Indian journal of clinical practice november 2014

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Volume 25, Number 6

November 2014, Pages 501–600

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American Family Physician

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Cardiology

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Community Medicine

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ENT

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Internal Medicine

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Medical Ethics

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Obstetrics and Gynecology

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

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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 6, November 2014 from the desk of THE group editor-in-chief

506 MTP (Amendment) Bill, 2014: A Retrograde Step by the Ministry of Health

KK Aggarwal

American Family Physician

508 Addison Disease: Early Detection and Treatment Principles

Aaron Michels, Nicole Michels

514 Practice Guidelines 515 Photo Quiz CARDIOLOGY

517 Floating Bodies in the Left Atrium by 2D-echo: A Differential Diagnosis

S Pratheep Kumar, N Chidambaram, R Umarani, E Balasubramanium, Gauri Shankar

522 High-risk Hypertension and Its Clinical Implications

C Venkata S Ram, KK Aggarwal

COMMUNITY MEDICINE

527 Global Pathway, Current Condition and Challenges in the Management of Dengue

Sathish Amirthalingam

ENT

532 Nasal Polyp Due to Aspergillus: A Case Report

Sumangala B, Munegowda, Kala B, Ravi D

Internal Medicine

535 Cytodiagnosis of Microfilaria at Unusual Sites

Kalpana Chandra, Praveen Kumar, Megha Garg

538 Association of Proton Pump Inhibitor with

Hypomagnesemia: A Cross-sectional Study at a Tertiary Care Hospital of Anand District

Dunkin U Shah, Punam D Sachdeva

MEDICAL ETHICS

544 Medical Ethics in Abortion

Alka B Patil, Pranil Dode, Amruta Ahirrao

Obstetrics AND Gynecology

552 Clinical Characteristics and Outcome of Obstetric

Patients Who Required Mechanical Ventilation in a Tertiary Care Hospital in North Kerala

Smitha Sreenivas K, Naseema Beevi A, Uma Devi N

558 Fetus Papyraceous in a Twin Pregnancy: A Case Report

Khushpreet Kaur, Parneet Kaur, Arvinder Kaur, Beant Singh, Sonam Walia, Mamta Rani

561 Ultrasonographic Prevalence of Polycystic Ovarian Syndrome in Different Age Groups

Tabassum K

ONCOLOGY 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

565 A Patient with Tracheal Leiomyoma and Meningioma: A Case Report

N Shah, R Hyderabadi, R Diwanji, DR Kothari, Varsha J Patel, PC Joshi, Meena Pandya

ORTHOPEDICS

568 Morquio’s Syndrome: A Rare Case

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

© Copyright 2014 IJCP Publications Ltd. All rights reserved.

Kiran S Patil, Mahantesh Y Patil, Deepak Kaladagi, Srinath M Gupta, Vinay K Gunjalli

572 A Study of Supracondylar Fractures of Humerus in Children by Open Reduction and Internal Fixation with Kirschner Wires

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.

Prasad M Gowda, Nabeel Mohammed

SURGERY

577 Management of Hemorrhoids

Anmol Chugh, Rajdeep Singh, PN Agarwal

Editorial Policies VenerEology

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.

581 Study of Pattern and Trend of Sexually Transmitted Infections at Tertiary Care Hospital in Central Rajasthan

Nirmala Saini, Ashok Meherda, Rajkumar Kothiwala

EXPERT VIEW

585 What are the Appropriate Secondary Prevention Strategies after MI?

KK Aggarwal, Ashok K Kar

Around the Globe

587 News and Views mediLAW

591 Real Consent and not Informed Consent Applicable in India (Part III)

KK Aggarwal

INSPIRATIONAL Story

594 Our Lives are Better Left to Chance…

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.

lighter reading

595 Lighter Side of Medicine

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

Padma Shri, Dr BC Roy National & 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)

MTP (Amendment) Bill, 2014: A Retrograde Step by the Ministry of Health

V

ide Notification No.12015/49/2008-MCH, dated the 29th October 2014, the Government of India has published on its website (http://www.mohfw.nic.in/showfile.php?lid=2986) the proposed amendment bill. The Ministry of Health has invited views/suggestions from the interested stakeholders and general public through email by 10th November 2014. The amendment proposes to raise the limit of permitting MTP up to 24 weeks pregnancy from the current limit of 20 weeks. The bill proposes to replace the term “registered medical practitioners” in Section 2(d) of the MTP Act, 1971, by the term “Registered healthcare providers” thus including vaids, hakims, Siddha practitioners, homeopaths as well as nurses and ANMs (auxiliary nurse midwives) under the preview of the act.

Analysis of the government stand ÂÂ It does not look like that the draft has approval from the health minister who himself is a doctor. ÂÂ Also the move probably was taken without any Indian Medical Association representative on the board. ÂÂ The proposed draft does not provide any rational for the amendments, which is against the general precedence

of issuing a statement regarding the background; need and objects of the proposed legislation whenever a bill or amendment is proposed by the government.

ÂÂ The amendment allows persons to perform MTP who are so far not allowed by law to do so. Currently, the

Section 2(d) of MTP Act, 1971, defines who can do MTPS. "Registered medical practitioner" means a medical practitioner who possesses any recognized medical qualification as defined in Clause (h) of Section 2 of the Indian Medical Council Act, 1956, (102 of 1956) whose name has been entered in a State Medical Register and who has such experience or training in gynecology and obstetrics as may be prescribed by rules made under this Act.

ÂÂ The current step by the government is against the interpretation given by the Honorable Supreme Court of

India in the Poonam Verma Vs. Ashwin Patel and Others (4 SCC 332, Kuldip Singh, S. Saghir Ahmad JJ, dated 10.05.1996), where the Court said; “41. A person who does not have knowledge of a particular System of Medicine but practices in that System is a quack and a mere pretender to medical knowledge or skill, or to put it differently, a charlatan.”

ÂÂ It also contradicts the Supreme Court of India Judgment Dr Mukhtiar Chand & Ors. Vs. State Of Punjab & Ors.,

(1998, 7 SCC 579, dated 8-1-1998 by judges K.T. Thomas and Syed Shah Mohammed Quadri) where the apex court further clarified the rights of non-allopaths as regards practicing allopathy as follows: ".............But after Sub-Section (2) of Section 15 was inserted in the 1956 Act, with effect from 15.09.1964, which inter alia, provides that no person other than a medical practitioner enrolled on a 'State Medical Register' shall practise modern scientific medicine in any State, the right of non-allopathic doctors to prescribe drugs by virtue of the declaration issued under the said drugs Rules, by implication, got obliterated. However, this does not debar them from prescribing or administering allopathic

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Indian Journal of Clinical Practice, Vol. 25, No. 6, November 2014

from the desk of THE group editor-in-chief drugs sold across the counter for common ailments." The apex court also observed: "... A harmonious reading of Section 15 of 1956 Act and Section 17 of 1970 Act leads to the conclusion that there is no scope for a person enrolled on the State Register of Indian Medicine or Central Register of Indian Medicine to practise modern scientific medicine in any of its branches unless that person is also enrolled on a State Medical Register within the meaning of 1956 Act". ÂÂ Also under the clause (d) of Sub-Section (3) of Section 17 of the Indian Medicine Central Council Act, 1970, the

right to practise modern scientific medicine in all its branches is confined to only such persons who possess any qualification included in the Schedules to 1956 Act.

Further issues ÂÂ As per sources, if they are correct, the proposed amendments are based on a study by Population Council

done in 2012; which showed that trained nurses and Ayurveda physicians provide medical abortion as safely as MBBS doctors. MTP Act 1971 was in place in 2012 and it does not allow anyone other than an MBBS doctor registered under the Act to conduct abortions. If the study conducted by Population Council included abortions conducted by Ayurveda doctors, was it not a violation of MTP Act. Who gave them the permission.

ÂÂ On the other hand, in one of the reports the Population Council mentions that even allopathic doctors require

more training for performing the abortions. "There is lack of knowledge even among doctors (allopathic) who provide abortion services about MTP and PC-PNDT Act as well as the different forms and registers that they have to maintain to comply with the procedures mentioned in the MTP and PC-PNDT Acts. Legal knowledge of what practices of theirs falls within which law and what forms they have to submit is gravely lacking. Training of health providers at all levels on the provisions of MTP Act and PC-PNDT Act is necessary. Within the framework of law, who can provide medical abortion and what things should be kept in mind while providing medical abortion, what could be the possible complications with medical and other forms of abortion, how to identify complications and provide services and referrals are also important area of training for providers.

Abortion providers need training in MVA (manual vacuum aspiration), EVA (electrical vacuum aspiration) and post abortion care. Practitioners are slow in adopting MVA either because of lack of equipments, training or both." (http://www.popcouncil.org/uploads/pdfs/2014STEPUP_IndiaCountryProfile.pdf)

So, when even the allopathic doctors require more retraining how can you expect non-allopathic healthcare providers to start MTP procedures. ÂÂ Also under the proposed amendment MTP involves both medical and surgical abortions. Medical abortion

means use of allopathic drugs not taught to healthcare providers of non-allopathic system of medicine. Also in India, nurses are not allowed to prescribe drugs. Medical abortion drugs are not over-the-counter drugs so, cannot be prescribed by non-allopathic healthcare providers as per above quoted apex court judgment. As of now, there are no homeopathic or Ayurveda drugs, which can be used for medical abortion. Also, MTP surgery requires allopathic anesthesia, sedation, sometimes antibiotics and often IV drips, a domain of Allopathic practice. We do not have ayurvedic or homeopathic anesthesia as of now. How will they do MTPs.

ÂÂ The proposed amendments will lead to a sudden uncontrollable increase in the incidence of unsafe MTPs with

high mortality and morbidity. They will also end up with violation of the PC-PNDT Act, 1994 and a resultant fall in the sex ratio.

ÂÂ Allowing abortion up to 24 weeks in the hand of nonqualified healthcare providers will lead to more sex

selective abortions. The move to increase the MTP weeks from 20-24 weeks is also a matter of concern, in fact any MTP after 12 weeks should have been allowed only by select recognized centers and under strict regulation to check selective sex selection abortions.

ÂÂ It is also to be seen that how will non-allopathic health care practitioners manage patients of pregnancy with

other comorbid conditions like underlying heart or kidney diseases. It will end up with high morbidity and mortality. Patients with serious heart, liver, kidney problems, blood clotting disorders or HIV are contraindicated to take medical abortion pills.

ÂÂ For any medical negligence or deficiency of service, which council will register the case. All councils acts will

need amendments. Also if anesthesia is given by allopath and abortion done by Ayurveda doctors, which council will regulate such situation.

ÂÂ How will the current Drug Controller Act allow homeopaths or Ayurveda doctors to prescribe medical abortion

pills. Finally, the proposed amendments are not on merit and need to be dropped.

(Note: Some of the inputs have been taken from Dr MC Gupta Blog)

Indian Journal of Clinical Practice, Vol. 25, No. 6, November 2014

507

American Family Physician

Addison Disease: Early Detection and Treatment Principles AARON MICHELS, NICOLE MICHELS

Abstract Primary adrenal insufficiency, or Addison disease, has many causes, the most common of which is autoimmune adre­ nalitis. Autoimmune adrenalitis results from destruction of the adrenal cortex, which leads to deficiencies in glucocor­ticoids, mineralocorticoids, and adrenal androgens. In the United States and Western Europe, the estimated prevalence of Addison disease is one in 20,000 persons; therefore, a high clinical suspicion is needed to avoid misdiagnosing a life-threatening adrenal crisis (i.e., shock, hypotension, and volume depletion). The clinical manifestations before an adrenal crisis are subtle and can include hyperpigmentation, fatigue, anorexia, orthostasis, nausea, muscle and joint pain, and salt craving. Cortisol levels decrease and adrenocorticotropic hormone levels increase. When clinically sus­pected, patients should undergo a cosyntropin stimulation test to confirm the diagnosis. Treatment of primary adrenal insufficiency requires replacement of mineralocorticoids and glucocorticoids. During times of stress (e.g., illness, inva­sive surgical procedures), stress-dose glucocorticoids are required because destruction of the adrenal glands prevents an adequate physiologic response. Management of primary adrenal insufficiency or autoimmune adrenalitis requires vigilance for concomitant autoimmune diseases; up to 50% of patients develop another autoimmune disorder during their lifetime.

Keywords: Primary adrenal insufficiency, Addison disease, autoimmune adre­nalitis, glucocor­ticoids, mineralocorticoids, adrenal androgens

M

ore than 150 years ago, Thomas Addison described a group of patients with anemia and diseased adrenal glands at autopsy, a condition now known as primary adrenal insufficiency.

Autoimmune adrenalitis is the most common cause of primary adrenal insufficiency, or Addison disease, in the United States. Less common causes include infection, hemorrhage, metastatic cancer, medication use, and adrenoleukodystrophy.

Autoimmune adrenalitis is a disorder in which the adrenal cortex is destroyed, resulting in the loss of mineralocorticoid, glucocorticoid, and adrenal androgen hormone production. Addison disease can be part of the autoimmune polyglandular syndromes (type 1 and 2), or it may present as an isolated disorder.1 This article focuses on the diagnosis and treatment of

AARONMICHELS,MD,isanassistantprofessorintheDepartmentofPedi­atricsand MedicineattheBarbaraDavisCenterforChildhoodDiabetesattheUniversityof Colorado–Denver in Aurora.

NICOLEMICHELS,PhD,isanassistantprofessorofphysiologyintheDepart­mentof Biomedical Sciences at Rocky Vista University in Parker, Colo.

Source: Adapted from Am Fam Physician. 2014;89(7):563-568.

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Indian Journal of Clinical Practice, Vol. 25, No. 6, November 2014

Addison disease as an isolated disorder, with a focus on the pathophysiology and treatment considerations of autoimmune adrenalitis.

Pathogenesis Autoimmune adrenalitis can be divided into stages of progression2,3 (Table 13). As the disease develops, individuals lose adrenocortical function over a period of years. In the first three stages, the human leukocyte antigen genes confer genetic risk; an unknown precipitating event initiates antiadrenal autoimmunity; and 21-hydroxylase antibodies are produced, which predict future disease. The production of these antibodies can precede symptom onset by years to decades, and they are present in more than 90% of recent-onset cases.2,4-7 In the fourth stage, overt adrenal insufficiency develops. One of the first metabolic abnormalities to occur is an increase in plasma renin level, followed by the sequential development of other abnormalities, including a decreased response to adrenocorticotropic hormone (ACTH) stimulation in the fifth stage. If symptoms of adrenal insufficiency are present but go undiagnosed, an addisonian crisis can occur.

American Family Physician Table 1. Development Stages of Autoimmune Adrenalitis Stage

Symptoms

Comments

Genetic risk

None

HLA-B8, -DR3, and -DR4 genes confer risk

Precipitating event starts antiadrenal autoimmunity

None

Possible environmental trigger

21-hydroxylase antibodies present

None

Antibodies appear before disease onset in 90% of cases

Metabolic decompensation

Fatigue, anorexia,nausea, hyperpigmentation

Increased ACTH and decreased 8 a.m. cortisol levels; high clinical suspicion needed for diagnosis

Decreased response to ACTH stimulation

Hypotension and shock (addisonian crisis)

Severe symptoms can be life-threatening

ACTH = Adrenocorticotropic hormone.

Information from reference 3.

Clinical Diagnosis

Table 2. Signs and Symptoms of Addison Disease

Because the estimated prevalence of Addison disease is one in 20,000 persons in the United States and Western Europe, a high clinical suspicion is needed to avoid misdiagnosing a life-threatening adrenal crisis.8 Signs and symptoms can be subtle and nonspecific.

Sign or symptom

Patients may experience fatigue, weakness, weight loss, and gastrointestinal upset9 (Table 210). Symptoms are gradual and worsen over a period of years, making early diagnosis difficult.10 The symptoms relate to the degree of cortisol, mineralocorticoid, and adrenal androgen deficiency at the time of presentation.

Addison disease is usually diagnosed after a significant stress or illness unmasks cortisol and mineralocorticoid deficiency, presenting as shock, hypotension, and volume depletion (adrenal or addisonian crisis).11 Cortisol and aldosterone deficiencies contribute to hypotension, orthostasis, and shock; however, adrenal crisis is more likely to occur in primary adrenal insufficiency compared with secondary adrenal insufficiency.

Hyperpigmentation is the physical finding most characteristic of Addison disease, arising from continual stimulation of the corticotrophs in the anterior pituitary.

Specifically, it results from cross-reactivity between the ACTH produced by the corticotrophs and the melanocortin 1 receptor on keratinocytes.

Hyperpigmentation is usually generalized over the entire body and can be found in palmar creases, buccal mucosa, vermilion border of the lips, and around scars and nipples. It is not a feature of secondary adrenal insufficiency because of the lack of increased ACTH in these patients.

Prevalence (%)

Anorexia

100

Weakness, fatigue

100

Hyperpigmentation

94

Gastrointestinal symptoms (e.g., nausea, vomiting, abdominal pain, constipation, diarrhea)

92

Hypotension (systolic blood pressure < 110 mm Hg)

~90

Salt cravings

16

Postural dizziness Vitiligo Muscle or joint pain

12 10 to 20 ~10

Information from reference 10.

Diagnosis

Metabolic Tests The goal of laboratory testing is to document a low cortisol level and determine whether the adrenal insufficiency is primary or secondary, as outlined in Figure 1. Low serum cortisol levels at 8 a.m. (less than 3 mcg per dL [83 nmol per L]) suggest adrenal insufficiency, as do low serum sodium and high serum potassium levels.12 Hyponatremia can be attributed to cortisol and mineralocorticoid deficiencies, whereas hyperkalemia is attributed solely to a lack of mineralocorticoids.

Because the adrenal hormones are gradually lost over years to decades, the levels vary. One of the first indications that there is adrenal cortex dysfunction is an elevated plasma renin level.13 A rise in ACTH

Indian Journal of Clinical Practice, Vol. 25, No. 6, November 2014

509

American Family Physician Diagnosis of Adrenal Insufficiency Patient presents with signs or symptoms of adrenal insufficiency

Imaging

Order basic metabolic panel and measurement of 8 a.m. serum cortisol level

Results inconsistent with adrenal insufficiency

Low cortisol level Normal to high potassium level Low to normal sodium level Perform cosyntropin stimulation test: measure basal ACTH level before administering intravenous ACTH (250 mcg); measure cortisol level again after 30 and 60 minutes after administration

Consider other diagnoses

specific for autoimmune adrenalitis and are detectable before symptom onset.

Radiographic imaging is also helpful in determining the cause of Addison disease, but it is relatively nonspecific in patients with autoimmune destruction. It is important to make a biochemical diagnosis of adrenal insufficiency before radiographic imaging. Computed tomography demonstrates small adrenal glands in patients with autoimmune adrenal destruction. In other causes of Addison disease, computed tomography may show hemorrhage, calcification associated with tuberculosis infection, or masses in the adrenal gland.

However, computed tomography is not necessary to diagnose adrenal insufficiency.

Treatment

Normal cosyntropin test result Consider other diagnoses

Low cortisol level High ACTH level

Low cortisol level Low ACTH level

Primary adrenal insufficiency

Secondary adrenal insufficiency

To identify etiology: Measure 21-hydroxylase antibody level Perform computed tomography of adrenal gland

Figure 1. Algorithm for the diagnosis of adrenal insufficiency.

(ACTH = adrenocorticotropic hormone.)

levels is concomitant with the loss of adrenal hormones. Yearly monitoring of ACTH levels in atrisk individuals shows that measurements greater than 50 pg per mL (11 pmol per L), which exceed the upper limit of normal, are indicative of cortisol deficiency.7 A cosyntropin stimulation test is the first-line test for diagnosing adrenal insufficiency. The serum cortisol, plasma ACTH, plasma aldosterone, and plasma renin levels should be measured before administering 250 mcg of ACTH. At 30 and 60 minutes after intravenous ACTH administration, the serum cortisol level should be measured again. A normal response occurs with peak cortisol levels greater than 18 to 20 mcg per dL (497 to 552 nmol per L); a smaller or absent response is diagnostic for adrenal insufficiency.14,15

Immunologic Tests Measurement of 21-hydroxylase antibody levels helps discern the cause of Addison disease. The 21-hydroxylase enzyme is necessary for cortisol synthesis in the adrenal cortex; antibodies directed against the enzyme are

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Indian Journal of Clinical Practice, Vol. 25, No. 6, November 2014

Hormone Therapy Treatment for Addison disease consists of lifelong hormone therapy with glucocorticoids and mineralocorticoids16 (Table 3). To date, there is no therapy available to stop the underlying immune destruction of the adrenal cortex. Generally, glucocorticoid replacement includes oral prednisone or hydrocortisone.17 Prednisone can be taken once daily, whereas hydrocortisone is divided into two or three doses per day.18-20 Mineralocorticoids are replaced with fludrocortisone at a dose sufficient to keep the plasma renin level in the upper limit of the normal range.21,22 Men who have Addison disease do not need replacement with androgens because their testes are able to produce adequate testosterone levels; however, women can benefit from androgen replacement because the adrenals are the main source of androgen production in women.

A meta-analysis of 10 randomized placebo-controlled trials found that dehydroepiandrosterone (DHEA) supplementation resulted in small improvements in health-related quality of life and depression in women with adrenal insufficiency.23

Stress Dosing of Glucocorticoids Patients should be counseled about the need for stressdose glucocorticoids for illnesses and before surgical procedures because destruction of the adrenal glands prevents an adequate physiologic response to stress.24 There are many expert recommendations for stress dosing of steroids based on the degree of stress; clinical trials comparing different approaches are lacking in the literature. In our practice, we use a stress-dose

American Family Physician Table 3. Medications for the Treatment of Addison Disease Medication

Dosage

Comments

Monitoring

Prednisone

3 to 5 mg once daily

Use stress doses for illness, surgical procedures, and hospitalization

Symptoms of adrenal insufficiency; low to normal plasma adrenocorticotropic hormone levels indicate over-replacement

Hydrocortisone

15 to 25 mg divided into two or three doses per day

Use stress doses for illness, surgical procedures, and hospitalization

Dexamethasone

0.5 mg once daily

Use intramuscular dose for emergencies and when unable to tolerate oral intake

0.05 to 0.2 mg once daily

Dosage may need to increase to 0.2 mg per day in the summer because of salt loss from perspiration

Blood pressure; serum sodium and potassium levels; plasma renin activity in the upper normal range

25 to 50 mg once daily

Available as an over-the-counter supplement; can improve mood and quality of life in women

Libido, mood, and sense of well-being

Glucocorticoids

Mineralocorticoid Fludrocortisone

Androgen Dehydroepiandrosterone (DHEA)

Table 4. Autoimmune Disorders Occurring with Addison Disease Disease

Lifetime Appropriate diagnostic tests prevalence (%)

Autoimmune thyroid disease (Hashimoto disease or Graves disease)8,28-32

22

Thyroid-stimulating hormone, thyroid peroxidase antibody, and thyroid-stimulating immunoglobulin levels

Celiac disease33

12

Tissue transglutaminase antibody level

Type 1 diabetes mellitus8,28-30,32

11

A1C, fasting blood glucose, and islet autoantibody levels

Hypoparathyroidism8,28-30,32

10

Calcium and parathyroid hormone levels

10

Follicle-stimulating hormone level

5

Complete blood count, vitamin B12 level, and parietal cell antibody level

Primary gonadal failure (testes)29

2

Testosterone, follicle-stimulating hormone, and luteinizing hormone levels

None8,28-34

50

â&#x20AC;&#x201D;

Primary ovarian Pernicious

insufficiency34

anemia8,28,29

Note: Data compiled from multiple studies across different populations.

Information from references 8, and 28 through 34.

strategy for outpatient procedures (e.g., colonoscopy, upper endoscopy) and invasive dental procedures (e.g., root canal) that patients can implement easily.

This involves a dose of glucocorticoids three times the maintenance dose the day of the procedure and two days after (i.e., three times three rule for stress-dose glucocorticoids). For minor illnesses such as influenza or viral gastroenteritis, the patient can take three times the steroid dose during the illness and resume

normal dosing after resolution of symptoms. Patients should also have an injectable form of glucocorticoid (intramuscular dexamethasone) available in cases of nausea, vomiting, or other situations when oral intake is not possible. Mineralocorticoid replacement generally does not need to be changed for illness or procedures.

However, the dose may need to be adjusted in the summer months when there is salt loss from excessive perspiration.

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American Family Physician Treatment Caveats Thyroid hormone therapy in persons with undiag­ nosed Addison disease may precipitate an adrenal crisis because the thyroid hormone increases the hepatic clearance of cortisol. In addition, patients with a new diagnosis can have a reversible increase in thyroid-stimulating hormone levels because glucocorticoids inhibit secretion.25,26 Glucocorticoid replacement can result in the normalization of thyroidstimulating hormone levels less than 30 mIU per L. In individuals with type 1 diabetes mellitus, unexplained hypoglycemia and decreasing insulin requirements may be the initial signs of Addison disease.27

Treatment of Confirmed Addison Disease Patients with Addison disease should be treated in conjunction with an endocrinologist and be monitored on a regular basis for appropriate hormone therapy (Table 3). Glucocorticoid doses should be titrated to the lowest tolerated dose that controls symptoms to minimize the adverse effects of excess glucocorticoid.

It is important to instruct patients to learn the proper guidelines for stress dosing of glucocorticoids, to have an injectable form of glucocorticoid available, and to wear an adrenal insufficiency medical alert identification.

Approximately 50% of persons with Addison disease caused by autoimmune adrenalitis develop another autoimmune disorder during their lifetime, necessitating lifelong vigilance for associated autoimmune conditions.28,29 Table 4 outlines concomitant autoimmune disorders and their relative prevalence, as well as appropriate autoantibodies and metabolic tests for patients with Addison disease who develop signs and symptoms of one of these disorders.8,28-34 Of note, 10% of women with Addison disease experience autoimmune premature ovarian failure, or primary ovarian insufficiency, in their reproductive years with signs and symptoms of estrogen deficiency (e.g., amenorrhea, flushing, fatigue, poor concentration).34 It is appropriate to offer these patients evaluation and counseling on other options for building a family.35 REFERENCES 1. Michels AW, Eisenbarth GS. Immunologic endocrine disorders. J Allergy Clin Immunol. 2010;125(2 suppl 2): S226-S237.

2. Betterle C, Dal Pra C, Mantero F, Zanchetta R. Autoimmune adrenal insufficiency and autoimmune polyendocrine syndromes: autoantibod­ies, autoantigens, and their applicability in diagnosis and disease pre­

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diction [published correction appears in Endocr Rev. 2002;23(4):579]. Endocr Rev. 2002;23(3):327-364.

3. Eisenbarth GS, Gottlieb PA. Autoimmune polyendocrine syndromes. N Engl J Med. 2004;350(20):2068-2079.

4. Betterle C, Volpato M, Rees Smith B, et al. II. Adrenal cortex and steroid 21-hydroxylase autoantibodies in children with organ-specific autoim­mune diseases: markers of high progression to clinical Addison’s dis­ease.

J Clin Endocrinol Metab. 1997;82(3):939-942.

5. Betterle C, Volpato M, Rees Smith B, et al. I. Adrenal cortex and ste­roid 21-hydroxylase autoantibodies in adult patients with organ-specific autoimmune diseases: markers of low progression to clinical Addison’s disease. J Clin Endocrinol Metab. 1997;82(3):932-938.

6. Coco G, Dal Pra C, Presotto F, et al. Estimated risk for developing auto­immune Addison’s disease in patients with adrenal cortex autoantibod­ies. J Clin Endocrinol Metab. 2006;91(5):1637-1645.

7. Baker PR, Nanduri P, Gottlieb PA, et al. Predicting the onset of Addison’s disease: ACTH, renin, cortisol, and 21-hydroxylase autoantibodies. Clin Endocrinol (Oxf).

2012;76(5):617-624.

8. Erichsen MM, Løvås K, Skinningsrud B, et al. Clinical, immunological, and genetic features of autoimmune primary adrenal insufficiency: observa­tions from a Norwegian registry. J Clin Endocrinol Metab. 2009;94(12): 4882-4890.

9. Burke CW. Adrenocortical insufficiency. Clin Endocrinol Metab. 1985;14(4):947-976.

10. Bleicken B, Hahner S, Ventz M, Quinkler M. Delayed diagnosis of adre­nal insufficiency is common: a cross-sectional study in 216 patients. Am J Med Sci. 2010;339(6):525-531.

11. Bouachour G, Tirot P, Varache N, Gouello JP, Harry P, Alquier P. Hemody­ namic changes in acute adrenal insufficiency. Intensive Care Med. 1994; 20(2):138-141.

12. Schmidt IL, Lahner H, Mann K, Petersenn S. Diagnosis of adrenal insuffi­ciency: evaluation of the corticotropinreleasing hormone test and basal serum cortisol in comparison to the insulin tolerance test in patients with hypothalamic-pituitary-adrenal disease. J Clin Endocrinol Metab. 2003;88(9):4193-4198.

13. Betterle C, Scalici C, Presotto F, et al. The natural history of adrenal func­tion in autoimmune patients with adrenal autoantibodies. J Endocrinol. 1988;117(3):467-475.

14. Dickstein G, Shechner C, Nicholson WE, et al.

Adrenocorticotropin stimu­lation test: effects of basal cortisol level, time of day, and suggested new sensitive low dose test. J Clin Endocrinol Metab. 1991;72(4):773-778.

15. May ME, Carey RM. Rapid adrenocorticotropic hormone test in practice. Retrospective review. Am J Med. 1985;79(6):679-684.

16. Arlt W, Allolio B. Adrenal insufficiency. Lancet.

2003;361(9372):1881-1893.

American Family Physician 17. Crown A, Lightman S. Why is the management of glucocorticoid defi­ciency still controversial: a review of the literature. Clin Endocrinol (Oxf). 2005;63(5):483-492.

18. Bleicken B, Hahner S, Loeffler M, et al. Influence of hydrocortisone dos­age scheme on health-related quality of life in patients with adrenal insufficiency. Clin Endocrinol (Oxf). 2010;72(3):297-304.

19. Debono M, Ross RJ, Newell-Price J. Inadequacies of glucocorticoid replacement and improvements by physiological circadian therapy. Eur J Endocrinol.

2009;160(5):719-729.

20. Quinkler M, Hahner S. What is the best long-term management strat­egy for patients with primary adrenal insufficiency? Clin Endocrinol (Oxf). 2012;76(1):21-25.

21. Smith SJ, MacGregor GA, Markandu ND, et al. Evidence that patients with Addison’s disease are undertreated with fludrocortisone. Lancet. 1984;1(8367):11-14.

22. Oelkers W, Diederich S, Bähr V. Diagnosis and therapy surveillance in Addison’s disease: rapid adrenocorticotropin (ACTH) test and measure­ment of plasma ACTH, renin activity, and aldosterone. J Clin Endocrinol Metab. 1992;75(1):259-264.

23. Alkatib AA, Cosma M, Elamin MB, et al. A systematic review and meta-analysis of randomized placebocontrolled trials of DHEA treatment effects on quality of life in women with adrenal insufficiency. J Clin Endocrinol Metab. 2009;94(10):3676-3681.

24. Oelkers W, Diederich S, Bähr V. Therapeutic strategies in adrenal insufficiency. Ann Endocrinol (Paris).

2001;62(2):212-216.

25. Kannan CR. Diseases of the adrenal cortex. Dis Mon. 1988;34(10):601-674.

26. Samuels MH. Effects of variations in physiological cortisol levels on thyrotropin secretion in subjects with adrenal insufficiency: a clinical research center study. J Clin Endocrinol Metab. 2000;85(4):1388-1393.

