 The professional students, including medical students are in a highrisk side when obesity is concerned. This is mainly because medical education is stressful throughout the whole course of training. The amount of material to be absorbed, social isolation, pressure of examination, discrepancies between expectation and reality all can be anticipated to bring psychological stress. Hence, this study was undertaken to find out the prevalence of overweight and obesity among undergraduate medical students. An attempt was made to find out the significance of presence or absence of factors influencing body weight.

A measuring tape was used for finding height, weighing machine was used by correcting the zero error for weight and a self-administered questionnaire was used. A systematic random sampling technique was applied for selecting students from each batches of medical students. We selected four batches 2010, 2011, 2012 and 2013 and from each batch equal number of 28 students were selected, the sampling interval was 4. Equal number of males and females could not be selected as there was no uniform composition of males and females in the campus. Results

Obesity and overweight in medical students is gradually becoming a health problem in many developing countries, including India as obesity appears to increase the risk of subsequent morbidity. It is difficult to reduce excessive weight in adults once it becomes established. Hence, it would be more sensible to begin prevention and treatment of obesity and overweight right from childhood itself.

We conducted the study on 112 students. Out of them, 34 (30.4%) were males and 78 (60.6%) were females. Out of 112 students, we found that underweight students were 5 (4.5%), normal students were 65 (58%), overweight were 35 (31.3%) and obese were 7 (6.3%). We also found that, 4 (3.6%) were vegetarians, 29 (25.9%) were nonvegetarian and 79 (70.5%) were mixed.

As there are few studies in India among medical students, the present study was taken up on this group who require early intervention to prevent these diseases among the future doctors.

We observed that, 45 (40.2%) were doing exercise and 67 (59.8%) were not doing exercise. Out of 112 students, 17 (15.2%) students did exercise daily, 28 (25%) students did exercise regularly and 67 (59.8%) students

Material and Methods Medical students were selected based on systematic random sampling technique. One hundred twelve students were selected for the study. The study included self-administered questionnaire, which included their dietary habits, level of physical activity, sleeping habits, stress, junk food consumption and association with thyroid and menstrual disorders. Weight and height of the students were taken and body mass index (BMI) was calculated as: Weight (kilogram) divided by square of height (meters). Data collected was entered in Microsoft Excel and analyzed further using SPSS software version 20.

334

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

80 70 60 50 40 30 20 10 0

28 17

Regularly

Daily

Occasionally

Exercise

Figure 1. Frequency of exercise.

No. of students

The objective of this study was to evaluate the prevalence of obesity and overweight among medical students in Azeezia Medical College and to assess the factors influencing the development of obesity and overweight among medical students and also to find the relationship of the following risk factors with obesity: a) Physical inactivity, b) sleeping habits, c) diet, d) stress and e) association with other diseases (thyroid disorders, menstrual disorders).

No. of students

Aims and objectives

100 90 80 70 60 50 40 30 20 10 0

20 No

Yes Family history

Figure 2. Family history of obesity.

No. of students

Community Medicine

70 60 50 40 30 20 10 0

63 39

10 9-10

6-8

In our study, we could establish a relationship between family history and obesity. This may be because these students were from different socioeconomic classes some of whose environment offered an abundance of calorie rich food and few opportunities for physical activity. Although changes in the genetic makeup of genetic population occurs too slow to be responsible for this rapid rise in obesity, genes do play a role in development of obesity.

Sleep duration (hours)

No. of students

Figure 3. Duration of sleep.

70 60 50 40 30 20 10 0

We also found a significant relationship between obesity and menstrual disorders among girls. Girls who have too much fat on their body may find that their monthly cycle is disrupted. Fat seems to increase levels of a hormone called testosterone in the body. This may also cause menstrual disorders. Girls with condition called polycystic ovarian disease tend to put on weight easily. They may also have irregular periods. They may be sometimes on medication which in turn also results in fat accumulation (Fig. 5).

Yes Junk food

No. of students

Figure 4. Habit of taking junk food.

60 50 40 30 20 10 0

51 34

NA Menstrual disease

our study noticed that 51 (71.4%) students had no menstrual disorders and 27 (24.1%) students had menstrual disorders, which was found relevant in our study. From the study conducted to screen the medical students of Azeezia Medical College for overweight and obesity prevalence was found to be 31.3% and 6.3%, respectively. Overall prevalence was 37.6%.

Yes

Figure 5. Menstrual disorders.

did exercise only occasionally (Fig. 1). Twenty (17.9%) students had family history of obesity and 92 (82.1%) students had no family history of obesity, which was found relevant in our study (Fig. 2). We also found that 80 (71.4%) students had a habit of snacking and 32 (28.6%) students did not. Out of 112 students, 10 (8.9%) students slept for 9-10 hours, 63 (56.3%) students slept for 6-8 hours and 39 (34.8%) students slept for <6 hours (Fig. 3). Forty-seven (42%) had a habit of taking junk food and 65 (58%) did not entertain that habit (Fig. 4). One hundred two (91.1%) students had no thyroid disorder and 10 (8.9%) students had thyroid disorder. We, in

We could not establish any significant association between junk food consumption and obesity. This may be because medical college here in Meeyannoor is a rural area, where there is less availability and accessibility of these food items. Most of the students took food in normal frequency. Being medical students they may be more conscious about their health and dietary habits. We noticed that most of the students go in for less food intake when stressed. Due to emotional disturbances, they might be having reluctance of having food. As the college canteen is situated far away from hostels students found it inconvenient to go and get the food. Also the landscape of the campus was so designed that it was difficult for students to go easily to canteen from the hostel, as the mess facility was limited to very few students. We also observed that students had less frequent meals due to and lack of time and nonavailability of variety and tasty food, inconvenience of climbing the uphill of stairs as it resulted in more fatigue. On analysis of data obtained we could not find any relationship between duration of sitting idle in front of

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

335

Community Medicine computer or TV and obesity. As there was no television in the hostel and the usage of computer was restricted, students resorted to indoor games and loose talks with peers. We could not establish relation between thyroid disorders and obesity. Their obesity may be due to family history and improper lifestyle habits. Though most of the students do not do regular physical exercise we could not establish any relevant association between lack of physical exercise and obesity. Even if some of the students were in a habit of doing exercise, they did it only occasionally. We also could not establish any relationship between practicing outdoor games and obesity. This was because only very few students were in habit of regularly practicing outdoor games. One interesting fact is that due to the landscape, in a day nearly three or four times the students had to climb the hill for their clinical posting, theory classes and to hostel which itself could be a contributory factor for no significant relationship with any factor other than family history and menstrual disorders for females. DISCUSSION Abdominal obesity is defined as an abdominal circumference >102 cm and >88 cm for men and women, respectively. However, abdominal obesity can be reduced by engaging in some physical activity. There are various options for the management of overweight and obese patients including dietary approaches, pharmacotherapy, surgery and combination of these techniques. Studies show that small changes in weight and increase in physical activity can make significant improvement in health. It is more desirable to calculate basal energy requirement for the individual and determine a reasonable energy intake accordingly. Many countries in South-East Asia including India are going through an economic and nutrition transition. The nutrition transition is associated with a change in dietary habits and decreased physical activity, which leads to rising prevalence of obesity and overweight. Obesity and overweight are the major risk factors for a number of chronic diseases including diabetes, cardiovascular diseases and cancer. Risk factors for obesity and overweight include: Poor balanced diet, excess sleep, lack of physical activity, medical conditions and medication, age and consumption of alcohol. Obesity is often expressed in terms of BMI. Overweight is usually due to obesity but can arise from other causes such as abnormal muscle development or fluid retention. However, obese individuals differ not only

336

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

in the amount of excess fat that they store, but also in the regional distribution of the fat within the body. The distribution of fat induced by the weight gain affects the risk associated with obesity, and the kind of disease that results. It is useful therefore, to be able to distinguish between those at increased risk as a result of abnormal fat distribution or android obesity from those with the less serious gynoid fat distribution, in which fat is more evenly and peripherally distributed around the body. Obesity is perhaps the most prevalent form of malnutrition. As a chronic disease, prevalent in both developed and developing countries, and affecting children as well as adults, it now so common that it is replacing the more traditional public health concerns including under nutrition. It is one of the most significant contributors to ill health. As obesity is a key risk factor in natural history of other chronic and noncommunicable diseases, the typical time sequence of emergence of chronic diseases following the increased prevalence of obesity is important in public health planning. Its adverse effects are hypertension, hyperlipidemia and glucose intolerance, while coronary heart disease and long-term complications of diabetics, such as renal failure begin to emerge several years later. The etiology of obesity is complex and is one of multiple causation. Like age, sex, genetic factors, physical inactivity, socioeconomic status, eating habits, psychological factors, familial tendency, endocrine factors, alcohol, education, smoking, ethnicity and drugs. BMI is a simple index of weight-for-height, it is used to classify underweight, overweight and obesity in adults. Body mass index = Weight in kg/Height in meter square Classification

BMI

Underweight

<18.50

Normal range

18.50-24.99

Overweight

â&#x2030;Ľ25

Pre-obese

25-29.9

Obese Class I

30-34.99

Obese Class II

35-39.99

Obese Class III

â&#x2030;Ľ40

The prevalence of obesity in our study was found out to be 6.3% and that of overweight was 31.3%. The overall prevalence is 37.6%. In the study conducted in Trivandrum Medical College, among 350 students, the prevalence of obesity

Community Medicine was 25.71% and that of overweight was 24.57%. The prevalence of overwieght in both studies were apparently similar, yet obesity patterns varied in the study population of Trivandrum and Kollam.2

should lead our country into the lights of better health, is at risk. They should be the role models, but when their health status itself is at stake it is really a matter of disappointment.

In the study conducted among 458 medical students of Kancheepuram district, prevalence of obesity was 8.6%. Here they had established a significant relation between family history and obesity. This relation has been also proved in our study.3 Since, their socioeconomic status offers a calorie rich environment similar to us. Their study also established association between frequency of eating meals and obesity, but this relation could not established by our study.

We could establish a significant relationship between obesity/overweight and family history. Also relation between overweight/obesity and menstrual disorders was found to be significant. We could not establish any relevant relationship between other variables of study because of limitations of study population.

A significant relation between obesity/overweight and consumption of junk food was established in a study conducted among medical students of Malaysia. In their study, the prevalence of obesity was 15.2% and that of overweight was 21.8%. This increased prevalence was attributed to their increased junk food consumption.4 The study conducted among medical students in Greece revealed a slightly higher prevalence of obesity, which was 22%. This was attributed to lack of regular physical activity and family history of obesity.5 In our study, we could establish a significant relation between obesity and family history, but to our surprise, the relation between obesity and physical activity was not found to be significant. CONCLUSION Our study concluded with the fact that the prevalence of obesity and overweight is increasing at an alarming rate of 37.6% out of 112 medical students of Azeezia Medical College, Kollam, Kerala. Prevalence of overweight is 31.3% and that of obesity is 6.3%. This fact is really distressing because the health status of future doctors of our country, who in turn

In the present day, people find no time to care for their health. This negligence may lead to several serious diseases like diabetes, increased blood pressure, stroke, etc. It is high time to think about it and make changes in their lifestyle to have a healthy future. REFERENCEs 1. World Health Organization. Obesity: preventing and managing the global epidemic. Report of a WHO Consultation on Obesity, Geneva, 3-5 June 1997. Geneva: World Health Organization; 1998. WHO document WHO/ NUT/NCD/98.1. Available from: URL: http://whqlibdoc. who.int/hq/1998/WHO_NUT_NCD_ 98.1_(p1-158).pdf; and URL: http://whqlibdoc.who.int/hq/1998/WHO_ NUT_NCD_98.1_(p159-276).pdf 2. Manojan KK, Benny PV, Anil Bindu. Prevalence of obesity and overweight among medical students based on New Asia-Pacific BMI guideline. IJPTM Volume 1, 2014. 3. Selvaraj K, Sivaprakasam P. A study on the prevalence of overweight and obesity among medical students of Kanchipuram district. NJRCM 2013;2(2):140-4. 4. Gopalakrishnan S, Ganeshkumar P, Prakash MV, Christopher, Amalraj V. Prevalence of overweight/obesity among the medical students, Malaysia. Med J Malaysia 2012;67(4):442-4. 5. Bertsias G, Mammas I, Linardakis M, Kafatos A. Overweight and obesity in relation to cardiovascular disease risk factors among medical students in Crete, Greece. BMC Public Health 2003;3:3.

■■■■

ÂÂ Quadrupling the US Food and Drug Administration’s approved dose of doripenem in patients with cystic

fibrosis (CF) and acute respiratory infection is safe and could serve as a new therapeutic option for those with advanced disease and evidence of resistant bacteria in their lungs, suggests a new study presented at the 54th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC).

ÂÂ Results of a new pharmacokinetic study have revealed that when first-line tuberculosis (TB) drugs are taken

with food, a reduction in maximum plasma concentration and bioavailability of the drug is noted, compared with when taken on an empty stomach. The study was presented at the European Respiratory Society (ERS) International Congress 2014.

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

337

DENTiSTRY

Mandibular Molar Protraction with Orthodontic Temporary Anchorage Devices: A Case Report Anurag Bhagat*, Meenu Goel†, Puneet Batra‡, Rajiv K Chugh#

Abstract Management of patients with congenitally missing mandibular second premolars continues to challenge clinicians to find the best treatment options. The Orthodontist must make the proper decision at the appropriate time regarding management of the edentulous space. If space is left for an eventual prosthetic replacement, the clinician should try to create the exact amount of space required and leave the alveolar ridge in an ideal condition for the future restoration. If the space is to be closed orthodontically, detrimental changes to the occlusion and facial profile must be prevented. Therefore, the correct decision must be made at the appropriate time. This paper presents a case report of a congenitally missing lower left second premolar where molar protraction with orthodontic temporary anchorage device has been done.

Keywords: Congenitally missing second premolar, orthodontic temporary anchorage device, mandibular molar protraction

any orthodontic patients have posterior spacing due to missing mandibular teeth. Excluding the third molars, the mandibular second premolar is the most common congenitally absent tooth, which is reported to occur in 2.5-5% of the population in the USA and Europe. Such absence ensues bilaterally in 60% of instances.1-3 There is an assortment of treatment options if the problem is diagnosed early during the period of mixed dentition. These treatment modalities can be broken down into two main groups based on the decision to keep or extract the primary molars. The Orthodontist must make the proper decision at the appropriate time regarding management of the edentulous space. If space is left for an eventual prosthetic replacement, the clinician should try to create the exact amount of space required and leave the alveolar ridge in an ideal condition for the future restoration. If the space is to be closed orthodontically, molar protraction can be an alternative to restoration with posterior dental implants or fixed partial dentures. Intraoral skeletal anchorage

*Consultant Orthodontist †Senior Lecturer ‡Professor and Head Dept. of Orthodontics Institute of Dental Studies and Technologies, New Delhi #Consultant Endodontist Dr Chugh’s Dental Centre, Greater Kailash, New Delhi Address for correspondence Dr Rajiv K Chugh W-5, Greater Kailash-1, New Delhi -110 048 E-mail: drchughs@gmail.com

338

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

(miniplates, screws) provides absolute anchorage for various tooth movements without requiring patient cooperation and anchorage preparation and gets predictable treatment results more rapidly..4-6 Orthodontic temporary anchorage devices (TADs) can provide skeletal anchorage for mandibular molar protraction, avoiding the problems often encountered with the use of dental anchorage. This article presents a case report of a congenitally missing unilateral second premolar for molar protraction with orthodontic temporary anchorage device. CASE REPORT A female aged 13 years was referred to the dental OPD for orthodontic consultation. Her chief complaint was noneruption of permanent tooth after the extraction of deciduous tooth in lower left quadrant. There was no remarkable medical history and temporomandibular joint function was normal (Fig. 1). A panoramic radiograph revealed congenitally missing 35 (Fig. 2). The two treatment options offered to the patient were: 1) The space to be closed orthodontically by complete mesialization of mandibular first molar taking advantage of fresh extraction socket; 2) create the exact amount of space required orthodontically for an eventual prosthetic replacement. Treatment plans were explained to the patient. The patient was not willing for any prosthetic replacement therefore; considering the age of the patient and taking advantage of fresh extraction socket, protraction of lower left

DENTiSTRY

Figure 1 a). Pre-treatment extraoral photographs.

Figure 1 b). Pre-treatment intraoral photographs.

Figure 2. Pre-treatment panoramic radiograph.

Figure 1 c). Pre-treatment lateral cephalogram.

first and second molar to fill the extraction space orthodontically was planned.

Figure 3. IOPA showing small odontomatous mass.

The patient was bonded with 0.022” MBT appliance using ceramic brackets and molar protraction was done on 0.019” x 0.025” stainless steel wire. Closing the space of a primary molar, which is often 10-11 mm, is difficult at best and may result in a midline shift and flattening of the face.7 If the patient has a protrusive

profile or moderate crowding, space closure is favored. However, in the absence of crowding and a good facial profile, space closure has undesirable side effects. The introduction of temporary anchorage devices, such as miniscrew implants, has created more options for space closure.8 By utilizing such implants, the molars can be

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

339

DENTiSTRY

Figure 4 a). Post-treatment extraoral photographs.

first molar without reciprocal retraction of the incisors or movement of the dental midline.9 The rate of molar protraction is inversely related to the radiographic density or cortical thickness of the resisting alveolar bone.10 Furthermore, if the buccal and lingual cortical plates in the edentulous region have collapsed, safe and effective protraction may be impossible.

Figure 4 b). Post-treatment intraoral photographs.

protracted without side effects on the anterior teeth of the arch. A microscrew of 8 mm length and 1.5 mm of diameter was placed mesial to the edentulous space to avoid impeding the molar protraction. A small odontomatous mass (Fig. 3) was observed which was extracted after placement of the microscrew. An open-coil spring with 100 g of force was used to protract the mandibular molar. The open-coil spring tips the crown enough to provide complete space closure. In this case, the protraction of mandibular molars was achieved without any detrimental effect on facial balance (Fig. 4). The minimal variation in incisor position and the extensive molar protraction confirmed the excellent anchorage control provided by TAD. DISCUSSION Congenital absence of mandibular second premolars affects many orthodontic patients. The clinician must make the proper decision at the appropriate time regarding management of the edentulous space. Protraction of mandibular molars is challenging because of the high-density of mandibular bone. The posterior mandible consists of thicker cortical bone with dense, radially oriented trabeculae. Anterior dental anchorage is often inadequate to protract even a single

340

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

TADs can provide skeletal anchorage for mandibular molar protraction, avoiding the problems often encountered with the use of dental anchorage. The failure rate of TADs is greater in the mandible than in the maxilla.11,12 The primary biological factors that determine miniscrew stability are bone density (or bone quality),11 peri-implant soft-tissue health,11 adequacy of peri-implant bone stock12 and operator technique.13 The greater failure rate of mandibular miniscrews, despite the thicker mandibular cortical bone, is probably due to root proximity (or inadequate peri-implant bone stock) and greater buccal tissue mobility. CONCLUSION There are numerous options for treating a patient with a congenitally missing mandibular second premolar. The key to successful management is to diagnose the problem early in the presence of mixed dentition. The miniscrew was able to withstand multidirectional heavy forces required for this patientâ&#x20AC;&#x2122;s treatment. Mandibular molar protraction with orthodontic TADs has become the standard of care for closing posterior edentulous spaces. REFERENCES 1. Thilander B, Myrberg N. The prevalence of malocclusion in Swedish schoolchildren. Scand J Dent Res 1973;81(1):12-21. 2. Fines CD, Rebellato J, Saiar M. Congenitally missing mandibular second premolar: treatment outcome with orthodontic space closure. Am J Orthod Dentofacial Orthop 2003;123(6):676-82.

DENTiSTRY 3. Josefsson E, Brattström V, Tegsjö U, Valerius-Olsson H. Treatment of lower second premolar agenesis by autotransplantation: four-year evaluation of eighty patients. Acta Odontol Scand 1999;57(2):111-5. 4. Arbuckle GR, Nelson CL, Roberts WE. Osseointegrated implants and orthodontics. Oral Maxillofac Surg Clin North Am 1991;3:903-19. 5. Wehrbein H, Diedrich P. Endosseous titanium implants during and after orthodontic load-an experimental study in the dog. Clin Oral Implants Res 1993;4(2):76-82. 6. Umemori M, Sugawara J, Mitani H, Nagasaka H, Kawamura H. Skeletal anchorage system for openbite correction. Am J Orthod Dentofacial Orthop 1999;115(2):166-74. 7. Northway W. Hemisection: one large step toward management of congenitally missing lower second premolars. Angle Orthod 2004;74(6):792-9. 8. Kokich VG, Kokich VO. Congenitally missing mandibular second premolars: clinical options. Am J Orthod Dentofacial Orthop 2006;130(4):437-44. 9. Deguchi T, Nasu M, Murakami K, Yabuuchi T, Kamioka H, Takano-Yamamoto T. Quantitative evaluation of cortical

bone thickness with computed tomographic scanning for orthodontic implants. Am J Orthod Dentofacial Orthop 2006;129(6):721.e7-12. 10. Roberts WE. Bone physiology, metabolism, and biomechanics in orthodontic practice. In: Orthodontics: Current Principles and Techniques. 2nd edition, Graber TM, Vanarsdall RL (Eds.), St. Louis: Mosby 1994:p. 193-234. 11. Miyawaki S, Koya I, Inoue M, Mishima K, Sugahara T, Takano-Yamamoto T. Factors associated with the stability of titanium screws placed in the posterior region for orthodontic anchorage. Am J Orthod Dentofacial Orthop 2003;124(4):373-8. 12. Kuroda S, Yamada K, Deguchi T, Hashimoto T, Kyung HM, Takano-Yamamoto T. Root proximity is a major factor for screw failure in orthodontic anchorage. Am J Orthod Dentofacial Orthop 2007;131(4 Suppl): S68-73. 13. Park HS, Jeong SH, Kwon OW. Factors affecting the clinical success of screw implants used as orthodontic anchorage. Am J Orthod Dentofacial Orthop 2006;130(1): 18-25.

■■■■

Dental Trauma: Guidelines for Pediatricians Updated Nondentists can play a key role in preventing and treating dental trauma, according to a new report by the American Academy of Pediatrics. In guidelines published online January 27 in Pediatrics, the academy lays out the basics of prevention, diagnosis, and treatment for injured teeth. In children 6 years of age and younger, oral injuries are the second most common injury, accounting for almost 20% of their injuries, writes Martha Ann Keels, DDS, PhD, chief of pediatric dentistry at Duke University in Durham, North Carolina, and her colleagues. Anyone who sees kids in urgent care settings needs to be prepared to treat dental trauma because often no dentist is available and time may be of the essence, they write. But even before considering treatment, the authors write, physicians who care for children should try to prevent injuries to their patients’ teeth. Physicians can do this by recommending safety measures, such as stairway gates and the removal of trip hazards. They should also counsel their patients to wear mouth guards during sports, the authors write. Recommendations vary, with the US National Collegiate Athletic Association recommending mouth guards for ice hockey, lacrosse, field hockey, and football, while the American Dental Association recommends them for 29 sports.

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

341

DIABETOLOGY

Prevalence of Gestational Diabetes Mellitus in a Medical College in South India: A Pilot Study K Sreekanthan*, A Belicita†, K Rajendran‡, Anil Vijayakumar†

Abstract Background: The prevalence of diabetes is increasing in India with projected rates of 79.4 million in 2030 — a 15.1% increase from 31.7 million in 2000. The increased prevalence is attributed to the aging population structure, urbanization, the obesity epidemic and physical inactivity. Though prevalence of diabetes is alarmingly high among Indians, there have been very few studies assessing the effect of diabetes on pregnancy outcomes. Diabetes in pregnancy causes maternal and neonatal complications like stillbirth, hydramnios, etc. Among ethnic groups in South Asian countries, Indian women especially south Indians have the highest frequency of gestational diabetes mellitus (GDM) necessitating universal screening. The recognition of glucose intolerance during pregnancy is more relevant as Indian women have 11-fold increased risk of developing GDM compared to other places. Aims and objectives: To find the prevalence of GDM in Kollam and to find the relation of GDM with various risk factors like age, obesity, previous large baby, abortion, previous abnormal glucose tolerance test (GTT), complications in previous pregnancy like hydramnios, bleeding, etc. Study design: A retrospective study of prevalence and possible risk factors associated with gestational diabetes was undertaken on 71 mothers between the age group of 20 and 35 years who were screened. Setting: Details on the medical history, family history of diabetes and obstetric history were collected using a performa. All the study subjects underwent a complete physical examination and biochemical assessment was done. Results and conclusion: This study on prevalence of GDM in Kollam district showed that the prevalence of GDM was 17%. It was found out that the factors such as increased age of pregnant women, overweight and obesity, lack of exercise and diet control, GDM in first-degree relatives, previous abnormal GTT predispose to GDM. Also women with previous large weight babies (macrosomia), previous loss of pregnancy, GDM in previous pregnancy, complications in previous pregnancy like hydramnios, bleeding, etc. have increased chances of getting GDM.

Keywords: Gestational diabetes mellitus, pregnancy, glucose intolerence

estational diabetes mellitus (GDM) is defined as any degree of glucose intolerance with onset or first recognition during pregnancy. The definition applies whether insulin or only diet modification is used for treatment and whether or not the condition persists after pregnancy. It does not exclude the possibility that unrecognized glucose intolerance may have antedated or began concomitantly with the pregnancy. The prevalence of diabetes is increasing globally and the total number of people with this condition is projected to rise from 171 million in 2000 to 366 million in 2030. India is no exception, with projected rates of 79.4 million in 2030 — a 15.1% increase from 31.7 million

*Professor †Associate Professor, Dept. of Medicine ‡Professor and Head, Dept. of Pediatrics Azeezia Institute of Medical Sciences and Research Center Meeyannoor, Kollam, Kerala Address for correspondence Azeezia Institute of Medical Sciences and Research Center Meeyannoor, Kollam - 37, Kerala E-mail: medicalcollge@azeezia.com

342

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

in 2000. The increased prevalence is attributed to the aging population structure, urbanization, the obesity epidemic and physical inactivity. Diabetes can complicate pregnancy, but it is not the major complication of pregnancy. Although prevalence of diabetes is alarmingly high among Indians there have been very few studies assessing the effect of diabetes on pregnancy outcomes. Diabetes in pregnancy causes maternal and neonatal complications like stillbirth, hydramnios, etc. Maternal complications occurring in GDM are pregnancy-induced hypertension, maternal infection, fasting hyperglycemia, etc. Pregnancy complications include abortion, preterm labor, hydramnios and unexplained fetal deaths. Fetal complications are fetal macrosomia, fetal malnutrition, neural tube defects and cardiac anomalies like ventricular septal defect, atrial septal defect, etc. Among ethnic groups in South Asian countries, Indian women especially south Indians have the highest frequency of GDM necessitating universal screening. The recognition of glucose intolerance during

DIABETOLOGY pregnancy is more relevant as Indian women have 11-fold increased risk of developing GDM compared to other places.

Yes (17%)

Aims and Objectives The objectives of this study was to find the prevalence of GDM in the Kollam district and to find the relation of GDM with various risk factors like age, obesity, previous large baby, abortion, previous abnormal GTT, complications in previous pregnancy like hydramnios, bleeding, etc.

No (83%)

Material and MethodS A study on the prevalence and possible risk factors associated with gestational diabetes was undertaken on 71 mothers between the age group of 20 and 35 years; among pregnant women recruited from Gynecology and Obstrectics outpatient of Azeezia Medical College, Kollam, Kerala, India from December 2013 to January 22, 2014. Details on the medical history, family history of diabetes and obstetric history were collected using a performa. All the study subjects underwent a complete physical examination and laboratory investigations were done. A self-administrative interview schedule was prepared and 71 pregnant ladies were selected for study. Data collected was entered in Microsoft Excel and analyzed further using SPSS Software version 20.0.

Figure 1. Frequency of diabetes mellitus.

Results

Figure 2. Frequency of BMI of pregnant women.

According to this study, it was found that prevalence of GDM in Kollam district was 17% and there was a significant relationship between GDM and its risk factors. With data collected the statistical and chisquare value to find out the correlation between the risk factors and development of GDM were calculated. Exercise (p = 0.019) and age (p = 0.013) are significant in relation with diabetes. There was no relation between diabetes and hypertension. Out of 71 pregnant women 12 (17%) were having diabetes (Fig. 1) 10 (14.1%) were having hypertension 1 (1.4%) person had body mass index (BMI) <18, 34 (47.9%) had BMI between 18-24.9, 30 (42.3%) had BMI between 25-29.9 and 6 (8.5%) had BMI above 30 (Fig. 2). In those who are having diabetes, a relationship between BMI and diabetes mellitus (DM) was noted. Eight (66.66%) women had normal BMI and 4 (33.33%) were overweight. The chi-square value obtained was 13.928 with third-degree of freedom and the p value was 0.003, which is <0.01, which shows that the relationship between BMI and DM was highly significant. Out of

15-20 21-25

26-30 31-35

1% 9% 42%

48%

12 diabetic women, eight of the pregnant women had history of abortion. The chi-square value obtained was 9.537 with first-degree of freedom and the p value was 0.002 which is <0.01, which shows that the relationship between history of abortion and diabetes was highly significant (Fig. 4). Out of 12, 9 (75%) had no control on diet. The chisquare value obtained was 10.187 with first-degree of freedom and the p value was 0.001 which is <0.01, which shows that the relationship between diet control and diabetes was highly significant (Fig. 6). While comparing with complications in present pregnancy 5 (41.66%) diabetics were having. The chi-square value obtained was 13.347 with first-degree of freedom and the p value was 0.000, which is <0.01, which shows that the relationship between complication in pregnancy and diabetes was highly significant (Fig. 7). Four diabetic women reported with diabetes in previous pregnancy. The chi-square value obtained was 15.248 with first-degree

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

343

DIABETOLOGY

No GDM GDM

No. of persons

25 20 15 10 5 0

3 18-24

25-32 Age

50 45

30 25 20 15

13 8

1 No

Yes

Diet control

No GDM GDM 56

Yes

History of abortion

30 20

No GDM GDM

70 58

50 40 30 20 10 2

1 No

Figure 4. Relationship between history of abortion and diabetes.

No. of persons

Exercise

Yes

Figure 5. Relationship between exercise and diabetes mellitus.

of difference and the p value was 0.000, which was <0.01, showing that the relationship between history of diabetes in previous pregnancy and diabetes

344

No GDM GDM

Figure 6. Relationship between diet control and diabetes mellitus.

>32

Figure 3. Relationship between age and diabetes.

No GDM GDM

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

3 No

Complication in pregnancy

Yes

Figure 7. Relationship between complication in pregnancy and diabetes mellitus.

in present pregnancy was highly significant (Fig. 8). Out of 12, 5 (41.66%) pregnant women had complication in previous pregnancy and 5 (41.66%) had history of diabetes in first-degree relatives. The chi-square value obtained was 9.017 with first-degree of difference, the p value was 0.003, which was <0.01, the relationship between complication during previous pregnancy and diabetes was highly significant (Fig. 10). Three women (25%) which shows that had baby of weight >3.5 kg in their previous delivery and 6 (50%) of them have baby within a range of 2.5足-3 kg and 3 (25%) had baby of weight <2.5. The chi-square value is 20.468 with third-degree of difference, the p value is 0.000, which is <0.01, the relationship between birth weight of baby and diabetes was highly significant (Fig. 9) Among the 12 diabetic pregnant women 10 (83.33%) were not doing any

DIABETOLOGY

70 58

60 No. of persons

<0.01, and hence the relationship between exercise and diabetes was significant (Fig. 5). In short the factors that found to be significant were BMI, history of abortion, diet control, complications in pregnancy, diabetes in previous pregnancy, complications during previous pregnancy, birth weight of baby and exercise.

No GDM GDM

50 40 30 20 8

No Yes History of diabetes in previous pregnancy

Figure 8. Relationship between history of diabetes in previous pregnancy and diabetes in present pregnancy.

No GDM GDM

No. of persons

15 10

4 2 <2.5

7 3

>3.5 2.5-3.5 Birth weight

Figure 9. Relationship between birth weight of baby and diabetes.

No GDM GDM 53

No. of persons

50 40 30 20 10 0

There exists a significant relationship between BMI and GDM (p = 0.003). The chance of getting GDM increases with obesity. Now-a-days, obesity is becoming a major health problems due to the lack of physical activity and diet control. Maternal health programs can be conducted by healthcare workers, focusing on prevention and control of modifiable risk factors during pregnancy period and introducing necessary corrective therapeutic interventions such as exercise and dietary modifications.

The study conducted on the basis of GDM and its risk factors showed that prevalence of GDM is 17%. According to the study, major significant risk factors were obesity, previous large birth weight baby (macrosomia), complications during previous pregnancy, history of abortion, diet control, DM in previous pregnancy and exercise.

No Yes History of diabetes in first-degree relatives

Figure 10. Relationship between history of diabetes in firstdegree relatives and diabetes.

exercise; only 2 (16.66%) were doing regular exercise. The chi-square value obtained was 5.523 with firstdegree of freedom and the p value was 0.019, which was

It was found out that there exists a highly significant relationship (p = 0.002) between abortion and GDM. Eighty percent of cases of abortions had history of GDM during previous pregnancy. It occurs mainly due to fetal hyperinsulinemia (when maternal insulin level falls fetal insulin level rises). Abortions occur mainly due to lack of knowledge and awareness that GDM leads to abortions and lack of proper precautions like regular glucose level monitoring. Discussion This study showed the prevalence of GDM as 17%. GDM prevalence has been reported variably from 0.7% to 31.6% in the previous studies conducted in India. A similar study in Keralite women gave a prevalence figure of 31.6%. GDM is an epidemically explosive problem, which is increasing at an unstoppable pace. The Diabetes in Pregnancy Study Group India (DIPSI) guidelines having suggested one time plasma sugar level as a measure to detect GDM is an attempt to preempt future possibility and predisposition for GDM. Finding of this study is largely at tandem with those literatures at the national as well as international level. We therefore, infer from the above study that Kerala, despite its varying ethnicity, food habits physical activities, living standards, etc. are very much a part

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

345

DIABETOLOGY of gestational diabetes spectrum the world over. In a study, it has seen that there was significant relationship between age of pregnant women and GDM (Fig. 3); 60.7% of women with GDM were above 25 years of age. In our study, 75% of women with GDM were also above 25 years of age. So, it is clear that there exists a significant relationship between age and GDM. The probable reason may be that in both studies considered population was well-educated and were working and most of them were multiparous. Even though, they are aware of chance of getting GDM with increasing age they never give it an importance in their busy schedule. A group of studies reveals that a significant proportion of subjects with GDM were overweight and obese. In a study, it was seen that 31.06% were overweight (BMI 25-30) and 27.2% were obese (BMI >30); according to our study, 45.2% of women with GDM were overweight (BMI 26-30) and 9% of them were obese (BMI 31-35). Hence, there exists highly significant relationship between overweight/obesity and GDM in both studies. In our state, there is a misbelief that during gestational period over nourishment is essential and even though they are educated, they follow this custom. They take lots of ayurvedic products for their nourishment and most of them hesitate to do even simple household works during gestational period due to fear of losing baby. In our study, along with these reasons lack of exercise and diet control plays an important role. In group of studies, family history of GDM had significant role in a large proportion of cases. The prevalence of family history of GDM in first-degree relative was found to be 36.2%, 86%, 11%, 85.7% and 16.6%, respectively. According to our study prevalence was 41.6%. All these studies express the role of family history of gestational diabetes in first-degree relatives was highly significant and this could be because of some genetic factors transmitting from generation-togeneration among the families. Some studies showed that 14%, 27.6% and 9% of cases had a previous macrosomic babies, respectively that is babies of birth weight >4 kg. Based on our study, 58.33% of diabetic pregnant women had a history of previous large birth weight babies (>3.5 kg). The reason may be that we took rural population and other studies considered urban population. Also, they considered babies of birth weight >4 kg as macrosomic and we considered babies of birth weight >3.5 kg as macrosomic so there is much variation in prevalence rates. As regards abortions, study showed the prevalence as 80%, whereas other studies showed prevalence as