27. Armstrong L, Bell PM. Addison’s disease presenting as reduced insulin requirement in insulin dependent diabetes. BMJ. 1996;312(7046):1601-1602.

28. Zelissen PM, Bast EJ, Croughs RJ. Associated autoimmunity in Addison’s disease. J Autoimmun.

1995;8(1):121-130.

29. Kasperlik-Zaluska AA, Migdalska B, Czarnocka B, Drac-Kaniewska J, Niegowska E, Czech W. Association of Addison’s disease with autoimmune disorders—a long-term observation of 180 patients. Postgrad Med J. 1991;67(793):984-987.

30. Blizzard RM, Chee D, Davis W. The incidence of adrenal and other antibodies in the sera of patients with idiopathic adrenal insufficiency (Addison’s disease). Clin Exp Immunol. 1967;2(1):19-30.

31. McHardy-Young S, Lessof MH, Maisey MN. Serum TSH and thyroid antibody studies in Addison’s disease. Clin Endocrinol (Oxf). 1972;1(1):45-56.

32. Nerup J. Addison’s disease—clinical studies. A report of 108 cases. Acta Endocrinol (Copenh). 1974;76(1):127-141.

33. O’Leary C, Walsh CH, Wieneke P, et al. Coeliac disease and autoimmune Addison’s disease: a clinical pitfall.

QJM. 2002;95(2):79-82.

34. Husebye ES, Løvås K. Immunology of Addison’s disease and premature ovarian failure. Endocrinol Metab Clin North Am. 2009;38(2):389-405.

35. Baker V. Life plans and family-building options for women with primary ovarian insufficiency. Semin Reprod Med. 2011;29(4):362-372.

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American Family Physician

Practice Guidelines ACS Releases Guideline on Screening for Lung Cancer with Low-Dose Computed Tomography

following benefits, uncertainties, and harms of lung cancer screening with those who meet the eligibility criteria above:

In late 2010, results from the National Lung Screening Trial showed that lung cancer mortality was significantly reduced in high-risk adults who received annual screenings using low-dose computed tomography (CT). After these results were announced, the American Cancer Society (ACS) joined with the American College of Chest Physicians, the American Society of Clinical Oncology, and the National Comprehensive Cancer Network to produce a systematic review on the evidence for screening for lung cancer using low-dose CT. The review focused on the following key questions: What are the potential benefits and harms of using lowdose CT to screen persons at high risk of lung cancer?

Which groups are likely to benefit? And in what setting would screening be most effective?

ÂÂ Low-dose CT screening substantially reduces the

The ACS used the findings from the systematic review to create recommendations for a process of informed and shared decision making between physicians and patients that should occur before any decision is made to initiate screening. The recommendations focus on the potential benefits, limitations, and harms associated with lung cancer screening using low-dose CT. If access to a high-volume, high-quality lung cancer screening and treatment center is available, physicians should discuss screening with patients 55 to 74 years of age who are in relatively good health and have a smoking history of 30 pack-years or more, who currently smoke, or who have quit within the past 15 years. Physicians should not discuss low-dose CT screening with patients who do not meet these criteria.

If screening is requested by a patient who does not meet the criteria, he or she should be told that there is too much uncertainty about the balance of harms and benefits in persons younger or older than 55 to 74 years who have less lifetime exposure to tobacco smoke, and that screening is therefore not recommended.

Physicians should ask about current and past smoking in all patients 55 to 74 years of age, and discuss the

Source: Adapted from Am Fam Physician. 2012;86(6):571-576.

risk of dying from lung cancer.

ÂÂ Low-dose CT will not detect all lung cancers, and

not all patients who have cancer detected will avoid dying from lung cancer.

ÂÂ There is a significant chance of a false-positive

result, which requires additional testing and, in some cases, an invasive procedure to determine whether the abnormality is actually lung cancer.

Fewer than one in 1,000 patients with false-positive results has a major complication resulting from a diagnostic workup.

Helping patients clarify their personal values can facilitate effective decision making. Those who value the opportunity to reduce their risk of dying from lung cancer and who are willing to accept the risks and costs associated with low-dose CT and the relatively high likelihood of the need for further testing may opt for annual screening. Those who place greater value on avoiding testing that carries a high risk of falsepositive results and a risk of complications, and who accept that they are at greater risk of death from lung cancer than from screening complications, may opt not to be screened.

Smoking cessation counseling remains a high priority for patients who smoke. Current smokers should be informed of their risk of lung cancer and referred to a smoking cessation program. Lung cancer screening is not an alternative to smoking cessation.

Adults who opt to be screened should be tested annually until 74 years of age. Chest radiography should not be used for lung cancer screening. Whenever possible, patients should enter a program at an institution with expertise in low-dose CT screening, with access to a multidisciplinary team skilled in the evaluation, diagnosis, and treatment of abnormal lung lesions.

If such a program is not available but the patient strongly wishes to be screened, he or she should be referred to a center that performs a reasonably high volume of lung CT, diagnostic testing, and lung cancer surgeries. If such a setting is not available and the Cont'd on page 516...

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American Family Physician

Photo Quiz Multiple Bullae on the Trunk A 62-year-old man with no significant medical history presented with multiple bullae on his trunk that had been present for one week. The rash was painful but not pruritic. He did not have a fever or sore throat, and had not used any new medications.

Physical examination revealed multiple vesicles, flaccid bullae, and erosions with crust formation on the chest, abdomen, and back (Figures 1 and 2). Mucosal erosions and the Nikolsky sign were also present.

There was no lymphadenopathy. Biopsy of a blister showed suprabasal acantholysis with intraepidermal blister formation and follicular involvement. Direct immunofluorescence revealed intercellular deposits of immunoglobulin G and C3 within the epidermis.

Question Based on the patientâ&#x20AC;&#x2122;s history and physical examination findings, which one of the following is the most likely diagnosis?

A. Bullous impetigo.

B. Bullous pemphigoid.

C. Dermatitis herpetiformis.

D. Pemphigus vulgaris.

Discussion The answer is D: pemphigus vulgaris. Pemphigus vulgaris is an autoimmune blistering disease of the skin and mucous membranes. It presents as flaccid, easily ruptured blisters arising on normal skin, with subsequent erosions and crust formation. It often appears on the face, scalp, trunk, intertriginous areas, and mucosal areas. The lesions are usually painful but rarely pruritic. The mean age of onset is 40 to 60 years.

The Nikolsky sign is typically present.

Pemphigus vulgaris is caused by the loss of the normal cell-to-cell adhesion in the epidermis because of autoantibodies against desmogleins. The

Source: Adapted from Am Fam Physician. 2014;89(1):7-8.

Figure 1.

Figure 2.

histologic findings are suprabasal acantholysis with intraepidermal blister formation and frequent follicular involvement. Direct immunofluorescence reveals intercellular deposits of immunoglobulin G and/ or C3 within the epidermis. Detection of circulating antibodies against desmogleins by indirect immunofluorescence or enzyme-linked immunosorbent assay may help to make a diagnosis.

Myasthenia gravis and thymoma are associated with pemphigus vulgaris. Without treatment, pemphigus vulgaris leads to death; however, the mortality rate is markedly reduced with the use of systemic steroids and immunosuppressive agents.1 Bullous impetigo is a superficial cutaneous infection caused by Staphylococcus aureus. It most commonly affects neonates and infants, but also occurs in older children and adults. The thin-walled, flaccid bullae usually arise on grossly normal skin in perioral and perinasal areas, and in body folds. The bullae contain clear yellow fluid that subsequently turns turbid and dark yellow. Brown to yellowish crusts may form after the bullae rupture. Patients may have fever and malaise.

Histologically, patients have subcorneal blisters filled with neutrophils, gram-positive cocci, and occasional acantholytic cells.1,2 Bullous pemphigoid is an autoimmune disease characterized by tense blisters filled with serous or hemorrhagic fluid. The blisters usually appear on the extremities and trunk, although widespread eruption is possible. Mucosal lesions occur in approximately 10% to 35% of patients. Urticarial papules and plaques may predominate in the early stage of the disease. There is usually marked pruritus. The typical age of onset is 60 to 80 years. Histologically, patients have a subepidermal blister with dermal infiltrates of lymphocytes and

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American Family Physician Summary Table Condition

Clinical characteristics

Histologic characteristics

Bullous impetigo

Most common in neonates and infants; usually appears Subcorneal blisters filled with neutrophils, gram-positive in perioral and perinasal areas, and in body folds; bullae cocci, and occasional acantholytic cells are thin-walled and flaccid with subsequent rupture and crust formation

Bullous pemphigoid

Onset between 60 and 80 years of age; tense blisters Subepidermal blister with dermal infiltrates of lymphocytes on extremities and trunk; mucous membranes less and eosinophils; linear deposits of immunoglobulin G involved; usually pruritic and C3 along the dermoepidermal junction on direct immunofluorescence

Dermatitis herpetiformis

Symmetrical, intensely pruritic papulovesicles on Microabscesses containing neutrophils in the dermal extensor surfaces and buttocks; associated with gluten papillary tips; pathognomonic granular immunoglobulin sensitivity A deposits at the dermoepidermal junction on direct immunofluorescence

Pemphigus vulgaris

Onset between 40 and 60 years of age; flaccid and easily ruptured blisters with subsequent erosions and crust formation; usually appears on the face, scalp, trunk, intertriginous areas, and mucosal areas; usually painful; positive Nikolsky sign

eosinophils. Direct immunofluorescence shows linear deposits of immunoglobulin G and C3 along the dermoepidermal junction.1 Dermatitis herpetiformis is an autoimmune disorder associated with gluten sensitivity. It presents as intensely pruritic papulovesicles symmetrically located on the extensor surfaces and buttocks. The characteristic microscopic feature is microabscesses containing neutrophils in the dermal papillary tips. Direct immunofluorescence showing immunoglobulin A deposits at the dermoepidermal junction is pathognomonic.3

Suprabasal acantholysis with intraepidermal blister formation and frequent follicular involvement; immunoglobulin G and/or C3 deposits within the epidermis on direct immunofluorescence

REFERENCES 1. Fitzpatrick TB, Wolff K, eds. Fitzpatrick’s Dermatology in General Medicine. 7th ed. New York, NY: Mcgraw-Hill; 2008.

2. Sladden MJ, Johnston GA. Current options for the treatment of impetigo in children. Expert Opin Pharmacother. 2005;6(13):2245-2256.

3. Suárez-Fernández R, España-Alonso A, Herrero-González JE, Mascaró-Galy JM. Practical management of the most common autoimmune bullous diseases [in Spanish].

Actas Dermosifiliogr. 2008;99(6):441-455

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patient is not willing or able to travel to one, the risks are sufficiently high that screening is not recommended.

At this time, few government or private insurance programs provide coverage for the initial low-dose

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CT to screen for lung cancer. Physicians who offer screening should tell patients how much the initial test will cost and help them determine whether they must pay for it themselves.

CARDIOLOGY

Floating Bodies in the Left Atrium by 2D-echo: A Differential Diagnosis S Pratheep Kumar*, N Chidambaram†, R Umarani†, E Balasubramanium‡, Gauri Shankar#

Abstract Two-dimensional echocardiography (2D-echo) is sensitive in detecting floating bodies in the left atrium. Identification of a freefloating left atrial thrombus, as a source of embolus, is a common indication for 2D-echo. Screening for other cardiac conditions such as valvular heart diseases often, if not common, reveal floating bodies in the left atrium. The differential diagnosis of a floating body in the left atrium will be discussed.

Keywords: Left atrial thrombus, left atrial myxoma, floating bodies

T

wo-dimensional echocardiography (2D-echo) is

used to diagnose a number of abnormalities pertaining to the left atrium. It is more sensitive than the M-mode echo in detecting floating bodies of the left atrium. These floating bodies are found incidentally or while screening for a source of emboli in the left atrium.

A left atrial thrombus is a common indication for screening with an echocardiogram. Left atrial myxoma usually presents as a pedunculated mass with a pedicle.

However, prolapsing type of left atrial myxomas present as free-floating bodies in the left atrium. A left atrial mass may lead to embolism of the major arteries.1 2D-echo helps in determining the nature, size, spatial orientation of these masses before surgical removal.2 Mentioned below are a few differential diagnoses of a free-floating body in the left atrium. ÂÂ

Left atrial thrombus

ÂÂ

Prolapsing type of left atrial myxoma

ÂÂ

Papillary fibroelastomas

*Postgraduate †Professor ‡Additional Professor #Lecturer Dept. of Medicine Rajah Muthiah Medical College and Hospital, Annamalai Nagar, Tamil Nadu Address for correspondence Dr S Pratheep Kumar T5, Aero Building, Chakra Avenue, Phase II Opposite Main Road, Annamalai Nagar - 608 002, Tamil Nadu E-mail: spkthedr@yahoo.co.in

ÂÂ

Lambl’s excrescences

ÂÂ

Fragments of vegetations

ÂÂ

zz

Bacterial vegetations

zz

Fungal vegetations

zz

Aseptic vegetations

Displaced pacemaker leads

LEFT ATRIAL THROMBUS The left atrium and its appendage is a common site of formation of thrombi in patients with mitral stenosis and atrial fibrillation who are not on anticoagulation.

This is due to stasis of blood or a poorly contracting left atrium. The left atrial thrombus may break into a number of smaller pieces, leading to embolic events such as a stroke. However, total or partial obstruction of the mitral valve may present as a low output state.

2D-echo is sensitive in detecting thrombi of the left atrium. The thrombus is initially attached by a pedicle, enlarges gradually and spins off in the left atrium and it acquires the characteristic rounded appearance.

Further deposition of thrombotic material in layers over the thrombi contributes to the shape. These have been described as the ‘Ball valve thrombus’.

2D-echo also allows the detection of a possibility of a thrombus formation by the presence of a spontaneous echo contrast. Those described as the `Ball valve thrombus’ must fulfill certain rigid criteria as defined

by Welch3 namely, there must be: ÂÂ

Entire absence of attachment with consequent free motility

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CARDIOLOGY ÂÂ

Imprisonment in consequence of an excess in the diameter of the first narrowing in the circulatory passage ahead of it

ÂÂ

Such consistency and shape that the thrombus will not of necessity lodge as an embolus in the passage.

Case example A 45-year-old female, a case of rheumatic mitral stenosis, presented with quadriparesis and altered sensorium.

ECG of the patient showed features of atrial fibrillation with controlled ventricular rate. 2D-echo findings of the patient are shown in (Figures 1-3). The trapping of the thrombus in the mitral valve predisposes the patient to sudden cardiac death. The patient was referred immediately for cardiac intervention. It is important to stress that oral anticoagulation may lead to fragmentation of the thrombus, leading to showers of emboli, which may be fatal.

LA Thrombus

Figure 2. Four chamber view of the patient showing an associated mitral regurgitation.

PROLAPSING TYPE OF LEFT ATRIAL MYXOMA Primary cardiac tumors of the heart are less common compared to metastatic disease of the heart. A three out of four, of these primary tumors are benign and a left atrial myxoma is the commonest (Fig. 4). Two different anatomic types of myxoma have been determined by means of echocardiography: ÂÂ

Round, which is solid and round with a nonmobile surface

ÂÂ

Polypoid, which is soft and irregular in shape with a mobile surface.4 Ha and co-workers showed that prolapsing and polypoid tumors were associated with embolism.

LA

Thrombus

Figure 3. Multiple serial images showing a ball valve thrombus in the left atrium getting trapped against the mitral orifice.

The incidence of systemic embolism is higher in tumors with an irregular and friable surface than in those with a smooth surface.5 PAPILLARY FIBROELASTOMAS

Figure 1. Four chamber view showing stenosis of the mitral valve.

LAD = 5.8 cm (left atrial diameter); MVA = 0.96 cm2 (mitral valve area).

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Papillary fibroelastomas account for 8-10% of the primary cardiac tumors. They are small, solitary and

CARDIOLOGY motile bodies, which are of <1 cm in size and often confused with vegetations (Fig. 5). They may become as large as 4 cm. They usually arise from the mid-portion of the valve frequently involving the aortic valve followed by the mitral valve. Patients with papillary fibroelastomas are usually asymptomatic and these are identified, while screening for cardiac surgery or other indications.

Although symptoms related to fibroelastomas are uncommon, there is a potential for serious morbidity, particularly among patients with large, mobile, leftsided lesions.6 Cardiac papillary fibroelastomas are present on valves, away from valvular lines of closure, and also on the endocardial surfaces of the atria and ventricles.7

Left atrial myxoma

Figure 4. A left atrial myxoma.

LAMBLâ&#x20AC;&#x2122;S EXCRESCENCES Lamblâ&#x20AC;&#x2122;s excrescences are filiform fronds that occur at sites of valve closure. They are fine thread like strands and originate as small thrombi on endocardial surfaces and have the potential to embolize to distant organs.8 In contrast to papillary fibroelastomas, they involve the mitral valve more frequently followed by the aortic valve.

FRAGMENTS of Vegetations

Papillary fibroelastoma

Bacterial Vegetations 2D-echo is very specific in detecting vegetations of infective endocarditis (Fig. 6). The specificity is as high as 98%.9 However, the sensitivity ranges between 40-50%. Detection of these vegetations is a part of three major criteria of the Dukeâ&#x20AC;&#x2122;s criteria for infective endocarditis.

The appearance and site of the vegetations depend on the etiology. Vegetations affect both the native and prosthetic valve. Detection of vegetations of the prosthetic valve is difficult. This is because of the echogenic nature of the prosthetic valves.

Bacterial vegetations as a complication of rheumatic fever are small, less friable, sterile and are known as verrucae. Vegetations, primarily due to infective endocarditis are large, bulky, more friable and are destructive in nature. They are most commonly seen in the upper parts of the valve cusps.

Figure 5. 2D-echo of a patient who presented with breathlessness showing a single small motile mass. The mass was later confirmed to be a papillary fibroelastoma by biopsy.

VEG

Fungal Vegetations Fungal vegetations are less common than bacterial vegetations and are easily identified by 2D-echo. They are larger than bacterial vegetations. They are friable

Figure 6. 2D-echo showing bacterial vegetations.

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CARDIOLOGY and have an easy tendency to break into smaller pieces and present as septic emboli.

Aseptic Vegetations Aseptic vegetations may be due to nonbacterial thrombotic endocarditis or systemic illnesses such as systemic lupus erythematosus (SLE) and antiphospholipid antibody syndrome. Nonbacterial thrombotic endocarditis is also known as marantic endocarditis, which literally means ‘wasting away’.

The vegetations are small masses of fibrin and platelets, which are easily friable and are seen along lines of closure of valves. They commonly affect the mitral and the aortic valves.

Common predisposing factors are hypercoagulable states such as malignancy, sepsis and burns. Libmann sack`s endocarditis is seen in patients with SLE. These vegetations are small, warty and have destructive potential. They are commonly associated with the mitral and tricuspid valve along the atrial and ventricular surfaces and do not have a predilection for the lines of closure.

PACEMAKER LEADS Pacemaker leads can produce an echocardiographic beam width artefact, but can be reduced by imaging from a different acoustic window.

Infection of the pacemaker leads makes it difficult to confirm whether vegetations are present or not, and to differentiate them from the vegetations of

infective endocarditis. Displaced pacemaker leads may also present as a floating body in specific chambers (Fig. 7). Early displacements are more frequent than late displacements and they usually affect atrial leads.10 SUMMARY A free-floating left atrial mass may be a major source of emboli or may be an incidental finding. The size, site of occurrence, the nature of the surface (e.g., smooth rounded or irregular) and its relation to lines of closure of valves, by 2D-echo, helps in determining the nature, characteristics and identification of the underlying condition. 3D-echo, transesophageal Echo and the more recent 4D-echo provide more detail and throw light on the hemodynamic threat these bodies pose. Early surgical removal and histopathological examination of these masses may be indicated in a majority of these cases. Anticoagulation may harmful in the case of a large left ball valve thrombus.

REFERENCES 1. Ando T, Abe H, Ro D. A case of embolism due to a floating thrombus migrating from the left atrial appendage to the ostium of the celiac artery. Ann Vasc Dis 2012;5(2):229-32.

2. Tahara A, Tahara N, Honda A, et al. Mobile left atrial round mass free floating in mitral regurgitation flow mimicking a whale spray. BMJ Case Rep 2014;2014. pii: bcr2013202725.

3. Welch W. Thrombosis. In: Allbutt’s System of Medicine.

Macmillan: London 1899, vol. 6, p. 720.

4. Ha JW, Kang WC, Chung N, et al. Echocardiographic and morphologic characteristics of left atrial myxoma and their relation to systemic embolism. Am J Cardiol 1999;83(11):1579-82, A8.

5. Goswami KC, Shrivastava S, Bahl VK, et al. Cardiac myxomas: clinical and echocardiographic profile. Int J Cardiol 1998;63(3):251-9.

6. Sun JP, Asher CR, Yang XS, et al. Clinical and echocardiographic characteristics of papillary fibroelastomas: a retrospective and prospective study in 162 patients. Circulation 2001;103(22):2687-93.

7. Lambl VD. Papillare excrescenzen an der semilunarklappe der aorta. Wien Med Wochenschr 1856;6:244-7.

8. Aziz F, Baciewicz FA Jr. Lambl’s excrescences: review and recommendations. Tex Heart Inst J 2007;34(3):366-8.

Pacemaker

Figure 7. Two chamber view showing a displaced pacemaker in the right ventricle. Pacemaker displacements are however more common in the atria.

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9. Erbel R, Rohmann S, Drexler M, Mohr-Kahaly S, Gerharz CD, Iversen S, et al. Improved diagnostic value of echocardiography in patients with infective endocarditis by transoesophageal approach. A prospective study. Eur Heart J 1988;9(1):43-53.

10. Bardy GH, Hofer B, Johnson G, Kudenchuk PJ, Poole JE, Dolack GL, et al. Implantable transvenous cardioverterdefibrillators. Circulation 1993;87(4):1152-68.

CARDIOLOGY

High-risk Hypertension and Its Clinical Implications C Venkata S Ram*, KK Aggarwal†

Abstract Hypertension (HT) is a well-established risk factor for cardiovascular disease (CVD) and chronic kidney disease (CKD). Only <50% of treated hypertensive patients have a BP of <140/90 mmHg, which is a cause for much concern. These treated but inadequately controlled hypertensive patients are at significant risk for developing CVD and other complications. Telmisartan is a long-acting angiotensin receptor blocker (ARB), which has multiple positive effects aside from its antihypertensive efficacy.

It reduces CV events in high-risk patients, has favorable effects on endothelial function including renoprotective effects. Trials like the MAPHY and BCAP have shown that β blockers (metoprolol) have beneficial effects on outcomes and survival along with reduction in BP. Most hypertensives need combination approach to control their high BP. Being cardioprotective drugs, combination of telmisartan and metoprolol is beneficial for secondary prevention of cardiovascular events in high-risk patients with HT.

Keywords: Hypertension, renoprotective, combination, cardioprotective

H

ypertension (HT) is a well-established risk factor1 for cardiovascular disease (CVD) and chronic kidney disease (CKD). High blood pressure (BP) is associated with development of CVD in a continuous and graded manner; risk increases with incremental BP, even within the normal range.2 HT is also associated with target organ damage viz. left ventricular hypertrophy (LVH), proteinuria and renal failure, retinopathy and vascular dementia.3 The Framingham study showed that HT often occurs in association with other atherogenic risk factors.4 The high prevalence of diabetes and insulin resistance in India may have a major role in the risk for HT.5 Presence of multiple risk factors greatly increase risk for cardiovascular events.6 Poorly-controlled BP accounts for 62% cases of cerebrovascular disease, 49% of ischemic heart disease (IHD) and 7.1 million deaths annually. With an aging population and the rising prevalence of obesity, diabetes and CKD, the incidence of resistant HT is only going to rise.7 The fact that only <50% of treated hypertensive patients have a BP of <140/90 mmHg also is a cause for much

*Senior Consultant, Apollo Hospitals Director, Apollo Institute of Blood Pressure Management and Director, Blood Pressure Clinics, Apollo Group of Hospitals, Hyderabad †Senior Physician and Cardiologist Moolchand Medcity, New Delhi

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concern. These treated but inadequately controlled hypertensive patients are at significant risk for developing CVD8 and other complications.

Uncontrolled HT increases risk of atherothrombotic stroke, myocardial infarction (MI), LVH, atrial fibrillation (AF) congestive heart failure, renal failure and hypertensive retinopathy.9 A 10 mm decrease in systolic BP and a 5 mm decrease in diastolic BP significantly reduced risk of all CVD events including stroke.10 Risk of clinical events associated with HT is determined by:11 ÂÂ Absolute and relative BP levels ÂÂ Calculated cardiovascular risk - estimated from factors like age, gender, smoking history, etc. ÂÂ Presence of target organ damage ÂÂ Presence of established CVD or comorbid disease such as diabetes or CKD associated with high CVD risk.

References: 1Benndorf RA, et al. J Hypertension 2008;26(5): 854-6. 2Sierra C, et al. Vasc Health Risk Manag 2008;4(2):28996. 3Nadar SK, et al. Curr Pharm Des 2006;12(13):1581-92.

4Kannel WB. J Hum Hypertens 2000;14(2):83-90. 5Ram CV, et al. J Clin Hypertens (Greenwich) 2012;14(8):561-5. 6Johnson ML, et al. Am J Manag Care 2004;10(12):926-32. 7Bravo E. Cleve Clin J Med 2013;80(2):91-6. 8Neutel JM. Nephrol Dial Transplant 2006;21(6):1469-73. 9Indian guidelines on hypertension (I.G.H.) - III. 2013. J Assoc Physicians India 2013;61(2 Suppl):6-36. 10Ram CV, et al. J Am Soc Hypertens 2014;8(2):142-3. 11National Clinical Guideline Centre (UK). Hypertension: The Clinical Management of Primary Hypertension in Adults: Update of Clinical Guidelines 18 and 34 [Internet]. London: Royal College of Physicians (UK);

CARDIOLOGY (13.0%) vs placebo (15.0%, p < 0.05) only in hypertensive patients.

2011 Aug. (NICE Clinical Guidelines, No. 127.) 8, Assessing cardiovascular risk, target organ damage and secondary causes of hypertension. Available from: http://www.ncbi.nlm. nih.gov/books/NBK83281/

Telmisartan in High-risk Patients with Hypertension Telmisartan, a long-acting angiotensin receptor blocker (ARB), has therapeutic effects that go beyond BP control.1 The very high lipophilicity and high volume of distribution give it the clinically important advantage of good tissue penetration.2 It has multiple positive effects not only on BP, but also on target organ protection.

Antihypertensive efficacy: Greater and more consistent lowering of BP over the full 24-hour period thereby protecting from adverse effects of early morning BP rise on cardiovascular risk.

ÂÂ

Favorable metabolic profile, especially on insulin sensitivity; neutral effects on sympathetic cardiovascular function and lipids.

ÂÂ

Cardioprotective effects zz

Effective in favoring the regression of cardiac and vascular organ damage

zz

Reduces arterial stiffness vascular distensibility

zz

Reverses endothelial dysfunction typical of HT, especially with comorbid diabetes, obesity, renal failure or metabolic syndrome

zz

Reduces central aortic BP.

and

improves

Telmisartan Reduces Cardiovascular Events in High-risk Patients ÂÂ

The Telmisartan Randomized AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease (TRANSCEND) study examined the effect of telmisartan on cardiovascular events in high-risk patients who were intolerant to ACE inhibitors. A post-hoc analysis investigated the hypothesis that telmisartan has a differential action in hypertensive vs nonhypertensive patients.5,6 zz

The primary composite endpoint (sum of cardiovascular death, nonfatal MI, nonfatal stroke and hospitalization due to heart failure) was nonsignificantly reduced in telmisartan-treated patients vs placebo (15.7% vs. 17%; relative risk reduction 8%).

zz

The occurrence of the secondary endpoint (cardiovascular death, MI and stroke) was significantly lower in telmisartan group

Post-hoc analysis suggested that MI could be further reduced by telmisartan in hypertensive patients.

zz

Telmisartan could also decrease new onset of LVH in both nonhypertensive and hypertensive patients and new onset of microalbuminuria and macroalbuminuria in hypertensive patients.

ÂÂ

AF is associated with increased cardiac and vascular risks, mainly stroke.7 The prevalence of AF in the society is increasing due to aging population. Telmisartan prevented AF recurrences more effective than other antihypertensive drugs among hypertensive patients with paroxysmal AF.8

ÂÂ

In the ONTARGET study in high-risk patients, telmisartan reduced cardiovascular events similar to ramipril, beyond BP-lowering alone, but with a better tolerability.3

Telmisartan: A ‘Cardiometabolic Sartan’3,4 ÂÂ

zz

Telmisartan has Favorable Effects on Endothelial Function Endothelial dysfunction is now a recognized marker for cardiovascular risk.7 ÂÂ A meta-analysis of seven randomized controlled trials of telmisartan for flow-mediated dilatation (FMD) from Japan enrolling a total of 398 patients confirmed the evidence of a significant increase in FMD with telmisartan, suggesting that telmisartan may improve endothelial dysfunction.

The pooled analysis of these seven trials revealed a statistically significant increase in FMD by 48.7%, with telmisartan relative to control in the randomeffects model. Removal of any single trial from the assessment had no significant effect on the overall result. No evidence of significant publication bias was evident.9 ÂÂ

In a study, 51 hypertensive patients with coronary artery stenosis but no coronary artery spasm, treated with a sirolimus-eluting stent, were randomly assigned to either telmisartan (n = 25) or amlodipine (n = 26) treatment. Telmisartan significantly improved endothelial dysfunction after coronary drug-eluting stent implantation vs amlodipine in patients with HT in terms of vasoconstriction induced by acetylcholine.10

Telmisartan: Renoprotective Effect The Atherosclerotic Risk In Communities (ARIC) cohort study and Cardiovascular Health Study have shown

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CARDIOLOGY an association between reduced glomerular filtration rate (GFR) and CVD. The lower the GFR, higher the cardiovascular risk.11 In a multicenter, prospective trial, telmisartan was not only effective and safe in reducing BP in diabetic and nondiabetic, hypertensive, proteinuric CKD patients, even in those who had mildto-moderate chronic renal failure, proteinuria also reduced considerably.12 Telmisartan administered once-daily was also effective and well-tolerated as treatment of mild/moderate HT in CKD patients, with preservation of renal function.13 Other clinical trial such as ARAMIS (614 patients with isolated systolic HT and albuminuria, no diabetes),14 INNOVATION (514 hypertensive or normotensive subjects with type 2 diabetes and microalbuminuria but no renal failure)15 and AMADEO (patients with type 2 diabetes with overt nephropathy)16 have demonstrated a beneficial effect of telmisartan on renal function.

Telmisartan Significantly Reduces LVH in Hypertensive Patients ÂÂ

Telmisartan causes greater LVH regression than hydrochlorothiazide, carvedilol and ramipril despite similar declines in BP.17-19

The ONTARGET and TRANSCEND studies show that telmisartan provides optimal cardioprotection, with good tolerability profile in high-risk hypertensive patients. ÂÂ

In a subanalysis of data from ONTARGET and TRANSCEND studies, new-onset LVH decreased by 37% in TRANSCEND trial. In ONTARGET study, telmisartan was slightly more effective than ramipril in reducing LVH (nonsignificant).20 This finding is of clinical significance.

References: 1Destro M, et al. Expert Opin Pharmacother 2011;12(17):2719-35. 2Wienen W, et al. Cardiovasc Drug Rev 2000;18(2):127-54. 3Asmar R. Eur Cardiol 2012;8(1): 10-6. 4Grassi G, et al. J Renin Angiotensin Aldosterone Syst 2008;9(2):66-74. 5Foulquier S, et al. J Hypertens 2014;32(6): 1334-41. 6de la Sierra A, et al. J Hypertens Suppl 2009;27(2): S22-5. 7Baguet JP, et al. Integr Blood Press Control 2010;3: 81-9. 8Pan G, et al. Cardiovasc Ther 2014;32(4):184-8. 9Takagi H, et al. Hypertens Res 2014 Apr 10. 10Terashima M, et al.