346

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

68.96%, 34%, 2.7%, 89.96%, 85.71%, respectively. The high prevalence rate obtained may be due to choosing a population who never considered GDM as an important complication. In a study, the prevalence rate is low when they give proper care and maintain blood sugar levels by proper medication and diet control. While considering about exercise and diet control in the study population a prevalence rate of 18% and 17% was seen. But, in our study it was shown to be 16.66% and 25%, respectively. The population we considered is aware of importance of exercise and diet control but ignorance and lack of proper instructions is the problem here. In study conducted in Trivandrum, the populations were ignoring exercise and diet control even though they too knew the value of both exercise and diet control. Diabetes in previous pregnancy gave prevalence rate of 29.1% in a study and 33.33% in our study. The recurrence was due to ignoring the condition, which occurred in previous pregnancy and lack of proper follow-up medication and repeated screening for increase in blood sugar level. The study was also conducted in same community set up followed hence they got almost similar prevalence. In two studies, the prevalence of previous pregnancy complications was 7% and 1.4%, respectively. And in our study, the prevalence of 41.66% is much higher because most of the subjects we considered were multiparous and in above studies most of women were primigravida. A case-control study (300 cases and 300 controls) in SAT Hospital, Trivandrum in 2010 showed that 60.7% cases above 25 years of age and 39.3% were <25 years of age. BMI â&#x2030;Ľ25 was significantly higher in cases (37.9%). Around 24% cases had a history of irregular menstrual cycle and 36% of them had a family history of diabetes among first-degree relatives, especially in mother. About 68.96% of the women had previous losses as compared controls. A study on prevalence of GDM in South Kerala during 2002 showed that the prevalence of GDM was found to be 11.2%, 7% reported with hydramnios, 34% had history of loss of pregnancy, 14% with macrosomia, 18% were found not exercising and 17% had not taken proper diet control. A study was conducted to determine the incidence of GDM in South India in 2005. Among the 980 mothers studied only 7 (0.7%) were diagnosed with GDM and the rate of GDM detected in worldwide women population is 4% every year. Among them, six of them gave history of miscarriages and five of them were above 25 years of age and had family history of DM. A prospective study on pregnancy outcomes in pre-gestational and

DIABETOLOGY gestational diabetic women in comparison to nondiabetic women in Asian Indian women (2006) showed the following results, 82.3% of women who reported with GDM had a family history of diabetes in their firstdegree relatives, 2.7% of them had history of abortion, 1.4% of their children showed congenital anomalies, 8.2% of them gave birth to low birth weight babies and 27.6% of them gave birth to large babies in their previous pregnancy.

pregnancy like hydramnios, bleeding, etc. have increased chances of getting GDM. Further studies including larger samples will substantiate our study results.

A prospective case-control study in diabetic women in a district tertiary hospital in South India (2008) showed that 89.96% cases reported with loss of pregnancy, 11.33% had incidence of diabetes in their first-degree relatives, 24% had irregular menstrual cycles and 21.33% had incidence of GDM in their first-degree relatives.

2. Paulose KP. Prevalence of gestational diabetes in south Kerala. Kerala Med J 2008;(3):14-6.

In Apollo Hospital, Chennai; a study on 1,251 pregnant women who underwent the 50 g oral glucose challenge test (OGCT) during 2004, 168 (18.9%) were diagnosed to have GDM. Taking only 2-hour plasma glucose for analysis, 144 (16.2%) had value ≥140 mg/dL, that they were diabetic.

SUGGESTED READING 1. Bhat M, K N R, Sarma SP, Menon S, C V S, S GK. Determinants of gestational diabetes mellitus: A case control study in a district tertiary care hospital in south India. Int J Diabetes Dev Ctries 2010;30(2):91-6.

3. Shefali AK, Kavitha M, Deepa R, Mohan V. Pregnancy outcomes in pre-gestational and gestational diabetic women in comparison to non-diabetic women--A prospective study in Asian Indian mothers (CURES-35). J Assoc Physicians India 2006;54:613-8. 4. Bose T. Incidence of gestational diabetes mellitus in general population. J Hum Ecol 2005;17(4): 251-4. 5. Wahi P, Dogra V, Jandial K, Bhagat R, Gupta R, Gupta S, et al. Prevalence of gestational diabetes mellitus (GDM) and its outcomes in Jammu region. J Assoc Physicians India 2011;59:227-30.

A perspective study in GDM all over India (2002) showed the results as follows - the study conducted in North Chennai showed the prevalence of 16.2%, in South Chennai 15%, 15% in Trivandrum, 17.5% in Ludhiana, 12% in Bangalore, 31.6% in Alwaye, Kerala and 18.8% was in Erode, Tamil Nadu.

6. Seshiah V, Balaji V, Balaji MS, Sanjeevi CB, Green A. Gestational diabetes mellitus in India. J Assoc Physicians India 2004;52:707-11.

Conclusion

8. Seshiah VS, Balaji V,Balaji M. Gestational diabetes mellitus - A prospective. Gestational Diabetes Mellitus 2011 November; p.21-40.

The prevalence of GDM in this study was 17%. It was found out that the factors such as increased age of pregnant women, overweight and obesity, lack of exercise and diet control, GDM in first-degree relatives and previous abnormal GTT predispose to GDM. Other factors were women with previous large weight babies (macrosomia) and previous loss of pregnancy. GDM in previous pregnancy, complications in previous

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

9. Ferrara A. Increasing prevalence of gestational diabetes mellitus: a public health perspective. Diabetes Care 2007;30 Suppl 2:S141-6. 10. Soheilykhah S, Mogibian M, Rahimi-Saghand S, Rashidi M, Soheilykhah S, Piroz M. Incidence of gestational diabetes mellitus in pregnant Women. Iranian J Reprod Med 2010;8(1): 24-8.

■■■■

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

347

DIABETOLOGY

Hypoglycemic Brain Injury: A Case Report MONIKA MAHESHWARI*, RAJESH JAIN†

Abstract Diverse neurologic manifestations of hypoglycemia have been reported. Hypoglycemia can cause various neurologic symptoms including profound memory loss, transient motor deficits, a persistent vegetative state and death in 2-4% of cases. Brain magnetic resonance imaging (MRI) is a useful technique to evaluate hypoglycemic brain damage. We describe herein characteristic brain MR diffusion imaging features in a diabetic patient who had severe hypoglycemia.

Keywords: Diabetes, post-hypoglycemic brain injury, MRI brain scan

iverse neurologic manifestations of hypoglycemia have been reported. These neurologic symptoms range from focal neurologic deficits to permanent dysfunction or death.1-3 The accumulation of excitatory amino acids and not simply glucose starvation of the neuron, seems to play an important pathogenetic role.4 Brain magnetic resonance imaging (MRI) is a useful technique to evaluate hypoglycemic brain damage. We describe herein characteristic brain MR diffusion imaging features in a diabetic patient who had severe hypoglycemia. Case Report A 45-year-old diabetic female was brought comatose in the casualty outdoor. On physical examination, her pulse rate was 108/min, blood pressure 100/70 mmHg and respiratory rate 26/min. Her extremities were cold clammy with profuse sweating. Jugular venous pressure (JVP) was normal. There was no pedal edema, cyanosis, icterus or lymphadenopathy. Lungs were clear. Neurological examination revealed power >3/5 in both upper and lower limbs with normal tone. Bilateral plantar reflex was extensor. Pupils were normal in size and reactive to light. Patient was then shifted for MRI brain scan, which showed hyperintense areas of restricted diffusion involving the bilateral basal ganglia (Fig. 1) characteristic of posthypoglycemic brain injury. Immediately blood glucose levels was then done, which

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

348

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

Figure 1. MRI brain scan showing hyperintense areas of restricted diffusion involving the bilateral basal ganglia and band like area in right parietal lobe.

confirmed hypoglycemia (blood sugar - 40 mg%). Patient was given 100 mL intravenous infusion of 25% dextrose stat. She regained consciousness. During her further hospital stay her insulin dose was resetted to optimal dose with proper instructions for dietary pattern and she was discharged on 10th day. Discussion Hypoglycemia can cause various neurologic symptoms including profound memory loss, transient motor deficits, a persistent vegetative state and death in 2-4% of cases.5 Some pathogenetic mechanisms for diffusion restriction picture in MRI brain have been proposed as follows: ÂÂ Energy failure ÂÂ Excitotoxic edema ÂÂ Asymmetric cerebral blood flow.

DIABETOLOGY Glucose deprivation leads to arrest of protein synthesis in many regions, incomplete energy failure and loss of ion homeostasis, cellular calcium influx and intracellular alkalosis. Consequently, neuroactive amino acid (aspartate) release into the extracellular space occurs and results in selective neuronal necrosis, predominantly in the cerebral cortex, caudoputamen and hippocampus.6 However, protein synthesis in the cerebellum, brainstem and hypothalamus remains unaffected because of the greater activity of the glucose transport mechanisms.7 Further in contrast to ischemic brain damage, inability to produce lactic acid during hypoglycemia is thought to account for the fact that infarction is not seen in controlled experimental conditions producing a pure hypoglycemic insult to the brain. Thalamic lesions exist in ischemic encephalopathy, but not in hypoglycemic coma. In hypoglycemia, due to focal loss of autoregulation, the frontal and parietal lobe areas have grossly decreased cerebral flow, whereas the cerebellum and brainstem show almost no fall in local cerebral blood flow as seen in our patient also. There was a characterisitic band like area localized to right parietal lobe (Fig. 1). The predominant release of aspartate into the extracellular fluid in hypoglycemia differs from the rise in extracellular glutamate in ischemia.8 Second, unlike ischemia, energy failure is only moderate during hypoglycemia because of the remaining glucose supply and oxidation of endogenous nonglucose fuels by the brain.8 In contrast to cytotoxic edema, excitotoxic edema does not imply neuronal damage, because glutamate induces edema of glial cells and myelinic sheaths might protect axons from intracellular edema and irreversible

damage. In addition, glutamate reuptake systems are not impaired in hypoglycemia. According to these mechanisms, hypoglycemic brain injury is usually transitory and MRI abnormalities normalize with time.9 REFERENCES 1. Böttcher J, Kunze A, Kurrat C, Schmidt P, Hagemann G, Witte OW, et al. Localized reversible reduction of apparent diffusion coefficient in transient hypoglycemiainduced hemiparesis. Stroke 2005;36(3):e20-2. 2. Finelli PF. Diffusion-weighted MR in hypoglycemic coma. Neurology 2001;57(5):933. 3. Shirayama H, Ohshiro Y, Kinjo Y, Taira S, Teruya I, Nakachi K, et al. Acute brain injury in hypoglycaemiainduced hemiplegia. Diabet Med 2004;21(6):623-4. 4. Auer RN. Progress review: hypoglycemic brain damage. Stroke 1986;17(4):699-708. 5. Albayram S, Ozer H, Gokdemir S, Gulsen F, Kiziltan G, Kocer N, et al. Reversible reduction of apparent diffusion coefficient values in bilateral internal capsules in transient hypoglycemia-induced hemiparesis. AJNR Am J Neuroradiol 2006;27(8):1760-2. 6. Auer RN, Siesjö BK. Hypoglycaemia: brain neurochemistry and neuropathology. Baillieres Clin Endocrinol Metab 1993;7(3):611-25. 7. Kiessling M, Xie Y, Kleihues P. Regionally selective inhibition of cerebral protein synthesis in the rat during hypoglycemia and recovery. J Neurochem 1984;43(6):1507-14. 8. Auer RN, Wieloch T, Olsson Y, Siesjö BK. The distribution of hypoglycemic brain damage. Acta Neuropathol 1984;64(3):177-91. 9. Gallucci M, Limbucci N, Paonessa A, Caranci F. Reversible focal splenial lesions. Neuroradiology 2007;49(7):541-4.

■■■■

Kids Who Eat Breakfast Daily may have Lower Diabetes Risk: Study NEW YORK (Reuters Health) - Nine and 10 years old who ate breakfast daily, particularly a high-fiber cereal, had lower fasting blood sugar and insulin levels and fewer other risk factors for type 2 diabetes, according to a new study from England. “The evidence from studies in adults suggests that there is a link between skipping breakfast and high diabetes risk - but this is the first study to confirm this pattern in children,” said Angela S. Donin of the Population Health Research Institute at St George’s University of London.

BMI Biggest Contributor to Increase in Type 2 Diabetes in US Rising obesity rates are the greatest contributor to the increasing prevalence of type 2 diabetes in the United States, accounting for all of the increase in women and about half of the increase in men, new comparative data from the National Health and Nutrition Examination Survey (NHANES) indicate. The study is published in the September 2 issue of Annals of Internal Medicine.

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

349

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

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

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

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

Who is Eligible?

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

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

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

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

To promote and train hands-only CPR.

Activities of the Fund Financial Assistance

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

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

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

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

Drug Subsidy

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

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

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

BPL Card (If Card holder)

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

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

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

Free Diagnostic Facility

Free Education and Employment Facility

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

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

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

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

About Heart Care Foundation of India

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

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

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

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

Committee Members

Chief Patron

President

Raghu Kataria

Dr KK Aggarwal

Entrepreneur

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

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

Advisors Mukul Rohtagi Ashok Chakradhar

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

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

Rishab Soni

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

http://heartcarefoundationfund.heartcarefoundation.org

ENT

Juvenile Nasopharyngeal Angiofibroma: A Tertiary Hospital-based Experience farooq a itoo*, IRFAN IQBAL†, LATIEF A CHIESTI‡

Abstract Juvenile nasopharyngeal angiofibroma (JNA) is a highly vascular histologically benign, locally aggressive neoplasm of the nasopharynx. It accounts for 0.5% of all head and neck neoplasms with a high incidence of persistence and recurrence. Modern

methods of investigation and ambitious surgical procedures have focused attention on the region of sphenopalatine foramen as the site of origin-based on the observation that larger tumors present as bilobed dumbbell swellings straddling the sphenopalatine foramen, with one component filling the nasopharynx and the other extending out into the pterygopalatine and infratemporal fossae. A prospective and retrospective hospital-based study was conducted in the Dept. of Otorhinolaryngology, Head and Neck Surgery, SMHS Hospital, Srinagar on patients of juvenile nasopharyngeal angiofibroma. A total of 24 cases of juvenile angiofibroma were included in this study. Keywords: Nasopharynx, epistaxis, CT scan, embolization

uvenile nasopharyngeal angiofibroma (JNA) is a highly vascular histologically benign, locally aggressive neoplasm of the nasopharynx that exclusively affects male adolescents, with an average age of onset being 14 years. It accounts for 0.5% of all head and neck neoplasms with a high incidence of persistence and recurrence. Anatomically, the point of origin is believed to be the posterolateral wall of the roof of the nose, where the sphenoid of palatine bone meets the horizontal ala of the vomer and the root of pterygoid process of sphenoid. This junction forms the superior margins of the sphenopalatine foramen. Modern methods of investigation and ambitious surgical procedures have focused attention on the region of sphenopalatine foramen as the site of origin and this would most reasonably explain the subsequent behavior of angiofibromas. This is based on the observation that larger tumors present as bilobed dumbbell swellings straddling the sphenopalatine foramen,

with one component filling the nasopharynx and the other extending out into the pterygopalatine and infratemporal fossae. The central stalk joining the two portions occupies the sphenopalatine foramen at the upper end of vertical plate of palatine bone without appearing to enlarge it very much. AIMS AND OBJECTIVES ÂÂ To evaluate the incidence of juvenile angiofibroma

in hospital attending population of Kashmir.

ÂÂ To evaluate the role of preoperative contrast-

enhanced computed tomography (CECT) and/or magnetic resonance imaging (MRI) in the diagnosis and management of patients of juvenile angiofibroma.

ÂÂ To evaluate the role of nasal endoscopy in the

juvenile angiofibroma.

ÂÂ To

evaluate the merits of various surgical approaches for juvenile angiofibroma depending upon the CECT or MRI stage and extent.

ÂÂ To evaluate the role of CECT in the postoperative *Postgraduate Scholar †Registrar ‡Ex-Head Dept. of ENT-Head and Neck Surgery Government Medical College, Srinagar, Jammu and Kashmir Address for correspondence Dr Irfan Iqbal Registrar Dept. of ENT-Head and Neck Surgery Government Medical College, Srinagar Jammu and Kashmir E-mail: irfaniqbal0809@yahoo.com

352

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

follow-up of patients of juvenile angiofibroma.

ÂÂ To identify the causes for the recurrence of juvenile

angiofibroma.

MATERIAL AND METHODS A prospective and retrospective hospital-based study was conducted in the Dept. of Otorhinolaryngology, Head and Neck Surgery, SMHS Hospital, Srinagar

ENT Table 1. Fisch Staging System

Table 4. Symptomatology of JNA

Types Details I Tumor limited to the nasopharyngeal cavity; bone destruction negligible or limited to sphenopalatine foramen. II Tumor invading the pterygopalatine fossa or the maxillary, ethmoid or sphenoid sinus with bone destruction. III Tumor invading the infratemporal fossa or orbital region yy Without intracranial involvement yy With intracranial extradural (parasellar involvement). IV Intracranial intradural tumor yy Without infiltration of the cavernous sinus, pituitary fossa or optic chiasm yy With infiltration of cavernous sinus, pituitary fossa or optic chiasm.

Symptoms and signs

Present (%)

Absent (%)

Nasal obstruction

100

Epistaxis

100

Facial swelling

Proptosis

12.5

87.5

Diminution of vision Protruding nasal mass

Table 5. Imaging Modalities Required for Diagnosis and Staging of JNA Table 2. Age Extremes of Presentation

Imaging modality

No. of patients

Percentage (%)

Lowest age of presentation

9 years

CECT

100

Highest age of presentation

26 years

CECT + MRI

Table 3. Intracranial Extension in JNA No. of patients with intracranial extension 6

Percentage (%) 25

Lateral rhinotomy with medial maxillectomy Transnasoantraltranspalatal Transpalatal

on patients of JNA. A total of 24 cases of juvenile angiofibroma were included in this study. Preadolescent and adolescent males presenting with progressive nasal obstruction and recurrent epistaxis were included in the study. All the patients were staged according to Fisch classification (Table 1). Observations and Results This study was carried out in the Dept. of ENT and Head and Neck Surgery in Government Medical College, Srinagar, Jammu and Kashmir. This study is a prospective-retrospective account of cases of JNA presenting to our hospital. The extremes of ages at presentation are shown in Table 2. During this study, a total of 24 cases of JNA attended the Dept. of ENT, Government Medical College, 12 out of the 24 patients (50%) had blood group â&#x20AC;&#x2DC;Oâ&#x20AC;&#x2122;. All except one patients were Rhesus (Rh) factor positive. Maximum number of patients (14) presented in Stage III. Earlier Stage (I and II) presentations are relatively rarer and there is a significant delay in

Anterior craniofacial resection Endoscopic assisted lateral rhinotomy

Figure 1. Surgical approaches to excision of angiofibroma.

diagnosis. Out of the 24 patients, 6 (25%) presented with intracranial extension (Table 3).

Nasal obstruction and epistaxis are the most common presentations of angiofibroma seen in all cases. Other common symptoms and signs are diminished vision, proptosis, facial swelling and protruding nasal mass (Table 4). CECT is the most common imaging modality utilized for diagnosis and staging of JNA and it is required in all cases. MRI is utilized as an additional investigation in cases with intracranial extention and was required in 25% of cases (Table 5). Lateral rhinotomy with medial maxillectomy was the most common surgical approach utilized for removal of angiofibroma - in 45.8% of cases followed by transnasoantral-transpalatal approach in 33% (Fig. 1).

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

353

ENT Table 6. Postoperative Complications for All Surgical Approaches Postoperative complications

No. of patients

Incidence of Recurrence in Different Stages Out of six cases who had invasion of basisphenoid, 4 (66.66%) had recurrence on follow-up, whereas only 3 (16.67%) out of 18 cases not having invasion of basisphenoid had recurrence (p value 0.038).

Palatal fistula

Malar defect

Ectropion

discussion AND CONCLUSION

Epiphora

In this study, a total of 24 cases of JNA were studied and following inferences and conclusions drawn.

Table 7. Total Complication Rate for All Surgical Approaches Total complication rate

7/24

29%

Table 8. Correlation Between Stage of Disease and Recurrence Stage

Total no. of patients

No. of patients with recurrence

Recurrence rate (%)

IIIa

45.3

IIIb

IVa

IVb

66.6

P value

ÂÂ Angiofibroma is essentially a disease of adolescent

males and peak age of presentation is 15 years.

ÂÂ The incidence of angiofibroma, as calculated from

the average number of patients attending ENT OPD, is 1.21/10,000 population.

ÂÂ Earlier Stage (I and II) presentations are relatively

rarer signifying that there is a significant delay in diagnosis.

ÂÂ About one-quarter of angiofibroma patients have

intracranial extension at presentation.

ÂÂ Nasal obstruction and epistaxis are the most

common presentations of angiofibroma and a high index of suspicion is required for diagnosis.

ÂÂ CECT is the most common imaging modality 0.000

Postoperative complications were not serious and only included malar defect, ectropion, epiphora and palatal defect (Table 6). Total complication rate in all was about 29%, seen in seven out of 24 patients (Table 7). All the cases were followed for a minimum of 6 months, and longest follow-up was of more than 3 years. All the cases underwent nasal endoscopy and check-CECT on follow-up.

Recurrence Rate of Operated Cases Angiofibroma

utilized for diagnosis and staging of JNA and MRI is utilized as an additional investigation in cases with intracranial extention.

ÂÂ A combination of various surgical approaches is

used to remove angiofibromas.

ÂÂ Lateral rhinotomy with medial maxillectomy was

the most common surgical approach employed in removal of juvenile angiofibroma.

ÂÂ The average blood loss has a direct correlation

with the stage of tumor.

ÂÂ Radiologic follow-up is essential in the early

identification of residual or recurrent disease.

ÂÂ The incidence of recurrent or residual disease is

high and is about 30%.

ÂÂ Risk factors for recurrence include large JNA with

Out of the 24 cases of nasopharyngeal angiofibroma diagnosed and followed for a minimum of 6 months, seven patients were diagnosed with recurrence, with a recurrence rate of about 30%.

SUGGESTED READING

These recurrences were diagnosed at varying intervals of follow-up five out of 11 cases with Stage IIIa and two out of three cases with Stage IVb diagnosed with recurrence (Table 8).

1. Pryor SG, Moore EJ, Kasperbauer JL. Endoscopic versus traditional approaches for excision of juvenile nasopharyngeal angiofibroma. Laryngoscope 2005;115(7):1201-7.

354

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

intracranial extension, skull base erosion, cavernous sinus involvement, young age at diagnosis.

ENT 2. Standefer J, Holt GR, Brown WE Jr, Gates GA. Combined intracranial and extracranial excision of nasopharyngeal angiofibroma. Laryngoscope 1983;93(6):772-9. 3. Handa KK, Kumar A, Singh MK, Chhabra AH. Extranasopharyngeal angiofibroma arising from the nasal septum. Int J Pediatr Otorhinolaryngol 2001;58(2):163-6. 4. Hwang HC, Mills SE, Patterson K, Gown AM. Expression of androgen receptors in nasopharyngeal angiofibroma: an immunohistochemical study of 24 cases. Mod Pathol 1998;11(11):1122-6. 5. Som ML, Neffson AH. Fibromas of the nasopharynx: juvenile and cellular types. Ann Otol Rhinol Laryngol 1940;49:211-8. 6. Bensch H, Ewing J. Neoplastic Disease. 4th edition, Saunders and Co.: Philadelphia, 1941. 7. Brunner H. Nasopharyngeal fibroma. Ann Otol Rhinol Laryngol 1942;51:29-65. 8. Osborn DA. The so called juvenile angiofibroma of the nasopharynx. J Laryngol Otol 1959;69:295-316. 9. Girgis IH, Fahmy SA. Nasopharyngeal fibroma: its histopathological nature. J Laryngol Otol 1973;87(11): 1107-23. 10. Mann WJ, Jecker P, Amedee RG. Juvenile angiofibromas: changing surgical concept over the last 20 years. Laryngoscope 2004;114(2):291-3.

11. Lowlicht RA, Jassin B, Kim M, Sasaki CT. Long-term effects of Le Fort I osteotomy for resection of juvenile nasopharyngeal angiofibroma on maxillary growth and dental sensation. Arch Otolaryngol Head Neck Surg 2002;128(8):923-7. 12. Close LG, Schaefer SD, Mickey BE, Manning SC. Surgical management of nasopharyngeal angiofibroma involving the cavernous sinus. Arch Otolaryngol Head Neck Surg 1989;115(9):1091-5. 13. Harman RA. Nasopharyngeal angiofibroma: a clinical and histopathological study. Acta Otolaryngol 1959;146: 1-76. 14. Krekorian EA, Kato RH. Surgical management of nasopharyngeal angiofibroma with intracranial extension. Laryngoscope 1977;87(2):154-64. 15. J afek BW, Nahum AM, Butler RM, Ward PH. Surgical treatment of juvenile nasopharyngeal angiofibroma. Laryngoscope 1973;83(5):707-20. 16. Lee JT, Chen P, Safa A, Juillard G, Calcaterra TC. The role of radiation in the treatment of advanced juvenile angiofibroma. Laryngoscope 2002;112(7 Pt 1):1213-20. 17. Cummings BJ, Blend R, Keane T, Fitzpatrick P, Beale F, Clark R, et al. Primary radiation therapy for juvenile nasopharyngeal angiofibroma. Laryngoscope 198494(12 Pt 1):1599-605.

■■■■

Rapid Streptococcus Tests Accurate Rapid antigen diagnostic tests (RADTs) are accurate in the diagnosis of strep throat, according to a systematic review and meta-analysis published online September 8 in Pediatrics. “RADTs can be used for accurate diagnosis of (group A Streptococcus [GAS]) pharyngitis to streamline management of sore throat in primary care,” write Wei Ling Lean, MBBS, from the Dept. of General Medicine, Royal Children’s Hospital, Melbourne, Australia, and colleagues. “RADTs may not require culture backup for negative tests in most low-incidence rheumatic fever settings. Newer molecular tests have the highest sensitivity, but are not true point-of-care tests.” Point-of-care tests ideally have a turn-around time of 1 to 3 hours, according to the authors.

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

355

ENT

Comparison of Finger Gloves Pack with BIPP Pack in Early Postoperative Period of Septal Surgery Narmaya Thapa

Abstract Objective: To compare early postoperative complications of nasal packing with finger gloves versus bismuth iodoform paraffin paste (BIPP) in patients after septal surgery. Material and methods: This prospective, longitudinal, randomized study was done in patients who underwent primary septoplasty from Aug. 2009 to July 2013 in the Dept. of ENT-Head and Neck Surgery, Tribhuvan University Teaching Hospital, Kathmandu, Nepal. Patients after septoplasty were randomly selected by lottery for nasal packing with BIPP or finger gloves prepared from latex surgical gloves. Patients and surgeon were blind folded. Pack was removed after 48 hours in both cases. Pain and bleeding during pack removal was assessed by 4 Score Numerical Rating Scale by one of the residents. Signs of infection and synechia noted in the first follow-up (2 weeks after discharge) by a faculty who was blind-folded about the material of nasal packing. Results: Total 79 patients were included in the study, 35 in finger packing and 44 in BIPP packing group. Age of the patients ranged from 15 to 51 years in finger glove packing and 13 to 65 years in BIPP packing with median age of 27 and 24.37 years, respectively. Mean pain score and bleeding was significantly more in BIPP packing group. Synechia was found in equal number of patients while infection was also more in BIPP packing group but it was statistically not significant. Conclusion: Finger gloves nasal packing is less painful and causes less bleeding at removal than BIPP packing, and also causes less infection, while there is no difference in synechia formation.

Keywords: Septoplasty, finger gloves, BIPP, bleeding, infection, pain, synechia

eptoplasty is one of the most common surgeries in otorhinolaryngology. Anterior nasal packing after septoplasty is basically done for hemostasis and apposition of septal flaps. However, it is associated with many immediate postoperative complications such as pain, hypoxia, hypoxemia, dryness in throat, headache, epiphora, etc. as well as late postoperative complications like vestibulitis, vestibular stenosis, crusting, synechiae, secondary infection.1,2

The procedure itself is very painful during insertion and even on removal.3,4 New materials have been tried to minimize these postoperative complications and there are many studies comparing different materials used for nasal packing.5-8 We routinely use bismuth iodoform paraffin paste (BIPP) pack and sometimes gloves finger pack after septoplasty. Gloves finger pack was used by Sirimanna et al in 1994, but it was more concentrated

Associate Professor Rhinology Unit Dept. of ENT-Head and Neck Surgery Tribhuvan University Teaching Hospital, Maharajgunj, Kathmandu, Nepal Address for correspondence Dr Narmaya Thapa Associate Professor, Rhinology Unit Dept. of ENT-Head and Neck Surgery Tribhuvan University Teaching Hospital, Maharajgunj, Kathmandu, Nepal E-mail: narmayat@gmail.com

356

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

in duration of pack placement.9 Comparison of complications between these two materials is lacking. Therefore, this prospective, longitudinal randomized study was carried out to compare early postoperative complications of nasal packing with finger gloves versus BIPP in patients after septal surgery. Material and Methods Those patients who underwent septoplasty from August 2009 to July 2013 in the Dept. of ENT-Head and Neck Surgery, Tribhuvan University Teaching Hospital, Kathmandu, Nepal and fulfilled the following inclusion criteria were included in the study. Classical septoplasty was done by single surgeon. Patients after septoplasty were randomly selected by lottery for nasal packing with BIPP or finger gloves prepared from latex surgical gloves. Written consent was taken. Ethical approval was obtained from Institutional Review Board. Patients and surgeons were blindfolded. Pack was removed after 48 hours in both cases.

Inclusion Criteria ÂÂ

Age >12 years.

ÂÂ

Both gender.

ÂÂ

Patients who underwent septoplasty under local anesthesia.

ENT Exclusion Criteria

Table 1. Demographic Profiles of the Patients Finger glove pack

BIPP pack

No. of patients Nasal cavities Age range (years)

15-51

13-65

24.37

Median age

No. of patients

Finger gloves

20 15

BIPP

14.5

16 12.5

5.5

4.5

1 3

Figure 1. Comparison of pain score.

No. of patients

BIPP

Finger gloves

25 18

20 15 10

12.5

4.5

5 0

Patient who underwent inferior turbinate reduction (ITR), septorhinoplasty, dacryocystorhinostomy (DCR) or other such procedures in same setting.

ÂÂ

Revision cases.

ÂÂ

Patients known to have allergy or hypersensitivity to latex.

Pain and bleeding during pack removal was assessed by 4 Score Numerical Rating Scale by one of the residents. Signs of infection and synechia were noted in the first follow-up (2 weeks after discharge) by a faculty who was blind-folded about the material of nasal packing. Comparison between two groups for difference of mean of pain and bleeding scores and for difference of proportion of synechia and infection was done by Z test. Data was analyzed by using latest version of SPSS. P < 0.05 was considered statistically significant. Results

Pain score

ÂÂ

Total 79 patients were included in the study, 35 in finger packing and 44 in BIPP packing group. Age of the patients ranged from 15 to 51 years in finger glove packing and 13 to 65 years in BIPP packing with median age of 27 and 24.37 years, respectively (Table 1). While comparing mean pain score and bleeding it was significantly more in BIPP packing group (Tables 2 & 3 and Figs. 1 & 2). However, synechia was found in equal number of patients (Table 4), while infection was also more in BIPP packing group, but it was statistically not significant (Table 5). Discussion

Bleeding score

Nasal packing after septoplasty is associated with increased pain and other complications like vestibulitis, septal perforation especially with BIPP.

Figure 2. Comparison of bleeding.

Table 2. Comparison of Mean Pain Score Mean pain score Right

Left

Total

Z test

P value

Significance

Glove pack

0.742

0.77

0.756

0.818

5.35

<0.01

Significant

BIPP pack

0.75

0.886

0.818

0.699

Table 3. Comparison of Mean Bleeding Score Mean bleeding score Right

Left

Total

Z test

P value

Significance

Glove pack

0.62

0.60

0.61

0.70

3.84

<0.01

Significant

BIPP pack

1.04

1.09

1.06

0.78

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

357

ENT Table 4. Comparison of Synechia Synechia Right

Left

Total

Z test

P value

Significance

Glove pack

0.2

0.80

0.665

>0.05

Not significant

BIPP pack

0.15

0.85

Table 5. Comparison of Infection Infection Right

Left

Total

Z test

P value

Significance

0.217

>0.05

Not significant

Glove pack

0.028

0.972

BIPP pack

0.034

0.966

Septal suturing techniques without pack has also been practiced nowadays to alleviate these complications but sometimes pack may be necessary to prevent persistent and troublesome hemorrhage. Bajaj et al reported 3.8% patients required nasal packing in their study.10 Comparisons were made regarding different materials used for packing (e.g., Merocel, Telfa, Rapid Rhino Reimann pack, calcium sodium alginate, paraffin gauze).5-8 In a study by Von Schoenberg, mean pain scores were increased 50% by the use of nasal packs and pack removal, particularly BIPP which, was a most painful event (p < 0.001). There was no significant difference in the incidence of adhesions between the groups who received packs and those who did not.11 Illum et al compared finger stall packs filled with gauze (32 patients) with a Merocel pack with a ventilation tube (27 patients). They reported that patients felt little benefit from the ventilation tube and that there was significantly more bleeding on removal of the Merocel pack than the finger stall pack (p = 0.02).12 Arya et al compared the Goodman pack with the Merocel pack in 14 patients, nine undergoing septal and/or turbinate surgery and five having endoscopic sinus surgery. They found significantly higher pain levels associated with Merocel pack removal than with Rapid Rhino Goodman pack removal (average pain scores 5.64 vs 1.64, p < 0.001).13 In this study, there was significantly less pain and bleeding with gloves finger pack (p < 0.01). There was less infection in gloves pack group than in BIPP pack group, but it was statistically not significant (p > 0.05), similarly synechia formation was equal in number. I did not find any other studies to compare postoperative infection between these two types of packs. Gloves finger pack is locally available

358

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

and sterile. No extra cost is required for pack as Merocel, or even BIPP. The only concerned thing is hypersensitivity to latex. Use of gloves made with more compatible material can be done in such case. Conclusion Finger gloves nasal packing is less painful and causes less bleeding at removal than BIPP packing and also causes less infection, while there is no difference in synechia formation. References 1. Fairbanks DN. Complications of nasal Otolaryngol Head Neck Surg 1986;94(3):412-5.

packing.

2. Weber R, Keerl R, Hochapfel F, Draf W, Toffel PH. Packing in endonasal surgery. Am J Otolaryngol 2001;22(5): 306-20. 3. Yilmazer C, Sener M, Yilmaz I, Erkan AN, Cagici CA, Donmez A, et al. Pre-emptive analgesia for removal of nasal packing: A double-blind placebo controlled study. Auris Nasus Larynx 2007;34(4):471-5. 4. Laing MR, Clark LJ. Analgesia and removal of nasal packing. Clin Otolaryngol Allied Sci 1990;15(4):339-42. 5. Garth RJ, Brightwell AP. A comparison of packing materials used in nasal surgery. J Laryngol Otol 1994;108(7): 564-6. 6. Repanos C, McDonald SE, Sadr AH. A survey of postoperative nasal packing among UK ENT surgeons. Eur Arch Otorhinolaryngol 2009;266(10):1575-7. 7. Cruise AS, Amonoo-Kuofi K, Srouji I, Kanagalingam J, Georgalas C, Patel NN, et al. A randomized trial of Rapid Rhino Riemann and Telfa nasal packs following endoscopic sinus surgery. Clin Otolaryngol 2006;31(1): 25-32. 8. Shinkwin CA, Beasley N, Simo R, Rushton L, Jones NS. Evaluation of Surgicel Nu-knit, Merocel and Vasolene

ENT gauze nasal packs: a randomized trial. Rhinology 1996;34(1):41-3. 9. S irimanna KS, Todd GB, Madden GJ. A randomized study to compare calcium sodium alginate fibre with two commonly used materials for packing after nasal surgery. Clin Otolaryngol Allied Sci 1992;17(3):237-9. 10. Bajaj Y, Kanatas AN, Carr S, Sethi N, Kelly G. Is nasal packing really required after septoplasty? Int J Clin Pract 2009;63(5):757-9.