JACC Cardiovasc Interv 2012;5(2):182-90. 11Dobre D, et al. Eur Heart J 2009;11(Suppl F):F39-F46. 12Rysavá R, et al. Blood Press Monit 2005;10(4):207-13. 13Sharma AM, et al. Clin Nephrol 2005;63(4):250-7. 14Vogt L, et al. J Hypertens 2005;23(11):2055-61.

15Makino H, et al. Diabetes Care 2007;30(6):1577-8. 16Bakris G, et al. Kidney Int 2008;74(3):364-9. 17Galzerano D, et al. J Hum Hypertens 2004;18(1):53-9. 18Galzerano D, et al. Am J Hypertens 2005;18(12 Pt 1):1563-9. 19Petrovic I, et al. J Int Med Res 2005;33 Suppl 1:39A-49A. 20Verdecchia P, et al. Circulation 2009;120(14):1380-9.

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Metoprolol in Patients with High-risk Hypertension β blockers have for long been used in the treatment of cardiovascular conditions.1 Metoprolol is a cardioselective (β1-selective) lipophilic adrenoceptor blocker. It has been suggested that lipophilic β blockers may be a better choice than hydrophilic β blockers with better outcomes vis-à-vis all-cause mortality.2 In a meta-analysis of β-blocker studies post-MI, greater risk reduction was associated with β1 selectivity, lipophilicity and absence of intrinsic sympathomimetic activity. Of the three most used β blockers (atenolol, metoprolol and propranolol), metoprolol, with many of these desirable properties, had the most pronounced beneficial effects including on survival.3

The MAPHY Study The MAPHY study, a major trial, enrolled patients from 11 countries and was conducted in 66 centers. It compared effects of metoprolol in 1,069 patients with pre-treatment diastolic BP of 100-130 mmHg, with those of a thiazide diuretic (hydrochlorothiazide or bendroflumethiazide) in 1,625 patients with moderately severe HT and included many patients with coronary artery disease and heart failure.4 Total mortality was significantly lower in metoprolol group. At the end of a mean follow-up period of 4.2 years, there were 28 deaths in the metoprolol group and 54 in the diuretic group, respectively; a difference of 48% in total mortality, which was statistically significant, mainly due to a highly significant reduction in coronary heart disease at this point in time.

The MAPHY study demonstrated that metoprolol was superior to a thiazide diuretic in reducing total mortality, cardiovascular mortality and sudden cardiac death for similar reduction of BP. The antiatherosclerotic effect of metoprolol provides a pathophysiological rationale for the improved prognosis with β blockers in patients with myocardial ischemia.5 This finding separates utility of metoprolol vs other β blockers such as atenolol.

The BCAP Study β blockers reduce angina symptoms and also have an antiatherosclerotic effect.5 By influencing pathophysiology of atheroma progression, they may improve prognosis. The BCAP study (β-blocker cholesterol-lowering asymptomatic plaque) compared effects of low-dose metoprolol (25 mg once-daily) and

CARDIOLOGY fluvastatin (40 mg once-daily) on carotid intima-media thickness (IMT) progression over 3 years in 793 subjects who had carotid plaque but no symptoms of carotid artery disease.5 ÂÂ

Metoprolol significantly reduced rate of plaque progression in the carotid bulb at both 18 and 36 months (‒0.058 mm/year and ‒0.023 mm/year, respectively).5

ÂÂ

Total mortality and cardiovascular events were significantly lower with metoprolol (8 vs 19; p = 0.031), probably due to the effect on plaque regression.6

The BCAP study show that a β-blocker can slow progression of carotid IMT in clinically healthy, symptom-free patients with carotid plaque suggesting a favorable effect on early stages of atherosclerosis.

β blockers in Hypertension and Cardiovascular Disease β blockers are among the most commonly used drugs in the treatment of HT. As they are also indicated for other conditions like angina, post-MI, arrhythmias, AF, chronic heart failure, and also in patients with hyperadrenergic states such as thyrotoxicosis and even migraine and essential tremor, they are very useful in hypertensives with these comorbidities.7 ÂÂ

Effective in long-term secondary prevention postMI.6,8

ÂÂ

Reduce preoperative cardiovascular events in high-risk ischemic patients before major vascular surgery.6

ÂÂ

Improve prognosis in patients with coronary artery disease by reducing adverse events in stable patients and high-risk patients.6

ÂÂ

Improve prognosis in patients with all grades of symptomatic heart failure by reducing mortality.6

ÂÂ

β blockers are an important choice in treatment and prevention of CVD despite the controversy attached to atenolol.

References: 1Ram CV. Am J Cardiol 2010;106(12):1819-25.

2Kohro T, et al. Circulation 2010;74(5):962-9. 3Soriano JB, et al.

Prog Cardiovasc Dis 1997;39(5):445-56. 4Wikstrand J, et al. Am Heart J 1988;116(1 Pt 2):338-47. 5Hedblad B, et al. Circulation 2001;103(13):1721-6. 6Ong HT. BMJ 2007;334:946-9. 7Larochelle P, et al. Can J Cardiol 2014;30(5 Suppl):S16-22. 8Freemantle N, et al. BMJ 1999;318(7200):1730-7.

Need for Combination Therapy High BP is not satisfactorily controlled with monotherapy in most patients.1 Monotherapy is especially not likely

to be a successful strategy in those with comorbidities like diabetes mellitus, heart failure.2 BP control is more rapidly achieved with an initial combination strategy.3 Early vs delayed combination treatment has the advantage of reducing risk of cardiovascular events in most patients, an effect which occurs mainly via greater BP decline and more rapid achievement of goal BP.4 In an overwhelming majority of patients with HT, combination therapy is required and mandated for BP to normal levels.

Determinants of BP The three major determinants of BP are renal sodium excretion and resultant plasma and total body volume, cardiac performance and vascular tone. These factors control intravascular volume, cardiac output and systemic vascular resistance, the immediate hemodynamic determinants of BP.3 The major hemodynamic finding associated with high BP is increase in peripheral vascular resistance.5 The rise in BP is usually multifactorial, so attempting to control it by interfering with only a single pressor mechanism is not easy. Drugs that are directed at any one component usually produce compensatory (counterregulatory) responses that decrease magnitude of response, even if it was accurately directed at the predominant pathophysiologic mechanism. A limited BP reduction is therefore seen with all available anti-HT drugs.3 Interfering with multiple pressor mechanisms causes greater and more consistent BP decrease and higher responder rates.6

Rationale of Combination Therapy Initiating treatment with more than one drug targets multiple physiologic pathways. This increases the probability that the predominant contributory mechanisms would be inhibited. Counterregulatory responses would also be reduced. The result is an increase in responder rates as well as increase in the extent of response in these patients.3 Greater Efficacy Using two complementary anti-HT drugs in combination will always result in greater efficacy than high-dose monotherapy.7 Combining drugs from complementary classes has 5-fold greater antiHT efficacy than increasing dose of one drug. Drugs known to reduce long-term incidence of cardiovascular endpoints are highly preferred.3 All the clinical trials in HT have tested the usefulness of combination therapy, not monotherapy.

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CARDIOLOGY Fewer Side Effects Improving the overall tolerability of treatment is a major factor influencing rational drug combinations.3 Side effects are fewer with complementary drugs used in combination than with high-dose monotherapy.7 Adherence to Treatment Combination therapy facilitates long-term adherence to treatment by reducing the number of medications as well as the frequency of dosing required.3 Combination therapy is more commonly indicated in those with comorbid diabetes, CKD and other highrisk patients and in general whenever treatment goal is to attain lower BP targets. In high-risk patients, the goal BP should be achieved more promptly, which favors initial combination therapy and quicker dos adjustment. A combination of two drugs at low doses should be preferred as first-step treatment when initial BP is in the Grade 2 or 3 range or total cardiovascular risk is high or very high.8 Rational combination therapy begins with the selection of two-drug combinations that exhibit additive BP reduction, excellent tolerability and a demonstrated ability to reduce cardiovascular endpoints in long-term clinical trials.5 While two-drug combinations are widely used, we should not hesitate to use triple-drug combinations to achieve the BP goals.

National Committee (JNC 8) and the American and International Societies of Hypertension (ASH/ ISH) have made recommendations for combination therapy.9-11 When the BP is >20/10 mmHg above goal, then administration of two drugs as first-line therapy should be considered as recommended by the ESH/ ESC, the ASH/ISH and by some members of JNC-8.

This approach may help to achieve target BP within a reasonable time period.

References: 1Canbakan B, et al. Kidney Int Suppl 2011 2013;3(4):349-51. 2Kalra S, et al. Diabetol Metab Syndr 2010;2(1):44. 3Gradman AH, et al. J Clin Hypertens (Greenwich) 2011;13(3):146-54. 4Gradman AH, et al.

Hypertension 2013;61(2):309-18. 5Sever PS, et al. Eur Heart J 2011;32(20):2499-506. 6Gradman AH, et al. Curr Opin Nephrol Hypertens 2012;21(5):486-91. 7Neutel JM, et al. Nephrol Dial Transplant 2006;21(6):1469-73. 8Sierra C, et al. Euro Cardiol 2009. 9Mancia G, et al. J Hypertens 2013;31(7):1281-357.

10James PA, et al. JAMA 2014;311(5):507-20. 11Weber MA, et al. J Hypertens 2014;32(1):3-15.

Telmisartan + Metoprolol: Rationale of Combination

Practice Recommendations

Telmisartan and metoprolol are both cardioprotective drugs. Used together, they are beneficial in hypertensive patients with coronary artery disease or heart failure for secondary prevention of cardiovascular events when the major goal of therapy is improvement of outcome.

There are well-conducted outcome trials wit telmisartan as well as metoprolol. Thus, the combination is likely to exert important benefits in patient with HT.

The European Society of Hypertension/European Society of Cardiology (ESH/ESC), the eighth Joint

Reference: 1Gradman AH, et al. J Clin Hypertens (Greenwich). 2011;13(3):146-54.

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COMMUNITY MEDICINE

Global Pathway, Current Condition and Challenges in the Management of Dengue Sathish Amirthalingam

Abstract Dengue is still a danger to communities around the world. Number of deaths resulting from dengue fever sharply are rising every year. As yet, there has been no confirmed medical cure or vaccine for dengue fever. So, prevention is still a question mark from the medical point of view. But, proper awareness and certain preventive methods are very effective as opposed to vaccination and other medications. This article mainly outlines the background of dengue and its implications in Malaysia.

The fight against the spread of dengue is a constant one, especially in all the tropical countries.

Keywords: Dengue fever, vaccination, global impact, challenges in dengue

It is believed that the increase in number of cases of dengue fever is caused by a few factors, which are urbanization, population growth and increase in international travel and global warming. The increase in dengue fever is affecting countries around the globe (Fig. 1). Currently, the experts are working to eradicate the dengue fever. A few articles are published regarding the vaccines of dengue, which are under research and development now. However, there are still a lot of

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Lecturer III Dept. of Pharmacy Practice International Medical University, Kuala Lumpur, Malaysia Address for correspondence Dr Sathish Amirthalingam 126, Jalan Jalil Perkasa 19, Bukit Jalil - 57000, Kuala Lumpur, Malaysia E-mail: asathish1981@gmail.com, SathishAmirthalingam@imu.edu.my

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In Asian countries and the pacific region, >70% (approximately 1.8 billion) of the populations are at risk of having dengue, which accounts for approximately 75% of the current global disease burden due to dengue.

Dengue is spreading to new geographical areas and causing high mortality. According to WHO, since 2000, dengue has spread into countries like Bangladesh, India, Maldives, Myanmar, Sri Lanka and Thailand.

Bhutan also reported the first dengue outbreak during

2004.1 This implicates that dengue is epidemic. WHO plans to aid the countries to reverse the rising trend of dengue outbreak by enhancing their preparedness to detect, characterize and stop the spread of dengue to other new areas.

Number of cases

D

engue is a type of mosquito-borne disease that occurs mainly in tropical countries. It is also known as breakbone-fever and is transmitted by a few species of mosquito with genus Aedes. Its classical symptoms include fever, headache, joint pain and its typical skin rashes. In 2009, the World Health Organization (WHO) classified dengue fever into two groups.1 They are uncomplicated and severe type.

Severe dengue can lead to serious bleeding due to plasma leakage in the body and causes severe organ dysfunction. All other cases besides severe dengue are classified as uncomplicated ones. Between 1960 and 2010, the number of dengue fever cases increased 30-fold.2

Year

Figure 1. Average annual number of DF/DHF cases reported to WHO and average annual number of countries reporting dengue.4

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COMMUNITY MEDICINE challenges in different aspects in eradicating dengue fever.

GLOBAL IMPACT OF DENGUE Dengue has spread throughout the world following a pandemic in South-East Asia that occurred after World War II, and has since developed most dramatically as a significant issue in terms of morbidity and economic impact.3 A pandemic in 1998, in which 1.2 million cases of dengue fever (DF) and dengue hemorrhagic fever (DHF) were reported from 56 countries worldwide, was unprecedented. In 2001, the Americas alone reported over 6,52,212 cases of dengue of which 15,500 were DHF, nearly double the cases reported for the same region in 1995.4 Dengue has highly impacted the economic growth of South-East Asian countries.5 Also, the mortality and the morbidity associated with dengue is a major economic burden to those it affects and a significant demand on healthcare resources.6 The occurrence of conditions that favor endemicity and epidemicity, namely the presence of large territories with Aedes mosquito infestation, sizeable susceptible human groups and the continuous introduction and/or circulation of one or more serotypes are factors responsible for endemic and epidemic spread of dengue.7 As a result, most of the South-East Asian countries are spending millions of dollars every year to spread awareness and create infrastructure to support the treatment of dengue.5 For an example, Singapore has set up a separate wing and ministry to control the epidemic diseases, especially dengue.8 In addition to direct medical costs, indirect costs incurred due to lost work days and earnings, and caregiver costs, may substantially increase the overall economic burden of the disease.3 At the individual family level, the economic impact of dengue may be particularly severe, incurring significant and extended debt.4 As dengue is epidemic and can easily spread within a region, government spends more money in educating the people by public address, television advertisement, distributing pamphlet and conducting group activities.9 Besides, there is a major social impact in those countries where large epidemics occur, often disrupting primary care for hospitalized patients.10 CHALLENGES IN DENGUE ERADICATION

Environment and Poverty The main challenge in dengue eradication is unplannedurbanization with the overcrowded population, which is characterized by lack of basic infrastructures,

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substandard housing conditions, deficiencies in water supply and sewage management.11,12 Improper water supply which has resulted from rapid urbanization contributes to the habitat expansion of the vector, Aedes aegypti as the residents have to reserve water in vessels, which promotes mosquitoes breeding.11-13 Evidence from research stated that low-income groups with no air-conditioning and poor street drainage are most likely to be infected.12 Furthermore, inappropriate disposal of nonbiodegradable materials like plastic containers and old tyres are potential breeding sites for mosquitoes due to the ability to serve as water reservoirs.14 Vector control method has been proven to be difficult to maintain over time.15 The main effective measure to control vector is source reduction and it is crucial to be able to distinguish the disposable sources and those are indoor versus outdoor as a study reported that 79% of the total breeding sites was indoor in Singapore.14

Transportation and Migration Rapid global migration with the aid of modern transport system creates an extensive urban network which increases the potential for vector and virus dissemination to new a territory.11-13 Global transmission and spread of virus leads to genetic expansion of virus which makes it more difficult to eradicate.11 Hence, tourism and immigration are risk factors of dengue transmission.14

Usage of Insecticides The extensive and indiscriminate use of insecticides worldwide is one of the main challenges in eradication of vector due to global pandemic of insecticide resistance.11 The ability of larvicides to control vectors also limited as it has low coverage in term of the large pool of breeding sites present in any urban environment. Insecticides are short lived in relation to the mortality of female adult A. aegypti and also short in reach when it comes to the issue of the effectiveness of insecticide penetration into vectorâ&#x20AC;&#x2122;s resting places.

In Asia and America, studies show that after application of the ultra-low volume (ULV), the population of adult mosquitoes returned to the pre-treatment level within 2 weeks and even with multiple applications, the impact resulted was minimal.14

Public Perception and Other Challenges Although community participation in eradication is crucial to success, public often perceives that dengue control is solely a responsibility of governmental agencies.13,14 Several studies revealed that people from

COMMUNITY MEDICINE dengue endemic countries understand the disease and its transmission, but the control practices are not equivalent to the knowledge about the disease.

There is no sense of urgency within the population even though the incidence of dengue has increased at an alarming rate. Education is important, but solely dependent on the interventions that rely on education strategies shown to have less impact on behavioral and entomologic indices.14 Most of the national programs regarding the eradication of dengue is under- funded, poorly managed with isolated operation from other healthcare delivery systems. Another negative issue is the field workers involved are less motivated and poorly supervised, they are under paid and they lack communication skills.

Most participants involved lose interest in vector control during the low transmission period; thus, resulting in subsequent increase in vectorâ&#x20AC;&#x2122;s population.14 Despite the current efforts made, there are many other challenges for dengue eradication, which include limited infrastructure and resources in control and surveillance, limited quality of diagnosis and clinical care and the need of more advance entomological tools to standardize and classify the vectors.11 DENGUE VACCINE DEVELOPMENT The development of dengue vaccines has been initiated since the 40s. However, the low appreciation of global disease burden and potential markets for the vaccine have brought the industryâ&#x20AC;&#x2122;s interests down until recent years, when the number of dengue infections and the prevalence of four, and the newly discovered fifth dengue serotypes have mounted drastically. These serotypes are DENV-1, DENV-2, DENV-3, DENV-4 and DENV-5.16,17 Development of dengue vaccines have become a great concern now-a-days. However, there are many issues that have to be addressed in order to successfully construct and introduce a safe and effective dengue vaccine to the public.16 These issues include enhancing adequate knowledge of the pathogenesis of dengue, obtaining sustainable financing, designing a vaccine, which is safe and effective against all dengue serotypes to maintain or decrease the level of DHF, deciding on vaccine delivery systems, integrating the vaccine into existing expanded immunization programs, conducting catch-up campaigns, establishing effective surveillance systems, integrating vector control programs and training immunization staff.18

Challenges of Dengue Vaccine Development The ideal dengue vaccine must be safe to be used without causing intolerable adverse effects caused by cross-reactive antibodies or T cells, should provide long-term protection to all serotypes and at the same time affordable to the populations at risk. The ultimate challenge of developing dengue vaccines would be in designing the ideal vaccine in the presence of obstacles such as insufficient knowledge of the complicated pathogenesis of the disease and a lack of suitable animal models. Although, DENV can affect non-human primates, it does not replicate as well in them as it does in humans. Mouse models were used to test the vaccine candidates before testing them in non-human primates. Immune-competent mice were found to be more suitable models to test the vaccine.

The drawback of using these animals; however, is that the replications of DENV in them are poor. Another significant challenge in developing a dengue vaccine is in determining a reasonable cost for it as it is important that those who need the vaccines the most are not hindered from accessing them due to excessively highpriced vaccines.19

Progress of Dengue Vaccine Development A number of vaccine options are under development even though there is no available licensed dengue vaccine present to date. Among these options are live attenuated virus vaccines, live chimeric vaccines, live recombinant, DNA and subunit vaccines, as well as inactivated virus vaccines. As of now, only the former two virus vaccines are undergoing clinical evaluations.

There are also nonviral vaccines, which include subunit vaccines that are centred on a protein, known as E protein or its derivatives. NS1 is yet another subunit vaccine option, which is not associated to any virus and possesses no adverse effects.19 The most clinically advanced contender among all the vaccines undergoing development is a live-attenuated tetravalent vaccine, which is based on chimeric yellow fever-dengue virus (CYD-TDV).20 It has, thus far, proceeded to phase III efficacy studies of clinical development. It was tested on a group of school children in Thailand, where dengue is particularly endemic and was found to possess a satisfactory safety profile in its phase IIb safety profile for up to 25 months after the first vaccination dose.

It was also estimated to be effective against DENV 1, 3 and 4 strains of the dengue virus, after between 1 and 3 doses.21 The worldwide expansion of DF is a growing health problem. The dengue vaccine is an urgent challenge

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COMMUNITY MEDICINE that needs to be overcome. It may be commercially available within a few years, when a vaccine that could provide protection against all five dengue viruses, is discovered. Until such a vaccine is fully developed, continuous efforts must be made to improve progress that has been made and to overcome challenges in the development of a dengue vaccination.

CONCLUSION Dengue is now a global threat and is endemic or epidemic in many countries and especially those located in the tropics including Malaysia is rapidly spreading. Existing vector control efforts have not prevented its rapid emergence and global spread.

Compare with 2013 scenario, 2014 dengue registered patients in hospital have increased triple fold. There are currently no licensed vaccines or specific treatment for dengue. However, the ever-expanding knowledge of the pathogenesis of dengue is providing more insights into the vaccine design. While waiting for new vaccines and antiviral drugs to be introduced to the market, challenges in dengue eradication should be overcome and better use should be made of the existing vector control interventions.

REFERENCES 1. World Health Organization. Dengue Guidelines for Diagnosis, Treatment, Prevention and Control. 2009.

[Cited 2014 Mar 15]. Available from: http://www.who. int/tdr/publications/documents/dengue-diagnosis.pdf 2. Whitehorn J, Farrar J. Dengue. Br Med Bull 2010;95: 161-73.

8. Carrasco LR, Lee LK, Lee VJ, Ooi EE, Shepard DS, Thein TL, et al. Economic impact of dengue illness and the cost-effectiveness of future vaccination programs in Singapore. PLoS Negl Trop Dis 2011;5(12):e1426.

9. Gubler DJ. The economic burden of dengue. Am J Trop Med Hyg 2012;86(5):743-4.

10. Bhatt S, Gething PW, Brady OJ, Messina JP, Farlow AW, Moyes CL, et al. The global distribution and burden of dengue. Nature 2013;496(7446):504-7.

11. Ng LC. Challenges in dengue surveillance and control.

APSAR 2011;2(2):1-3.

12. Phillips ML. Dengue reborn: widespread resurgence of a resilient vector. Environ Health Perspect 2008;116(9):A382-8.

13. Morrison AC, Zielinski-Gutierrez E, Scott TW, Rosenberg R. Defining challenges and proposing solutions for control of the virus vector Aedes aegypti.

PLoS Med 2008;5(3):e68.

14. Gómez-Dantés H, Willoquet JR. Dengue in the Americas: challenges for prevention and control. Cad Saude Publica 2009;25 Suppl 1:S19-31.

15. Brathwaite Dick O, San Martín JL, Montoya RH, del Diego J, Zambrano B, Dayan GH. The history of dengue outbreaks in the Americas. Am J Trop Med Hyg 2012;87(4):584-93.

16. Rodrigues HS, Monteiro MT, Torres DF. Vaccination models and optimal control strategies to dengue. Math Biosci 2014;247:1-12.

17. Tomasulo A. Fifth Dengue Serotype Discovered. Health Map. 2013. [Cited 2014 Mar 15]. Available from: http:// healthmap.org/site/diseasedaily/article/fifth-dengueserotype-discovered-102513

3. Singh P, Jacobson J. Dengue disease dynamics. J Clin Virol 2009;46:S1-S2.

18. Planning for the Introduction of Dengue Vaccines.

Americas Dengue Prevention Board, Dengue Vaccine Initiative (DVI), Brasília: Brazil 2011:p.1.

4. World Health Organization. Impact of Dengue. 2014.

[Cited 2014 Mar 20]. Available from: http://www.who.int/ csr/disease/dengue/impact/en/

19. Wan SW, Lin CF, Wang S, Chen YH, Yeh TM, Liu HS, et al. Current progress in dengue vaccines. J Biomed Sci 2013;20:37.

5. Global Impact of Dengue Fever and the Fight Against The Disease. 2010. [Cited 2014 Mar 20]. Available from: http:// www.contraeldengue.com/global-impact-of-dengue fever- and-the-fight-against-the-disease. Php

20. World Health Organization. Dengue Vaccine Research.

2014. [Cited 2014 Mar 15]. Available from: http://www. who.int/immunization/research/development/dengue_ vaccines/en/

6. Guzman MG, Halstead SB, Artsob H, Buchy P, Farrar J, Gubler DJ, et al. Dengue: a continuing global threat. Nat Rev Microbiol 2010;8(12 Suppl):S7-16.

21. Roehrig JT. Current status of dengue vaccine development.

Centres for Disease Control and Prevention. 2013 April.

[Cited 2014 Mar 21]. Available from: http://www.who. int/immunization/sage/meetings/2013/april/2_Roehrig_ Dengue_SAGE_April2013.pdf

7. Guzman A, Istúriz RE. Update on the global spread of dengue. Int J Antimicrob Agents 2010;36 Suppl 1:S40-2.

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ENT

Nasal Polyp Due to Aspergillus: A Case Report Sumangala B*, Munegowda†, Kala B‡, Ravi D#

Abstract Different studies have found a 6-9% incidence of allergic fungal sinusitis (AFS) among chronic sinusitis patients requiring surgery. Invasive rhinosinusitis due to Aspergillus causing nasal polyposis, bony erosion has been reported. Nasal discharge and nasal obstruction are said to be the commonest presentation. We report the case of a 48-year-old man who presented with complaints of nasal obstruction and foul-smelling nasal discharge from the past 6 months. He was investigated and found to have a nasal polyp involving left maxillary sinus and nasal cavity. Plain X-ray showed no bony involvement.

Keywords: Allergic fungal sinusitis, Aspergillus, invasive rhinosinusitis, nasal polyposis, nasal obstruction

F

ungal involvement in rhinosinusitis is classified into four major forms: Allergic, mycetoma, chronic invasive (indolent) and acute invasive (fulminant).

It can become life-threatening if not diagnosed and treated properly. The preliminary diagnosis is usually made by nasal endoscopy and computed tomography (CT) imaging, but tissue biopsy and culture are of vital importance in confirming the disease and in planning treatment.1

Aspergillus species were initially suspected as the causative agent. Subsequent reports include a number of non-Aspergillus-related cases.2 Different studies have found a 6-9% incidence of allergic fungal sinusitis (AFS) among chronic sinusitis patients requiring surgery.2,3 Relapse after surgical debridement and aeration is common and often responds to systemic corticosteroids.3 The diagnosis of AFS should be considered in all atopic patients with nasal polyps and chronic sinusitis.3

*Professor and Head Dept. of Microbiology Mandya Institute of Medical Sciences, Mandya, Karnataka †Senior Research Fellow Dept. of Microbiology Kasturba Medical College, Manipal, Karnataka ‡Associate Professor Dept. of Pathology #Associate Professor Dept. of ENT Mandya Institute of Medical Sciences, Mandya, Karnataka Address for correspondence Dr Sumangala B #367, 18th Main ‘D’ Block I-Stage JP Nagar, Mysore - 570 008, Karnataka E-mail: sharadasuma7@gmail.com

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CASE REPORT A 48-year-old male client attending the ENT outpatient department with a complaint of nasal obstruction and foul-smelling nasal discharge from the past 6 months was investigated by plain X-ray and CT scan (Figs. 1 and 2). Nasal polyp involving left maxillary sinus and nasal cavity was reported. Plain X-ray showed no bony involvement.

He was operated and the resected polyp was received in Mycology Section, Dept. of Microbiology, Mandya Institute of Medical Sciences, Mandya for investigation.

Potassium hydroxide (KOH) mount of the resected polyp showed fungal colony, septate hyphae with branching and fruiting heads of Aspergillus (Figs. 3 and 4).

Culture yielded mixed growth of Aspergillus niger

Figure 1. Plain X-ray of PNS (soft tissue mass in left maxillary sinus). No bony erosion seen.

ENT

Figure 4. Fruiting heads of A. niger and A. fumigatus in KOH.

Figure 2. CT scan of PNS (sinonasal polyposis involving left maxillary sinus and nasal cavity).

Figure 5. Fungal culture showing mixed growth of A. niger and fumigatus.

Figure 3. KOH of resected polyp.

and fumigatus. It was confirmed by slide culture (Fig. 5). Histopathological section was stained by hematoxylin and eosin (H&E) (Fig. 6), Grocott or Gomori methenamine silver (GMS) and periodic acidSchiff (PAS) (Fig. 7). In all these stained slides, fungal colony, septate hyphae with dichotomous branching and fruiting heads of Aspergillus could be made out.

Mixed infection by Aspergillus fumigatus and A. niger was reported.

DISCUSSION In 1983, Katzenstein et al, first described a form of noninvasive sinusitis in adults.4 Invasive rhinosinusitis due to Aspergillus causing nasal polyposis, bony

erosion has been reported.5 Nasal discharge and nasal obstruction are said to be the commonest presentation (95.8%).6 Fungi have been reported in 96% of chronic sinusitis. Aspergillus is the commonest isolate (95.8%).6 Alternaria, Penicillium, Cladosporium, A. niger, A. flavus, Candida, Fusarium are the fungi reported from nasal polyps. Mixed infection is also reported.

Maxillary sinus and ethmoidal sinuses are commonly involved. Mixed infection due to Schizophillum commune and A. niger was reported as a cause of allergic fungal rhinosinusitis (AFRS).7 One case of mixed infection with Aspergillus and Curvularia sinusitis6 and another with Candida albicans and C. tropicalis was reported.8 One case of Dreshlera sinusitis was also identified.6 A. flavus

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ENT decreases in surgical recurrence rates for this recurrent hypertrophic rhinosinusitis10 chronic rhinosinusitis and nasal polyps and asthma represent different stages of one chronic inflammatory disease of the mucosa of the nasal cavity and paranasal sinuses.1 Medical treatment of AFS includes postoperative oral corticosteroids, antiallergic inflammation therapy, surgical debridement, aeration, oral itraconazole and steroids.5,8 References

Figure 6. H&E staining of tissue section showing fruiting heads and filaments.

1. Taj-Aldeen SJ, Hilal AA, Chong-Lopez A. Allergic Aspergillus flavus rhinosinusitis: a case report from Qatar.

Eur Arch Otorhinolaryngol 2003;260(6):331-5.

2. Schwietz LA, Gourley DS. Allergic fungal sinusitis.

Allergy Proc 1992;13(1):3-6.

3. Schubert MS. Allergic fungal sinusitis: pathophysiology, diagnosis and management. Med Mycol 2009;47 Suppl 1: S324-30.

4. Gourley DS, Whisman BA, Jorgensen NL, Martin ME, Reid MJ. Allergic bipolaris sinusitis: clinical and immunopathologic characteristics. J Allergy Clin Immunol 1990;85(3):583-91.

5. Agarwal S, Kanga A, Sharma V, Sharma DR, Sharma ML. Invasive aspergillosis involving multiple paranasal sinuses: a case report. Indian J Med Microbiol 2005;23(3):195-7.

Figure 7. PAS staining of tissue section showing fungal colony and fruiting heads.

was predominantly isolated from nasal polyps.1,9,10 Regional variation in incidence of AFS has been reported. AFS allergic mucin typically cultures, positive for either dematiaceous fungi such as Bipolaris spicifera or Curvularia lunata or Aspergillus species such as A. fumigatus, A. flavus or A. niger.

The use of follow-up measurements of total serum IgE during treatment of AFS can help to monitor disease activity. AFS pilot study of AFS will lead to further insights into pathogenesis, improved treatments,

6. Rupa V, Jacob M, Mathews MS, Job A, Kurien M, Chandi SM. Clinicopathological and mycological spectrum of allergic fungal sinusitis in South India. Mycoses 2002;45 (9-10):364-7.