11. v on Schoenberg M, Robinson P, Ryan R. Nasal packing after routine nasal surgery - is it justified? J Laryngol Otol 1993;107(10):902-5. 12. Illum P, Grymer L, Hilberg O. Nasal packing after septoplasty. Clin Otolaryngol Allied Sci 1992;17(2): 158-62. 13. Arya AK, Butt O, Nigam A. Double-blind randomised controlled trial comparing Merocel with Rapid Rhino nasal packs after routine nasal surgery. Rhinology 2003;41(4):241-3.

■■■■

Neck Mass, Persistent Sore Throat Could Mean Throat Cancer A prolonged sore throat and a neck mass are the most common initial symptoms of oropharyngeal squamous cell carcinoma, and primary care clinicians whose patients report such symptoms should refer them immediately for screening. These symptoms are usually the first signs of human papillomavirus (HPV)-positive throat cancer, which is increasingly occurring in young healthy people, researchers report. Other early symptoms of throat cancer are pain or difficulty swallowing and difficulty opening the mouth; these are usually indications of HPV-negative oropharyngeal cancer. These findings come from a retrospective study 88 patients with known HPV status, published online today in JAMA Otolaryngology – Head & Neck Surgery.

Antimicrobial Treatment of Acute Otitis Media Shortens Duration of Middle Ear Effusion Antimicrobial Treatment Accelerates the Resolution of Middle Ear Effusion Associated with Acute Otitis Media, Researchers from Finland Report “Our results imply that the children with acute otitis media are likely to benefit from antimicrobial treatment regardless of their age,” Dr Terhi Tapiainen from University of Oulu told Reuters Health by email. “Some experts have suggested that only infants should be treated, but it appears that the duration of possible hearing impairment and the risk of persistent middle ear effusion decreases in all children.” “However, clinicians should try to restrict the antimicrobial treatment to children with acute otitis media, i.e., children who have both acute respiratory symptoms and signs of inflammation of tympanic membrane and middle ear effusion at the same time,” Dr. Tapiainen said. Middle ear effusion resolved an average of 2.0 weeks earlier in the 42 children who received antimicrobial therapy (mean, 18.9 days) than in the 42 children not treated with antibiotics (mean, 32.6 days), according to the May 5 JAMA Pediatrics online report. Mean duration of middle ear effusion was decreased by 8 days in children younger than 2 years, by 20 days in children aged 2-6 years, and by 1 day among older children. To prevent persistent middle ear effusion at day 14 in one child required treatment of 3.2 children with antimicrobials. Similarly, to prevent persistent middle ear effusion at 2 months in one child required treatment of 5.3 children with antimicrobials. Antimicrobial treatment also reduced the number of days of ear pain by about 1 day, researchers say. (Medscape 2014)

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

359

Gastroenterology

A Case of Gastric Diverticulum (Solitary Fundal Diverticulum) – Pictorial CME Praveen Kumar*, Kalpana Chandra†

Abstract Gastric diverticula are uncommon form of diverticular disease. Akerlund classified gastric diverticula as congenital and acquired. The congenital gastric diverticulum is a ‘true diverticulum’ and involves all layers of the gastric wall. True diverticula make up 75% of all gastric diverticula, most commonly located near the gastroesophageal junction on the lesser curvature of the stomach. We report the case of a 46-year-old female patient who came for upper gastrointestinal endoscopy with history of upper abdominal pain; which was mild, continuous and increased after meals. She was diagnosed to have reflux esophagitis with mild antral gastritis and solitary fundal diverticulum.

Keywords: Upper gastrointestinal endoscopy, reflux esophagitis, antral gastritis, fundal diverticulum CASE REPORT A 46-year-old female patient who came for upper gastrointestinal endoscopy with history of upper abdominal pain; which was mild, continuous and increased after meals. Patient was also having intermittent vomiting. Her upper gastrointestinal endoscopy revealed reflux esophagitis with mild antral gastritis and gastric diverticulum (solitary fundal diverticulum) (Fig. 1 a-c).

DISCUSSION Gastric diverticula are uncommon form of diverticular disease. The incidence ranges from 0.02% in autopsy studies to 0.01% to 0.11% at endoscopy. Gastric diverticula are often single, varying in size from 1 to 3 cm and most commonly found in middle-aged patients with equal sex incidence.1 Akerlund classified gastric diverticula as congenital and acquired. The congenital gastric diverticulum is a ‘true diverticulum’ and involves all layers of the gastric

*Associate Professor Dept. of Medicine †Associate Professor Dept. of Pathology Shri Ram Murti Smarak Institute of Medical Science, Bhojipura Bareilly, Uttar Pradesh Address for correspondence Dr Praveen Kumar Associate Professor Dept. of Medicine Shri Ram Murti Smarak Institute of Medical Science, Bhojipura Bareilly, Uttar Pradesh - 243 202 E-mail: praveen_kmr_23@yahoo.co.in

360

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

Figure 1 (a-c). Showing fundal diverticulum in retroflexed view.

Gastroenterology wall, whereas the acquired variety lacks the muscular or serosal layer referred as ‘false diverticulum’. True diverticula make up 75% of all gastric diverticula, most commonly located near the gastroesophageal junction (juxtacardiac) on the lesser curvature of the stomach on the posterior aspect. Intramural or partial gastric diverticula are formed by the projection of the mucosa of the stomach through the muscular layer and are found more commonly in prepyloric region usually on lesser curvature.2 Patients with gastric diverticula are often asymptomatic, although juxtacardiac diverticula may present with dyspepsia, vomiting and abdominal pain. Intramural diverticula do not usually cause any symptoms.3,4 Diverticulum is diagnosed incidentally by gastrointestinal endoscopy, radiological investigation (lateral view of barium study and CT scan) and on autopsy. Rarely, it may be associated with complications such as ulceration, perforation, hemorrhage, torsion and malignancy. There is no specific treatment required for an asymptomatic diverticulum. Surgical resection (open or laparoscopic diverticulectomy) is recommended in large symptomatic and/or complicated juxtacardiac

diverticulum. intervention.5

Intramural

diverticula

require

Acknowledgment I take this opportunity to extend my gratitude and sincere thanks to all those who helped me to complete this study. I owe great sense of indebtedness to Dean Shri Ram Murti Smarak Institute of Medical Sciences (SRMS-IMS), Bhojipura, Bareilly for permitting me to carry out this study.

REFERENCES 1. Jeyarajah R, Harford W. Diverticula of the Hypopharynx, Esopahgus, Stomach, Jejunum and Ileum. In: Sleisenger & Fordtran’s Gastrointestinal and Liver Disease: Pathophysiology/Diagnosis/Management. 7th edition, WB Saunders: Philadelphia 2002:p.363-4. 2. Akerlund D. Gastric diverticulum. Acta Radiol 1923;2: 476-85. 3. Palmer ED. Gastric diverticulosis. Am Fam Physician 1973;7(3):114-7. 4. Anaise D, Brand DL, Smith NL, Soroff HS. Pitfalls in the diagnosis and treatment of a symptomatic gastric diverticulum. Gastrointest Endosc 1984;30(1):28-30. 5. Fork FT, Tóth E, Lindström C. Early gastric cancer in a fundic diverticulum. Endoscopy 1998;30(1):S2.

■■■■

ÂÂ A French study has shown that patients who have used immunosuppressive thiopurines to treat inflammatory

bowel disease (IBD) have a 7 times higher risk of developing a myeloid disorder. The study has been published in the August issue of Clinical Gastroenterology and Hepatology.

ÂÂ Statins, a class of drugs commonly used to lower cholesterol levels, significantly reduce a patient’s risk of

developing Barrett’s esophagus, according to a new study in Gastroenterology, the official journal of the American Gastroenterological Association. Obese patients experienced the greatest level of risk reduction with statin use. “Patients who received statins had a 43% reduction in the odds of having Barrett’s esophagus compared to nonusers,” said study author Hashem B. El-Serag, MD, MPH, from the Houston VA Medical Center and Baylor College of Medicine, Houston, TX. “This is the first study to find a significantly lower risk of Barrett’s esophagus with statin use, independent of other known risk factors. Further studies are needed to examine this association.”

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

361

OBSTETRICS AND GYNECOLOGY

Progesterone and Prevention of Preterm Labor Ruchika Garg*, Urvashi Verma*, Rajni Rawat†, Somya shrivastava‡, Renu Rajvanshi#

Abstract Objectives: To evaluate the effect of vaginal progesterone in the prolongation of duration of pregnancy in women at highrisk of developing preterm labor. Material and methods: This is a prospective case-control study carried out in the Dept. of Obstetrics and Gynecology, SN Medical College, Agra on 100 patients chosen from inpatient and outpatient department (50 cases and 50 controls). Women with singleton pregnancy having history of preterm labor, uterine malformation, prophylactic cerclage, currently suffering from premature pains were given daily vaginal progesterone 200 mg from 24 weeks and discontinued at 34 weeks of gestation. In both groups rate of preterm labor and neonatal outcome was determined. Results: The incidence of preterm labor in progesterone group was 17.8% and in control group 36%, p value is <0.05. Conclusion: Administration of progesterone in women at high-risk of developing preterm labor reduces the incidence of preterm labor, neonatal mortality and morbidity and increases baby weight <2.5 kg.

Keywords: Preterm labor, progesterone

reterm labor is defined by World Health Organization (WHO) as contraction of sufficient strength and frequency to effect progressive effacement of cervix between 20-37 weeks. Worldwide incidence of preterm labor is 6-10%.1 Vidaeff et al promoted the progesterone see-saw theory, according to it high progesterone levels prevent uterine contractions and low levels facilitate such contractions.2 Aims of study To compare the effect of vaginal progesterone versus placebo on the prevention of preterm labor, among women at increased risk of preterm labor. Material and methods The study was conducted at the Dept. of Obstetrics and Gynecology, SN Medical College Agra (UP). High-risk patients seen in outpatient department and admitted in emergency were recruited. Women with singleton pregnancy in the age group 20-35 years having history of preterm labor, prophylactic cerclage, uterine

*Assistant Professor, Dept. of Obstetrics and Gynecology SN Medical College, Agra, Uttar Pradesh †Assistant Professor, Dept. of Obstetrics and Gynecology UP Rural Institute of Medical Sciences and Research, Saifai, Etawah, Uttar Pradesh ‡Senior Resident #Resident, Dept. of Obstetrics and Gynecology SN Medical College, Agra, Uttar Pradesh Address for correspondence Dr Ruchika Garg D1, Sulahkul Nagar Bodla Road, Agra, Uttar Pradesh E-mail: ruchikagargagra@gmail.com

362

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

malformation or currently suffering from premature pains on the basis of clinical information and evaluation of ultrasonography (USG) were included in the study. Fifty antenatal women were given 200 mg micronized sustained-release progesterone, while another 50 antenatal women were provided placebo. Daily micronized sustained-release vaginal progesterone 200 mg 12-hourly was started beyond 12-14 weeks and discontinued after 36 weeks gestation or early if they get into labor. Patients with multiple pregnancy, major fetal anomaly, allergy to progesterone, premature rupture of membrane, cervical dilation >4 cm, coexisting maternal medical disease, fetal distress and chorioamnionitis were excluded from the study. Results and discussion The incidence of preterm labor was 36% in placebo and 17.8% in progesterone group in our study (p < 0.05) (Table 1). The incidence of preterm labor was 54.9% in placebo group and 36.3% in progesterone-treated group in the study by Sibai et al.3 In the study by Fonseca et al,4 it was 28.5% and 13.8%, respectively, while it was 35.9% and 26.2% in the study by Luis Sanchez et al (Table 2). In the study by Meis et al,5 babies with birth weight <2.5 kg were 27% in progesterone-treated group and 41% in control group with relative risk (0.66), confidence interval (CI) 0.51-0.87. In our study, babies with birth weight <2.5 kg were 28% in progesteronetreated group and 54% in control group (Table 3). It was found that labor was postponed by 2-4 weeks in 88% of cases. In the study done by Johnson et al6 and Da Fonseca et al7 delivery of cases occurred at 38.6 weeks

OBSTETRICS AND GYNECOLOGY

Group A (progesterone)

Group B (placebo)

Mean age (years)

28.6 years

27.6 years

Gravida 2

24 (48%)

22 (44%)

Gravida >3

26 (52%)

28 (56%)

Class III - 20 (40%)

Class III - 28 (44%)

progesterone had significantly lower rate of necrotizing enterocolitis, intraventricular hemorrhage and need for supplemental oxygen. Dodd et al,9 found that infants with intraventricular hemorrhage were very less in progesterone-treated group. In our study, it was found that number of days of neonatal intensive care unit (NICU) stay was significantly reduced in infant delivered to progesterone-treated group.

Class IV - 30 (60%)

Class IV - 22 (56%)

Conclusion

16 (32%)

24 (48%)

18 (36%)

10 (20%)

8 (16%)

Table 1. Distribution of Women According to Profile Patient profile

Socioeconomic status Preterm deliveries

Table 2. Incidence of Preterm Labor in Progesteronetreated Group vs Placebo Study done by

Cases (progesteronetreated group)

Controls (placebo group)

Sibai et al

36.3%

54.9%

Fonseca et al

13.8%

28.5%

Luis Sanchez Ramos et al

26.2%

35.9%

Johnson et al

12.8%

40.9%

Present study (p â&#x2030;¤ 0.05)

17.8%

36%

Preterm birth complicates one in eight deliveries and remains a major cause of perinatal morbidity and mortality. Appropriate candidates should be counseled about the potential benefits of progesterone supplementation from 16 to 20 weeks up to 36 weeks of gestation to prevent preterm birth in any subsequent pregnancy. The results of current study has shown promising result in reducing the incidence of preterm birth and low-birth weight babies. References 1. Goldenberg RL. The management of preterm labor. Obstet Gynecol 2002;100(5 Pt 1):1020-37. 2. Vidaeff AC, Ramin SM. From concept to practice: the recent history of preterm delivery prevention. Part I: cervical competence. Am J Perinatol 2006;23(1):3-13.

Table 3. Birth Weight (<2.5 kg) in Progesterone Group vs Placebo Group

3. Sibai B, Meis PJ, Klebanoff M, Dombrowski MP, Weiner SJ, Moawad AH, et al; Maternal Fetal Medicine Units Network of the National Institute of Child Health and Human Development. Plasma CRH measurement at 16 to 20 weeksâ&#x20AC;&#x2122; gestation does not predict preterm delivery in women at high-risk for preterm delivery. Am J Obstet Gynecol 2005;193(3 Pt 2):1181-6.

Study done by

4. Fonseca EB, et al. J Obstet Gynecol 1990;97;149-54.

Meis et al (RR = 0.66) Present study (RR = 0.65)

Cases

Controls

27%

41%

38.02%

55%

Table 4. Mean Gestational Age in Progesterone Group vs Placebo Group Study done by

Cases (weeks)

Controls (weeks)

38.6

35.2

Da Fonseca et al

Our study

34.5

Johnson et al

and 35.2 weeks, respectively while that of controls, occurred at 37 weeks and 36 weeks, respectively. In our study, delivery of cases postponed up to 38 weeks and of controls up to 34.5 weeks (Table 4). In the study of Meis et al,8 infants treated with

5. Meis PJ; Society for Maternal-Fetal Medicine. 17 hydroxyprogesterone for the prevention of preterm delivery. Obstet Gynecol 2005;105(5 Pt 1):1128-35. 6. Johnson JW, Lee PA, Zachary AS, Calhoun S, Migeon CJ. High-risk prematurity-progestin treatment and steroid studies. Obstet Gynecol 1979;54(4):412-8. 7. American College of Obstetricians and Gynecologists. ACOG Committee Opinion. Use of progesterone to reduce preterm birth. Obstet Gynecol 2003;102(5 Pt 1):1115-6. 8. Spong CY, Meis PJ, Thom EA, Sibai B, Dombrowski MP, Moawad AH, et al; National Institute of Child Health and Human Development Maternal Fetal Medicine Units Network. Progesterone for prevention of recurrent preterm birth: impact of gestational age at previous delivery. Am J Obstet Gynecol 2005;193(3 Pt 2):1127-31. 9. Dodd JM, Jones L, Flenady V, Cincotta R, Crowther CA. Prenatal administration of progesterone for preventing preterm birth in women considered to be at risk of preterm birth. Cochrane Database Syst Rev 2013;(7):CD004947.

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

363

Obstetrics and gynecology

Term Pregnancy in an Achondroplastic Dwarf: A Case Report REKHA RANI*, SHIKHA SINGH†, SAROJ SINGH‡, URVASHI VERMA*, RUCHIKA GARG*, HARI SINGH#, DIBYA SINGH$

Abstract Achondroplasia is a rare disorder occurring in 1 in 15,000 to 1 in 40,000 live births. However, it is the commonest disorder among more than 100 different types of dwarfism. It is inherited as an autosomal dominant trait but most cases (80%) are due to mutations of fibroblast growth factor receptor 3 (FGFR3). These individuals have normal mental and sexual development and life-span may also be normal. However, problems such as pre-eclampsia, polyhydramnios, respiratory compromise, contracted pelvis necessitating lower-segment cesarean section, prematurity and fetal wastage, etc., have been reported. General anesthesia is preferred to regional anesthesia because of spinal abnormalities. The aim of this report is to describe the surgical management of these patients discussing the surgical consideration and emphasizing the difficulties encountered. Such a patient is considered high-risk in terms of anesthesia and obstetric outcome. A case of achondroplasia with pregnancy is reported. A 28-year-old achondroplastic parturient underwent cesarean section under general anesthesia for contracted pelvis. We did not encounter problems related to cesarean section. The most important point is the careful preoperative assessment. Anesthesia plan should be specified to individual basis.

Keywords: Achondroplasia, dwarfism, cesarean section, anesthesia

arious uncommon disorders present in pregnant women can create dilemma for obstetricians and obstetric anesthetists as to how to best manage these patients. Achondroplastic dwarfism is one of these disorders and the clinical management remains controversial. Achondroplasia is the commonest form of dwarfism in which a large number of cases result from spontaneous mutation. Females are affected more frequently than males. We describe a patient with achondroplasia undergoing cesarean section and discuss the anesthetic considerations in an achondroplastic individual.

CASE REPORT A 28-year-old achondroplastic dwarf female, G1P0A0, married for 2 years, reported here with complaints of

*Lecturer †Associate Professor ‡Professor and Head Dept. of Obstetrics and Gynecology #Lecturer Dept. of Radiodiagnosis $III Year Junior Resident Dept. of Obstetrics and Gynecology SN Medical College, Agra, Uttar Pradesh Address for correspondence Dr Rekha Rani Lecturer, Dept. of Obstetrics and Gynecology SN Medical College, Agra - 282 002, Uttar Pradesh E-mail: drrekha.gynae@gmail.com

364

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

amenorrhea since 8 ½ months and pain in abdomen since 1 day. On examination, her general condition was average, temperature was 37.2⁰C, blood pressure was 130/80 mmHg and pulse rate was 100/min; per abdomen 34 weeks, presentation cephalic, fetal health surveillance (FHS) was regular - 150/min, with 1/10 uterine contraction. Patient was anemic. A complete blood count showed: Hemoglobin - 8 g/dL, total leukocyte count (TLC) - 10,000/mm3, differential leukocyte count (DLC) - P62L32M03; her renal function tests (RFTs), bleeding times (BTs), clothing times (CTs) and prothrombin times (PTs) were within normal limits. She was prenatally screened with ultrasonography to rule out similar anomaly in baby. She had no history any surgery and her pregnancy had been uneventful. Physical examination revealed a 42 kg, 135 cm, normal intelligent female with large head, short limbs and mild kyphoscoliosis. P/S-NAD, except slight blood mixed mucoid discharge P/V-cervix 1 F, early effaced, head floating, membrane present, pelvis contracted. Under general anesthesia, lower-segment cesarean section was performed and an alive male baby weighing 2,600 g was delivered with Apgar score of 8 and 9 at 1st and 5th minute, respectively. Pediatrician examined the neonate and ruled out achondroplasia in baby. Patient was given oxytocin IV, misoprostol per rectally

Obstetrics and gynecology

Figure 1. Rhizomelic shortening of the bilateral femurs with metaphyseal flaring.

Figures 3 and 4. The fibula was disproportionately longer compared with tibia.

results in cephalopelvic disproportion during the later stages of pregnancy. These patients have a number of anatomical and physiological abnormalities that contribute to problems with the administration of obstetric anesthesia and performance of cesarean section. Intelligence is usually normal unless central nervous system complications develop. Achondroplastic patients have facial features that alert the anesthetists to potential problems in airway management. There are reports describing the achondroplastic patients with classical symptoms and signs of upper airway obstruction but no difficulty was encountered in our patient in intubation and she also had no respiratory discomfort postoperatively.

Figure 2. Rhizomelic shortening of the humerus with posterior bowing and an incomplete glenoid fossa.

after the umbilical cord was clamped. There was no problem encountered during the cesarean section. Her postoperative period was uneventful and her Foleys was removed on 8th and stitches were removed on 9th postoperative day. Delayed removal of catheter was done because achondroplastic dwarf patient was not able to walk without assistance. The patient and neonate were discharged on 9th postoperative day. DISCUSSION Achondroplastic dwarfs characteristically have low fertility rates; however, they often require delivery by cesarean section because the normal sized fetal head and smaller than normal maternal pelvic diameter

Postoperatively, skeletal radiographs of upper and lower limbs (Figs. 1 and 2) were done, which confirmed the diagnosis. The calvarias bones were large, whereas the cranial base and facial bones were small. The vertebral pedicles were short throughout the spine. The iliac bones were short and round, and acetabular roofs were flat. The tubular bones were short with mildly irregular and flared metaphyses. The fibula was disproportionately longer compared with tibia (Figs. 3 and 4). Prenatal diagnosis of homozygous achondroplasia can be made by mutation detection at 10-12 weeks of gestation as against 16-20 weeks by ultrasonographic examination. Ultrasonographic examination can detect shortening of long bones that is only in late pregnancy (third trimester). Prenatal diagnosis can be provided early in pregnancy by DNA-based methods on chorionic villi. Risk of recurrence in family with sporadic cases is estimated to be 1 in 443. This is said

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

365

Obstetrics and gynecology to be due to mosaicism in one of parents. If one of the parent is affected with achondroplasia the risk to offspring of recurrence is 50% for either sex. In our case mother of the patient was also affected with achondroplasia. If both parents are affected then 25% children will be normal, 50% heterozygous and 25% will be homozygous mutation. Homozygous achondroplasia is always lethal. Suggested reading 1. Bellus GA, Hefferon TW, Ortiz de Luna RI, Hecht JT, Horton WA, Machado M, et al. Achondroplasia is defined by recurrent G380R mutations of FGFR3. Am J Hum Genet 1995;56(2):368-73. 2. Chitayat D, Fernandez B, Gardner A, Moore L, Glance P, Dunn M, et al. Compound heterozygosity for the Achondroplasia-hypochondroplasia FGFR3 mutations: prenatal diagnosis and postnatal outcome. Am J Med Genet 1999;84(5):401-5.

3. Shiang R, Thompson LM, Zhu YZ, Church DM, Fielder TJ, Bocian M, et al. Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism, achondroplasia. Cell 1994;78(2):335-42. 4. Ikegawa S, Fukushima Y, Isomura M, Takada F, Nakamura Y. Mutations of the fibroblast growth factor receptor-3 gene in one familial and six sporadic cases of achondroplasia in Japanese patients. Hum Genet 1995;96(3):309-11. 5. Oberklaid F, Danks DM, Jensen F, Stace L, Rosshandler S. Achondroplasia and hypochondroplasia. Comments on frequency, mutation rate, and radiological features in skull and spine. J Med Genet 1979;16(2):140-6. 6. Modaff P, Horton VK, Pauli RM. Errors in the prenatal diagnosis of children with achondroplasia. Prenat Diagn 1996;16(6):525-30. 7. Gooding HC, Boehm K, Thompson RE, Hadley D, Francomano CA, Biesecker BB. Issues surrounding prenatal genetic testing for achondroplasia. Prenat Diagn 2002;22(10):933-40.

■■■■

Gestational Weight Gain in Obese Women Better with Program Obese women who took part in a weight management program during pregnancy gained significantly less gestational weight and had a lower proportion of large-for-gestational age (LGA) babies than obese women who received only one-time dietary advice, investigators found. Of 114 pregnant women with a body mass index (BMI) higher than 30 kg/m2, those who were randomly assigned to a group-based weight management intervention gained a mean 5.0 kg in weight from the time of randomization to 34 weeks gestation compared with 8.4 kg for women who received a single advice session from a dietician (p < 0.001), report Kimberly K. Vesco, MD, MPH, a practicing obstetrician/gynecologist and clinical investigator with the Kaiser Permanente Center for Health Research in Portland, Oregon, and colleagues. Their article was published in the September issue of Obesity.

Salpingectomy as a Primary Sterilization Procedure Salpingectomy should be the primary female sterilization procedure because it is permanent and may prevent some types of ovarian cancer that actually begin in the Fallopian tube, according to a commentary published online August 5 in Obstetrics and Gynecology. Recent research findings that ovarian cancer may frequently originate in the Fallopian tube, along with advances in technology making salpingectomy no greater risk than tubal occlusion, warrant consideration of this practicechanging move, Mitchell D. Creinin, MD, chair of obstetrics and gynecology at the University of California, Davis, and Nikki Zite, MD, MPH, associate professor of obstetrics and gynecology at the University of Tennessee, Knoxville, write in their commentary.

366

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

Obstetrics and gynecology

Highly Aggressive Small-cell Neuroendocrine Carcinoma Cervix: A Rare Case Report Taru Gupta*, Sangeeta Gupta†, Pushpa Bhatia‡, Sanjana Wadhwa#, Nupur Gupta$

Abstract Neuroendocrine tumors consist of a spectrum of malignancies that arise from the diffuse neuroendocrine cell system. Prognosis is dependent on histologic subtype and site of origin. The family of well-differentiated neoplasms (carcinoid and atypical carcinoid) is morphologically and clinically distinct from high-grade neuroendocrine carcinoma (small cell and large cell). This latter entity is closely related to pulmonary small-cell carcinoma, is highly aggressive and is generally managed with a multimodality approach including platinum-based chemotherapy. Neuroendocrine tumors primary to the gynecologic tract are still considered to be uncommon, with limited prospective data available to guide decision making. We are reporting a case of a highly aggressive small-cell neuroendocrine carcinoma cervix in a 38-year-old female with good initial response with chemotherapy and is under our follow-up.

Keywords: Neuroendocrine tumors, high-grade neuroendocrine carcinoma, platinum-based chemotherapy, small-cell neuroendocrine carcinoma cervix Case Report Mrs. X, a 38-year-old lady, P3L3 attended Gyne OPD of ESI-PGIMSR, Basaidarapur, New Delhi on 13.5.2013 with the chief complaint of irregular bleeding per vaginum since 6 months. There was history of postcoital bleeding on and off since 6 months. Her past menstrual history was of regular periods. She was P3L3 with all full-term normal deliveries and her last childbirth was 15 years back. There was no history of any contraceptive usage. There was no history of tuberculosis (TB), thyroid disorder, diabetes mellitus (DM), hypertension (HTN). She was not addicted to smoking. Her vitals were stable. There was no lymphadenopathy. Per speculum examination revealed a cauliflower growth, about 4 × 4 cm in sizes on the anterior lip of cervix. Four pea-sized growths were present on middle-third of vagina. On per vaginal examination,

*Associate Professor †Senior Consultant ‡Professor #Senior Resident $Assistant Professor Dept. of Obstetrics and Gynecology Employee State Insurance Post Graduate Institute of Medical Sciences and Research, New Delhi Address for correspondence Dr Taru Gupta Associate Professor Dept. of Obstetrics and Gynecology Employee State Insurance Post Graduate Institute of Medical Sciences and Research, New Delhi E-mail: tarugupta1971@yahoo.com

the findings of per speculum were confirmed, uterus appeared normal size with bilateral parametrium free. On per rectal examination, the rectal mucosa was free. Examination triggered active bleeding from the growth. The provisional diagnosis of cancer cervix ? cancer vagina was made. Patient was admitted and prepared for cervical biopsy and biopsy from the vaginal growth. Cervical smear for human papilloma virus (HPV) detection and typing along with the biopsy from cervical growth and vagina was taken. Patient was discharged with advice to follow-up with histopathology report. After 7 days, she reported with histopathology report showing ‘small-cell

Figure 1. M/E: Normal squamous epithelium, subepithelium shows tumor composed of small cells in sheaths (4X).

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

367

Obstetrics and gynecology

Figure 2. Immunohistochemistry: Synaptophysin.

Figure 3. Review examination with vaginoscopy showing irregular growth 4 x 4 cm present on anterior vaginal wall, 2 cm below urethral meatus, extending up to the cervix. Cervix was replaced by fungating growth 6 cm in diameter.

Cervix

P Vaginal mass

Figure 4. MRI abdomen and pelvis showing a cervical and vaginal growth.

neuroendocrine carcinoma of cervix and vaginaâ&#x20AC;&#x2122; (Fig. 1). The histopathologic diagnosis was facilitated with immunohistochemistry (IHC), which showed neuron specific enolase (NSE)-positive, chromogranin-positive,

368

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

Figure 5. PET scan whole body showing metabolically active lesions in cervix, vagina, both lung fields, axillary, mediastinal and pelvic lymph nodes and multiple skeletal lesions likely metastatic.

synaptophysin-positive, epithelial membrane antigen (EMA)-positive and carcinoembryonic antigen (CEA)positive markers (Fig. 2). Since, these tumors originate from subepithelium, the marker of epithelial tissue cytokeratin-pan antibody monoclonal (CK-PAN) was negative. Cervical smear was negative for HPV infection. She still had complaint of bleeding pervaginum on and off. There was no history of foul-smelling discharge. Her routine investigations including chest X-ray were within normal range. Review examination under anesthesia with vaginoscopy was planned. It showed an irregular growth 4 Ă&#x2014; 4 cm present on anterior vaginal wall, 2 cm below the urethral meatus, extending up to the cervix. Cervix was replaced by 6 cm fungating growth (Fig. 3). Per vaginum showed uterus multiparous size with bilateral parametrium free.

Obstetrics and gynecology Ultrasonography (USG) upper abdomen was done and showed no abnormality. On per rectum, rectal mucosa was free. Clinical staging of Ca Cx Stage IIA 2 was made. Magnetic resonance imaging (MRI) abdomen and pelvis (30/5/2013) showed a heterogeneous mass lesion of 47 Ă&#x2014; 36 Ă&#x2014; 38 mm involving anterior wall of cervix and upper two-thirds of vagina (Fig. 4). The lesion was abutting posterior bladder wall, however, fat planes were maintained. Rest of uterus and ovaries were normal. There was no evidence of lymphadenopathy or free-fluid in the pelvis. Positron emission tomography-computed tomography (PET-CT) scan (8/6/013) revealed metabolically active and bulky cervix and vagina, consistent with known primary. There were metabolically active small nodular opacities in both lung fields predominantly in subpleural regions in bilateral lungs suggestive of deposits. Metabolically active axillary, mediastinal and pelvic lymph nodes, bilateral obturator regions likely metastatic were present (Fig. 5). Metabolically active multiple skeletal lesions likely metastatic were identified. Imaging modalities staged the disease as an advanced case. Patient was planned for chemotherapy with cisplatin and etoposide. Etoposide 100 mg/m2 on Day 1, 2 and 3 and cisplatin 30 mg/m2 on Day 1, 2 and 3 was given. After three cycles of chemotherapy, response assessment with PET-CT was done, which showed good treatment response and therefore, it was decided to give three more cycles with same chemotherapy. Presently, patient has received five cycles of chemotherapy and is under follow-up. Discussion Most neuroendocrine cancers of the cervix are smallcell carcinomas, which account for up to 2% of cervical carcinomas.1 They are characterized by high mitotic rate, extensive necrosis, frequent lymphovascular space involvement (LVSI) and a strong association with HPV-18.2 Though, our case was negative for HPV infection, it was highly aggressive. These highly aggressive tumors have a prognosis that is much worse than that for stage comparable with poorly differentiated squamous-cell carcinoma of the cervix. The median age of diagnosis is in the fifth decade (range 21-87 years). The usual presenting symptom is vaginal bleeding, and a cervical mass can often be identified on examination. Some patients have an abnormal Pap smear. The diagnosis is made on cervical biopsy. The staging of neuroendocrine carcinomas (NECs) of

the cervix follows that for traditional cervical cancer. However, it is important to recognize the increased risk for lymphovascular space invasion and high rate of extrapelvic recurrences, which correlate with a poor prognosis. The mean time to recurrence was 19.9 months. Bone, supraclavicular lymph nodes and lung were the most common sites of extrapelvic disease spread. Radiographic evaluation should generally include either a CT or PET/CT scan. Early stage disease are treated with multimodality regimens; recent reports have achieved an 80% 3-year disease-free survival. Radical hysterectomy with regional lymphadenectomy remains a component of the primary management. Patients with evidence of lymphadenopathy or fluorodeoxyglucose (FDG)avid nodal basins may also be candidates for primary chemoradiation.3 Etoposide/cisplatin (EP) concurrent with pelvic radiation regimens are generally preferred over vincristine, actinomycin and cyclophosphamide (VAC)-containing regimens because they are less toxic. Combination chemotherapy (EP) in addition to concurrent radiation can be used for advanced stage and recurrent disease. While initial response rates are high (50-79%), recurrent or progressive chemoresistant disease frequently develops. The prognostic factors of the disease are advanced stage, tumor size, presence and number of lymph node metastases, pure small-cell histology.4,5 Smoking has been linked to a worse clinical outcome for small cell cervical cancer. Small-cell cervical cancers have a reported 5-year survival of 36%. Clinical stage was the only independent predictor for disease-free survival, 80% at 3 years for Stage I/II and 38% for Stage III/IV.6 For surveillance frequent clinical evaluation including symptom review and pelvic examination is appropriate. Periodic full body imaging with either CT or PET/CT to evaluate for distant metastatic disease is appropriate. Brain imaging either with head CT or MRI should be considered in presence of neurologic symptoms or pulmonary metastasis. Newer chemotherapy treatments such as temozolomide and multiple molecular targets for treatment of NECs have been identified. Potential therapeutic targets include CD56, a neural cell adhesion molecule that is expressed by neuroendocrine cancers. A monoclonal antibody for CD56, linked to the cytotoxic compound DM-1 is in phase II trials. Src kinase, a tyrosine kinase, which has differential expression in both small cell and nonsmall-cell lung cancer, is another potential target.

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

369

Obstetrics and gynecology The Hedgehog pathway and Bcl-2 represent other areas of investigation. Conclusion To conclude, small-cell neuroendocrine tumor cervix is a rare tumor, accounting for up to 2% of all cervical carcinomas. It is closely related to pulmonary smallcell carcinoma, is highly aggressive and is generally managed with a multimodality approach. It has poor prognosis. Treatment for advanced stage is with chemoradiation.

Acknowledgments ÂÂ Dr Chandok, Dr Onkar Kaur - Senior Pathologist, ESIPGIMSR, New Delhi ÂÂ Dr Kohli, Dr Anu Singhal - Senior Radiologist, ESIPGIMSR, New Delhi.