7. Ahmed MK, Ishino T, Takeno S, Hirakawa K. Bilateral allergic fungal rhinosinusitis caused by Schizophillum commune and Aspergillus niger. A case report. Rhinology 2009;47(2):217-21.

8. Surya Prakash Rao G, Mann SB, Talwar P, Arora MM. Primary mycotic infection of paranasal sinuses.

Mycopathologia 1984;84(2-3):73-6.

9. Fadl FA, Hassan KM, Faizuddin M. Allergic fungal rhinosinusitis: report of 4 cases from Saudi Arabia. Saudi Med J 2000;21(6):581-4.

10. Xess I, Mohanty S, Jain N, Banerjee U. Prevalence of Aspergillus species in clinical samples isolated in an Indian tertiary care hospital. Indian J Med Sci 2004;58(12): 513-9.

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Internal Medicine

Cytodiagnosis of Microfilaria at Unusual Sites Kalpana Chandra*, Praveen Kumar†, Megha Garg‡

Abstract Filariasis is a major public health problem especially in tropical countries like India. It is routinely examined in night peripheral blood smears. Fine-needle aspiration cytology (FNAC) is not routinely used for its identification. It has always been detected incidentally, while doing FNACs for evaluation of other lesions. It has been found in lymph nodes, breast, thyroid, cystic lesions, etc.

In few reported cases, it has been found even with primary/metastatic malignancy. We also found two cases of microfilaria incidentally. One on USG-guided FNAC of liver SOL (space-occupying lesion) reported as metastatic adenocarcinoma with microfilaria and other in a case of asymptomatic epitrochlear swelling reported as reactive hyperplasia of lymph node with microfilaria.

Keywords: Liver SOL, epitrochlear lymph node, microfilaria

F

ilariasis is a global problem. It is a major social and economic scourge in the tropics and subtropics of Africa, Asia, Western Pacific and parts of the Americas, affecting over 83 countries.

The disease is endemic all over India1 and is caused by two closely related nematode worms, Wuchereria bancrofti and Brugia malayi transmitted by the Culex mosquito. Despite high incidence, it is less frequent to find microfilaria in the peripheral smear. The disease mainly involves the lymph node and lymphatic system of the body.

In lymphatic filariasis, the commonly involved sites are lungs, bronchial aspirates, cervicovaginal smears, pleural and pericardial fluids.2 It is very unusual and quite incidental to find microfilaria on fine-needle aspiration cytology (FNAC) in liver SOL (spaceoccupying lesion) and in epitrochlear lymph node, which itself is very rarely involved by any diseases pathology.

*Associate Professor Dept. of Pathology †Associate Professor Dept. of General Medicine ‡Resident Dept. of Pathology ShriRamMurtiSmarkInstituteofMedicalSciences,Bhojipura,Bareilly,UttarPradesh Address for correspondence Dr Kalpana Chandra A-1, Doctor’s Residence Shri Ram Murti Smark Institute of Medical Sciences Bhojipura, Bareilly - 243 202, Uttar Pradesh E-mail: kalpana_chandra_14@yahoo.co.in

This case is reported only because of peculiarity of site where it was not clinically suspected and how careful and vigilant screening of smear led to its identification and helped in further management.

CASE REPORTS

Case 1 A 60-year-old male presented with breathlessness and pain in abdomen since 1 month. Patient was admitted in our hospital and investigated with routine hematological examination, ultrasonography (USG) abdomen and contrast-enhanced computed tomography (CECT) thorax. Findings were suggestive of lung mass with multiple liver metastases and advised USGguided FNAC. On USG-guided FNAC, hemorrhagic aspirate was obtained. Smears revealed moderately cellular aspirate and composed of neoplastic cells morphologically resembling adenocarcinoma cells.

Background showed small clusters of benign hepatocytes, few chronic inflammatory cells and microfilarial parasites (Figs. 1 and 2). The diagnosis of metastatic epithelial malignancy of glandular origin with microfilaria was made.

Case 2 A 22-year-old male presented with a painless swelling of right arm, since 1 month with no other significant clinical symptom. On examination, a small subcutaneous swelling in right elbow of about 1.5 × 1 cm was noted.

Swelling was firm, nontender and movable.

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Figures 1 and 2. Clusters of neoplastic cells and microfilaria (MGG-40X).

Figures 3 and 4. Straight and curved microfilaria with lymphoid cells in the background (MGG-40X).

FNAC was performed from the swelling, which yielded blood mixed aspirate. Smears revealed polymorphous cell population of small and large lymphoid cell along with numerous ensheathed coiled and slightly curved microfilaria (Figs. 3 and 4). A final diagnosis of reactive lymphoid hyperplasia with microfilaria was made. This patient took the treatment and remained asymptomatic after therapy.

Microfilaria displays nocturnal periodicity. That is why, three consecutive night blood samples are commonly used for its detection but considered less sensitive tools for its diagnosis. Other methods are circulating filarial antigen (CFA) detection test, which is now regarded as the gold standard and demonstration of organism in histopathological sections.3 FNAC are not applied for routine diagnosis of clinically suspected filariasis.

Incidental detection on FNAC has been reported in cytological smears from almost any part of body and it is the most frequently diagnosed parasite and microfilaria is the most common form. The presence of microfilaria along with neoplasm is generally regarded as a chance association. In our case also, where there was a strong clinical suspicion of metastatic malignancy involving liver, microfilaria was a chance finding. This may be due to its transmigration along with metastatic emboli.

It has also been suggested that such aberrant migration to these dead- end sites is probably determined by local factors such as lymphatic blockage by scars or tumors and damage to the vessel wall by inflammation, trauma

DISCUSSION Filariasis is a global health problem of huge magnitude.

Adult worms are found in the lymphatic vessels and lymph nodes of human beings only, whereas larval forms (microfilaria) may circulate in the peripheral blood. Humans are exclusive and definitive host for W. bancrofti. The major vectors are Culex mosquitoes in most of the urban areas and Anopheles mosquitoes in rural areas. A significant number of infected individuals in endemic areas remain asymptomatic throughout their life.

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Internal Medicine or stasis. Rich blood supply in the tumors could be a reason for concentration of parasites at these sites.3 Gupta has emphasized that microfilariae wander in tissue fluid and may get entrapped in needle during aspiration.4

I am highly thankful to Dept. of Pathology, Medicine, Microbiology and Radiology department for providing me adequate facility, which helped me to carry out this study.

I owe great sense of indebtedness to Dean (SRMS-IMS), Bhojipura, Bareilly for permitting me to carry out this study.

Microfilariae have been reported in association with malignant lesions as well as benign lesions. Some malignant lesions where microfilariae have been detected are Ewing’s sarcoma of the bone, nonHodgkin’s lymphoma, squamous cell carcinoma of the maxillary antrum, craniopharyngioma of the third ventricle, transitional cell carcinoma of the bladder, follicular carcinoma of the thyroid, seminoma of undescended testis, etc.3 Benign lesion sites are breast, testis, epididymis, thyroid, lung, lymph nodes, skin, etc.4,5 Kumar et al6 reported a case of microfilaria in the supraclavicular lymph node in the background of malignant cells where the primary was in the stomach.

In our case, the chance detection of microfilariae from liver in a case of metastatic malignancy and from isolated swelling in the epitrochlear region, which is an infrequent site for lymphadenopathy signifies the value of FNAC and careful screening of the smears in the detection of asymptomatic and clinically unsuspected cases of filariasis.

REFERENCES

Acknowledgment I take this opportunity to extend my gratitude and sincere thanks to all those who helped me to complete this study.

1. Park K. Lymphatic filariasis, epidemiology of communicable diseases. In: Textbook of Preventive and Social Medicine. 22nd edition, Banarasidas Bhanot Publishers: Jabalpur; pg.245.

2. R Veena Kumar, R Sridhar Reddy. Adult filarial worms in tissue sections of a painless breast mass. J Cont Med A Dent 2014;2(1):48-50.

3. K atti TV, Athanikar VS, Ananthrao AS, Rathod CV. Cytodiagnosis of microfilarial lymphadenitis coexistent with metastatic squamous cell carcinoma in a left cervical lymph node: An unusual presentation. Ann Nigerian Med 2012;6:47-9.

4. Gupta S, Gupta R, Bansal B, Singh S, Gupta K, Kudesia M. Significance of incidental detection of filariasis on aspiration smears: a case series. Diagn Cytopathol 2010;38(7):517-20.

5. Garg PK, Jain BK, Rathi V, Singh N, Mohanty D. Mid-arm and epitrochlear lymphadenopathy: a clinico-radiological surprise. J Infect Dev Ctries 2011;5(11):820-4.

6. Kumar R. Microfilariae in lymph node aspirate associated with metastatic gastric carcinoma: a case report. Acta Cytol 2010;54(3):319-20.

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Atrial Fibrillation Doubles Risk for Silent Stroke Atrial fibrillation (AF) is associated with a more than two-fold increase in the odds for silent cerebral infarction (SCI), or a stroke that has no outward signs or symptoms, according to a review being published in Annals of Internal Medicine. AF is the most common arrhythmia in the elderly, affecting more than 2.7 million Americans.

Patients with AF have up to five times greater risk for stroke and poorer post-stroke outcomes than those without AF. Research indicates that AF is associated with a 40% increase in the risk for cognitive impairment, independent of a history of symptomatic stroke and comorbid conditions, suggesting another underlying cause, such as SCI.

Bleeding Risks in Patients with Atrial Fibrillation Two new studies have provided more data on the bleeding risks among patients with atrial fibrillation (AF) treated with dabigatran, with one showing that the oral anticoagulant carries a significantly higher risk of major bleeding, as well as gastrointestinal bleeding, when compared with warfarin. The first report is published in JAMA: Internal Medicine while the second one is published in Circulation. In the second report, there was no increased risk of major bleeding with dabigatran, but there was a 28% greater risk of gastrointestinal hemorrhage.

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Internal Medicine

Association of Proton Pump Inhibitor with Hypomagnesemia: A Cross-sectional Study at a Tertiary Care Hospital of Anand District Dunkin U Shah*, Punam D Sachdeva*

Abstract Proton pump inhibitors (PPIs) are one of the most chronically used class of drugs for gastroesophageal reflux disease and number of other common persistent conditions. Hence, risk of long-term potential side effects associated with their use is increasing. On March 2, 2011, US FDA informed the public the risk of hypomagnesemia associated with prolonged use of PPIs. Hence, the present study was undertaken to estimate the risk of development of hypomagnesemia in patients who have been on PPIs therapy for at least 1 month and to check whether PPI-induced hypomagnesemia is a long-term drug class effect of all PPIs. General demographic data, type of PPI used with its duration of use and dose, morbid conditions, concomitant illness and several other confounders available from the basic metabolic panel of 60 patients (30 long-term PPI users and 30 nonusers of PPIs), was collected and documented on a structured questionnaire. Serum magnesium (S. Mg) levels of all 60 patients was estimated and the data collected was analyzed using t-test and ANOVA. PPI users had mean S. Mg/level 1.848 Âą 0.023 mg/dL and nonusers 2.167 Âą 0.34 mg/dL, the difference being statistically significant (p = 0.00) and it was independent of age, gender and concomitant drugs prescribed. However, female PPI users had slightly lower S. Mg levels of 30 recruited PPI users, four were asymptomatic hypomagnesemic (S. Mg levels <1.7 mg/dL). Mean S. Mg level of esomeprazole users were slightly higher than omeprazole or pantoprazole users with statistically insignificant difference.

Keywords: Proton pump inhibitors, hypomagnesemia, omeprazole, serum magnesium

P

roton pump inhibitors (PPIs) are now one of the most widely used class of drugs. They have proven to have a very favorable safety profile and it is unusual for a patient to stop the drug because of side effects. However, increasing number of patients are chronically taking PPIs for gastroesophageal reflux disease and number of other common persistent conditions, therefore long-term potential side effects are receiving increased attention.1

Epidemiological studies have demonstrated that their use is associated with an increased risk for pneumonia, enteric microbial growth and sepsis, although the attributed risk may be dependent upon the confounding

*Dept. of Clinical Pharmacy AR College of Pharmacy Vallabh Vidhyanagar, Gujarat Address for correspondence Dr Dunkin U Shah B Wing-204, Lake Bloom Residency Near Larsen and Toubro Gate #6, Powai, Mumbai - 400 072 E-mail: dunkinshah@gmail.com

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factors. One area that is receiving much attention and generally that has been poorly studied is long-term effect of chronic acid suppression on the absorption of vitamins and nutrients.1 On March 2, 2011, US Food and Drug Administration (FDA) informed the public of risk of hypomagnesemia associated with prolonged use of PPIs.2 Although recognized as a rare side effect of PPIs, hypomagnesemia is a serious condition that can be complicated by life-threatening arrhythmias and neurologic manifestations.3,4 Most reports on PPI-induced hypomagnesemia concern omeprazole or esomeprazole, S-isomer of omeprazole, but recurrence after substitution by other PPIs suggest that this is a class effect commonly found for PPIs.5 A direct retrospective data analysis of hospitalized patients identified PPI use to be associated with lower magnesium (Mg) levels.6 A few case reports show the use of PPIs resulting in profound but reversible isolated hyponatremia, hypocalcemia and hypokalemia.7-10 And importantly, over the last 5 years, several clinical case reports have been published that demonstrate PPI use to induce severe hypomagnesemia.11-14

Internal Medicine Hypomagnesemia (PPIH) leads to severe symptoms such as seizures, tetany, convulsions, cardiac arrhythmia and puts patients at risk for concomitant secondary electrolyte disturbances such as hypocalcemia.15 Thus, the present study was undertaken to investigate the dynamics of S. Mg in patients who have been on PPI therapy for at least 1 month and to investigate whether or not proton pump-induced hypomagnesemia (PPIH) is a true, long-term drug class effect of all PPIs. MATERIAL AND METHODS

Research Design Cross-sectional study.

Inclusion Criteria Adult male or female patients in the age group of 18-80 years who had been on PPI therapy for a period of at least 1 month and those who were not taking PPI therapy belonging to similar morbid conditions.

Exclusion Criteria Patients with hepatic or renal impairment, pregnant or nursing women, patients suffering from acute pancreatitis, diarrhea and congestive heart failure.

Also, the patients taking the drugs which affect S. Mg levels such as ethacrynic acid, furosemide, gentamycin, amphotericin B, cyclosporine, digitalis, cisplatin and antihypertensives such as b-blockers and angiotensinconverting enzyme (ACE) inhibitors were excluded from the study.

It was a cross-sectional study of 4-month duration.

Approval was obtained from the Human Research Ethics Committee of Shree Krishna Hospital of the Anand district. As per the protocol, 60 patients were recruited in the study of which 30 were the cases of patients who were on PPI therapy for at least 1 month, while the remaining 30 were the cases of patients with similar morbid conditions but who were not on PPI therapy.

The scientific data of these 60 subjects had been collected based on inclusion-exclusion criteria. Informed consent of the recruited patients was taken before enrolling them into the study. S. Mg levels of all the 60 patients was estimated at Pathological Laboratory of Shree Krishna Hospital by colorimetric method. Data of patients was collected and recorded in Case Record Form (CRF), which included general demographic data, condition for which PPI is prescribed, type of PPI, dose and its duration of use, concomitant drugs prescribed, S. Mg level and other parameters such

as S. creatinine, S. albumin, S. sodium, S. potassium, S. chloride, S. total calcium, if available and symptoms associated with hypomagnesemia. The scientific data was analyzed using appropriate statistical tests such as frequency distribution, t-test and ANOVA. RESULTS Of all 60 patients, whose data was collected, 28 were male and 32 were female. Based on their age, subjects were categorized into three categories: 20-40 years, 41-60 years and 61-80 years. Mean age for PPI users was found to be 50.73 ± 2.785 years, while that of nonPPI users was found to be 45.27 ± 2.533 years.

Serum Mg Levels in PPI Users and Nonusers The normal S. Mg level in a healthy adult is 1.7-2.4 mg/dL. Hypomagnesemia is defined as S. Mg levels less than the normal range. Table 1 shows mean S. Mg levels in PPI users and non- PPI users. As it is evident from the Table 1 that S. Mg level in both the groups fall almost within the normal range but comparing the mean S. Mg level in PPI users as well as PPI nonusers, it was observed that users of PPIs had significantly lower S. Mg levels (p < 0.05). An important observation of this study was that of the 30 users of PPIs, whose data was collected, four patients had S. Mg levels <1.7 mg/dL (i.e., they showed hypomagnesemia but were asymptomatic).

Serum Mg Levels with Respect to the Age Group of Subjects Table 2 shows the comparison of mean S. Mg level in PPI users and PPI nonusers based on age group of patients. As it is evident from the table that mean S. Mg level was found to be lower in PPI users of all age groups as compared to PPI nonusers and the difference was found to be statistically significant (p < 0.05).

Mean Serum Mg Levels in PPI Users and NonPPI users Based on Sex Table 3 shows mean S. Mg levels in PPI users and PPI nonusers based on their sex. As it is evident from the Table 1. Mean Serum Mg Levels in PPI Users and Non PPI Users Parameter

PPI users (n = 30)

S. Mg (mg/dL) 1.848 ± 0.02448

PPI nonusers (n = 30) 2.167 ± 0.03419

P value 0.000*

Values are mean ± SEM; *p < 0.05, statistically significant by t-test.

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Internal Medicine table that mean S. Mg level is found to be significantly (p = 0.000) lower in females as compared to males in both PPI users as well as PPI nonusers.

Mean Serum Mg Levels with Respect to the Duration of Use of PPI Of the 30 patients using PPIs, whose data was collected, it was observed that the duration of the use of PPIs in those patients ranged from 32 to 780 days. Table 4 shows the mean S. Mg levels of PPI users with respect to the duration of use and type of PPIs prescribed.

It is evident from Table 4 that mean S. Mg level of esomeprazole users was slightly higher as compared to omeprazole or pantoprazole users. However, the difference in mean S. Mg level between the users of pantoprazole, omeprazole and esomeprazole was not statistically significant by one way ANOVA.

Mean Serum Mg Levels in PPI Users and Nonusers of PPIs Based on Concomitant Drugs PPIs are widely used by patients who receive antihypertensives, antidiabetics, analgesics, antibiotics, anticonvulsants, antiemetics, statins, psychiatric drugs to suppress dyspepsia associated with the use of these drugs. Patients who used other drugs were the users of corticosteroids, thyroxine sodium, acyclovir, cyclopam, baclofen, sucralfate and tolperisone. Data of the nonusers of PPIs was also obtained from patients using similar categories of drugs. Table 5 shows mean S. Mg levels in PPI users and PPI nonusers based on concomitant drugs. It is evident from the Table 5 that S. Mg level in all PPI users was low as compared to PPI nonusers with highly significant difference (p < 0.05), irrespective of the concomitant drugs prescribed.

Mean Serum Levels of Various Variables Among PPI Users and PPI Nonusers To check the influence of the use of PPIs on various other variables like creatinine, sodium, potassium, chloride, calcium and albumin, the data of their serum levels was obtained from case sheets of patients in whom they were routinely carried out. Table 6 shows mean serum level of various variables among PPI users and PPI nonusers. Comparing the values of these variables with the normal range provided in the table, it is evident that values of all the variables are within the normal range.

DISCUSSION Our cross-sectional study revealed that PPI users had significantly lower S. Mg levels compared to

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Table 2. Mean Serum Mg Levels in PPI Users and PPI Nonusers Based on Age of Users Age group (years)

Mean S. Mg level of PPI users (n = 30) (mg/dL)

Mean S. Mg level P value of PPI nonusers (n = 30) (mg/dL)

20-40

1.892 ± 0.02798

2.173 ± 0.05742

0.000*

41-60

1.862 ± 0.04080

2.174 ± 0.04148

0.000*

61-80

1.784 ± 0.05124

2.133 ± 0.1936

0.035*

Values are mean ± SEM; *p < 0.05, statistically significant by one way ANOVA.

Table 3. Mean Serum Mg Levels in PPI Users and PPI Nonusers Based on their Sex Sex

Mean S. Mg level in PPI users (n = 30)

Mean S. Mg level in PPI nonusers (n = 30)

Male

1.873 ± 0.04561 (n = 12)

2.212 ± 0.05536 (n = 16)

0.000*

Female

1.831 ± 0.02768 (n = 18)

2.116 ± 0.03419 (n = 14)

0.000*

P value

Values are mean ± SEM, *p < 0.05, statistically significant by t-test.

Table 4. Mean Serum Mg Levels with Respect to the Duration of Use of PPI Type of PPI

Duration of use (mean)

Pantoprazole

141.9 days

1.829 ± 0.03220

Omeprazole

99.86 days

1.860 ± 0.05757

Esomeprazole 90 days

Mean S. Mg level (mg/dL) of PPI users

P value

0.5269

1.913 ± 0.01652

Values in the table are mean ± SEM, p > 0.05, statistically insignificant by one way ANOVA.

PPI nonusers, which is in correlation with the results reported by Gau et al.6 They also reported that PPI users had significantly lower S. Mg levels than nonusers of PPIs. An important observation of our study was that of the 30 users of PPIs, whose data was collected, four of the patients had S. Mg levels <1.7 mg/dL (i.e., they showed hypomagnesemia). However, they were asymptomatic. Our results correlate with those of Hess et al,16 who reported that many cases of PPIs-induced hypomagnesemia are asymptomatic. Also, Tamura, et al5 reported that symptoms of PPIH did not occur until plasma concentrations of Mg were <1.22 mg/dL. A very interesting observation of our study is low S. Mg levels in users of PPIs in all age groups of patients suggesting that age is not a factor influencing S. Mg

Internal Medicine Table 5. Mean Serum Mg Levels in PPI Users and Nonusers of PPIs Based on the Concomitant Drugs Prescribed Drug class

Mean S. Mg level of PPI users (n = 30) (mg/dL)

Mean S. Mg level of PPI nonusers (n = 30) (mg/dL)

P value

Antihypertensives

1.817 ± 0.04569 (n = 13)

2.237 ± 0.08403 (n = 7)

0.000674362*

Anticonvulsants

1.785 ± 0.05130 (n = 6)

2.423 ± 0.09939 (n = 3)

0.005334873*

Analgesics

1.876 ± 0.04018 (n = 8)

2.144 ± 0.05976 (n = 14)

0.000688*

Antidiabetics

1.794 ± 0.05352 (n = 9)

2.066 ± 0.1179 (n = 5)

0.0403736*

Antibiotics

1.842 ± 0.02884 (n = 12)

2.226 ± 0.06944 (n = 11)

0.000*

Antiemetics

1.808 ± 0.05160 (n = 6)

2.168 ± 0.1322 (n = 4)

0.032329817*

Calcium supplements

1.853 ± 0.05220 (n = 6)

1.997 ± 0.05103 (n = 6)

0.0389915*

Psychiatric drugs

1.893 ± 0.02068 (n = 8)

2.174 ± 0.04407 (n = 9)

0.000*

Antiasthmatics

1.882 ± 0.02437 (n = 5)

2.183 ± 0.04626 (n = 4)

0.001117941*

Multivitamin prep

1.836 ± 0.04448 (n = 10)

2.168 ± 0.06680 (n = 6)

0.001259086*

Statins

1.617 ± 0.05783 (n = 3)

2.200 ± 0.09460 (n = 5)

0.000949855*

Antihistamines

1.895 ± 0.01500 (n = 2)

2.157 ± 0.04449 (n = 19)

0.000*

Antiplatelets and anticoagulants

1.797 ± 0.04724 (n = 7)

2.145 ± 0.05500 (n = 2)

0.008615286*

Thyroid hormones

1.810 ± 0.05930 (n = 4)

2.355 ± 0.1150 (n = 2)

0.02600332*

Others

1.940 ± 0.06940 (n = 4)

2.094 ± 0.02952 (n = 8)

0.055558

Values in the table are mean ± SEM, *p < 0.05, statistically significant by t-tests.

Table 6. Mean Serum Levels of Various Variables among PPI Users and PPI Nonusers Variable

PPI users

PPI nonusers

Normal range

P value

Serum creatinine (mg/dL)

0.6858 ± 0.05586 (n = 12)

0.6871 ± 0.06046 (n = 7)

0.7-1.3 (Male) 0.6-1.1 (Female)

0.49375865

Serum sodium (mmol/L)

135.2 ± 1.589 (n = 11)

138.0 ± 1.592 (n = 6)

135-145

0.11610784

Serum potassium (mmol/L)

3.591 ± 0.3625 (n = 11)

3.783 ± 0.6187 (n = 4)

3.5-5

0.400003148

Serum Cl (mEq/L)

107.0 ± 1.69 (n = 6)

104.3 ± 2.175 (n = 4)

96-106

0.178449534

Serum calcium (mg/dL)

9.315 ± 0.08253 (n = 6)

9.043 ± 0.2013 (n = 4)

8.5-10.2

0.13930954

Serum albumin (gm/dL)

4.530 ± 0.4437 (n = 5)

4.495 ± 0.3193 (n = 6)

3.4-5.4

0.475258938

Values are mean ± SEM, p > 0.05, statistically insignificant by t-test.

levels. Similar observation has been reported by Hess et al.15 Another notable observation of our study is that S. Mg levels in female PPI users were significantly lower as compared to male PPI users. The reason for female preponderance in low S. Mg levels is unclear, but it correlates with the results reported by Mackay and Bladon.3 Evidence of hypomagnesemia-induced due to longterm use of PPIs is available from various case reports wherein the use of PPIs ranged from 14 days up to 13 years (mean 5.5 years).15 Duration of PPI use in our population ranged from 32 to 780 days, which is a very short period to get confirmed evidence of association between the use of PPIs and hypomagnesemia.

Tamura et al5 reported that PPIH was observed more in patients using omeprazole or esomeprazole. Comparing the S. Mg levels in patients prescribed with different PPIs like omeprazole, esomeprazole or pantoprazole, we observed that there was no significant difference in their respective mean S. Mg levels. However, use of PPIs lowers S. Mg levels, irrespective of their types which suggests that PPIH may be a commonly found drug class effect which correlates with the results reported

by Hess et al15 and Gau et al.6 Other observations reveal that S. Mg levels in all PPI users were significantly low as compared to nonusers of PPI, which is irrespective of their morbid conditions and concomitant drugs prescribed.

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Internal Medicine A few case reports show that the use of PPIs result in profound but reversible isolated hyponatremia, hypocalcemia and hypokalemia.7-10 In some cases, the hypomagnesemia is accompanied by hypokalemia and/or hypocalcemia.3,12,17 Mackay reported that hypocalcemia was evident in association with severe hypomagnesemia.3 Gau et al6 reported that patients with lower S. albumin levels are more likely to be magnesium depleted. Based on these reports, in order to check the influence of the use of PPIs on various other variables like creatinine, sodium, potassium, chloride and albumin, the data of their serum levels was also recorded down for those patients in whom they were routinely carried out. However, we could not observe these electrolyte disturbances probably since the sample size was small.

Reports of other studies state that, there was no typical patient profile that was unique for PPIH and the final attribution of the symptoms and electrolyte abnormalities to PPIH sometimes took years16 and in the absence of symptoms, identification of PPIH was purely dependent on chance.3,18 The mechanisms that explain lower S. Mg levels observed in PPI users are not clear. Almost all of the cases reported in the literature have no evidence of renal Mg wasting12 except one case that suggested that a reduced efficiency of renal Mg conservation may be involved.19 Mg absorption from the gastrointestinal (GI) tract is a complex process, in which both passive and active transports are involved.3,20 It is not known how PPI therapy may disturb each transport system in the GI tract despite some researchers suggesting that PPI may affect Mg active transport channels, transient receptor potential melastatin subtype 6 (TRPM6), which is responsible for the absorption of Mg in the kidney and GI tract.20-22 Thus, results of our study depict that long-term use of PPIs reduces the S. Mg levels though not to the extent of causing significant hypomagnesemia, which support the general notion that PPI therapy may lead to subclinical degrees of low Mg levels or deplete Mg stores as suggested by the FDA2 and others.23 Limitations ÂÂ

The sample size was too small because of fund limitation and shortage of time.

ÂÂ

Dietary intake of Mg was not taken into account while taking the patient data.

ÂÂ

Data of S. Mg level before and after the initiation of PPI therapy was unavailable.

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ÂÂ

Because our study was cross-sectional, our findings can only imply an association but not a cause-andeffect relationship.

CONCLUSION Our cross-sectional study revealed that significantly lower S. Mg levels were observed in PPI users as compared to nonusers of PPIs and it implies that longterm use of PPIs could be associated with subclinical Mg insufficiency or deficiency status.

Thus, we conclude that PPI users are at increased risk of developing hypomagnesemia, which could be asymptomatic in the initial stage, but patient may develop symptoms in the long run. Hence, routine monitoring of S. Mg levels is essential for the patients who are on long-term PPI therapy to prevent them from the risk of developing PPIH. Our results also suggested that since different types of PPIs were involved with low S. Mg levels or hypomagnesemia, collectively we can conclude that it is a class effect of all PPIs. Future prospective studies that include pre-treatment and post-treatment Mg levels when initiating PPI therapy will provide more direct evidence for the association of PPIs and hypomagnesemia and shall clarify its underlying mechanism(s).

Acknowledgment We are very grateful to the Charutar Vidya Mandal to have provided us financial support to estimate S. Mg levels of all the patients recruited into the study. We’re very thankful to Dr Ajay Mishra, MD (General Medicine) from Shree Krishna Hospital, Karamsad for his valuable suggestions and guidance throughout the study.

REFERENCES 1. I to T, Jensen RT. Association of long-term proton pump inhibitor therapy with bone fractures and effects on absorption of calcium, vitamin B12, iron, and magnesium.

Curr Gastroenterol Rep 2010;12(6):448-57.

2. U S Food and Drug Administration. FDA Drug Safety Communication: Low magnesium levels can be associated with long-term use of Proton Pump Inhibitor drugs (PPIs).

Drug Safety Communication March 2011. Available from: www.fda.gov/Drugs/DrugSafety/ucm245011.htm 3. M ackay JD, Bladon PT. Hypomagnesaemia due to proton-pump inhibitor therapy: a clinical case series. QJM 2010;103(6):387-95.

4. Cundy T, Mackay J. Proton pump inhibitors and severe hypomagnesaemia. Curr Opin Gastroenterol 2011;27(2):180-5.

Internal Medicine 5. Tamura T, Sakaeda T, Kadoyama K, Okuno Y. Omeprazoleand esomeprazole-associated hypomagnesaemia: data mining of the public version of the FDA Adverse Event Reporting System. Int J Med Sci 2012;9(5):322-6.

6. Gau JT, Yang YX, Chen R, Kao TC. Uses of proton pump inhibitors and hypomagnesemia. Pharmacoepidemiol Drug Saf 2012;21(5):553-9.

and famotidine in severe hypomagnesaemia due to omeprazole. Neth J Med 2010;68(10):329-30.

15. Hess MW, Hoenderop JG, Bindels RJ, Drenth JP. Systematic review: hypomagnesaemia induced by proton pump inhibition. Aliment Pharmacol Ther 2012;36(5):405-13.

16. Burtis CA, Ashwood ER, Bruns DE. Tietz fundamentals of Clinical Chemistry. VIth edition, Elsevier; 2008.

7. Melville C, Shah A, Matthew D, Milla P. Electrolyte disturbance with omeprazole therapy. Eur J Pediatr 1994;153(1):49-51.

17. Hoorn EJ, van der Hoek J, de Man RA, Kuipers EJ, Bolwerk C, Zietse R. A case series of proton pump inhibitor-induced hypomagnesemia. Am J Kidney Dis 2010;56(1):112-6.