References 1. Gardner GJ, Reidy-Lagunes D, Gehrig PA. Neuroendocrine tumors of the gynecologic tract: A Society of Gynecologic

Oncology (SGO) clinical document. Gynecol Oncol 2011;122(1):190-8. 2. Stoler MH, Mills SE, Gersell DJ, Walker AN. Smallcell neuroendocrine carcinoma of the cervix. A human papillomavirus type 18-associated cancer. Am J Surg Pathol 1991;15(1):28-32. 3. Lee YJ, Cho A, Cho BC, Yun M, Kim SK, Chang J, et al. High tumor metabolic activity as measured by fluorodeoxyglucose positron emission tomography is associated with poor prognosis in limited and extensive stage small-cell lung cancer. Clin Cancer Res 2009;15(7):2426-32. 4. Viswanathan AN, Deavers MT, Jhingran A, Ramirez PT, Levenback C, Eifel PJ. Small cell neuroendocrine carcinoma of the cervix: outcome and patterns of recurrence. Gynecol Oncol 2004;93(1) 27-33. 5. Chan JK, Loizzi V, Burger RA, Rutgers J, Monk BJ. Prognostic factors in neuroendocrine small cell cervical carcinoma: a multivariate analysis. Cancer 2003;97(3): 568-74. 6. Pecorelli S, Zigliani L, Odicino F. Revised FIGO staging for carcinoma of the cervix. Int J Gynaecol Obstet 2009;105(2):107-8.

■■■■

ÂÂ ÂÂ

ÂÂ ÂÂ ÂÂ ÂÂ ÂÂ ÂÂ ÂÂ ÂÂ ÂÂ ÂÂ

370

Women Above 65 to Take Extra Care of their Health Women aged 65 and above should take low-dose aspirin routinely to prevent heart attack and paralysis. All women are urged to exercise a minimum of 30 minutes/day, but women who need to lose weight or maintain weight loss are now advised to engage in 60-90 minutes of moderate-intensity activity on most, or preferably all, days of the week. A heart-healthy diet should be rich in fruits, whole grains and fiber foods with a limited intake of alcohol and sodium. Saturated fat should be reduced to less than 7% of calories. Women at very high-risk for heart disease should try to lower their LDL ('bad') cholesterol to <70 mg/dL. Women aged 65 and over should consider taking low-dose aspirin on a routine basis, regardless of their risk. Aspirin has been shown to prevent both heart attacks and stroke in this age group. The upper dose of aspirin for high-risk women is 325 mg/day. Hormone replacement therapy, selective estrogen receptor modulators nor antioxidant supplements such as vitamins C and E should be used to prevent heart disease. Folic acid should also not be used to prevent cardiovascular disease. Women should eat oily fish or some other source of omega-3 fatty acids at least twice a week. Women should not only quit smoking but should use counseling, nicotine replacement or other forms of smoking cessation therapy.

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

ORTHOPEDICS

Atypical Fracture of Femur: Likely Related to Long-term Bisphosphonate Use Muhammed Zohaib Ghatala*, Shriraam Mahadevan†

Abstract Bisphosphonates are widely prescribed and highly effective at limiting the bone loss that occurs in many disorders characterized by increased osteoclast-mediated bone resorption, including senile osteoporosis in both men and women. Although, they are generally well-tolerated, potential adverse effects may limit bisphosphonate use in some patients. Optimal use of bisphosphonates for osteoporosis requires adequate calcium and vitamin D intake before and during therapy. Long-term adverse effects of bisphosphonate therapy include osteonecrosis of the jaw and atypical fractures of femur. We report a case of a 78-year-old man who presented with pain and inability to move the left thigh from 11 am on the day of admission. He was diagnosed to have transverse subtrochanteric fracture of the left femur with relatively thick cortex. He had been religiously taking alendronate (a bisphosphonates) 70 mg once a week along with calcium preparation (elemental calcium 500 mg with cholecalciferol 250 units twice-daily) for 5 years. With this background of a ‘chalk stick’ like transverse fracture of the subtrochanteric region of femur in an otherwise healthy elderly man, an ‘atypical fracture of femur’ from long-term use of bishphosphonates was the likely cause.

Keywords: Bisphosphonates, senile osteoporosis, adverse effects, atypical fractures of femur, alendronate

isphosphonates are widely prescribed and highly effective at limiting the bone loss that occurs in many disorders characterized by increased osteoclast-mediated bone resorption, including senile osteoporosis in both, men and women, glucocorticoidassociated osteoporosis and malignancies metastatic to bone. Although, they are generally well-tolerated, potential adverse effects may limit bisphosphonate use in some patients. Long-term adverse effects of bisphosphonate therapy include osteonecrosis of the jaw and atypical fractures of femur.1

The World Health Organization (WHO) fracture risk assessment algorithm, to determine absolute fracture risk in patients with low bone mass, is a useful tool for clinicians to identify patients who are most likely to benefit from pharmacological intervention and may facilitate shared decision-making, especially when patients are wary of the rare but serious adverse effects that have recently been described for this class of drugs.1

*Senior House Officer Dept. of Internal Medicine †Consultant Endocrinologist Sundaram Medical Foundation, Anna Nagar, Chennai, Tamil Nadu Address for correspondence Dr Muhammed Zohaib Ghatala 67-A, J Block, 3rd Street, Anna Nagar, Chennai - 600 040, Tamil Nadu E-mail: zghatala@gmail.com

372

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

CASE REPORT A 78-year-old gentleman presented with pain and inability to move the left thigh from 11 am on the day of admission. He was trying to get-up from the chair when he heard a cracking noise in the left mid-thigh. At admission, his vitals were stable and the X-ray showed transverse subtrochanteric fracture of the left femur with relatively thick cortex (Fig. 1). On further evaluation, there was no history of pain in the affected or the other lower limb preceding the fracture. He had no chronic comorbid conditions like diabetes, hypertension or asthma. There was no prior history of fracture or any family history of fracture. He had never

Figure 1. Subtrochanteric fracture of left femur.

orthoPEDICS used corticosteroids or alternative medications in the past. He was evaluated for nonspecific low backache 5 years before presentation, when his X-ray lumbosacral spine and hip were normal. Based on a dual-energy X-ray absorptiometry (DEXA) scan report of T score2.2 in the femoral neck (left side), he was placed on alendronate 70 mg once a week. He had been taking it religiously for 5 years along with calcium preparation (elemental calcium 500 mg with cholecalciferol 250 units twice-daily) for 5 years. Serum chemistries for renal and liver functions were normal. Bone mineral profile showed calcium 9.1 mg/dL (8.5-10.5 N), phosphorus 3.8 mg/dL (3.5-5.5 N), 25-hydroxyvitamin D 30.2 ng/mL (sufficiency >20 ng/mL) and intact parathyroid hormone (PTH) 45.2 pg/mL (9.8-72 N). Serum alkaline phosphatase (total) was relatively low at 92 IU/L (90-140). With this background of a ‘chalk stick’ like transverse fracture of the subtrochanteric region of femur in an otherwise healthy elderly man, an ‘atypical fracture of femur’ from long-term use of bishphosphonates was the likely cause. After the fixation surgery, he

was planned for teriparatide therapy. However, due to affordability issues he denied teriparatide therapy and was discharged on calcium and vitamin D preparation.2 Conclusion

Osteonecrosis of the jaw and atypical femoral fracture are complications of long-term bisphosphonate use. It is advised to stop bisphonates after 5 years of use, as there is residual benefit on bone mineral density (BMD) and fractures. They should be evaluated with DEXA scan every 2 years and restarted if needed. ReferenceS 1. Kennel KA, Drake MT. Adverse effects of bisphosphonates: implications for osteoporosis management. Mayo Clin Proc 2009;84(7):632-7; quiz 638. 2. Composton J, Bowring C, Cooper A, Cooper C, Davies C, Francis R, et al; National Osteoporosis Guideline Group. Diagnosis and management of osteoporosis in postmenopausal women and older men in the UK: National Osteoporosis Guideline Group (NOGG) update 2013. Maturitas 2013;75(4):392-6.

■■■■

Tranexamic Acid may Improve Orthopedic Surgery Outcomes Tranexamic acid appeared to decrease the need for blood transfusions without increasing the risk for thromboembolic events or renal failure in patients undergoing joint replacement surgery, a new study shows. Jashvant Poeran, MD, PhD, from the Institute of Healthcare Delivery Science in the Mount Sinai Hospital System in New York City, and colleagues present the results of their retrospective cohort study in an article published online August 12 in the BMJ. The population-based study included 8,72,416 total hip and knee arthroplasty procedures. The investigators were able to control for individual-level factors as well as hospital clusters in multivariable analyses.

FDA Okays Submicron Diclofenac for Osteoarthritis The US Food and Drug Administration (FDA) has approved diclofenac capsules (Zorvolex, Iroko Pharmaceuticals) for the management of osteoarthritis (OA) pain, the company announced today. OA pain is the second indication for Zorvolex, first approved by the FDA in October 2013 for mild-to-moderate acute pain in adults, as reported by Medscape Medical News. The recommended dosages are 18 or 35 mg 3 times per day for acute pain and 35 mg 3 times daily for OA pain.

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

373

Pediatrics

A Prevalence Study on Myopia Among School Going Children in a Rural Area of South India K Rajendran*, Mohammed Haneef†, Kailas Chandrabhanu‡, Krishnamoorthy#, Manil Muhammed$, Ratheesh T Pillai¶

Abstract Introduction: Myopia or short sightedness is a type of refractive error in which parallel rays coming from infinity are focused in front of retina when accommodation is at rest. It is a vision condition in which close objects are seen clearly, but objects farther away appear blurred. Myopia occurs if the eyeball is too long or cornea has too much curvature. Myopia is a common vision condition affecting nearly 30% of population. It occur more frequently among school children aged between 8 and 12 years. Because the eye continues to grow during childhood, it typically progresses until about age 20. Aims and objectives: This study aimed at finding the prevalence of myopia among the students aged 10-12 years of a school in a rural area of Kollam and the influence of environmental factors, indoor activities like reading, computer games and outdoor activities and genetic factors in development of myopia. Materials and methods: Study population included students of a nearby school. Students of age >10 years were considered, so students of 5th, 6th and 7th standard students were selected. Each of the division was considered as one strata and simple random sample of clusters had been selected from each standard. All the students of the selected division were selected to sample. Thus, a total of 68 students from that school were taken for the study. The study setting was in a rural area in Kollam district of Kerala. Results: Snellen’s chart along with unilateral vision blinders were used for evaluating vision. Details of factors influencing were obtained using a pretested questionnaire in a pilot study. The prevalence of myopia in school children of rural community in Kollam was found to be 51.47% in which a group of hidden myopic of 43.1% were discovered.

Keywords: Myopia, refractive error, diopter

yopia is a refractive error, which means that the eyes do not bend or refract light properly to a single focus to see images properly. In myopia, close objects look clear but distant objects look blurred. It is an eye focusing disorder, not an eye disease. Myopia is inherited and is often discovered in children when they are between the ages 8 and 12 years old. During the teenage years, when the body grows rapidly, myopia may become worse. Between the ages 20 and 40, there is usually little change. Myopia can also occur in adults.1 The incidence of myopia with in sampled population often rises with age, country, sex, race, ethnicity, occupation environment and other factors. The prevalence of myopia has been reported as high as 70-90% in some Asian countries.1-3

*Professor and Haed, Dept. of Pediatrics †Professor and Head, Dept. of Ophthalmology ‡Professor, Dept. of Pediatrics #Assistant Professor, Dept. of Ophthalmology $Assistant professor, Dept. of Pediatrics ¶Associate Professor Azeezia Institute of Medical Sciences and Research Center Meeyannoor, Kollam, Kerala Address for correspondence Azeezia Institute of Medical Sciences and Research Center Meeyannoor, Kollam - 37, Kerala E-mail: medicalcollge@azeezia.com

374

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

In India, up to 41% of adult population is myopic to 1D and up to 80% to 0.5D. Myopia occurs more frequently below the age of 20 years. Risk of myopia is increased particularly in those children who have a reading habit, increased indoor activities and family history. Close reading at a distance <30 cm and continuous reading for >30 minutes and in a low illumination adds upon the progression of myopia. The risk of development of myopia further increases with the habit of reading in supine position.3 There is an increased incidence of myopia among students. Alteration in visual power is common in age group 10-12 years. Students are found to be associated with lot of near work and prolonged accommodation. So, we were keen to observe risk factors that increase the incidence of myopia in this age group. Myopia is more common in children who are constantly engaged in indoor activities like watching TV, computer, mobile and videogames. Incidence of myopia is more in children who watch TV and use computer in a low illumination. Lower levels of outdoor activities in children increase the risk of myopia. Unhealthy reading habits like reading in supine position at a distance >30 cm and in a low illumination. Genetics also play an important role in development of myopia.

Pediatrics Myopia is a common vision condition affecting nearly 30% of population. It occur more frequently among school children aged between 8 and 12 years. Because the eye continues to grow during childhood, it typically progress until about age 20. However, myopia may also develop in adult due to visual stress or health condition such as diabetes.2-5

Visual acuity was tested using Snellen`s chart. All students were interviewed by using self-administered questionnaire. Students were placed 6 m from Snellen’s chart and asked to read the chart. Each eye was tested separately. From the findings of this, students were grouped as myopic and nonmyopic. This is to correlate the habits and their myopic stage.

Types of myopia

Students who are not having 6/6 vision for at least one eye were considered as myopic.

ÂÂ Etiological classification: Axial myopia, curvature

myopia, positional myopia, index myopia and myopia due to excessive accommodation.

ÂÂ Clinical classification: Congenital myopia, simple

myopia, pathological myopia and acquired myopia.

AIMS AND OBJECTIVES This study aimed at finding the prevalence of myopia among the students aged 10-12 years of a school in a rural area of Kollam and the influence of environmental factors, indoor activities like reading, computer games and outdoor activities and genetic factors in development of myopia and find the influence of unhealthy reading habits like reading in supine position, in low illumination at a near distance for >30 minutes in development of myopia. MATERIAL and METHODS Study population included students of a school in Kollam district, Kerala, India. Students of age >10 years were considered, so students of 5th, 6th and 7th standard students were selected. Sample size, n = 4PQ/L^2

= (4 × 60 × 40)/(12 × 12)

= 67

We selected 68 students to equalize the number of boys and girls. P = Prevalence rate; Q = 100-P L = Allowable error of P (20%)

Sampling Technique Each of the division was considered as one strata and simple random sample of clusters had been selected from each standard. Thus, we took 5th, 6th and 7th standard students. Each standard consists of 3 divisions each with 45-50 students. A division was selected at random from all the classes. All the students of the selected division were selected to sample. Thus, a total of 68 students from that school were taken for the study.

Results From the study conducted, it was found that the prevalence of myopia is 51.47%. According to our study, the significant risk factors were: ÂÂ Reading in supine position ÂÂ Reading books at a distance >30 cm. ÂÂ Watching TV in low illumination ÂÂ Lower levels of outdoor activities

In a study of 68 students, we found that 35 students were myopic. Among the 35 myopic students, 20 are females and 15 are males (Figs. 1 and 2). We found that only 10 students were using spectacles. The rest did not use spectacles and had not approached the eye clinic before. Twenty-five students were having undiagnosed myopia. The cause of this hidden group was due to lack of awareness or due to poor parental education and lack of proper care and attention given to the children and may be due to lack of healthcare facilities in the community. Most of the cases of myopia in children can be detected in the school by the teachers, if they give proper attention and care. A properly illuminated and ventilated class is a necessity and the school environment should be such that it helps in proper development of health of the child. Here we found that, the class rooms were not properly illuminated and ventilated and they were also overcrowded. The student in the last row was not able to see the blackboard due to the above-said problem. Proper awareness guidelines and medical camps should be conducted in school on myopia, so as to prevent and also detect new cases of myopia (Fig. 3 and 4). After the interview, students were found to have many risk factors which contribute to development of myopia as well as many factors, which prevent the incidence. In our study, we found that, girls were more myopic than boys, it was true but our hypothesis was not proved since p value is >0.05. In our study, we found

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

375

Pediatrics Time spent for continuous reading >30 minutes

35.5

33.5 33

33 32.5 32

Yes

No. of students

Females Males

Myopic

Yes

Figure 2. Gender distribution of myopia.

Myopic (No) Myopic (Yes)

No. of students

12 10 8 6

4 2 0 >4

2-4

Myopic

Yes

Time spent for continuous reading

Figure 1. Frequency of myopia.

Valid myopia

Time spent for reading in a day (hours)

Figure 3. Frequency of myopia with reading duration.

that the relation between myopia and family history had no significance. It may be because of number of students having family history of myopia was less in our study (Fig. 5). Indoor activities like watching TV or looking at computer at a near distance of <30 cm

376

34.5

No. of students

Time spent for continuous reading <30 minutes

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

Figure 4. Relationship between myopia and continuous reading.

may cause eye strain and reduced blinking rate, signs of which include blurred vision and red or watery eyes. About 5% of population is light sensitive, experiencing discomfort from flickering light of specific frequency, colors and patterns. Some students get headache from spending excessive time in front of TV or computer. To avoid some of these problems, it is advisable not to watch TV in a dark room, to sit a little further from the TV, to angle the computer screen straight ahead and to use antiglare screen. Very close viewing of TV or computer screen may slightly increase the temperature of eye tissue due to electromagnetic radiation from screen (Figs. 7 and 8). Playing mobile games for long time induces greater stress on the eye as mobile screen is so small and greater stress is needed to play the game. Many of the parents are not aware of these side effects that mobile phones can make, so let their children to play with these for a longer period of time. Unhealthy reading habits have an influence in the development of myopia. This was proved by our study. Unhealthy reading habits followed by children like reading in low illumination at a near distance and for longer duration add on the progression of myopia. It has been proposed that hyperopic defocus induced by accommodative lag during near work stimulate eye growth, since imposed hyperopic defocus is a powerful stimulus for eye growth. Attempt to decrease myopic progression by decreasing the need for accommodation or accommodative lag by providing clear vision over a range of viewing distance has shown clinical significance. Reading in supine position

Pediatrics Myopic (No) 18

10 5

Father, mother & siblings

1 1

Mother & siblings

Father & siblings

2 Father & mother

None

Siblings

1 1

Mother

Father

No. of students

14 10

Watching TV distance <30 cm

16 12

Watching TV distance >30 cm

Myopic (Yes)

Yes

Myopic Watching TV distance

Figure 7. Relationship between myopia and television watching. Myopic (No) Myopic (Yes)

Family member wearing spectacle

Figure 5. Frequency of myopia with family history.