8. Nealis TB, Howden CW. Is there a dark side to long-term proton pump inhibitor therapy? Am J Ther 2008;15(6): 536-42.

18. Gutiérrez Macías A, Ibarmia Lahuerta J, Alvarez De Castro M, Lizarralde Palacios E. Severe hypomagnesemia related to omeprazole. Rev Clin Esp 2011;211(9):488-9.

9. Lodato F, Azzaroli F, Turco L, Mazzella N, Buonfiglioli F, Zoli M, et al. Adverse effects of proton pump inhibitors.

Best Pract Res Clin Gastroenterol 2010;24(2):193-201.

19. Regolisti G, Cabassi A, Parenti E, Maggiore U, Fiaccadori E. Severe hypomagnesemia during long-term treatment with a proton pump inhibitor. Am J Kidney Dis 2010;56(1):168-74.

10. Insogna KL. The effect of proton pump-inhibiting drugs on mineral metabolism. Am J Gastroenterol 2009;104 Suppl 2:S2-4.

11. Broeren MA, Geerdink EA, Vader HL, van den Wall Bake AW. Hypomagnesemia induced by several proton-pump inhibitors. Ann Intern Med 2009;151(10):755-6.

12. Kuipers MT, Thang HD, Arntzenius AB. Hypomagnesaemia due to use of proton pump inhibitors - a review. Neth J Med 2009;67(5):169-72.

20. Quamme GA. Recent developments in intestinal magnesium absorption. Curr Opin Gastroenterol 2008;24(2):230-5.

21. Schlingmann KP, Weber S, Peters M, Niemann Nejsum L, Vitzthum H, et al. Hypomagnesemia with secondary hypocalcemia is caused by mutations in TRPM6, a new member of the TRPM gene family. Nat Genet 2002;31(2):166-70.

13. Quasdorff M, Mertens J, Dinter J, Steffen HM. Recurrent hypomagnesemia with proton-pump inhibitor rechallenge. Ann Intern Med 2011;155(6):405-7.

22. Schlingmann KP, Waldegger S, Konrad M, Chubanov V, Gudermann T. TRPM6 and TRPM7 - Gatekeepers of human magnesium metabolism. Biochim Biophys Acta 2007;1772(8):813-21.

14. Fernández-Fernández FJ, Sesma P, Caínzos-Romero T, Ferreira-González L. Intermittent use of pantoprazole

23. Yang YX, Metz DC. Safety of proton pump inhibitor exposure. Gastroenterology 2010;139(4):1115-27.

■■■■

Isolating Most Severe Ebola Patients may Stop Epidemic Isolation of the most severely ill patients with Ebola within the first few days of symptoms may be the key to ending the epidemic. A new mathematical model of the Ebola epidemic in Liberia reveals that a shift in the focus of public health efforts from case isolation and hygienic burial of the dead to the isolation of infected individuals before they progress into critical condition and the late phase of illness may slow disease transmission.

Dan Yamin, PhD, from the Yale School of Public Health in New Haven, Connecticut, and colleagues report the results of their stochastic transmission model in an article published online October 28 in the Annals of Internal Medicine. The investigators used contact tracing data from Liberia for their model. They could only use available data and acknowledge that the actual case fatality rate from the ongoing Ebola outbreak is still uncertain.

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MEDICAL ETHICS

Medical Ethics in Abortion Alka B Patil*, Pranil Dode†, Amruta Ahirrao†

Abstract Abortion is one of the controversial issues discussed in medical ethics. Abortion is advocated by the persons who have themselves been born. Abortion is a human right issue because human beings have a right to life. When does a person begin to exist is a moral issue. By all the criteria of modern molecular biology, life is present from the moment of conception. First step in the evolution of ethics is the solidarity with the other human being. In this article, principalisms of medical ethics are discussed. Ethics concerning medical termination of pregnancy are analyzed. Dilemmas of aborting a malformed fetus are explored. In the system of human rights against each other, the right to the life of the mother and the same right of the fetus.

Keywords: Medical ethics, abortion, malformed fetus, fetal rights

“The vanity of sciences will not console for the ignorance of mortality in the time of affliction. But the science of ethics will always console for the ignorance of the physical science.”

–Blaise Pascal Obstetrics is a specialty dealing with two lives, closed linked, whose interests may not always coincide.

Abortion raises a lot of ‘heat and dust’ during policy discussions. In some countries elections have been lost on this issue. Hippocrates considered termination of pregnancy as unethical. Time have changed and abortion has been accepted by many societies, the health of the mother being the most important consideration. Abortion is one of the most controversial issues in today’s world. People tend to turn to the law when trying to decide what is the best possible solution to an unwanted pregnancy. ‘Antagonistic relationship’ between the woman and her unborn child may occur.

Whether fetus in utero has rights before viability is a subject of dispute and opinion. In any case, the embryo or fetus of any age is protected by Hippocratic code.

“I will maintain the utmost respect for human life, from the time of conception.”

*Professor and Head †Resident Dept. Obstetrics and Gynecology ACPM Medical College, Dhule, Maharashtra Address for correspondence Dr Alka B Patil Professor and Head ACPM Medical College, Dhule - 424 001, Maharashtra E-mail: alkabpatil@rediffmail.com

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Ethics is an essential dimension of the obstetrics practice.

Ethics is the disciplined study of mortality. Ethical principles and virtues should be applied to all the physicians, regardless of their personal, religious and spiritual beliefs. Thus, medical ethics are transnational, transcultural and transreligious1 ethics are professional standards. Ethics may be extended to professional responsibility, mortality, etiquette, values and attitudes.

Ethics tends to be focused on moral goods rather than natural goods. Obstetricians should have their own professional ethical values, ethics core value and ethics family values. While morality in behavior may be concerned with one’s personal convictions and legality the result of what the society considers acceptable, ethicality is often decided by professional consensus.

Thus, there is a thin line between what is ‘ethical’ and what is ‘legal’.2 Ethical issues are identified and framed through a ‘naturalized bioethics’ approach. This approach critiques traditional bioethics and gives attention to everyday ethics and the social, economic and political context within which ethical problems exist. Moral problems of healthcare extend well-beyond the issues that interest the media and ethical experts. Expanding our concept of an ethical problem to include the moral problems of everyday life strengthens the moral imagination we need to create ‘good’ obstetric care.

Ethical questions about health, illness and medical care were once considered to be best left to the judgment of physicians. Bioethics replaced the notion that ‘doctor knows best’ with theoretically grounded approaches to decision-making in medicine. In order to help resolve the dilemmas that arise in healthcare, academic

MEDICAL ETHICS bioethicists have called upon a number of ethical theories-deontology, teleology, virtue theory, care ethics, feminist ethics, to name a few but the day-to-day work of bioethicists in the clinic and on research review committees is, for the most part, guided by a method of ethical problem solving known as ‘principalism’.3 In this much used, much-cited text the authors set forth four principles.

Respect for: ÂÂ

Autonomy

ÂÂ

Beneficence

ÂÂ

Nonmaleficence

ÂÂ

Justice4

Autonomy This principle acknowledges the fact that the patient has a perspective of her interest based on her values and beliefs. The patient has the right to choose or refuse treatment.

Autonomy in Medical Ethics We live in the “time of the triumph of autonomy in bioethics” in which “the law and ethics of medicine are dominated by one paradigm-the autonomy of the patient”. This is perhaps not surprising given that “from the outset, the conceptual framework of bioethics has accorded paramount status to the valuecomplex of individualism, underscoring the principles of individual rights, autonomy, self-determination and their legal expression in the jurisprudential notion of privacy”. The patient-doctor relationship only works when each can trust the other.

Beneficence A doctor should always have the best interest of the patient as the supreme consideration. Doctor should assess objectively and meticulously all the available diagnostic and therapeutic options and to implement those that protect and promote the interest of the patient by ensuring a balance of good over harm.

Nonmaleficence A doctor must make sure that in the first place, he does no harm.

Justice It is the fair distribution of health resources and the decision of who gets what treatment is fairness and equality. Central issue concerns the moral status of

the human fetus. It concerns the nature and attributes that an entity requires to have ‘full moral standing’ or ‘moral inviolability’ including a ‘right to life’. But what of the human being, as it develops from newly fertilized ovum, to pre-embryo, embryo, fetus, new born baby, to unequivocally mature autonomous person with full moral standing including a moral and legal right not to be killed at least.5 Right to Life Every human has the inherent right to life. Right to life is inherent in a person, a human being.

Who is a human? When does a developing embryo become a person. It is extremely difficult to draw a line and say that the developing zygote or fetus become a person from a particular time. The fertilized ovum has within it all components needed for the growth and development into full person. Damages are claimed, if an injury is caused to the fetus in the womb. It would mean that fetus is a person. Can the life of a person be ended by procedures by others?

Some people have interpreted that the developing fetus can be considered a person, when the fetus is viable and capable of independent existence if removed from the milieu of the uterus. The period is progressively being reduced due to advances in medicine. Others have stated that the developing embryo can be considered a person when the brain starts developing, drawing the analogy of brain death.6 This is a significant moral consideration. There is a difference between killing or destroying something and preventing something from coming into existence.

Preventing something coming into existence denies a future of value, as does destruction. People tend to turn to the law when trying to decide what is the best possible solution to an unwanted pregnancy.7 Abortion is One of the Controversial Issues Discussed in Medical Ethics The opponents of abortion argue as follows: ÂÂ

Fetus has to be regarded as human being

ÂÂ

Killing an innocent human being is morally wrong

ÂÂ

Aborting is an example of killing and terminating a human being’s life. So, being engaged in aborting is morally wrong.

If one is adamantly opposed to abortion, one is committed to some set of values, which requires that women who become pregnant (whether intentionally or unintentionally)

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MEDICAL ETHICS must endure the process of pregnancy and birth, no matter how distressing, painful and risky it is for them. The justification given for this is usually based on an abstract notion of the value of ‘fetal life’, rather than on the ground that suffering is morally improving for the women concerned. Extreme opponents of abortion argue that abortion is equivalent to murder and that, no matter how much women may suffer, they cannot be allowed to ‘kill their children’.

Termination of pregnancy brings out conflicts of right between two persons, the right of mother and the right of child in womb. Has the mother right to have the child in the womb destroyed? Does that the unborn child have right of life? Has the doctor right to kill the child in the womb at the request of the mother.8 Abortion, Embryo Destruction and the Future of Value Argument According to the proponents of abortion, committing abortion is morally justified. A person is not under an obligation to conceive children if it would be harmful to her life or stop her achieving other worthwhile things.

But in certain circumstances, when a person does not have better courses of action open, and has sufficient material and emotional supports, conceiving children can be the best thing that person can do. A person can have most reason not to have a child. The reason for this is that having an unwanted child can have a massively detrimental effect on the lives of its parents.

In spite of legislation of abortion for specific indications, there is a controversy in many countries as to whether pregnancy should be terminated at all. On the other hand, some women’s organizations emphasize that a women has a fundamental right to decide for herself as to whether pregnancy should be terminated or not.

It is understandable when a pregnancy is terminated in an unmarried girl with all precautions to avoid complications immediate and remote. But how to explain the termination of the first pregnancy in married women which sometimes gives rise to uterine synechiae. There is also sometimes tubal blockage and cervical incompetence arising out of the termination. It is felt that proper counseling by a senior gynecologist can avoid such terminations.

In the cine film shown in USA entitled ‘the silent screen’ it has been demonstrated that even a 12week fetus feels terrible pain during the process of suction evacuation. Though medical termination of pregnancy (MTP) should remain a back-up service along with other methods of population stabilization,

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some couples take recourse to this as the only method of family planning and go for repeated terminations.

This has not only moral and ethical implications for the practitioner, but also gives rise to physical and psychological complications for the patients.9 When the diagnosis of congenital malformation of fetus is made after the legally permitted period for the termination of a pregnancy, it becomes an ethical issue.7 People tend to turn to the law when trying to decide what is the positive solution to an unwanted pregnancy. Ethics of an abortion is required when translating fetal life into law.

There is no doubt that more has been learned about terminaton of pregnancy as a medical procedure and as a social phenomenon during the past 30 years then at any other time. The changes are motivated by need to: ÂÂ

Eliminate the practice of criminal abortion

ÂÂ

Avoid the economic and other stress which the birth of baby imposes on an unmarried mother

ÂÂ

Remove unwanted pregnancy which result in unwanted and therefore neglected children

ÂÂ

Disruption of education and employment

ÂÂ

Lack of support from father

ÂÂ

Desire to provide for existing children

ÂÂ

Relationship problems with husband or partner

ÂÂ

Young women to have child

ÂÂ

Provide an additional means for family planning and population control.10

In traditional societies, the decision to abort is often taken not by the mother, but by the elders in the family.

The mother may be forced to do something which she may not want to do. In other instances, the pregnant woman may herself request an abortion. Sometimes, the mother feels guilty about the termination of the life of the child and may have deep regret over the abortion done. Give time for reflection over the complemented action. The doctor should discuss the matter with the mother and others concerned. Calm reflection can lead to avoidance of abortion. The mother herself may want to rear the child or may give the child for adoption.8 Doctors may take into account the pregnant woman’s actual or reasonably foreseeable environment, in assessing the risk of injury to her health. The World Health Organization (WHO) defines health as a “state of complete physical, mental and social well-being that does not consist only in the absence of infirmity”. Royal College of Obstetricians and Gynecologists (RCOG), The Care of Women Requesting-induced Abortion, most doctors

MEDICAL ETHICS apply the WHO definition of ‘health’ in interpreting the Abortion Act. The RCOG’s guideline development group views induced abortion as a healthcare need.

ÂÂ

Down’s syndrome (92%)

ÂÂ

Spina bifida (64%)

ÂÂ

Anencephaly (84%)

MTP in Adolescent

ÂÂ

Turner syndrome (72%)

Proper counseling is mandatory undertaking such a procedure:

ÂÂ

Klinefelter syndrome (58%).

Psychological trauma: Severe mental trauma may result in long-term mental instability and psychiatric problems. Absolute secrecy of the whole procedure to be maintained in order to get total confidence of the patient, necessary for moral boosting. MTP carried out in adolescent girl should be on compassionate humanitarian ground. All care should be taken to ensure that their future obstetric life remains unaffected.

Aborting a Malformed Fetus Parents have a desire to have a child of a certain quality.

Bringing up the child with disability can cost money and use up resources. Congenital anomalies contribute a significant proportion of infant morbidity and mortality, as well as fetal mortality. A debate regarding aborting a malformed fetus still exists.

A congenital anomaly is defined as an abnormality of structure, function or body metabolism that is present at birth and results in physical or mental disability, or is fatal. They are generally grouped into major categories: ÂÂ

Congenital heart defects

ÂÂ

Orofacial clefts

ÂÂ

Down syndrome

ÂÂ

Neural tube defects

ÂÂ

Several prenatal diagnostic procedures have been introduced: zz

Cytogenetic: Chorion biopsy Amniocentesis Funiculocentesis

zz

Biophysical: Ultrasound 2-D 3-D Ultrasonography with Doppler.

Although making the diagnosis antenatally through recent advances in ultrasound and prenatal testing is important; providing information to make an informed decision of whether to continue or interrupt a pregnancy is quite crucial. A review of 20 studies by Al-Alaiyan et al. found overall termination rates following antenatal diagnosis of congenital malformation, are as follows:

Moreover, late termination of pregnancy for fetal abnormality is permitted on differing grounds in different countries, depending on: ÂÂ

Type of malformation

ÂÂ

Gestational age at diagnosis

ÂÂ

Abortion legislation

The severity of structural anomalies directly correlated with abortion rates of anomalous fetuses. The prenatal ultrasound at 18-20 weeks can detect major structural anomalies in approximately 60% of such cases. In addition, it is recommended that ultrasound examination should be repeated to assess the evolution of the anomaly and attempt to detect other anomalies not previously identified.

Once a fetal structural anomaly is identified by 2-D ultrasound, the Genetics Committee of the Society of Obstetricians and Gynecologists of Canada recommends that other imaging techniques such as fetal echocardiography, 3-D obstetrical ultrasound, ultrafast fetal magnetic resonance imaging (MRI) and occasionally fetal X-ray and fetal computed tomography (CT) scan (using a low-dose protocol) may be helpful in specific cases. Parental blood testing and invasive prenatal testing may also be required to clarify the diagnosis for a fetus with isolated or multiple structural anomalies. Information regarding the abnormal ultrasound findings should be delivered to women in a clear, sympathetic and timely fashion and in a supportive environment that ensures privacy.

What we seek to justify is availability of choice to pregnant women to prevent the creation of disabled people by aborting fetuses with abnormalities that would disable the people they would become—if they were allowed to develop into people.11 DISCUSSION First step in the evolution of ethics is the solidarity with the other human being. Marthin Fiscuer states, only one rule in medical ethics need concern you-that action on your part which best conserves the interest of your patient. Ethical dimensions are unique to obstetrics.

There are two interwoven patient interests, which may be at odds. Abortion is an issue that overwhelmingly

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MEDICAL ETHICS concerns the autonomy and dignity of the pregnant woman, herself. Until recently, the mother was the patient to be cared for, fetus was another maternal organ. Many advances in diagnosis and treatment has now established fetus as a patient have contributes to ethical and legal considerations involving the fetus.

Abortion involves killing of a fetus. By killing a fetus is deprived of future of value. The loss of these possible futures is bad. It makes the killing of a fetus wrong.

This is Don Marquis’s arguments against abortion which does not rest on the logical promises.

In the countries, when safe abortion is illegal or unavailable, this results in self-imposed or back street abortion and all the ills that flow from that injury, infection, infertility, wastage of female life could be condoned in ethical terms. As Ann Furedi has said, “The issue is not so much whether or when the embryo is deserving of respect per se, but how much respect and value we accord to a life that does not even know it is alive, relative to the respect and value we have for the life of the woman who carries it”.

To compel women to bear unwanted children is a form of ethical despotism. In Mill’s words: Compelling each to live as seems good to positive rest. If people are to be free, that freedom must include freedom to make these difficult and extremely personal choices.

Promotion of freedom and the prevention of suffering are fundamental goals, which society ought to support.

Denying woman abortion is, leading woman to reproductive end.

Opponents of abortion maintain that killing embryo or fetus is morally wrong. But it is not established that either abortion or embryo destruction is wrong all thing considered. There are other important considerations that outweigh our obligation not to destroy embryo or fetuses. In the case of embryonic stem cell research, the enormous potential to save people’s lives and to improve their quality-of-life outweigh the wrong of the destruction of source of some embryos.

Abortion is inherently different from other procedures because no other procedure involves the purposeful termination of potential life. If the fetus is a person, then it has the rights that belong to persons, including right to life. The concept of person-hood, in other words is the bridge that connects the fetus with the right to life (Fig. 1). Thus, in the system of human rights, there is

Person-hood

Fetus

Figure 1. Balance of rights of the mother and the fetus.

often a need to balance rights against each other. The right to the life of the mother and the same right of the fetus.

References 1. Frank Chervenak, Laurence McCullough. Current progress in obstetrics and gynecology. Vol. 5, The Relevance of Ethics in Gynecology Practice.

2. Witoonpanich P. Ethics and Rule in Obstetrics and Gynecology Rule of Ethics for Obstetricians and Gynecologists. Thai J Obstet Gynaecol 2011;19:155-7.

3. Torres JM, De Vries RG. Birthing ethics: what mothers, families, childbirth educators, nurses, and physicians should know about the ethics of childbirth. J Perinat Educ 2009;18(1):12-24.

4. Mose JC. Aspects of ethics in obstetrics ultrasound.

Indones J Obstet Gynecol 2008;32-2:65-71.

5. Gillon R. Is there a ‘new ethics of abortion’? J Med Ethics 2001;27 Suppl 2:ii5-9.

6. Right to life L.M. Francis Medical ethics- Jaypee brothers 2004 edition.

7. Essential Obstetrics University Press Hyderabad S. Soundara Raghvan Ethical issues Asha Oumachigui.

8. Hewson B. Reproductive autonomy and the ethics of abortion. J Med Ethics 2001;27:ii10-ii.

9. K.M. Gun. Ethical Aspects of Medical Termination of Pregnancy. Manual of Medical Termination of Pregnancy Biman Chakraborty, H. Dasgupta FOGSI 2nd edition by Gualitas Premere, Culculta.

10. Sterilization and Termination of Pregnancy. In: Jeffcoate’ Principles of Gynaecology. 7th International Edition, Jaypee Brothers p.: 824-38.

11. Al-Alaiyan S, AlFaleh KM. Aborting a malformed fetus: A debatable issue in Saudi Arabia. J Clin Neonatol 2012; 1(1):6-11.

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Rights

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

Obstetrics AND Gynecology

Clinical Characteristics and Outcome of Obstetric Patients Who Required Mechanical Ventilation in a Tertiary Care Hospital in North Kerala Smitha Sreenivas K*, Naseema Beevi A*, Uma Devi Nâ&#x20AC;

Abstract Objectives: To describe the clinical characteristics of obstetric patients requiring mechanical ventilation in a tertiary referral hospital and their maternal and perinatal outcome in order to identify their risk factors and clinical outcome and determine adverse prognostic factors in these patients. Study design: A prospective study was conducted in the Dept. of Obstetrics and Gynecology, Government Medical College, Kozhikode on all pregnant women up to 6 weeks postpartum from January 1, 2011 to December 31, 2013 and who subsequently required mechanical ventilation. Data was recorded in a predesigned proforma and was analyzed and frequency, and percentages were calculated. Results: In the 3-year period, 75 obstetric patients required mechanical ventilation. Majority were between 20-35 years (88%) and were primipara (53.3%). Eighty percent were admitted in the antepartum period and most were in the gestational age of 30-36 weeks (41.3%). Hypertensive disorder is an important antepartum complication (29.3%). Postpartum hemorrhage was the important cause (45.3%) of ICU admission. About 49.3% required mechanical ventilation for <24 hours and multiorgan failure was the important complication encountered (13.3%).

Conclusions: Providing optimal prenatal care and improving the management of hemorrhagic complications and hypertensive disease can improve the morbidity and mortality of critically ill obstetric patients requiring mechanical ventilation.

Keywords: High-risk pregnancy, mechanical ventilation, critical illness, maternal death

P

regnancy, delivery and puerperium can have catastrophic complications necessitating intensive care unit (ICU) admission, although these patients are young and healthy in general. The critically ill pregnant patients present a challenge to the physician due to their unique physiology and the specific medical disorders that occur during pregnancy and peripartum period. The physiological changes that occur in the pregnant state in several systems including the cardiovascular, respiratory, renal, hematologic and endocrine systems, stress the reserve of the body and may compromise responses needed to combat diseased state. The critical illness can be due to pregnancy per se or can be due to a concurrent medical illness.

*Associate Professor â&#x20AC; Professor Dept. of Obstetrics and Gynecology InstituteofMaternalandChildHealth,GovernmentMedicalCollege,Kozhikode,Kerala Address for correspondence Dr Smitha Sreenivas K No 47,Thriveni, Eranhipalam Colony Eranhipalam, Kozhikode - 673 006, Kerala E-mail: smithaprashanth05@gmil.com

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Indian Journal of Clinical Practice, Vol. 25, No. 6, November 2014

Hypertensive disorders of pregnancy, hemorrhage and sepsis are the leading causes of maternal morbidity and ICU admissions in Asia. Management of a critically ill pregnant lady requires the cooperation of obstetrician, intensivist and anesthetist.

Mechanical ventilation has revolutionized the management of critically ill patients with pulmonary dysfunction. It was introduced in the latter half of the 20th century. It is essential for the support of those patients whose respiratory dysfunction threatens homeostasis and life. Most aspects of mechanical ventilation are identical for pregnant and nonpregnant women. It has two simple functions, to give an adequate supply of oxygen and eliminate carbon dioxide. The indications for instituting mechanical ventilation are based on clinical assessment. Tachypnea, tachycardia, alae flaring, use of accessory muscles of respiration, sweating and a thorough understanding of the underlying pathology constitute enough evidence for intubation and ventilation. Physiological changes of pregnancy and concerns for fetal well-being complicate the use of mechanical ventilation. Maternal morbidity and mortality are significantly elevated in obstetric

Obstetrics AND Gynecology patients requiring mechanical ventilation. Fetal mortality is also high when critical care is required.

Early gestational age, severe maternal illness, maternal shock and the absence of prenatal care are associated with fetal mortality. Upon resolution of underlying pathology mechanical ventilation may be withdrawn.

Successful maternal and neonatal outcomes are largely dependent on a multidisciplinary approach to management requiring input from critical care personnel, obstetricians, anesthetists, neonatologists and nursing personnel.

Increased surveillance in the peripartum period in a critical care facility allows earlier detection of maternal compromise and detailed management. Analysis of these critical care obstetric patients help to improve future pregnancy outcomes.

Material and methods We included in our study, pregnant women up to 6 weeks postpartum admitted in our department from January 1, 2011 to December 31, 2013 and who subsequently required mechanical ventilation. Data collected include maternal age, parity, gestational age, booking status, presence of antepartum complications, mode of delivery, requirement of blood and blood products and hysterectomy, indication of ICU admission, duration of ventilation, length of hospital stay, complications encountered in ICU and fetal outcome. These were recorded in a predesigned proforma. Data was analyzed and frequency and percentages were calculated.

Results A total of 75 obstetric patients required mechanical ventilation during the 3-year period. Majority of the patients belonged to the age group of 20-35 years, 66 (88%). Only 4 (5.3%) were below 20 years and 5 (6.67%) were above 35 years. Forty (53.3%) were primipara and 33 (44%) were multipara. Sixty (80%) were admitted in the antepartum period. Fifty-four cases (72%) were referred from another institution (Table 1).

Most of the patients were in the gestational age of 30-36 weeks, 30 cases (40%). Only 15 (20%) were in the postpartum period. Cesarean section was an important risk factor amounting to 41 (54.67%) patients. Twenty cases (26.67%) had undergone hysterectomy, may be due to high incidence of postpartum hemorrhage in our study. Eight cases required relaparotomy due to intraperitoneal hemorrhage. There were 51 live births

of which 6 (11.76%) ended in neonatal death, may be related to early gestational age and severe maternal illness.

Hypertensive disorder was the most important antepartum risk factor, which included pre-eclampsia 5 (6.67%), eclampsia 4 (5.3%), gestational hypertension 4 (5.3%) and hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome in 4 (5.3%) and both eclampsia and HELLP syndrome in 5 (6.67%). Other obstetric complications included placenta accreta present in 7 (9.3%), abruption in 5 (6.67%), multiple pregnancy in 4 (5.33%), gastational diabetes mellitus (GDM) in 2 (2.67%) and acute fatty liver of pregnancy (AFLP) in 2 (2.67%) (Table 2).

Pre-existing medical complications included heart disease in three cases (4%). Chronic hypertension, pregestational diabetes, sickle cell disease, systemic lupus erythematosus (SLE) and rheumatoid arthritis contribute in 1.3% each (Table 2). Thirty-two percent required transfusion of >10 blood and blood products, which can be due to more cases of postpartum hemorrhage (Table 3).

The most important obstetric complication necessitating ICU admission was postpartum hemorrhage (PPH) 22 (29.3%). PPH with disseminated intravascular Table 1. Demographic Characteristics of Patients Characteristics

Number

Percentage (%)

<20

4

5.3

20-35

66

88

>35

5

6.67

Primipara

40

53.3

Multipara

33

44

Grandmultipara

2

2.67

Antepartum

60

80

Postpartum

15

20

Referred

54

72

Booked

21

28

<30

5

6.67

30-36

30

40

37-41

25

33.3

Postpartum up to 42 days

15

20

Age (years)

Parity

Time of admission

Mode of admission

Gestational age (weeks)

Indian Journal of Clinical Practice, Vol. 25, No. 6, November 2014

553

Obstetrics AND Gynecology Table 2. Presence of Antepartum Complications

Table 4. Cause of ICU Admission

Complications

Obstetrics cause

Number

Percentage (%)

Obstetric complications

Number Percentage (%)

PPH

22

29.3

Placenta accreta

7

9.3

PPH, DIC

12

16

Pre-eclampsia

5

6.67

Eclampsia + HELLP

5

6.67

Eclampsia + HELLP

5

6.67

HELLP syndrome

3

4

HELLP syndrome

4

5.3

Amniotic fluid embolism

3

4

Eclampsia

4

5.3

3

4

Gestational hypertension

4

5.3

Posterior reversible encephalopathy syndrome

Abruption

5

6.67

Inversion uterus

1

1.3

Multiple pregnancy

4

5.3

Peripartum cardiomyopathy

1

1.3

AFLP

2

2.67

Gestational diabetes

2

2.67

Sepsis

6

8

Pulmonary edema

4

5.33

Heart disease

3

4

Pulmonary embolism

4

5.33

SLE

1

1.3

Status epilepticus

3

4

Chronic hypertension

1

1.3

Heart disease

3

4

Pregestational diabetes

1

1.3

Sickle cell disease

1

1.3

Rheumatoid arthritis

1

1.3

Medical complications

Nonobstetric cause

Hepatic failure

2

2.67

Intracranial hemorrhage

2

2.67

Anaphylaxis

1

1.3

Delayed recovery after general anesthesia

1

1.3

Table 3. Number of Units of Blood and Blood Products Number

Percentage (%)

<5

19

25.3

5-10

16

21.3

>10

24

32

Nil

16

21.3

Table 5. Duration of Mechanical Ventilation and Hospital Stay Number Duration of mechanical ventilation (days) <1 37 1-2 23

Percentage (%) 49.3 30.67

3-4

6

8

â&#x2030;Ľ5

9

12

<10

16

21.3

10-19

30

40

20-30

23

30.67

>30

6

8

coagulation was the cause in 12 cases (16%).

Hypertensive disorders followed closely including eclampsia with HELLP syndrome in 5 (6.67%) and HELLP syndrome in 3 (4%). Posterior reversible encephalopathy syndrome was present in 3 (4%).

Amniotic fluid embolism was responsible in 3 (4%) and peripartum cardiomyopathy and inversion contributed in 1.3% each (Table 4). Majority required mechanical ventilation for <24 hours, 37 (49.3%). Only nine cases (12%) required ventilation for 5 days and more. Thirty cases (40%) required hospital stay for 10-19 days and only 6 (8%) required hospital stay for more than a month (Table 5).

each (4%). Ventilator-associated pneumonia developed in 2 (2.67%). Hepatic failure, cardiac arrhythmias, deepvein thrombosis and burst abdomen complicated in one case each (1.3%) (Table 6).

Multiorgan failure was the most important complication encountered while on mechanical ventilation, seen in 10 (13.3%). Pulmonary edema developed in 4 (5.3%) and renal failure and seizures were found in 3 cases

There were 26 maternal deaths in patients who required mechanical ventilation. Postpartum hemorrhage (30.76%), sepsis (23.08%) and hypertensive disorders (19.02%) were the important causes of maternal

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Indian Journal of Clinical Practice, Vol. 25, No. 6, November 2014

Duration of hospital stay (days)

Obstetrics AND Gynecology Table 6. Complications Encountered While on Mechanical Ventilation Complications

Number

Percentage (%)

Multiorgan failure

10

13.3

Pulmonary edema

4

5.3

Renal failure

3

4

Seizures

3

4

Ventilator-associated pneumonia

2

2.67

Hepatic failure

1

1.3

Cardiac arrhythmias

1

1.3

Burst abdomen

1

1.3

Deep-vein thrombosis

1

1.3

Table 7. Maternal Mortality-26 Cases (34.67%) Diagnoses

Number of patients

Percentage of maternal deaths (%)

Postpartum hemorrhage

8

30.76

Sepsis

6

23.08

Hypertensive disorders

5

19.02

Pulmonary embolism

2

7.69

Intracranial hemorrhage

2

7.69

Amniotic fluid embolism

1

3.85

Acute fatty liver of pregnancy

1

3.85

Heart disease

1

3.85

mortality. Other causes were pulmonary embolism (7.69%), intracranial hemorrhage (7.69%), amniotic fluid embolism (3.85%), acute fatty liver of pregnancy (3.85%) and heart disease (3.85%) (Table 7).

Discussion Maternal and perinatal morbidity and mortality are significantly elevated in obstetric patients requiring mechanical ventilation possibly due to severity of maternal illness and early gestational age. A critically ill pregnant woman poses major challenges to physicians.

The serious illnesses that complicate pregnancy may be unique to pregnancy, but other medical conditions that affect nonpregnant women also may complicate pregnancy. Early identification of critical illness is essential to provide aggressive support and resuscitation including ventilatory support and reduce maternal mortality.

Majority of the patients belonged to 20-35 years age group (88%) similar to the study of Shaikh et al.

In our study, 53.3% were primipara, which contradicts the same study. Eighty percent were admitted antepartum similar to 78% in study by Shaikh et al and Monsalve et al. Most were in the gestational age between 30 and 36 weeks (40%), similar to study by Togal et al. Seventy-two percent were transferred from another institution similar to study by Barrett et al. Hypertensive disorders were found to be the most important antepartum risk factor (29.3%), similar to study by Kumar V. Other antepartum complications included placenta accreta 9.3%, abruption 6.67%, multiple pregnancy 5.33%, AFLP 2.67% and GDM in 2.67%. The most important pre-existing medical complication was heart disease in 3 cases (4%). Thirty-two percent required transfusion of >10 units of blood and blood products probably due to the high incidence of postpartum hemorrhage.

The most common mode of delivery was cesarean section (54.67%) similar to study by Shaikh et al, where it was 49.4%. Obstetric hysterectomy was required in 26.67%, since postpartum hemorrhage was the most important cause of ICU admission. Stillbirths were 32% and of the 51 live births, 11.76% ended in neonatal death, which was higher than the study of Suarez et al.

The most common obstetric cause of ICU admission was postpartum hemorrhage 34 (45.3%) of which 12 cases were complicated with disseminated intravascular coagulation, which is similar to study by Suarez et al and Barrett et al but contradicts the study

by Simsek et al. where hypertensive disorder was the most common cause.

Other causes were hypertensive disorders including HELLP syndrome in 4% and eclampsia with HELLP syndrome in 6.67%, amniotic fluid embolism in 4%, posterior reversible leukoencephalopathy syndrome in 4%, peripartum cardiomyopathy in 1.3% and inversion uterus in 1.3%. Sepsis was the most important nonobstetric cause of ICU admission (8%) similar to study by Shaikh et al, followed by pulmonary edema in 5.33% and pulmonary embolism in 5.33%. Intracranial hemorrhage was present in 2.67%. There was only one case each of anaphylaxis and delayed recovery from general anesthesia.

Majority required mechanical ventilation for <24 hours, 37 (49.3%) where as the mean duration was 3 days in a study by Suarez et al. Only 9 cases (12%) required for 5 days and more. Thirty cases (40%) required hospital stay for 10-19 days and only six cases (8%) required hospital stay for >30 days.

Indian Journal of Clinical Practice, Vol. 25, No. 6, November 2014

555

Obstetrics AND Gynecology Multiorgan failure was the most important complication encountered while on mechanical ventilation in 10 (13.3%). Pulmonary edema developed in 4 (5.3%) and renal failure and seizures were found in three cases each (4%) and ventilator-associated pneumonia in 2.67%. Hepatic failure, cardiac arrhythmias, deep-vein thrombosis and burst abdomen complicated one case each (1.3%). There were 26 maternal deaths in patients who required mechanical ventilation (34.67%) similar to study by Suarez et al. Postpartum hemorrhage (30.76%), sepsis (23.08%) and hypertensive disorders (19.02%) were the important causes of maternal mortality. Other causes were pulmonary embolism (7.69%), intracranial hemorrhage (7.69%), amniotic fluid embolism (3.85%), acute fatty liver of pregnancy (3.85%) and heart disease (3.85%).

Conclusions A close follow-up of high-risk patients and an optimal stabilization of their condition before intervention are well-known to improve the outcome of these patients and decrease the morbidity and mortality. The problems faced by the critically ill parturients including mechanical ventilation may be reduced by providing optimal prenatal care, improving the management of hypertensive disease during pregnancy and reducing the incidence of hemorrhagic complications.

Suggested Reading 1. Shaikh S, Shaikh NB, Abassi R, Balouch R. Obstetric admission to the intensive care unit: a one year review.

Medical Channel 2013;19:59-63.

2. Kilpatrick SJ, Matthay MA. Obstetric patients requiring critical care. A five-year review. Chest 1992;101(5):1407-12.

3. Togal T, Yucel N, Gedik E, Gulhas N, Toprak HI, Ersoy MO. Obstetric admissions to the intensive care unit in a tertiary referral hospital. J Crit Care 2010;25(4):628-33.

4. Kumar V. Critical illness in pregnancy. Medicine Update 2012;22:700-10.

5. Simsek T, Eyigor C, Uyar M, Karaman S, Moral AR. Retrospective review of critically ill obstetrical patients: a decade’s experience. Turk J Med Sci 2011;41(6):1059-64.

6. Monsalve GA, Martínez CM, Gallo T, González MV, Arango G, Upegui A, et al. Maternal critical care: outcomes and patient characteristics in a combined obstetric high dependency unit in Medellin, Colombia. Rev Col Anest 2011;39(6):190-205.

7. Suarez JR, Duenas C, Paternina A, Miranda J, Castillo E, Bourjeily G. Clinical characteristics and outcomes of obstetric patients requiring mechanical ventilation in Colombia Chest 2012;10:142.

8. Barrett HL, Devin R, Clarke S, Nitert MD, Boots R, Fagermo N, et al. A fifteen year retrospective review of obstetric patients requiring critical care. Obstet Med 2012;5:166-70.

Acknowledgment

9. Clardy PF, Reardon CC. Critical illness during pregnancy and the peripartum period. UpToDate 2014.

We acknowledge all the staff and residents involved in the care of these patients.

10. Muckart DJ.Ventilation and the critically ill parturient.

Best Pract Res Clin Obstet Gynaecol 2011;15:545-56.

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Systemic Estradiol Absorption Low with Vaginal Capsule An investigational solubilized estradiol capsule (VagiCap, Therapeutics MD) could offer an option for treating vulvovaginal atrophy with even less systemic absorption than the currently available tablet (Vagifem, Novo Nordisk), early data suggest.

James H Pickar, MD, adjunct professor of obstetrics and gynecology at Columbia University College of Physicians and Surgeons, New York City, presented the findings from phase 2 and pharmacokinetic studies here at the North American Menopause Society (NAMS) 2014 Annual Meeting.

"I think people are always concerned about systemic absorption.... Admittedly, the amount of absorption with Vagifem is pretty small, but this is even less. And that's the plus," Dr Pickar told Medscape Medical News.

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Indian Journal of Clinical Practice, Vol. 25, No. 6, November 2014

Obstetrics AND Gynecology

Fetus Papyraceous in a Twin Pregnancy: A Case Report Khushpreet Kaur*, Parneet Kaur†, Arvinder Kaur†, Beant Singh‡, Sonam Walia#, Mamta Rani$

Abstract Fetus papyraceous or compress is the compressed, mummified, parchment-like remains of a dead twin, which is retained in utero after intrauterine death in the second trimester. It is an uncommon finding. The incidence of fetus papyraceous is reported as 1 in 17,000 to 1 in 20,000 pregnancies. Incidence of fetus papyraceous in twin pregnancy is 1 in 184 to 1 in 200 pregnancies.

Here we report a case of fetus papyraceous in a twin pregnancy with no adverse effects on mother.

Keywords: Fetus papyraceous, intrauterine death, twin pregnancy, diamniotic dichorionic

F

etus papyraceous or compress is the compressed, mummified, parchment-like remains of a dead twin, which is retained in utero after intrauterine death in the second trimester1,2 and the other fetus(es) continue to grow. When the fetus dies in early pregnancy, the amniotic fluid and placental tissue are absorbed and the fetus is compressed between the membranes with the co-living twin. The incidence of fetus papyraceous has been reported at 1 in 17,000 to 20,000 pregnancies and 1 in 184 to 1 in 200 twin pregnancies.2,3 CASE REPORT Mrs XYZ, 23 years old, G2P0A1 visited OPD of Government Medical College and Rajindra Hospital, Patiala, with gestational age of 37 weeks 4-day on 03/05/13 with twin pregnancy. Her ultrasonography (USG) (dt 25/04/13), which she brought along with showed fetus 1 alive with biparietal diameter (BPD)

*Professor †Associate Professor ‡Assistant Professor Dept. of Obstetrics and Gynecology #Junior Resident Dept. of Radiodiagnosis $Junior Resident Dept. of Obstetrics and Gynecology Government Medical College and Rajindra Hospital, Patiala, Punjab Address for correspondence Dr Parneet Kaur H. No.: 151, Punjabi Bagh Near Klair Orthopedic Centre, Patiala - 147 001, Punjab E-mail: parneetkd@yahoo.co.in

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Indian Journal of Clinical Practice, Vol. 25, No. 6, November 2014

35 weeks 6-day, femur length (FL) 36 weeks 5-day, head circumference (HC) 36 weeks 3-day, arm circumference (AC) 35 weeks 2-day and demise of fetus 2 with crownrump length (CRL) of 13 weeks. She was admitted (vide CR No. 13153) and detailed history was taken. Patient had conceived spontaneously and had her antenatal visits at a private nursing home.

She had her earlier scan of 10/12/12, which showed two alive fetusus at 16 weeks 5-day with two separate placenta one posterior and second anterior upper. Her routine investigations were done showing hemoglobin (Hb) 9.8 g, urine C/E NAD and her blood group was O, Rh-positive. Blood sugar levels was within normal limits. Her coagulation profile was as under: Bleeding time (BT) - 1’40’’; clotting time (CT) - 2’22’’; platelet count - 2,10000/mm3 and prothrombin time index (PTI) - 92%.

A fresh ultrasound was done from radiology department of hospital to confirm findings and presentation, which showed fetus 1 alive with breech presentation BPD 37 weeks 4-day, FL 37 weeks with right lateral upper placenta and demise of fetus 2 at 13 weeks 2-day. Patient went into labor next day in the evening.

Emergency cesarean section was done because of first twin presenting as breech.

Twin 1, an alive female was extracted as breech with birth weight 2,500 g with Apgar 9, and thereafter papyraceous twin 2 along with placenta (Fig. 1). On separating membranes twin 2 fetus papyraceous was extracted out. It was a female fetus and weight was 80 g (Fig. 2). Her postoperative period and further stay in hospital was asymptomatic and she and her baby

Obstetrics AND Gynecology grow. In most situations, the fluid of the dead tissue is gradually absorbed, the amniotic fluid disappears, and the fetus is compressed and becomes incorporated into the membranes.4 Prior to the use of ultrasound, the diagnosis of fetus papyraceous could only be made after delivery of the surviving twin. The advent of real-time ultrasound permits the diagnosis of multiple gestations as early as 4 weeks after conception using the intravaginal probe.2 In our case, we report a diamniotic and dichorionic pregnancy. Perinatal mortality of monochorionic twin pregnancies is higher than with dichorionic twin pregnancies. A study by McPherson and colleagues investigated the association between chorionicity and intrauterine fetal demise (IUFD) of one or both fetuses in twin pregnancies. They reported that monochorionic twins carry an increased risk of fetal death as compared to dichorionic twins.5 No specific complications of fetus papyraceous in either mother or the surviving twin are reported in the literature. It would be expected that, as in singleton pregnancies, in utero retention of a fetus after its death would trigger disseminated intravascular coagulation in the mother. In twin pregnancies; however, the incidence of this complication is very low.6 Figure 1. Fetus papyraceous along with placenta.

In the study by Malinowski et al, it was also found that none of the live born fetuses had evidence of hematological abnormalities.7 A similar case reported

by Bozkurt and Kara showed no maternal and fetal complications in diamniotic and diachorionic pregnancy with fetus papyraceous.8 No specific complication of fetus papyraceous in either mother or the surviving twin were reported by Airede and Ahmed.9 CONCLUSION

Figure 2. Twin 1 normal with fetus papyraceous.

were discharged on 10/5/13 in satisfactory condition.

Histopathology of placenta showed a diamniotic and dichorionic pattern.

DISCUSSION Fetus papyraceous occurs in subjects with multiple gestation and is characterized by the death of one or more fetuses early in the gestation period (i.e., at 15-20 weeks), whereas the other fetuses continue to

A case of fetus papyraceous with no confirmed adverse effect on the mother or surviving twin is described.

The cause of intrauterine death of the fetus could not be ascertained. Routine ultrasound examination with better training and use of modern ultrasound machines with good resolution is important for detection of multiple gestations. This will allow the diagnosis of fetus papyraceous early in pregnancy and may prevent obstetrical complications and reduce the risk of mortality and morbidity for surviving twin.

REFERENCES 1. Fisk NM. Multiple pregnancies. In: Dewhurstâ&#x20AC;&#x2122;s Textbook of Obstetrics and Gynaecology for Postgraduates.

Edmonds DK (Ed.), Blackwell: Oxford 1999:p.298-307.

2. Bush M, Pernoll ML. Multiple pregnancy. In: Current Obstetric and Gynecologic Diagnosis and Treatment.

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Obstetrics AND Gynecology DeCherney AH, Nathan L (Eds), McGraw-Hill: New York 2003:p.315-25.

3. Leppert PC, Wartel L, Lowman R. Foetus papyraceous causing dystocia: Inability to detect blighted twin antenatally. Obstet Gynecol 1979;54(3):381-83.

4. Mittal PS, Khanna M. Two papyraceous fetuses in a triplet pregnancy. J Obstet Gynecol India 2007;57(1):77-8.

5. McPherson JA, Odibo AO, Shanks AL, Roehl KA, Macones GA, et al. Impact of chorionicity on risk and timing of intrauterine fetal demise in twin pregnancies. Am J Obstet Gynecol 2012;207(3):190.e1-6.

6. Campbell S, Lees C. Multiple gestation. In: Obstetrics by Ten Teachers. Campbell S, Lees C (Eds.), Arnold: London 2000:p.187-95.

7. Malinowski W, Janowski J, Lokociejewski J, Rozewicki K, Tomala J. Intrauterine death of one twin in the third trimester. Ginekol Pol 2003;74:135-43.

8. Airede LR, Ahmed Y. Fetus papyraceous: a case report.

Ann Afr Med 2005;4(3):136-8.

9. Bozkurt M, Kara D. Fetus papyraceous in a twin pregnancy: a case report without any maternal and fetal complications. Proc Obstet Gynecol 2013;3(2):4.

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Two Steroid Courses Safe after Preterm Membrane Rupture Two courses of antenatal corticosteroids can be administered to pregnant women with preterm premature rupture of membranes (PROM) without increasing the risk for neonatal sepsis, according to an article published online October 6 in Obstetrics and Gynecology.

Since 2000, the recommendation from the Eunice Kennedy Shriver National Institute of Child Health and Development has been to limit administration to a single course of steroids. However, the data supporting that recommendation are thin, according to Cynthia Guamfi-Bannerman, MD, and Moeun Son, MD, from the Department of Obstetrics and Gynecology at Columbia University Medical Center, New York City.

Biomarker for Pre-eclampsia Detected as Early as 6 Weeks into Pregnancy University of Iowa researchers have discovered a biomarker that could give expecting mothers and their doctors the first simple blood test to reliably predict that a pregnant woman may develop pre-eclampsia, at least as early as 6 weeks into the pregnancy.

Pre-eclampsia is a cardiovascular disorder generally occurring late in pregnancy and often resulting in an early delivery, creating immediate and potentially lifelong risks to both mother and baby. It causes high blood pressure and protein in the urine, and is typically diagnosed in the late second or third trimester of pregnancy. Between 5 and 7% of all pregnancies in the United States are affected with pre-eclampsia, equating to roughly 4,000 pregnancies in Iowa or around 5,00,000 in the United States per year. More than 1,00,000 women worldwide die from the disease each year.

In their paper, “Vasopressin in Pre-eclampsia: A Novel Very-Early Human Pregnancy Biomarker and ClinicallyRelevant Mouse Model,” study authors Mark Santillan, MD, assistant professor of Obstetrics and Gynecology and a Maternal Fetal Medicine specialist, Justin Grobe, PhD, assistant professor of Pharmacology and a Fellow of the American Heart Association (FAHA), and Donna Santillan, PhD, research assistant professor of Obstetrics and Gynecology, demonstrate that elevated secretion of arginine vasopressin can be a very early biomarker of a pre-eclamptic pregnancy.

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Obstetrics AND Gynecology

Ultrasonographic Prevalence of Polycystic Ovarian Syndrome in Different Age Groups Tabassum K

Abstract Introduction: Polycystic ovarian syndrome (PCOS) is a common female endocrine disorder with prevalence ranging from 2.2% to 26%. The incidence is gradually increasing in India. In most studies, adult women ages 18-45 years were found affected.

It is characterized by presence of any two of the three features i.e., amenorrhea or oligomenorrhea, hyperandrogenism and presence of more than 10 cysts, 2-8 mm in diameter in pelvic ultrasound scan. Objective: The aim of this study was to observe the ultrasonographic (USG) prevalence of PCOS in different age groups. Methodology: It was a hospital data-based prevalence study. The data for this study was extracted from USG record of Radiology Unit of NIUM, Hospital, Bangalore. One thousand USG reports were recorded and they were divided into three age groups with class intervals of 10 years, starting from 15 years. In different age groups, USG prevalence of PCOS was observed. Results and conclusion: Regarding the prevalence of PCOS, it was observed that the maximum patients were found in the age group of 15-24 years and least patients were found in the age group of 35-44 years. It was concluded that PCOS is high in early reproductive age group and incidence gradually decreases as the age advances.

Keywords: Prevalence, polycystic ovarian syndrome, age, complications and USG

P

olycystic ovarian syndrome (PCOS) is one of the most common complex endocrinopathy affecting women due to anovulation. Its onset is usually peripubertal, so it is a disorder of significant health concern. This necessitates estimation of proportion of women who are affected by PCOS.1 According to Rotterdam, oligomenorrhea, hirsutism and obesity together with enlarged polycystic ovary are the diagnostic criteria of PCOS.2

It is now accepted that this problem is arising from persistent anovulation with a spectrum of etiologies and clinical manifestations. It has a complex clinical presentation and is traditionally thought as a triad of oligomenorrhea, hirsutism and obesity and is now recognized as a heterogeneous disorder that results in overproduction of androgens, primarily from the ovary and is associated with insulin resistance.3

Reader Dept. of Ilmul Qabalat wa Amraze Niswan (Obstetrics and Gynecology) National Institute of Unani Medicine, Bangalore, Karnataka Address for correspondence Dr Tabassum K Reader Dept. of Ilmul Qabalat wa Amraze Niswan (Obstetrics and Gynecology) National Institute of Unani Medicine, Bangalore - 91, Karnataka E-mail: drtabassum.nium@gmail.com

The first recognition of an association between glucose intolerance and hyperandrogenism was by Archard and Thiers in 1921.4 The exact prevalence of PCOS is not known as the syndrome is not defined precisely and depends on the choice of diagnostic criteria. World Health Organization (WHO) estimates that it affected 116 million women worldwide in 2012 (3.4% of women).5 Studies conducted on Indian women with PCOS suggested that abnormalities of the insulin receptor are more common in Indian women as compared to white women.6 The prevalence of menstrual dysfunction in women with PCOS is 14.6-22.8% and irregularities range from amenorrhea to menorrhagia with a classic peripubertal onset.7,8 Insulin resistance is central to the pathogenesis of PCOS and Indians are known to have high prevalence of insulin resistance, so the prevalence of PCOS is expected to be high in the Indian population.9 In India, the prevalence is gradually increasing.

In Indian Express in 2013, it was published that PCOS becoming â&#x20AC;&#x2DC;epidemicâ&#x20AC;&#x2122; in Bangalore city, because of the lifestyle that people have adopted. Almost all foods are packed with chemicals that lead to hormonal imbalance.

The cause of PCOS remains unclear. Theories focus on the impact of luteinizing hormone (LH) stimulation and

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Obstetrics AND Gynecology the role of insulin in the production of ovarian hyperandrogenism. Increased LH pulse amplitude and frequency have been demonstrated in women and adolescents with PCOS, suggesting an aberrant pattern of hypothalamic gonadotropin-releasing hormone (GnRH) secretion as a causative factor.10-12 PCOS produce symptoms in approximately 5-10% of women of reproductive age. It is thought to be one of the leading causes of female subfertility and pregnancy complications.13,14 Major symptoms include amenorrhea, oligomenorrhea, dysfunctional uterine bleeding, acne, hirsutism, obesity, etc.15 PCOS is a major health concern because patients with PCOS are at increased risk of infertility, pregnancy loss, obesity, cardiovascular disorders,16,17 diabetes mellitus,18 obstructive sleep apnea,19,20 depression, nonalcoholic fatty liver disease,21 endometrial hyperplasia22 and endometrial carcinoma,23 etc. Infertility occurs in 75% due to anovulation.24 Other risks have been reported in different percentage as cutaneous hyperandrogenism in the form of obesity is found in 40-60% cases25 acne in 15-25%, hirsutism in 65-75%, alopecia in 5-50% cases8 Metabolic syndrome like diabetes in up to 43.6%,9,26 depression in 40%,27 increase risk of early spontaneous abortion, preterm delivery, hypertensive disorders, gestational diabetes and perinatal mortality in 30-50%,28,29 and increased risk of multiple gestation from infertility treatment.30 Threeâ&#x20AC;?dimensional and Doppler ultrasound studies may be useful in the diagnosis of PCOS.31 This paper focuses on the prevalence of PCOS in different age groups of women as revealed by USG pelvis/abdomen of women who attended the OPD and were sent for scanning.

Objective To observe the ultrasonographic (USG) prevalence of PCOS in different age group of women.

including pelvic inflammatory disease (PID). In other cases, ultrasonologist visualized the ovary and reported.

The recorded patients then were divided into five age groups with class intervals of 10 years, starting from 15 years. In different age group USG prevalence of PCOS was observed.

Study design: Prevalence study.

Sample size: 1,000 USG reports.

Method of collection of data: Hospital USG record.

Inclusion criteria: Reports of all female patients between the ages of 15-65 years.

ResultS and Discussion For this study, hospital data was taken to see the prevalence of PCOS among patients with different gynecological complaints. Data were analyzed statistically and observed as below: Out of 1,000 patients 415 had normal pelvic scan, 100 had PCOS and remaining 485 patients had different pelvic pathology (Table 1 and Fig. 1).

Age-wise Prevalence On age distribution analysis, it was observed that PCOS was prevalent throughout reproductive age. No patient of PCOS was found beyond 45 years of age.

The maximum prevalence (i.e., 4.8%) was found in the Table 1. Scanning Report Analysis (n = 1,000) Patients

No. of patients

Percentage (%)

Normal pelvic scan

415

41.5

PCOS

100

10

485

48.5

1,000

100

Other pelvic pathology Total

Methodology

About up to 300 USG are recorded per month irrespective of both male and females. The female patients are often scanned for pelvic pathology

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Indian Journal of Clinical Practice, Vol. 25, No. 6, November 2014

450 400

485 415

350 No of patients

It was a hospital data-based prevalence study. The data for this study was extracted from USG record of Radiology Unit, NIUM, Hospital, Bangalore. The abdominal and pelvic sonographic reports of all women irrespective of pathology were taken. One thousand USG reports were recorded and the prevalence of PCOS was observed. For this study, the USG reports of all women were taken.

500

300 250 200 150

100

100 50 0

Normal pelvis

PCOS

Figure 1. Scanning report analysis.

Other pelvic pathology

Obstetrics AND Gynecology Table 2. Distribution of the PCOS Patients According to Age Group (n = 100) Age (years)

No. of PCOS patients

Percentage (%)

15-24

48

4.8

25-34

44

4.4

35-44

8

0.8

45-54

0

0

55-64

0

0

Total

100

10

15-24 years

25-34 years

35-44 years

8 48 44

of women had PCOS and that 70% of them were previously undiagnosed.1 The observed prevalence in the present study is commensurate with the reported prevalence in reference studies.

Summary and Conclusion The present study was carried out to observe the USG prevalence of PCOS in patients of different age groups.

It was observed that it was an age-related disease and the incidence tends to decrease with age. The highest prevalence was seen in the age group of 15-24 years and least in the age group of 35-44 years. No patients with PCOS were found above the age of 45 years.

On the basis of above observation it is concluded that the prevalence of PCOS is increasing gradually in India and it may be a major health concerned in future. Hence, early diagnosis and intervention will reduces the longterm health complications associated with PCOS. References

Figure 2. Distribution of patients with PCOS according to age group.

age group of 15-24 years. This prevalence was almost similar and insignificantly different from the observed prevalence in age group of 25-34 years (i.e., 4.4%).

The overall prevalence in under study age group was found to be 10%. It was observed that the prevalence of PCOS declined with advancing age and the observed prevalence in the age group of 35-44 years was only 0.8% (Table 2 and Fig. 2).

According to a prospective study conducted by Nidhi et al, on 460 girls aged 15-18 years in a residential college in Andhra Pradesh, South India, the prevalence of PCOS was found to be 9.13% in adolescents.32 Similarly, another study conducted by Williamson et al reported that PCOS women of different ethnicity presented with different clinical manifestations.33 They reported the prevalence between 2.2-26%. These variations in prevalence are due to difficulties in hormonal evaluation and lack of consensus on diagnostic criteria.

According to an ovarian ultrasonographic study, the prevalence has been reported to be 4.0-11.9% in the community from three different countries.34 In one community-based prevalence study, using the Rotterdam criteria it was found that about 18%

1. Teede H, Deeks A, Moran L. Polycystic ovary syndrome: a complex condition with psychological, reproductive and metabolic manifestations that impacts on health across the lifespan. BMC Med 2010;8:41.

2. Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril 2004;81(1):19-25.

3. Stein IF, Leventhal ML. Amenorrhea associated with bilateral polycystic ovaries. Am J Obstet Gynecol 1935; 29:181-91.

4. Dunaif A. Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis.

Endocr Rev 1997;18(6):774-800.

5. Vos T, Flaxman AD, Naghavi M, Lozano R, Michaud C, Ezzati M, et al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012;380(9859):2163-96.

6. Chatopadya, Michaud C, Ezzati M, Shibuya K, et al.

Prevalence of PCOS in White women. Int J Obstet Gynecol 2011:11(1):297-8.

7. Norman RJ, Mahabeer S Menstrual irregularities in Indian women with polycystic ovary syndrome. Fertil Steril 1995;6:58-62.

8. Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Futterweit W, et al; Task Force on the Phenotype of the Polycystic Ovary Syndrome of The Androgen Excess and PCOS Society. The Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report. Fertil Steril 2009;91(2):456-88.

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Obstetrics AND Gynecology 9. Goodarzi MO, Korenman SG. The importance of insulin resistance in polycystic ovary syndrome. Fertil Steril 2003;80(2):255-8.

10. Waldstreicher J, Santoro NF, Hall JE, Filicori M, Crowley WF Jr. Hyperfunction of the hypothalamic-pituitary axis in women with polycystic ovarian disease: indirect evidence for partial gonadotroph desensitization. J Clin Endocrinol Metab 1988;66(1):165-72.

11. Apter D, Bützow T, Laughlin GA, Yen SS. Accelerated 24hour luteinizing hormone pulsatile activity in adolescent girls with ovarian hyperandrogenism: relevance to the developmental phase of polycystic ovarian syndrome. J Clin Endocrinol Metab 1994;79(1):119-25.

12. Veldhuis JD, Pincus SM, Garcia-Rudaz MC, Ropelato MG, Escobar ME, Barontini M. Disruption of the joint synchrony of luteinizing hormone, testosterone, and androstenedione secretion in adolescents with polycystic ovarian syndrome. J Clin Endocrinol Metab 2001;86(1): 72-9.

13. Goldenberg N, Glueck C. Medical therapy in women with polycystic ovarian syndrome before and during pregnancy and lactation. Minerva Ginecol 2008;60(1): 63-75.

14. Boomsma CM, Fauser BC, Macklon NS. Pregnancy complications in women with polycystic ovary syndrome.

Semin Reprod Med 2008;26(1):72-84.

15. Michelmore K, Ong K, Mason S, Bennett S, Perry L, Vessey M, et al. Clinical features in women with polycystic ovaries: relationships to insulin sensitivity, insulin gene VNTR and birth weight. Clin Endocrinol (Oxf) 2001;55(4):439-46.

16. Bohler H Jr, Mokshagundam S, Winters SJ. Adipose tissue and reproduction in women. Fertil Steril 2010;94(3): 795-825.

17. Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, et al; American Heart Association; National Heart, Lung, and Blood Institute. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation 2005;112(17):2735-52 18. Farrell K, Antoni MH. Insulin resistance, obesity, inflammation, and depression in polycystic ovary syndrome: biobehavioral mechanisms and interventions.

Fertil Steril 2010;94(5):1565-74.

19. Vgontzas AN, Legro RS, Bixler EO, Grayev A, Kales A, Chrousos GP. Polycystic ovary syndrome is associated with obstructive sleep apnea and daytime sleepiness: role of insulin resistance. J Clin Endocrinol Metab 2001;86(2):517-20.

20. Tasali E, Van Cauter E, Ehrmann DA. Relationships between sleep disordered breathing and glucose

metabolism in polycystic ovary syndrome. J Clin Endocrinol Metab 2006;91(1):36-42.

21. Cerda C, Pérez-Ayuso RM, Riquelme A, Soza A, Villaseca P, Sir-Petermann T, et al. Nonalcoholic fatty liver disease in women with polycystic ovary syndrome. J Hepatol 2007;47(3):412-7.

22. Hardiman P, Pillay OC, Atiomo W. Polycystic ovary syndrome and endometrial carcinoma. Lancet 2003;361(9371):1810-2.

23. Giudice LC. Endometrium in PCOS: Implantation and predisposition to endocrine CA. Best Pract Res Clin Endocrinol Metab 2006;20(2):235-44.

24. Patel SM, Nestler JE. Fertility in polycystic ovary syndrome.

Endocrinol Metab Clin North Am 2006;35(1):137-55, vii.

25. Moran LJ, Pasquali R, Teede HJ, Hoeger KM, Norman RJ. Treatment of obesity in polycystic ovary syndrome: a position statement of the Androgen Excess and Polycystic Ovary Syndrome Society. Fertil Steril 2009;92(6):1966-82.

26. Glueck CJ, Papanna R, Wang P, Goldenberg N, SieveSmith L. Incidence and treatment of metabolic syndrome in newly referred women with confirmed polycystic ovarian syndrome. Metabolism 2003;52(7):908-15.

27. Hollinrake E, Abreu A, Maifeld M, Van Voorhis BJ, Dokras A. Increased risk of depressive disorders in women with polycystic ovary syndrome. Fertil Steril 2007;87(6): 1369-76.

28. Glueck CJ, Wang P, Goldenberg N, Sieve-Smith L. Pregnancy outcomes among women with polycystic ovary syndrome treated with metformin. Hum Reprod 2002;17(11):2858-64.

29. Cresswell JL, Barker DJ, Osmond C, Egger P, Phillips DI, Fraser RB. Fetal growth, length of gestation, and polycystic ovaries in adult life. Lancet 1997;350(9085):1131-5.

30. Thessaloniki ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Consensus on infertility treatment related to polycystic ovary syndrome. Hum Reprod 2008;23(3):462-77.

31. Stankiewicz M, Norman R. Diagnosis and management of polycystic ovary syndrome: a practical guide. Drugs 2006;66(7):903-12.