Reading distance >30 cm

Reading distance <30 cm

No. of students

30 25

20 15 8

5 14

10 5 0

No. of students

1-2 <1 Computer duration (hours)

Figure 8. Relationship between myopia and computer use.

1 No

3 1

Myopic

Yes

Reading distance

Figure 6. Relationship between myopia and reading distance.

increases the chance of being myopic. Multiple reading style increases the stress on eye muscles, to overcome the stress they tend to read at a close distance. A child who habitually reads while lying on left side will probable develop more myopia in left side than in right eye because the left eye is more closer to the book and vice versa. The lengthening of eyeball that results from the stretching allows reading to be done with lens focusing effort and is the way of revealing the stress of prolonged close work. The importance of good lighting is that it causes the pupil to become smaller, requiring less accommodation. Parents are not properly aware of possible problems that can occur due to unhealthy reading habits. It may possibly be due

to poor education and lack of health professionals to properly guide them. Students who spent more time for outdoor activities have less chances of development of myopia because they spent less time for near work. DISCUSSION From our study, it was found that the prevalence rate of myopia among the rural school children was 51.47%. Our study found some relationship between environmental factors like indoor activities (watching TV, computer, mobile phone playing, etc.) and low levels of outdoor activities and unhealthy reading habits with myopia. It was found that prevalence of myopia was 8.6% among school children in South India. In another study, it was found that the prevalence of myopia increased from 34% in 2,000 to 59% in 2005. In study 11, it was found that 2,317 children in age group of 5-10 years showed a prevalence of 14.02%. In study 13, it was

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

377

Pediatrics found that 12,800 school children of age group 5-15 years brought out a prevalence of 45.7%. But in our study, we found that the prevalence is 51.47%. The reduction in prevalence of myopia is due to regional variation and due to the study conducted in rural area.1 It was found that there were no significant difference in myopia between girls and boys among Indian school children. In study 10, it was shown that prevalence of myopia in school children was 65.03%. Prevalence of myopia was more in females (60.7%) and less (39.3%) in males. In study 12, prevalence of myopia among girls was more than that of boys. According to our study, there were no significant relationship between sex and myopia (prevalence of myopia among girls is 57.17% and among boys is 42.83%). Our hypothesis is true that the prevalence of myopia is more among girls than boys. But, it was not proved because; now-a-days, boys are more interested in indoor activities like playing mobile games, computer, etc. than outdoor activities.2,3 The prevalence of myopia is 52-60%. It is associated with increasing educational pressure combined with life changes, which have reduced the time children spend outside. In study 2, it was proved that higher levels of outdoor activities were associated with more hyperopic refraction and lower myopia in 12 years old students. According to our study, we found that the prevalence of myopia decreases with increasing levels of outdoor activities. This may be due to higher outdoor activities were associated with more hyperopic refractions and lower myopia. Increased outdoor activities during summer months decrease eye growth in children.4 ÂÂ A study on myopia among school children in India

was done by medical students of Al-Ameen Medical College. In the study conducted from 2003 to 2006 among 549 students (279 boys and 270 girls), it was found that prevalence of myopia was 8.6% among school children in South India.1

ÂÂ In a study conducted in Sydney, the relationship

school children in Kuala Lumpur children. In this study among 749 students aged between 7-18 years (49.7% boys and 50.3% girls), for right eye, 15.1% of girls are myopic and 16.9% of boys were myopic. For left eye 18.8% girls and 16.45% boys are myopic. So, the prevalence was 16%. It was found that there were no significant differences in myopia between girls and boys among Indian school children.3 ÂÂ A

study on “Myopia-major health issue among school children in East Asia” published by The Lancet; it was found that the prevalence of myopia was 52-60% in school children in East Asia. It was associated with increasing educational pressure combined with life changes, which have reduced the time children spend outside.4

ÂÂ A study on “Prevalence of myopia in Taiwanese

school children” was done by Dept. of Ophthalmology, National Taiwan University. This study was conducted from 2000 to 2005 among school children aged between 16 and 18 years. It was found that the prevalence of myopia increased from 34% in 2000 to 59% in 2005.5

ÂÂ A

study on relationship of reading habit and prevalence of myopia was conducted by Dept. of Ophthalmology, Quassim University. In this study undertaken from 2000 to 2003 among 320 students aged 7-12 years, it was found that those who read book at a distance >30 cm for >30 minutes in low illumination and in supine position were more prone to develop myopia. Prevalence was found to be 46%.6

ÂÂ A study on prevalence of myopia in children with

family history of myopia by Dept. of Ophthalmology, Singapore University, it was found that children with family history of myopia were more prone to myopia.7

ÂÂ A study on “Reading, writing, working on computer

or watching television and myopia” by Dept. of Ophthalmology, Pomeranian Medical University, Poland among 5,865 school; it was proved that myopia occurs more often in those who read and write >2 hours/day, work 0.8 hours/day on computer and watch TV >2 hours/day.8

between near, mid-working distance and outdoor activities with prevalence of myopia was evaluated. In the study conducted from 2003 to 2005 among 2,367 students, it was proved that higher levels of outdoor activities were associated with more hyperopic refraction and lower myopia in 12 years old students. Students with higher levels of near work and lower levels of outdoor activities had the least hyperopic mean refraction (+0.27 D), 95% confidence interval (CI), 0.02-0.52.2

ÂÂ In a study on prevalence of myopia in school children

ÂÂ A study was conducted in Kuala Lumpur; on

ÂÂ In study on prevalence of myopia in primary school

association between myopia and gender in Indian

378

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

by Dept. of Community; National University of Singapore, it was proved that prevalence of myopia was more in the cities than in the countryside. The prevalence of myopia in the city was 19.3% and 6.6% in the countryside.9 children of Qazuin University of Iran by Mohammed

3 Dimensional Approach To Win Over Diabetes

Lowers FPG & HbA1c

Sustained Improvement In Glycaemic Control

2014

Delays Insulin Therapy

Pediatrics Nijad, Shafaq Ali Rahmath and Mohammed Baraka showed that prevalence of myopia in school children was 65.03%. Prevalence of myopia was more in females (60.7%) and less (39.3%) in males.10 CONCLUSION It was found that the prevalence of myopia in school children of rural community in Kollam was found to be 51.47% in which a group of hidden myopic of 43.1% were discovered. The main risk factors which add to the incidence of developing myopia are reading books at a distance less than 30 cm, reading in supine position and watching TV in low illumination. Higher levels of outdoor activities will decrease the development of myopia. Further studies including other environmental and genetic etiologic factors of myopia are expected. REFERENCES 1. Gogate P, Soneji FR, Kharat J, Dulera H, Deshpande M, Gilbert C. Ocular disorders in children with learning disabilities in special education schools of Pune, India. Indian J Ophthalmol 2011;59(3):223-8.

2. Naidoo KS, Jaggernath J. Uncorrected refractive errors. Indian J Ophthalmol 2012;60(5):432-7. 3. Basu M, Das P, Pal R, Kar S, Desai VK, Kavishwar A. Spectrum of visual impairment among urban female school students of Surat. Indian J Ophthalmol 2011;59(6):475-9. 4. Mark A, Jung L, Chintal K. The Lancet Journal 2009;379(2):123. 5. Chen AH, Norazman FN, Buari NH. Comparison of visual acuity estimates using three different letter charts under two ambient room illuminations. Indian J Ophthalmol 2012;60(2):101-4. 6. Mujad F, Sawad M, Jazir A, Al-Malik H. Oman J Ophthalmol 2011;4(2):57. 7. Anamaneni S, Bindu H, Reddy KP, Vishnupriya S. Am J Ophthalmol 2005;4(3):213. 8. Jenny M.Ip, Seang-Mei Saw, Kathryn A. Rose, Ian G M Morgan, Annette. Kifley, Jie Jin Wang, et al. Euro J Sci Res 2006;28(2):174. 9. Mitchell GL, Moeschberger ML, Jones LA, Zadnik K. Br J Ophthalmol 2009;15(2):69 10. M ohammed N, Ali Rahmath S, Mohammed B. Journal of IMA 2007;105(4):169.

■■■■

ÂÂ A new study by researchers from Massachusetts General Hospital noted that among cannabis-using

adolescents undergoing treatment for substance abuse, 40% displayed withdrawal symptoms, a hallmark of drug addiction. The study was published in the Journal of Addiction Medicine.

ÂÂ An epidemiological study, published in the journal Epidemiology, has suggested that exposure to certain

phenols during pregnancy, especially parabens and triclosan, may disrupt growth of boys during fetal development and the first years of life. Bisphenol A, however, was not associated with any definite modification in growth.

380

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

Respiratory Infections

Respiratory Problems Among Smokers in a Rural Area in South India: A Pilot Study Anil Vijayakumar*, K Sreekanthan*, A Belicita*, Rajendra*

Abstract Background: Smoking is a practice in which a substance, most commonly tobacco, is burned and the smoke is tasted or inhaled and often forms a habit hard to break because tobacco contains nicotine, which is highly addictive. Cigarette smoking is the single most important identifiable etiological agent in chronic obstructive pulmonary disease. Aims and objectives: To find out the prevalence of respiratory problems among smokers and compare the respiratory problems with duration of smoking, socioeconomic status, occupation, number of cigarettes. Also find out the percentage of persons who are willing to quit the habit of smoking. Material and methods: Male smokers above the age of 35 years residing in Pooyapally, a rural area at Kollam were selected as study area. Simple random sample of smokers above the age of 35 were selected. Sample size was 64. Data was collected by interview schedule. Conclusion: At present, smoking has become a vital problem among the people. The number of adults who have the habit of smoking has increased in the recent years. Now-a-days, people begin the habit of smoking at a very young age. The average age of habit of initiation is considered to be 20 years. In spite of knowing the complications they still continue with the habit of smoking. Smoking can lead to respiratory complications like COPD, aggravation of bronchial asthma, lung cancer and various respiratory infections. It is necessary to make the people aware of the respiratory complications they may have to face in future life and also about the quitting patterns.

Keywords: Smoking, tobacco, pulmonary disease

moking is a practice in which a substance, most commonly tobacco, is burned and the smoke is tasted or inhaled and often forms a habit hard to break because tobacco contains nicotine, which is highly addictive. Cigarette smoking is the single most important identifiable etiological agent in chronic obstructive pulmonary disease (COPD). However, only 10-20% of smokers develop clinically significant COPD; in general smoker have greater risk of developing COPD. Cigarette smoke harms respiratory system through two means-smoke and tar. Four thousand harmful chemicals produced by the combustion of tobacco leads to clogging of hair like cilia along the nasal passage and trachea and when cilia slow down mucus is not passed and gets clogged along trachea, which produces smokers cough. Smoking is becoming a very common habit among all age groups. In spite of statutory warnings, a number

*Associate Professor â&#x20AC; Professor Dept. of Medicine Azeezia Institute of Medical Sciences and Research Center, Meeyannoor, Kollam, Kerala Address for correspondence Azeezia Institute of Medical Sciences and Research Center Meeyannoor, Kollam - 37, Kerala E-mail: medicalcollge@azeezia.com

of people continue to smoke cigarettes. Besides causing irreversible damage to their bodies, they pollute the air around and foster passive smoking. The effects of smoking on the respiratory system are formidable. Respiratory diseases associated with smoking may be related to factors such as age, socioeconomic status, number of cigarettes smoked/day, duration of smoking, occupation, etc. Prevalence of respiratory diseases associated with smoking in developing countries is as high as 65-75%. In developed countries it is 54%. In India, more than 60% of respiratory diseases are linked to smoking habits of the persons. Risk of development of respiratory problems increases with increase in number and duration of smoking. It may also be high in lower socioeconomic status due to lack of awareness among rural population. In developing country like India, 90% of COPD patients have history of continuous smoking, which is the single most identifiable etiological agent in COPD. The relative risk of developing lung cancer increases about 1- to 3-fold by long-term passive exposure to cigarette smoking. Lung cancer death rate is related to the total amount of cigarette smoked such that the risk is increased 60- to 70-fold for a man smoking

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

381

Respiratory Infections

Quitting of smoking can reduce the risk of developing respiratory problem to half. But, changes in the lung due to tobacco are not completely reversible. The adverse health effects of smoking on the respiratory system can be COPD, increased severity of asthma, various respiratory infection, lung cancer, etc. A person who has history smoking over 5 years or more can develop above-mentioned complication in later life. Socioeconomic status, occupation, duration of smoking, number of cigarettes smoked has effect on respiratory problems associated with smoking. Aims and ObjectiveS The objective of the study was to find out the prevalence of respiratory problems among smokers, to compare the respiratory problems with duration of smoking, socioeconomic status, occupation, number of cigarettes smoked and to find out the percentage of persons who are willing to quit the habit of smoking. MATERIAL and METHODS Male smokers above the age of 35 years residing in Pooyapally, a rural area at Kollam were selected for the study. A simple random sample of 64 persons was selected by house-to-house visits. Sample size was calculated with the allowable error of 5%. A pre-tested interview schedule was applied to collect the data.

occupation has a significant effect on duration of smoking. Development of respiratory problems increases with number of cigarettes smoked per day, as number of cigarettes increases, nicotine load on the lungs increases, leading to severe respiratory problems. Duration of smoking has also a significant effect on development of respiratory problems, as duration increases time of exposure of lungs to smoke increases (Fig. 1). Relation between socioeconomic status and respiratory problems are insignificant because now-a-days, men are highly educated and they are more conscious about their health. They are also aware of the complications of cigarette smoking (Fig. 2). There exist a significant relation between socioeconomic status and duration of smoking since people in upper socioeconomic classes are well-educated and

There exists a significant relation between occupation and cough, since laborers are mainly uneducated and are unaware of the complications of smoking and also

382

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

20 15

15 10

5-10

10-20

>20

Duration of smoking (years)

Figure 1. Frequency on duration of smoking.

Any problem (No) Any problem (Yes) 30 No. of persons

From the study, it was found that there is high prevalence (76.5%) of respiratory problems among smokers above 35 years of age. The risk factors for the development of respiratory problems are occupation, number of cigarettes smoked and duration of smoking.

An individual who smokes more than 5 cigarettes/day is considered as a smoker. A person having the habits of smoking over a period of 5 years or more can have complication. All 64 persons were interviewed with questionnaire by four group members in 4 days. Results

30 No. of persons

two packs a day for 20 years as compared to a nonsmoker. Passive smoking is also a cause for respiratory disease. Complication due to smoking is more seen in older age (above 40 years) due to increased duration of smoking and more exposure of lung to smoke.

25 20 15

15 10

5 1

Upper middle Lower middle

Upper lower

Lower

Socioeconomic status

Figure 2. Relationship between socioeconomic status and any respiratory problem.

Respiratory Infections

SES upper middle SES lower middle

20 18

SES upper lower SES lower

No. of persons

16 14 12 10 8

DISCUSSION

6 4 2 0

5-10

10-20

>20

Duration of smoking (years)

Figure 3. Socioeconomic status and duration of smoking.

Occupation laborer Occupation business

No. of persons

Occupation others

Occupation Govt./Pvt. employee

5-10

10-20

>20

Duration of smoking (years)

Figure 4. Relationship between occupation and duration of smoking.

40 35

35 29

No. of persons

30 25 20 15 10 5 0

People who were willing to quit the habit of smoking were only 45%. It indicates that tobacco addiction is hard to break (Fig. 5). In our study population, only 9.4% of people attended health education classes regarding hazards of smoking. This may be due to lack of time since they had to strive for their livelihood.

Yes Willing to quit smoking

Figure 5. Frequency of persons willing to quit smoking.

they know about the hazards of smoking (Fig. 3). Occupation had a significant relation on frequency and duration of cough. This is because people claim that smoking can reduce the stress during their work (Fig. 4).

In a study, incidence of COPD among smokers was 50%. In our study, it was 76.65%. The first study was done in both younger and older age group. Development of COPD is more common in older age group due to long-term exposure to smoke. And prevalence is less in younger age groups. We selected individuals above age of 35. The area we selected is a rural area. This may be the reason why our prevalence became high. In a prevalence study, 62% of smokers belonged to poor socioeconomic status. In our study, 60% belonged to poor socioeconomic status. Both the values are nearly same. Both studies were conducted in rural areas. Peoples in poor economic status will be less aware of the hazard effect of smoking due to their lack of education and attitude. In a study, 59% of continuous smokers developed COPD in 25 years. From our study, it is found that 57% smokers developed COPD in 15 years. Values are nearly the same but in our study group COPD developed earlier. This may be because even after the appearance of symptoms, they ignore it and continue their chronic smoking. In a prevalence study, 48% persons who smoked more than 15 cigarettes/day developed respiratory problems earlier. In our study, it was 50% which is imperatively the same. In both studies, the study groups were of age more than 40 years and the study was conducted in a village area were laborers are involved in smoking. In a study, it was found that 32% of all smokers in the study group were laborers having consequent respiratory problems. In our study, it was 44%. Referred study was conducted in an urban area. Our study was conducted in a rural area were most people were heavy workers. This may be the reason for difference in prevalence of smoking and associated respiratory problems in heavy workers. Most heavy workers claim that smoking reduces their work load. This can be considered to be the reason for increased prevalence of smoking among them. In a case-control study, it was found that 82% cases of asthma were aggravated by smoke. In our study,

Indian Journal of Clinical Practice, Vol. 25, No. 4, September 2014

383

Respiratory Infections it was found to be 84%. This apparent similarity can be attributed to the pathological changes caused by smoking aggravates asthma.