32. Nidhi R, Padmalatha V, Nagarathna R, Amritanshu R. Prevalence of polycystic ovarian syndrome in Indian adolescents. J Pediatr Adolesc Gynecol 2011;24(4):223-7.

33. Williamson K, Gunn AJ, Johnson N, Milsom SR. The impact of ethnicity on the presentation of polycystic ovarian syndrome. Aust N Z J Obstet Gynaecol 2001;41(2):202-6.

34. Farquhar CM, Birdsall M, Manning P, Mitchell JM, France JT. The prevalence of polycystic ovaries on ultrasound scanning in a population of randomly selected women.

Aust N Z J Obstet Gynaecol 1994;34(1):67-72.

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ONCOLOGY

A Patient with Tracheal Leiomyoma and Meningioma: A Case Report N Shah*, R Hyderabadi†, R Diwanji‡, DR Kothari#, Varsha J Patel¶, PC Joshi$, Meena Pandya€

Abstract Most of the tumors that form in the trachea and bronchi in adults are malignant but a few are benign. Common benign tumors of the trachea are squamous cell papilloma, fibroma, hemangioma and leiomyoma. Leiomyoma of trachea constitute only 1% of the common benign tumors of the trachea and hence few cases are reported in the literature. Meningiomas are a diverse set of tumors arising from the meninges, majority of these tumors are usually benign and only 8% are either atypical or malignant, which could recur after treatment or removal. Presence of both this uncommon tumors in a single patient is quite rare. We present a case of a woman with both the tumors.

Keywords: Trachea, bronchi, benign, leiomyoma, meningiomas

L

eiomyomas are benign, circumscribed, firm whitish-pink tumors. Only around 43 cases of leiomyoma of the trachea have been reported till 2006.1 Grillo and Mathisen reported 198 cases of primary tracheal tumors in their 26 years series. Out of these 21 were benign and only 2 (1%) were tracheal leiomyomas.2 Leiomyoma of the trachea occurs mostly in the lower part of the trachea. The clinical manifestations are related to the obstructive nature of lesion, ulceration and secondary infections.

interlace in every direction. There are occasional areas of cystic degeneration due to poor vascularization. They are usually sessile or widely pedunculated, endophytic, obstructive tumors. Chest X-ray, computed tomography (CT) scan, magnetic resonance imaging (MRI), bronchoscopy and histopathology are confirmative diagnostic procedures. Bronchoscopic local surgical excision, and open surgical removal of the tumor have all been described. Incidence of recurrence after total local excision is unknown.3-7

Histopathologically, leiomyomas are composed of smooth muscle fibers arranged in parallel rows. Bundles

Meningiomas are a diverse set of tumors arising from arachnoidal cells of the leptomeninges. Majority of these tumors are usually benign (92%) and (8%) are either atypical or malignant and grow back after treatment or removal. Patients with neurofibromatosis type 2 (NF-2) have a 50% chance of developing one or more meningiomas. An atypical meningioma, also called Grade II meningioma, is a meningeal tumor that could be malignant and grow back after treatment or removal.8-10

*Consulting Pulmonologist †Consulting Cardiothoracic Surgeon ‡Consulting Neurosurgeon #Director and Medical Superintendent Dr Jivraj Mehta Smarak Health Foundation Bakeri Medical Research Center, Ahmedabad, Gujarat ¶Ret. Head Dept. of Pharmacology NHL Municipal Medical College, Ahmedabad, Gujarat ¶Secretary, Research Department Dr Jivraj Mehta Smarak Health Foundation Bakeri Medical Research Center, Ahmedabad, Gujarat $Research Co-ordinator Research Department €I./C./ Research Department Dr Jivraj Mehta Smarak Health Foundation Bakeri Medical Research Center, Ahmedabad, Gujarat Address for correspondence Dr Varsha J Patel Dr Jivraj Mehta Smarak Health Foundation Bakeri Medical Research Center, Ahmedabad - 380 007, Gujarat E-mail: drvarsha4@rediffmail.com

Meningiomas are readily visualized with contrast CT scan or MRI and arteriography all attributed to the fact that meningiomas are extra-axial and vascularized. Tumor location is a critical factor determining prognosis and therapy options, especially surgical resectability.8 Meningiomas can be surgically resected and result in a permanent cure if the tumor is superficial on the dural surface and easily accessible. Postoperative radiation therapy is indicated only if they are atypical in nature or rarely due to the eloquent location; a small residual tumor is left behind.9

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ONCOLOGY We report a rare case of concurrent occurrence of leiomyoma trachea and meningioma in a female patient.

Case report A female patient aged 48 years, presented with chief complaints of breathlessness, inability to sleep in supine position and occasional orthopnea since 2½ months.

These symptoms were aggravated since last 2 days.

She was being treated in the past as a case of acute asthmatic bronchitis with status asthmatics. She also complained of attacks of severe headache off and on since 3 months. There was no history of vomiting, vertigo or visual disturbances. She was also under treatment for hypothyroidism since 2 months. There was no family history of asthma or malignancy.

Investigations Her hematology and biochemistry reports were: Hemoglobin (Hb) - 10.7%, total white blood cell (WBC) 21,500/mm­3, platelets - 3,53,000/mm3, malarial parasites negative. Serum creatinine was 0.57 mg%, Serum sodium 153 mEq/L and serum potassium - 5.1 mEq/L. Her previous chest X-rays were normal. Her CT scan thorax (plain) reported - an exophytic endotracheal

Figure 2. MRI Brain showing well-defined intense inhomogenously enhancing extra-axial lesion in the left parasagittal frontal region with disproportionate perilesional edema and mass effect suggesting atypical meningioma.

lesion arising from right posterior wall of infraglottic trachea involving all of tracheal wall and peritracheal soft tissue. Possibility of malignancy appears likely (Fig. 1).

Her MRI brain showed well-defined intense inhomogenously enhancing extra-axial lesion in the left parasagittal frontal region with disproportionate perilesional edema and mass effect suggesting atypical meningioma (Fig. 2).

Treatment Rigid bronchoscopy done under general anesthesia revealed necrotic vascular tumor. Tumor biopsy was taken along with airway clearance. Biopsy was reported as benign spindle cell tumor ? neurofibroma ? leiomyoma.

After 5 days, open total excision of the tumor was done.

Biopsy of the excised tumor was reported as benign spindle cell tumor, leiomyoma. Postoperative period was uneventful except mild surgical emphysema.

After 2 months of her surgery for leiomyoma trachea, a left frontal craniotomy with total excision of left frontal parasagittal meningioma with excision of the adjacent dura was performed.

Figure 1. CT scan thorax (plain) showing an exophytic endotracheal lesion arising from right posterior wall of infraglottic trachea involving all of tracheal wall and peritracheal soft tissue.

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Her postoperative period was uneventful. Postoperative radiotherapy was advised. Patient on follow-up after completion of radiotherapy is completely asymptomatic and has resumed her previous lifestyle. She is kept under close observation for signs and symptoms of recurrence.10

ONCOLOGY Conclusion The onset of asthmatic-like attacks in individuals over 40 years of age without any significant improvement with medical treatment should arouse the suspicion of an obstructive tracheobronchial lesion and patient should be investigated accordingly. Recognition and diagnosis of the nature of the obstructive lesion tumors (e.g., leiomyoma) is important as dramatic relief of symptoms follows surgical resection.

The combination of leiomyoma of the trachea and an intracranial meningioma makes it an even rarer entity.

To our knowledge reference of such dual presentation in a patient is not found in the literature. Patient has undergone surgery for both the lesions and resumed a normal life after being treated.

References 1. Maehara M, Ikeda K, Ohmura N, Kurokawa H, Sakaida N, Sawada S. Leiomyoma of the trachea: CT and MRI findings. Radiat Med 2006;24(9):643-5.

2. Grillo HC, Mathisen DJ. Primary tracheal tumors: treatment and results. Ann Thorac Surg 1990;49(1):69-77.

3. Sanders JS, Carnes VM. Leiomyoma of the trachea. Report of a case, with a note on the diagnosis of partial tracheal obstruction. N Engl J Med 1961;264:277-9.

4. D orenbusch AA. Leiomyoma of the trachea; a case report.

AMA Arch Otolaryngol 1955;61(4):470-1.

5. Bharadwaj SC, Unruh HW. Leiomyoma of the trachea.

Ann Thorac Surg 2012;93(2):669-70.

6. Park JS, Lee M, Kim HK, Choi YS, Kim K, Kim J, et al.

Primary leiomyoma of the trachea, bronchus, and pulmonary parenchyma - a single-institutional experience.

Eur J Cardiothorac Surg 2012;41(1):41-5.

7. Gupta V, Vishwakarma R, Patel K, Desai H. Tracheal leiomyoma: A clinical dilemma. J Laryngol Voice 2013;3(1):29-31.

8. Saraf S, McCarthy BJ, Villano JL. Update on meningiomas.

Oncologist 2011;16(11):1604-13.

9. Yang SY, Park CK, Park SH, Kim DG, Chung YS, Jung HW. Atypical and anaplastic meningiomas: prognostic implications of clinicopathological features. J Neurol Neurosurg Psychiatry 2008;79(5):574-80.

10. L ee JH. Meningiomas: Diagnosis, Treatment, and outcome. Spinger-Verlag: Cleveland, Ohio, USA ISBN 978-1-84882-910-7; 2009.

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Japanese Mushroom Extract could Help Treat HPV Infections A Japanese mushroom extract, active hexose correlated compound (AHCC), appears to be effective in eradicating persistent human papillomavirus (HPV) infection, according to results of a small pilot study.

Ten women with persistent HPV infection received a once-daily oral dose (3 g) of AHCC for up to 6 months, and half of the participants achieved a negative result for HPV infection.

Three of these women with a confirmed eradication have stopped using AHCC, and the remaining two responders are continuing on the study. The results were presented at the 11th International Conference of the Society for Integrative Oncology.

Injecting Oncolytic Viruses in Melanoma: Durable Responses Injecting melanoma lesions with specific common cold or herpes simplex viruses destroys tumor cells and induces systemic immune responses, according to research presented here at the European Society for Medical Oncology Congress 2014.

A phase 2 study of a product that uses coxsackievirus A21 (CVA21) (Cavatrack) won the best poster award, and clinical data from a phase 3 trial were presented for talimogene laherparepvec (T-VEC).

The injection of oncolytic viruses directly into lesions is an active area of research in melanoma, said Sanjiv S. Agarwala, MD, professor of medicine at St. Luke’s University Hospital in Bethlehem, Pennsylvania and Temple University in Philadelphia, who was not involved in either study.

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ORTHOPEDICS

Morquio’s Syndrome: A Rare Case Kiran S Patil*, Mahantesh Y Patil*, Deepak Kaladagi†, Srinath M Gupta‡, Vinay K Gunjalli‡

Abstract Morquio’s syndrome is an autosomal recessive disorder due to deficiency of N-acetylgalactosamine-6 sulfate. Presented here is the case of a 4-year-old girl with complaints of deformity of bilateral lower limbs since 6 months. Examination revealed widely spaced teeth, corneal opacity, pectus carinatum, bilateral genu valgum and flat feet. X-rays of femur showed minimal metaphyseal widening, widened carpal bones and pointing metacarpals and beaking of the thoracic and lumbar vertebrae.

She was diagnosed to be suffering from Morquio’s syndrome. Mucopolysaccharidoses (MPS) are a rare group of metabolic disorders due to deficiency of enzymes responsible for degradation of glycosaminoglycans. Treatment is mainly symptomatic.

Keywords: Morquio’s syndrome, MPS, mucopolysaccharidoses type IV

M

orquio’s syndrome is an autosomal recessive disorder due to deficiency of N-acetylgalactosamine-6 sulfate. This results in abnormal degradation of keratin sulfate leading to accumulation of mucopolysaccharides.1 The incidence ranges from 1 in 76,000 to 1 in 5,00,000 live births. This was first described by Morquio and Brailsford in 1929.2

metaphyseal widening (Fig. 3), widened carpal bones and pointing metacarpals (Fig. 4) and beaking of the thoracic and lumbar vertebrae (Fig. 5).

Case report A 4-year-old female child presented to Orthopedic OPD with complaints of deformity of bilateral lower limbs since 6 months. Deformity became more prominent on standing. There was no difficulty in squatting and sitting. Delayed milestones were present. She was able to speak only monosyllable words. Birth history revealed full-term normal vaginal delivery with history of baby not crying immediately after birth. History of first-degree consanguineous marriage was present.

Examination revealed widely spaced teeth (Fig. 1), corneal opacity, pectus carinatum (Fig. 2), bilateral genu valgum and flat feet. X-rays of femur showed minimal

*Professor †Assistant Professor ‡Postgraduate Dept. of Orthopedics Jawaharlal Nehru Medical College, KLE University, Belgaum Address for correspondence Dr Kiran S Patil Professor Dept. of Orthopedics Jawaharlal Nehru Medical College, KLE University, Belgaum - 590 010 E-mail: srigups@gmail.com

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Figure 1. Widely spaced teeth.

Figure 2. Pectus carinatum.

ORTHOPEDICS

Figure 5. Beaking of vertebrae.

Figure 3. Minimal metaphyseal widening.

Discussion Mucopolysaccharidoses (MPS) are a rare group of metabolic disorders due to deficiency of enzymes responsible for degradation of glycosaminoglycans (dermatan sulfate, heparan sulfate, keratin sulfate).

Based on clinical and radiological studies, these are grouped into six types. Mucopolysaccharidosis 4 is subdivided in two types. MPS 4A and MPS 4B, both are difficult to differentiate clinically. They are spondyloepiphysio-metaphyseal dysplasias generally diagnosed in the second year of life when the child starts walking.

Figure 4. Widened carpal bones and pointing metacarpals.

Skeletal deformities can range from kyphosis, scoliosis, pectus carinatum, genu valgum and long bone deformities which become more pronounced as the child grows.3 Joint hyperlaxity is accompanied by frequent luxations (hips, knees). This leads to impaired walking and early growth arrest. At 5-6 years age, there is risk of cord compression due to hypoplasia of odontoid vertebrae and hyperlaxity at first two cervical vertebrae. Extra-skeletal manifestations include respiratory problems, hepatomegaly, valvulopathies, hearing loss and corneal clouding.4 Intelligence can be normal. Dental manifestations include tapered

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ORTHOPEDICS teeth with pointed cusps, spaced and flared maxillary teeth with deficient enamel and normal radiodensity.5 Treatment is mainly symptomatic as definitive treatment is not available. Recombinant enzyme therapy targeting the bone tissues is currently under development.6

3. Langer LO Jr, Carey LS. The roentgenographic features of the KS mucopolysaccharidosis of Morquio (MorquioBrailsford’s disease). Am J Roentgenol Radium Ther Nucl Med 1966;97(1):1-20.

REFERENCES

4. Von Noorden GK, Zellweger H, Ponseti IV. Ocular findings in Morquio-Ullrich’s disease. With report of two cases. Arch Ophthalmol 1960;64:585-91.

1. Koto A, Horwitz AL, Suzuki K, Tiffany CW, Suzuki K. The Morquio syndrome: neuropathology and biochemistry.

Ann Neurol 1978;4(1):26-36.

5. Kinirons MJ, Nelson J. Dental findings in mucopolysaccharidosis type IV A (Morquio’s disease type A). Oral Surg Oral Med Oral Pathol 1990;70(2):176-9.

2. Piccirilli CB, Chadduck WM. Cervical kyphotic myelopathy in a child with Morquio syndrome. Childs Nerv Syst 1996;12(2):114-6.

6. Dr. Rosaline froissart, Dr. Irene maire – Mucopolysaccharidosis. Available from: http://www.orpha.net/ consor/cgi-bin/OC_Exp.php?lng=EN&Expert=582.0

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Tolerability of COX-2 Inhibitors for Rheumatological Manifestations of IBD Unclear The jury is out on the tolerability and safety of selective cyclooxygenase 2 (COX-2) inhibitors for treatment of rheumatological manifestations of inflammatory bowel disease (IBD), according to a new Cochrane review.

"Clinicians need to continue to weigh the risks and benefits of these drugs when treating IBD patients with rheumatological manifestations in order to avoid disease exacerbation and other adverse effects," says a report released October 23 by The Cochrane Library.

Child’s Genes Affect Mom’s Risk for Rheumatoid Arthritis Children’s genes might increase their mother’s risk for rheumatoid arthritis, a new study shows. The finding could change the way physicians look at family history when advising women who are planning to conceive.

“You could ask the husband about his genetic background,” said Giovanna Cruz, MS, a graduate student at the University of California, Berkeley.

“Normally, the spouse would not be considered family,” she told Medscape Medical News. However, fetal microchimerism, in which a small number of fetal cells circulate in the mother’s body, can persist for several decades in some women.

Cruz presented the study here at the American Society of Human Genetics 2014 Annual Meeting.

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ORTHOPEDICS

A Study of Supracondylar Fractures of Humerus in Children by Open Reduction and Internal Fixation with Kirschner Wires Prasad M Gowda*, Nabeel Mohammed†

Abstract Background: Supracondylar fractures of humerus is the commonest injury, constitutes about 65.4% of all fractures about the elbow in children. Displaced supracondylar fracture of humerus demand great respect and challenging one to treat, since it requires accurate anatomical reduction and internal fixation to prevent complications. So, in this study, we reported the results of open reduction and internal fixation with K-wires in the displaced (Gartland’s type III) supracondylar fracture humerus in children. Material and Methods: Thirty cases of displaced (Gartland’s type III) supracondylar fractures treated by open reduction and internal fixation with K-wires were studied between September 2011 to August 2013 at our institution and followed for an average of 24 months. Results: We came across 36 male patients and 14 female patients. Majority of the cases (38) were due to high energy trauma of road traffic accidents involving relatively younger patients. At the end of 5 months, all except four patients could mobilize independently without any aid. We did not come across complications like fracture of femur and failure of fixation and no reoperations were required. Conclusions: Open reduction and internal fixation with K-wires is the most commonly accepted treatment of displaced supracondylar fracture humerus in children when done at appropriate time. It gives more stable fixation, better anatomical reduction with negligible complication.

Keywords: Supracondylar fracture humerus, K-wire, internal fixation, Gartland’s

S

upracondylar fracture of humerus is the commonest injury around elbow in children. It constitutes about 65.4% of all the fractures about the elbow in children. The occurrence rate increases progressively in the first 5 years of life to peak between 5-7 years of age.1 The supracondylar fracture of humerus demand great respect in treatment because if it is not treated properly it may give rise to many complications such as Volkmann’s ischemic contracture, neurovascular injury, myositis ossificans, stiffness of elbow and malunion.2 It needs accurate anatomical reduction and internal fixation. So, no longer is it acceptable to near ‘not bad for a supracondylar fracture’.3 Various

*Associate Professor †Orthopedic Resident Dept. of Orthopedic Surgery Sri Siddhartha Medical College, Tumkur, Karnataka Address for correspondence Dr Nabeel Mohammed Orthopedic Resident Dept. of Orthopedic Surgery Sri Siddhartha Medical College, Tumkur - 572 107, Karnataka E-mail: drnabeel99@gmail.com

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modalities of treatment have been proposed for the treatment of displaced supracondylar fractures of the humerus in children, such as closed reduction and plaster of paris slab application, skin traction, overhead skeletal traction, closed reduction and percutaneous pin fixation and open reduction with internal fixation.4 Closed reduction with splint or cast immobilization and treatment with traction has traditionally been recommended for displaced supracondylar fractures, but difficulty in reduction, loss of reduction postoperatively or during follow-up leads to malunion and elbow stiffness.5 During early part of the century, there was a reluctance to recommend open reduction of supracondylar fracture. But, now a lot of changes in medical field has taken place especially in orthopedic trauma. A better understanding of biomechanics quality of implants, principles of internal fixation, soft tissue care antibiotics and asepsis have all contributed to the radical changes. Thus, we have advanced from the conservative approach to open reduction and internal fixation in fractures as an acceptable mode of treatment.6 Our objectives were to study age, sex and side incidence of supracondylar fracture of humerus

ORTHOPEDICS and average time duration for union of these fractures after surgical treatment of supracondylar fracture of humerus by open reduction and internal fixation with K-wires along with any complications they may arise.

Material and Methods Thirty closed extension type of supracondylar fractures (Gartland’s type III) of the humerus were treated by open reduction and internal fixation with K-wires between September 2012 to August 2013. The study was conducted in Sri Siddhartha Medical College, Tumkur.

Inclusion Criteria ÂÂ

Age <15 years.

ÂÂ

Irreducible fracture by closed reduction.

ÂÂ

Closed supracondylar fractures with vascular compromise.

ÂÂ

Open fractures.

Exclusion Criteria ÂÂ

Age >15 years.

ÂÂ

Patients medically unfit for surgery.

The ethical clearance for this study was taken from the institution. All patients selected for this study were admitted in Sri Siddhartha Medical College Hospital and examined according to protocol and associated injuries if any were noted. X-rays were taken in two planes. A trial closed reduction was done in 27 patients and three patients who had gross swelling, were taken for elective surgery at the earliest without closed reduction. All fractures were classified according to Gartland’s classification chart: ÂÂ

Type I - Nondisplaced

ÂÂ

Type II - Displaced (with intact posterior cortex)

ÂÂ

Type III - Displaced (no cortical contact) zz

Posteromedial

zz

Posterolateral.

Operative Technique Under general anesthesia, patients were put in lateral position with fractured elbow facing the surgeon. The standard posterior Campbell’s approach was used in all patients. Ulnar nerve was identified and isolated.

Triceps muscle was vertically split to expose fractured site. Hematoma was evacuated and saline wash was given to clearly visualize fractured site. Fracture was reduced by leaving the distal end of proximal fragment posteriorly. Reduction was assessed by taking into

consideration the medial and lateral pillar anatomy.

Once good reduction was confirmed and if the fracture was of posteromedial type, the medial pin was placed first through the apex of the medial epicondyle.

The lateral pin was placed at the center of lateral epicondyle obliquely across fracture site to engage the opposite cortex of the proximal fragment. The fractures were secured with 1.2-2.0 mm K-wires depending upon the age of the patient at an angle of 30° in coronal plane to engage in opposite cortex on both side.

Fracture stability was assessed, the elbow extended and carrying angle was measured and compared to that on the nonaffected side. The pins were bent and cutoff outside the skin to allow removal in the outpatient clinics without anesthesia. Wound was closed in layers and sterile dressing was applied. Tourniquet was released.

Postoperatively, the extremity was placed in wellpadded posterior splint with elbow flexed to 90° and patient was shifted to the ward after recovery from anesthesia. Patients were called for follow-up after 3 weeks and the POP slab was removed. Active range of motion exercises were encouraged and a special mention and warning was given after the removal of splint about avoiding massage and passive stretching of elbow joint. The K-wires were removed after 4-6 weeks with further follow ups done at 12 weeks and 24 weeks. The patients were examined clinically and radiologically, assessed for range of motion and carrying angle. The final results obtained were evaluated by Flynn’s criteria.7 The results were graded as excellent, good, fair and poor according to loss of range of motion and loss of carrying angle.

Results Observation and analysis of results were done in 30 patients who were operated in our hospital in relationship to age, sex, type of injury, laterality of fracture, fracture pattern, associated injuries, time of surgery, duration of hospital stay, complications of treatment and functional outcome.

In our series, majority of patients, 18 (60%) were found to be between age group of 4-6 years (Table 1). The least number of cases are found in the age group between 13-15 years. The average age of the patient was 7 years. Majority of the patients were males i.e., 18 (60%) and 12 (40%) patients were females. The most commonest cause of injury was fall while playing 15 patients, followed by fall from bicycle in

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ORTHOPEDICS Table 1. Age-wise Distribution of Patient Age in years

No. of patients

Percentage (%)

4-6

18

60

7-9

6

20

10-12

3

10

13-15

3

10

Discussion

Table 2. Cause of Injury Nature of trauma

No. of patients

Percentage (%)

Fall from bicycle

12

40

Fall while playing

15

50

Fall from tree

3

10

Table 3. Postoperative Complications in the Patients Complications

No. of patients

Percentage (%)

Traumatic median nerve palsy

1

3.3

Superficial pin tract infection

4

13.3

Iatrogenic ulnar nerve palsy

3

10

Migration of K-wires

1

3.3

Malunion – varus

4

13.3

Table 4. Functional Results based on Flynn’s Grading Results

Rating

Satisfactory

Excellent

18

60

Good

7

23.3

Fair

3

10

Poor

2

6.7

Unsatisfactory

No. of patients

Percentage (%)

12 patients and in three patients it was due to fall from tree (Table 2). There was a left-sided predominance (23 patients, 76.6%) compared to the right side (7 patients, 23.4%). In our clinical study, we had 20 patients with posteromedial displacement and 10 patients with posterolateral displacements.

Majority of the patient underwent surgery on second day of hospitalization out of which 19 patients were discharged on the second postoperative day.

Postoperative complications ranging from traumatic median nerve palsy, superficial pin tract infection, iatrogenic ulnar nerve palsy, migration of K-wires and malunion were encountered (Table 3). Twenty-one

574

patients had loss of range of motion between 0-5°, one patient had >15° loss of range of motion. Eighteen patients had carrying angle loss of 0-5°, two had >15° and remaining patients 6-15° carrying angle loss.

Functional results based on Flynn’s grading system showed that we had 93% (28 patients) satisfactory results and two patients with unsatisfactory results (Table 4).

Indian Journal of Clinical Practice, Vol. 25, No. 6, November 2014

Supracondylar fracture of humerus is the commonest injury around elbow in children.1 Supracondylar fracture of humerus demand great respect in treatment because if it is not treated properly, it may give rise to neurovascular compromise, difficulty in obtaining or maintaining reduction and poor late results because of stiffness of elbow or malunion.2 Most frequently used methods of treatment are closed reduction and application of cast, skeletal traction, closed reduction and percutaneous K-wire fixation and open reduction and internal fixation with K-wires.4 The present study was undertaken to verify the claims of various authors regarding surgical management of supracondylar fracture humerus in children and outcome of treatment of these fracture by open reduction and internal fixation with K-wires.

In our series of 30 patients, (80%) of the patients were between 4-9 years age group with an average age being 7 years. Majority of our patients 15 (50%) sustained fractures due to fall while playing, remaining due to fall from tree and from bicycle. In Edward et al7 series of 78 patients with supracondylar fractures, 69 patients sustained injury due to fall while playing.

Fransworth et al,8 in her series 70% of cases sustained fracture due to fall.

In our study of 30 patients 20 (66.7%) had posteromedial displacement, 10 (33.3%) had posterolateral displacement which was consistent with other studies. In our study two patients had fractures of distal end of radius on same side. In Mazda et al9 series of 116 patients seven patients had ipsilateral forearm bone fracture. Pirone AM,4 et al in their series of 230 patients, observed 20 injuries of the ipsilateral forearm, 18 fractures of the distal third of the radius and ulna, one fracture of the middle third of radius and ulna and one monteggia fracture dislocation. Millis,10 et al noted 8.33% of associated fractures. Ninteen (63.4%) patients were operated on second day of hospitalization in our study. In Ramsey, et al11 study of 15 cases all cases were operated within 24 hours of injury.

ORTHOPEDICS Skaggs et al,12 in their study of 204 patients, found that average interval between time of injury and operation was 1.4 days. In Weiland et al,2 study of 58 cases, 51 patients underwent surgery within 24 hours. In our series, majority of patients were operated with in 48-72 hours and delay in operation was due to late admission to hospital.

the K-wire, but there was no deep or bone infection.

In Srivastava14 study group of 42 patients about 14% had superficial pin tract infection. In Ramsey et al11 study of 15 cases, one patient had pin tract infection that had healed after 2 weeks of treatment.

In our study, we had four cases of cubitus varus deformity, one case of proximal migration of K-wire, this may be due to failure to pierce in the opposite cortex during insertion. Later the K-wire was removed under general anesthesia.

In our series of 30 patients, about 80% of the patients were discharged within 2-3 days of operation and five patients discharged at 5 days due to presence of swelling. So, these patients were kept for observation in our study. Regarding complications, one traumatic median nerve and three iatrogenic ulnar nerve palsies were encountered. Median nerve palsy occurred in a patient with posterolateral displacement but luckily that patient did not have any vascular injury.

Loss of Range of Motion In our study of 30 patients, 21 patients (70%) had loss of range of motion of 0-5°, six had 6-10°, two had 11-15° and only one patient had >15° loss of range of motion. In Weiland et al2 series of 52 patients, five patients suffered a moderate loss in range of motion.

One patient had extension loss of <10° and three had flexion loss of <10° and last patient had flexion and extension loss of >10°.

We had three iatrogenic ulnar nerve palsies. Though in our study, we isolated ulnar nerve during operation, we thought it may be due to over stretching of nerve during operation especially while putting K-wires on medial side and may be also due to compression of nerve by the K-wire postoperatively, but all patients recovered in a matter of 3-6 months. In Kumar et al,13 series of 44 patients five patients had postoperative temporary nerve palsy and they recovered full function.

Loss of Carrying Angle In the present study at final follow-up 0-5° of carrying angle loss were seen in 18 patients (60%), two (6.7%) patient had >15° loss of carrying angle.

In Ramsey, et al11 series of 15 patients, 12 were considered essentially normal with carrying angle loss of <3-4°, but three patient had 5-15° of varus deformity without significant motion at elbow. In Weiland et al,2 study of 52 patients, five patients had varus angulation of <10°, six had 10-20° and two had varus deformity of >20°.

In a Weiland et al2 series of 52 cases he came across five preoperative neurological deficits. Two patients had combined radial and median nerve and one each of radial, ulnar and median nerve deficit. All patients recovered in 2 weeks postoperatively. In Srivatsava,14 study group, 42.2% of the patient had nerve injury. We had four cases of superficial pin tract infection. Three out of 4 subsided with antibiotics in 10 days, but in one patient infection disappeared after removal of

In our study of 30 patients majority of the patients underwent surgery with in 48 hours. We have started

Table 5. Comparison Between Present Study and Other Methods of Treating Displaced Supracondylar Fracture Treatment

Author

Total no. of cases

Flynn’s Grading system Excellent

Good

Fair

Poor

Closed reduction and application of a cast

Pirone et al

101

51 (51%)

27 (27%)

3 (3%)

20 (20%)

Skeletal traction

Pirone et al

24

16 (67%)

5 (21%)

1 (4%)

2 (8%)

Open reduction and internal fixation

Reitman et al

65

18 (55%)

8 (24%)

3 (9%)

4 (12%)

Closed reduction and percutaneous K-wire fixation

Flynn et al

52

42 (80%)

7 (14%)

2 (4%)

1 (2%)

Open reduction and internal fixation with K-wries

Pirone et al

9

6 (66%)

1 (11%)

0

2 (22%)

Mazda et al

26

24 (92%)

1 (4%)

0

1 (4%)

Present study (2006)

30

18 (60%)

7 (23.3%)

3 (10%)

2 (6.7%)

Open reduction and K-wire fixation

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575

ORTHOPEDICS flexion and extension elbow exercises at the end of 3 weeks and K-wire were removed between 4 and 6 weeks and all patient showed radiological union at 4 weeks of follow-up. In our series, we had one traumatic median nerve palsy and three iatrogenic ulnar nerve palsy. Though in all cases ulnar nerve was isolated before putting K-wire, the palsy was thought to be due to stretching of nerve and all recovered in a matter of 4-6 months postoperatively. Four patients had superficial pin tract infection and recovered with a course of antibiotics. One patient had proximal migration of K-wire, which was removed later. Five patients had cubitus varus deformity and they were advised to undergo corrective osteotomy but all patients refused because they had good range of painless motion with only cosmetic deformity.

The results of our study showed favorably excellent results when compared together studies of open reduction and internal fixation with 93% satisfactory results according to Flynn’s criteria of treatment of type III supracondylar fracture of humerus in children (Table 5).

To conclude, open reduction and internal fixation with K-wires gives more stable fixation, better anatomical reduction with negligible complication. So, open reduction and internal fixation with K-wires is the most commonly accepted treatment of displaced supracondylar fracture humerus in children when done at appropriate time.

References 1. Kasser JR, Beaty JH (Eds.). Supracondylar fractures of the distal humerus (Chapter14). In: Rockwood and Wilkins Fractures in Children. 6th edition, Lippincott Williams and Wilkins: Philadelphia 2006:p.543-89.

2. Weiland AJ, Meyer S, Tolo VT, Berg HL, Mueller J. Surgical treatment of displaced supracondylar fractures of the humerus in children. Analysis of fifty-two cases followed for five to fifteen years. J Bone Joint Surg Am 1978;60(5):657-61.

3. Terry CS(Ed.). Fractures and dislocations in children (Chapter33). In: Campbell’s Operative Orthopaedics. 10th edition, Vol. 2, Mosby: New York 2003:p.1437-51.

4. Pirone AM, Graham HK, Krajbich JI. Management of displaced extension-type supracondylar fractures of the humerus in children. J Bone Joint Surg Am 1988;70(5): 641-50.

5. Yusof A, Razak M, Lim A. Displaced supracondylar fracture of humerus in children - comparative study of the result of closed and open reduction. Med J Malaysia 1998;53 Suppl A:52-8.

6. Fleuriau-Chateau, McIntyre, Letts. To review with irreducible supracondylar fractures requiring open reduction in children and to propose guidelines f or an open approach to supracondylar fractures. Can J Surg 1998;41(2):112-8.

7. Edward E, Palmar, et al. Supracondylar fractures of the humerus. In children. JBJS 1978;60-A:652.

8. Farnsworth CL, Silva PD, Mubarak SJ. Etiology of supracondylar humerus fractures. J Pediatr Orthop 1998;18(1):38-42.

9. Mazda K, Boggione C, Fitoussi F, Penneçot GF. Systematic pinning of displaced extension-type supracondylar fractures of the humerus in children. A prospective study of 116 consecutive patients. J Bone Joint Surg Br 2001;83(6):888-93.

10. Millis MB, Singer IJ, Hall JE. Supracondylar fracture of the humerus in children. Further experience with a study in orthopaedic decision-making. Clin Orthop Relat Res 1984;(188):90-7.

11. Ramsey RH, Griz J. Immediate open reduction and internal fixation of severely displaced supracondylar fractures. Clin Orthop 1973; 90:130-4.

12. Skaggs DL, Hale JM, Bassett J, Kaminsky C, Kay RM, Tolo VT. Operative treatment of supracondylar fractures of the humerus in children. The consequences of pin placement.

J Bone Joint Surg Am 2001;83-A(5):735-40.

13. Kumar R, Kiran EK, Malhotra R, Bhan S. Surgical management of the severely displaced supracondylar fracture of the humerus in children. Injury 2002;33(6):517-22.

14. Srivastava S. The results of open reduction and pin fixation in displaced supracondylar fractures of the humerus in children. Med J Malaysia 2000;55 Suppl C:44-8.

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Most Splints Misapplied in Children ■ ■ ■ ■ at pediatric emergency departments and urgent care As many as 93% of splints applied to fractures in children centers may be done incorrectly, according to the results of a new study.

The rates of misapplied splints were "much higher than I anticipated," said Joshua Abzug, MD, director of pediatric orthopedics and assistant professor of orthopedics at the University of Maryland School of Medicine, in Baltimore. Dr Abzug presented the research here at the American Academy of Pediatrics (AAP) 2014 National Conference and Exhibition.

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SURGERY

Management of Hemorrhoids Anmol Chugh*, Rajdeep Singh†, PN Agarwal‡

Abstract This article discusses the pathophysiology, risk factors, classification, clinical evaluation and current nonoperative and operative treatment of hemorrhoids. Hemorrhoids are defined as the symptomatic enlargement and distal displacement of the normal anal cushions. The most common symptom of hemorrhoids is rectal bleeding associated with bowel movement. The abnormal dilatation and distortion of the vascular channel, together with destructive changes in the supporting connective tissue within the anal cushion, is a paramount finding of hemorrhoids. It appears that the dysregulation of the vascular tone and vascular hyperplasia might play an important role in hemorrhoidal development, and could be a potential target for medical treatment. In most instances, hemorrhoids are treated conservatively, using many methods such as lifestyle modification, fiber supplement, suppository-delivered anti-inflammatory drugs and administration of venotonic drugs. Nonoperative approaches include sclerotherapy and, preferably, rubber band ligation. An operation is indicated when nonoperative approaches have failed or complications have occurred. Several surgical approaches for treating hemorrhoids have been introduced including hemorrhoidectomy and stapled hemorrhoidopexy, but postoperative pain is invariable. Some of the surgical treatments potentially cause appreciable morbidity such as anal stricture and incontinence. The applications and outcomes of each treatment are discussed.

Keywords: Hemorrhoids, pathophysiology, treatment, management, outcome

H

emorrhoids are abnormally enlarged anal cushions containing arteriovenous anastomosis, traditionally described as occurring in the 3, 7, and 11 o’clock positions.1 The vascular supply is from branches of the superior rectal artery, which are drained by veins (internal venous plexus) emptying into the superior rectal vein. Internal hemorrhoids, which originate from above the dentate line of the anal canal, occur when these anal cushions are dragged down the canal. They affect millions of people around the world, and represent a major medical and socioeconomic problem. Multiple factors have been claimed to be the etiologies of hemorrhoidal development, including constipation and prolonged straining.

Pathophysiology The muscular fibers of the anal canal and anal sphincters lie within the connective tissue matrix. Studies have

*Postgraduate †Professor ‡Director Professor and Head Dept. of General Surgery, Maulana Azad Medical College, New Delhi Address for correspondence Dr Anmol Chugh E-187, New Rajinder Nagar - 110 060, New Delhi E-mail: anmolchugh1987@gmail.com

shown that, this matrix muscle ratio changes with age, showing an increase in connective tissue with age.2 This leads to a loss of elasticity, allowing the anchoring muscle fibers that give support to the anal cushions and sphincter complex to fragment resulting in prolapse of hemorrhoidal tissue. Other risk factors are constipation, straining and also diarrhea. Straining while sitting for long in toilet with an unsupported and relaxed perineum leads to engorgement of the anal cushions and increases the downward shearing force upon them.2 Along with the loss of supporting muscle fibers the venous plexus distends causing the hemorrhoids to bulge.

Hemorrhoids are common in the later stages of pregnancy and may be due to the gravid uterus causing compression on the pelvic venous system. External hemorrhoids are those that originate from varicosities of veins (external venous plexus) draining the territory of the inferior rectal artery and they occur distal to the dentate line.

Conservative management The single most important conservative intervention is increasing the daily fiber intake to >25 g/day via the diet with/without fiber supplements. Together with increasing liquid intake, minimizing time on the

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SURGERY toilet and evacuating soon after feeling the urge, these interventions are aimed at minimizing constipation and straining.3 Bathing in warm water has a soothing effect on anal discomfort.3 Venotonic agents, such as diosmin (a flavonoid), used in addition to the above measures may improve the outcome of conservative treatment; venotonic injection at the hemorrhoidal site is also possible but has a poor outcome.3 For quick relief of symptoms topical agents containing local anesthetics, steroids, astringents and/or antiseptics may be satisfactory, but prolonged application may induce maceration and allergy. Conservative management is sufficient to improve or resolve symptoms in many Table 1. Internal Hemorrhoids: Goligher Grading and Management Grade

Symptoms and signs Management

First degree

Bleeding; no prolapse

Second degree

Prolapse with Rubber band ligation spontaneous reduction Bleeding, seepage

Dietary modifications

Coagulation Dietary modifications

Third degree

Prolapse requiring digital reduction

Surgical hemorrhoidectomy

Bleeding, seepage

Rubber band ligation

Prolapsed, cannot be reduced

Surgical hemorrhoidectomy

Strangulated

Urgent hemorrhoidectomy

Dietary modifications Fourth degree

Dietary modifications

patients. Overall, fiber supplementation can decrease severity of symptoms by a mean of around 50% in patients with Grade Ι-ΙΙΙ hemorrhoids. In fact, fiber supplementation is as effective as sclerotherapy (Table 1).

Nonoperative Managements Nonoperative procedures are usually considered first for persistent Grade Ι-ΙΙΙ hemorrhoids.

Rubber Band Ligation The gold-standard is rubber band ligation (Fig. 1).

It has the lowest recurrence rate at 12 months compared to sclerotherapy and infrared photocoagulation. It is recommended as the first-line treatment for Grade Ι and ΙΙ hemorrhoids. The patient should be warned of anticipated rectal bleeding at 5-14 days after the procedure. Mild/moderate pain occurs in roughly 30% of cases. Success rate is around 75% and the complication rate stands at 0.7%.4 Recurrence at 4-5 years is around 70%, but repeating the procedure is usually sufficient; only 10% of cases would require eventual hemorrhoidectomy. A significant bleeding tendency and treatment with warfarin or heparin are absolute contraindications for banding. Antiplatelet agents, such as aspirin, should be withdrawn for a week before and after the procedure. When banding is contraindicated, other nonoperative approaches can be offered.

This method has been shown to be the most effective nonsurgical treatment for hemorrhoids.4 It is particularly effective for Grade II, but less for Grade

Internal hemorrhoid

Rubber band

Ligator

Figure 1. Rubber band ligation.

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Indian Journal of Clinical Practice, Vol. 25, No. 6, November 2014

SURGERY III hemorrhoids because of recurrence. Comparison of rubber band ligation with excisional hemorrhoidectomy has shown no significant difference in control of bleeding and complication rate; however, ligation has higher recurrence rate.

Sclerotherapy Sclerotherapy for hemorrhoids is a less-invasive, less-painful procedure that causes the problematic hemorrhoid to shrivel and dissipate within a short period of time.

Sclerotherapy usually is successful, but it is not a permanent solution and might need to be repeated, and there is a chance of fairly heavy bleeding. Five percent phenol in almond oil is injected in submucosa just above the base of hemorrhoid causing inflammation and scarring. It is an OPD procedure but complications like prostatitis and sepsis can occur.

Bipolar Diathermy Bipolar diathermy for hemorrhoid uses electric current of very high frequency. The electrical energy is then used to thicken the affected tissue. Bipolar diathermy for hemorrhoid may just require several sessions before one could get rid of all the piles though.

Infrared Photocoagulation Infrared photocoagulation (also called coagulation therapy) is a procedure used to treat small- and medium-sized hemorrhoids. During the procedure, device that creates an intense beam of infrared light is used. Heat created by the infrared light causes scar tissue, which cuts off the blood supply to the hemorrhoid. The hemorrhoid dies, and a scar forms on the wall of the anal canal. The scar tissue holds nearby veins in place; so, they don’t bulge into the anal canal.

Only one hemorrhoid can be treated at a time. Other hemorrhoids may be treated at 10- to 14-day interval.

Risks of coagulation therapy include: Considerable pain during the procedure, bleeding from the anus, infection in the anal area and temporary inability to urinate.

Cryotherapy Cryotherapy is based on the concept that freezing the internal hemorrhoid at low temperatures can lead to tissue destruction. A special probe is used, through which nitrous oxide at −60° to −80°C or liquid nitrogen at −196°C is circulated.

The procedure is time consuming and associated with a foul-smelling profuse discharge, irritation and pain.

The procedure is no longer recommended for the treatment of internal hemorrhoids.

Operative Managements For symptomatic Grade ΙΙΙ-ΙV hemorrhoids and hemorrhoids resistant to nonoperative procedures, a surgical approach can be adopted. This is required in only 5-10% of patients.5

Open Milligan-Morgan Hemorrhoidectomy3 The Milligan-Morgan procedure is the most widely practiced technique and is considered the current gold standard’ for surgical management.5 Indications are when patients fail to respond satisfactorily to repeated attempts at conservative measures, hemorrhoids are severely prolapsed and require manual reduction, hemorrhoids are complicated by strangulation or associated pathology, such as ulceration, fissure, fistula or hemorrhoids are associated with symptomatic external hemorrhoids or large anal tags.

Complications of Open Hemorrhoidectomy The major considerations accompanying open hemorrhoidectomy are the significant postoperative pain and the protracted recovery time (a minimum of 4 weeks with the MMH). A postoperative plan for pain relief devised in alliance with the patient is very important for better recovery.3 Other possible short-term complications include urinary retention, bleeding and infection.3 Long-term concerns include anal stenosis, fecal incontinence, anal fissure and fistula-in-ano.3

Closed Ferguson Hemorrhoidectomy This differs from Milligan-Morgan hemorrhoidectomy (MMH) as the wound is sutured primarily. MMH may be overall better than Ferguson hemorrhoidectomy (FH) particularly as regards complication rate (Table 2).

Circular Stapled Hemorrhoidopexy It is a recently introduced, operative technique for hemorrhoids. This technique is also known as ‘procedure for prolapse and hemorrhoids (PPH)’ or stapled anopexy/mucosectomy/prolapsectomy. PPH was introduced by Longo A in 1998.

It employs a circular stapling device, which removes mucosa and submucosa circumferentially 2-3 cm above the dentate line, anastomosing the proximal and distal edges, interrupting the blood supply to the remnant hemorrhoidal tissue. PPH is significantly less

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SURGERY Table 2. Randomized, Prospective Studies of Open versus Closed Hemorrhoidectomy Author

N

Pain

Complete wound healing

Analgesics

Hospital stay

Complications

Ho

67

NS

O>C

NS

NS

NS

Carapeti

36

NS

NS

NS

NS

NS

Arbman

77

NS

C>O

NS

NS

NS

Gencosmanoglu

80

C>O

C>O

C>O

NS

C>O

C = Close; O = Open; NS = Not significant.

painful and allows quicker recovery than MMH, but the recurrence rate may be higher in the long run. One study showed the recurrence rate of PPH versus MMH to be 5.7% versus 1% at 1 year and 8.5% versus 1.5% overall.5 A recent meta-analysis showed that although the short-term benefits of stapled hemorrhoidectomy may be better, the recurrence rate is significantly higher.

Doppler-guided Hemorrhoidal Artery Ligation A promising procedure, first described by Morinaga et al in 1995, this technique can be performed under sedation and/or local anesthesia. It involves a proctoscope with a Doppler transducer integrated in the probe allowing sequential identification of the position and depth of superior rectal arterial branches (usually 5-7 are found at one level), which are then selectively ligated 2-3 cm above the dentate line at two levels 1-1.5 cm apart by absorbable sutures via a lateral ligation window within the scope. The interference with the blood supply suppresses the bleeding and volume of the hemorrhoids and symptomatic relief is usually evident within 6-8 weeks. Several studies have found this technique to give good results for Grade ΙΙ and ΙΙΙÂ hemorrhoids as it results in minimal postoperative discomfort, but randomized clinical trials and longterm follow-up are awaited to compare this technique with the open method.

Other techniques for hemorrhoidectomy include the application of the LigaSure System, Harmonic Scalpel.

Dissection and coagulation are achieved via the application of pressure with graded electrical energy with the LigaSure or fine oscillatory motion with Harmonic Scalpel instruments, providing precision, a relatively bloodless field and minimal collateral tissue

damage. These methods are not widely used yet but some reports show initial positive results.

Conclusion Conventional hemorrhoidectomy is the gold standard operation against which other hemorrhoidal procedures should be compared. Nonetheless, it has its own postoperative morbidity, including pain, bleeding and infection. This has led to the application of more recent techniques to improve the treatment of this very common disease. General practitioners and colorectal surgeons have to be familiar with these novel treatment options so as to be able to guide their patients appropriately.

References 1. Burkitt HG, Quick CRG, Reed JB. Anal and perianal disorders. In: Essential Surgery-Problems, Diagnosis and Management. 4th edition, Hunter L, Hewat C, Swan R (Eds.), Churchill Livingstone Elsevier: China, 2007.

2. Hosking SW, Smart HL, Johnson AG, Triger DR. Anorectal varices, haemorrhoids, and portal hypertension. Lancet 1989;1(8634):349-52.

3. Sneider EB, Maykel JA. Diagnosis and management of symptomatic hemorrhoids. Surg Clin North Am 2010;90(1):17-32, Table of Contents.

4. MacRae HM, McLeod RS. Comparison of hemorrhoidal treatment modalities. A meta-analysis. Dis Colon Rectum 1995;38(7):687-94.

5. Jayaraman S, Colquhoun PH, Malthaner RA. Stapled versus conventional surgery for hemorrhoids. Cochrane Database Syst Rev 2006;(4):CD005393.

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VenerEology

Study of Pattern and Trend of Sexually Transmitted Infections at Tertiary Care Hospital in Central Rajasthan NIRMALA SAINI*, ASHOK MEHERDA†, RAJKUMAR KOTHIWALA‡

Abstract Background: Sexually transmitted infections (STIs) are one of the most disastrous events of human health causing huge psychosocial and economic morbidity in young and sexually active adults. Population explosion, migration from rural to urban areas, commercial sex and lack of awareness has all led to enormous spread of STIs in the community. Knowledge of the pattern of STIs in different geographical regions is necessary for proper implementation of control measures. Aim: To study the pattern and clinical profile of STIs at a tertiary care hospital in Ajmer. Material and methods: This study was conducted at Dept. of Dermatology, Venereology and Leprology, JLN Medical College, Ajmer, Rajasthan. This included 247 consecutive STI patients of age between 15-55 years. Diseases were diagnosed on the basis of detailed history, clinical examination and relevant investigations. Results: Most common age group affected was 21-30 years (42.51%). Herpes genitalis was most common STI in 30.76%, condylomata acuminata (13.76%), molluscum contagiosum (5.3%). Bacterial STIs like syphilis (2.02%), nonherpetic genital ulcer disease (1.21%) were less common. About 4.85% cases were HIV positive. Conclusions: Study concluded that bacterial STIs like syphilis, chancroid and gonorrhea having declining trend and viral STIs like herpes genitalis and condylomata acuminata are having upward trend.

Keywords: Pattern, bacterial STIs, viral STIs

S

exually transmitted infections (STIs) are a loosely defined constellation of infections and syndromes that are epidemiologically heterogeneous, but all of which are almost always or at least often transmitted sexually.1 STIs constitute a major public health problem for both developing and developed countries having tremendous health and economic consequences. The pattern of STIs differs from country-to-country and from region-to-region, especially in large countries such as India. STIs increases the risk of transmission of human immunodeficiency virus (HIV) infection causing immense need to understand the pattern of STIs prevailing in the regions of a country for proper

planning and implementation of STI control strategies.

Therefore, we planned this study to understand the pattern, clinical profile and trend of STIs in Central Rajasthan with special concern on origin of STI (viral vs bacterial).

*3rd Year Resident †Professor and Head ‡Associate Professor Dept. of Dermatology, Venereology and Leprology JLN Medical College, Ajmer, Rajasthan Address for correspondence Dr Nirmala Saini C/o: Sushila Sharma 70, Nagina Bagh, Ajmer - 305 001, Rajasthan E-mail: nirmala.saini84@gmail.com

Thorough general physical and systemic examination and relevant laboratory investigations like rapid plasma reagin (RPR) test, antibodies to herpes simplex virus (HSV) (immunoglobulin G and M [IgG and IgM]), urethral smear, vaginal smear, Whiff’s test, Gram’s stain, Tzanck smear, disseminated gonococcal infection (DGI), Pap smear, gynecological and colposcopic examination,

MATERIAL AND METHODs The present study was conducted at Dept. of Dermatology, Venereology and Leprology, JLN Medical College, Ajmer, Rajasthan. This study included 247 consecutive patients of age between 15-55 years, having clinically diagnosed STI and who had given a written consent. Each patient was evaluated for STI in detail, including history regarding duration, risk factors, sexual history, occupation, marital status, serostatus of spouse, socioeconomic and education status.

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VenerEology HIV enzyme-linked immunosorbent assay (ELISA), Western blot, CD4 count, viral load done. All patients were counseled about risk involved in unprotected sexual intercourse, risk of HIV transmission in the presence of other STIs, importance of treatment of partner and condom use.

combination of cervicovaginal discharge 48 (55.81%) followed by genital ulcer disease: Herpes genitalis 15 (17.44%), lower abdominal pain syndrome 8 (9.30%) and condyloma acuminata 7 (8.13%), molluscum contagiosum 6 (6.97%), syphilis 1 (1.16%) and others 1 (1.16%) were the STIs detected (Table 3).

HIV ELISA and RPR testing were done in all patients.

STIs were categorized in different syndromes according to National AIDS Control Organization (NACO) guideline. STIs, which were not included in the syndromic management was also identified by clinical features and relevant laboratory investigations. Partner identification and condom promotion were also done.

All patients were treated as per NACO’s guidelines.

Herpes genitalis (76 patients, 30.76%) was the most common STI in both sexes and also common in HIV seropositive than seronegatives.

Prevalence of HIV in the present study was 4.85% (12/247) out of which, eight were males and four were females. RPR test was reactive in 2.02% (5/247) patients.

Heterosexual contact was the commonest type of sexual contact seen in 242 (97.97%) patients and homosexual contact in 5 (2.02%) patients.

RESULTS

Condom acceptance was seen in 57% cases. Partner identifications and management was done only in 66% and 46%, respectively.

Out of 247 patients having STIs, these were 161 male and 86 female patients with male-to-female ratio 1.87:1. Maximum number of patients were seen in 21-30 years of age group (male - 25.91%, female - 16.6%) (Tables 1 and 2). In male patients, most common STI was genital ulcer disease: Herpes genitalis 61 (37.89%) followed by balanoposthitis 32 (19.89%), condyloma acuminata 27 (16.78%), urethral discharge 22 (13.67%), molluscum contagiosum 7 (4.35%), syphilis 4 (2.48%), genital ulcer disease-nonherpetic 3 (1.86%), inguinal bubo 2 (1.24%) and others 3 (1.86%) were the STIs detected. Among females, the most common STI was

DISCUSSION Maximum STI cases were seen in 21-30 years of age group in both sexes because this age group is more sexually active and vulnerable to STI acquisition, as they generally have greater number of sexual partners and more concurrent partnerships and change partners more often than patients from older age groups. This is also observed in other Indian studies.2-4

Table 1. Age-wise Distribution of STIs in Male Patients Age (years)

HG

GW

MC

BP

UD

Syphilis

GUD (Nonherpetic)

IB

Others

≤20

8

2

1

1

2

0

1

0

0

21-30

24

11

4

8

11

2

1

2

1

31-40

18

8

1

12

7

1

1

0

1

41-50

7

4

1

6

2

1

0

0

1

>50

4

2

0

5

0

0

0

0

0

HG = Herpes genitalis; GW = Genital wart (condyloma acuminata); MC = Molluscum contagiosum; BP = Balanoposthitis; UD = Urethral discharge; GUD = Genital ulcer disease; IB = Inguinal bubo; Others (Scabies etc.).

Table 2. Age-wise Distribution of STIs in Female Patients HG

GW

MC

CVD

Syphilis

LAPS

Others

≤20

Age (year)

2

1

1

2

0

0

0

21-30

7

2

3

26

0

2

1

31-40

5

3

2

14

1

4

0

41-50

1

1

0

4

0

2

0

>50

0

0

0

2

0

0

0

CVD = Cervicovaginal discharge; LAPS = Lower abdominal pain syndrome.

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VenerEology Table 3. Distribution of STIs in Male and Female Patients Type of STI

Total (247)

Male (161)

Female (86)

Herpes genitalis

76 (30.76%)

61 (37.89%)

15 (17.44%)

Condyloma acuminata

34 (13.76%)

27 (16.77%)

7 (8.14%)

13 (5.3%)

7 (4.35%)

6 (6.98%)

Balanoposthitis

32 (12.96%)

32 (19.88%)

-

Cervicovaginal discharge

Molluscum contagiosum

48 (19.43%)

-

48 (55.81%)

Urethral discharge

22 (8.9%)

22 (13.66%)

-

Syphilis

5 (2.02%)

4 (2.48%)

1 (1.16%)

Genital ulcer disease (nonherpetic)

3 (1.21%)

3 (1.86%)

-

Lower abdominal pain syndrome

8 (3.24%)

-

8 (9.30%)

Inguinal bubo

2 (0.8%)

2 (1.24%)

0

Others

4 (1.62%)

3 (1.86%)

1 (1.16%)

In our study, males outnumbered females (65.18% males and 34.82% females). Laborers, agricultural workers, truck drivers and students constituted majority of the patients. Most of the female patients were housewives.

Most of the patients were married, as also seen in other studies.5-7 Majority of patients were educated up to primary level. These cases were less likely to have knowledge regarding transmission and prevention of STIs.8 History of exposure to female sex workers (FSWs) was seen in 46.4% males. Amongst females, most common mode of STI transmission was through their husband.

Although, STIs are equally prevalent in females, but less detected because of asymptomatic nature of most of STIs in females, lack of knowledge about STI/RTI and their consequences, social and cultural restrictions in attending STI clinics.8 More indulgence of male in extramarital sexual relations also explains the higher prevalence in the male.9 In our study, herpes genitalis (30.76%) was most common STI followed by condylomata acuminata (13.76%) and molluscum contagiosum (5.3%).

Bacterial STIs like syphilis (2.02%), genital ulcer disease-nonherpetic (1.21%) were less common. Results are concordant with other studies.2,10,11 There is an increasing trend of viral STIs over bacterial. Bacterial STIs are decreasing due to widespread use of antibiotics by general physicians, healthcare workers at the primary level as a part of syndromic management and most of these organisms (bacteria and treponema) are responding to antibiotics. Greater infectivity, persistent and recurrent nature of viral infections is responsible for their increasing trend in the current STI scenario.12

Viral STIs were also more common in HIV positive patients. Out of 12 HIV positive cases, seven cases presented with herpes genitalis, followed by syphilis (2), genital ulcer disease nonherpetic (1), condyloma acuminata (1) and molluscum contagiosum (1).

Similarly, Ibarrola Vidaurre13 and Kaliaperumal14 also showed that herpes, syphilis and chancroid were the most common genital ulcers encountered among HIVAIDS patients, and they in turn increase the risk of contracting HIV by several fold.

REFERENCES 1. Marfatia YS, Sharma A, Joshipura SP. Overview of sexually transmitted diseases. In: IADVL Textbook of Dermatology.

3rd edition, Valia RG, Valia AR (Eds.), Bhalani Publishing House: Mumbai 2008;59:1766-78.

2. Devi SA, Vetrichevvel TP, Pise GA, Thappa DM. Pattern of sexually transmitted infections in a tertiary care centre at Puducherry. Indian J Dermatol 2009;54(4):347-9.

3. Saikia L, Nath R, Deuori T, Mahanta J. Sexually transmitted diseases in Assam: an experience in a tertiary care referral hospital. Indian J Dermatol Venereol Leprol 2009;75(3):329.

4. Chandragupta TS, Badri SR, Murty SV, Swarnakumari G, Prakash B. Changing trends of sexually transmitted diseases at Kakinada. Indian J Sex Transm Dis 2007;28(1):6-9.

5. Aggarwal K, Jain VK, Brahma D. Trends of sexually transmitted diseases at Rohtak. Indian J Sex Trans Dis 2002;23:19-21.

6. Murugesh SB, Sugareddy, Raghunath S. Pattern of sexually transmitted diseases at Davangere. Indian J Sex Trans Dis 2004;25:9-12.

7. Chandragupta TS, Badri SR, Murty SV, Swarnakumari G, Prakash B. Changing trends of sexually transmitted diseases at Kakinada. Indian J Sex Trans Dis 2007;28:6-9.

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VenerEology 8. Bhavsar C, Patel RM, Marfatia Y. A study of 113 cases of genital ulcerative disease and urethral discharge syndrome with validation of syndromic management of sexually transmitted diseases Indian J Sex Transm Dis 2014;35(1):35-9.

9. Mehta B. A clinico-epidemiological study of ulcerative sexually transmitted diseases with human immunodeficiency virus status. Indian J Sex Transm Dis 2014;35(1):59-61.

etiological diagnosis in patients attending the sexually transmitted infection clinic of a tertiary care hospital.

Indian J Sex Transm Dis 2010;31(2):104-8.

12. Vora R, Anjaneyan G, Doctor C, Gupta R. Clinicoepidemiological study of sexually transmitted infections in males at a rural-based tertiary care center. Indian J Sexually Transm Dis AIDS 2011;32(2):86-9.

10. Jain VK, Dayal S, Aggarwal K. Changing trends of sexually transmitted diseases at Rohtak. Indian J Sex Transm Dis 2008;29(1):23-5.

13. Ibarrola Vidaurre M, Benito J, Azcona B, Zubeldía N. Infectious pathology: vulvovaginitis, sexually transmitted diseases, pelvic inflammatory disease, tubo-ovarian abscesses. An Sist Sanit Navar 2009;32 Suppl 1:29-38.

11. Choudhry S, Ramachandran VG, Das S, Bhattacharya SN, Mogha NS. Pattern of sexually transmitted infections and performance of syndromic management against

14. Kaliaperumal K. Recent advances in management of genital ulcer disease and anogenital warts. Dermatol Ther 2008;21(3):196-204.

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Ever Wondered why Scratching Makes Itching Worse?

Scratching an itch causes the brain to release the mood-regulating and pain-controlling neurotransmitter serotonin, according to new research from Washington University School of Medicine in St. Louis, MO. The researchers suggest that serotonin has the effect of intensifying the itch sensation.

Scientists know from previous studies that a mild amount of pain in the skin is caused by scratching, which temporarily interferes with the itching sensation. This interference happens because, while scratching, nerve cells in the spinal cord carry pain signals to the brain instead of itch signals.

In Search for Beauty, Some Find Vision Loss Some patients who get facial injections to look good may end up seeing very poorly as a result of retrograde occlusion of ocular arteries, warn researchers.

“The risk of complications is higher when injections are made to the area supplied by the dorsal nasal and supratrochlear arteries, and when the injections are performed by inexperienced or noncertified personnel,” said Tharikarn Sujirakul, MD, a research fellow in ophthalmology at Columbia University College of Physicians and Surgeons in New York City.

Reporting here at the 14th EURETINA Congress, Dr Sujirakul described six patients who received dermal filler injections in their faces with either hydrophilic gel, collagen, silicone or an unknown material and developed retrograde arterial occlusions, causing either temporary or permanent vision loss in one eye.

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Indian Journal of Clinical Practice, Vol. 25, No. 6, November 2014

EXPERT VIEW

What are the Appropriate Secondary Prevention Strategies after MI? KK Aggarwal*, Ashok K Kar†

M

yocardial infarction (MI) is caused by blockage of a coronary artery leading to tissue death and consequently the typical features of a heart attack.1 According to the 2013 National Institute for Health and Care Excellence (NICE) guidelines, the significant secondary prevention strategies include the following:1

ÂÂ Smoking cessation: All patients should be advised

Cardiac Rehabilitation

A recent study determined the association between ideal lifestyle factors and recurrent coronary heart disease (CHD) and all-cause mortality in REasons for Geographic and Racial Differences in Stroke study participants with CHD. The study concluded that maintaining smoking cessation, physical activity and Mediterranean diet adherence is significant for secondary CHD prevention.2

All patients should be advised about and offered a cardiac rehabilitation program with an exercise component. Cardiac rehabilitation should be initiated as soon as possible after admission and before discharge from hospital. Comprehensive cardiac rehabilitation programs should always include health education and stress management components.

Lifestyle Changes ÂÂ Diet: Eating a Mediterranean-style diet should be

recommended (more bread, fruits, vegetables and fish; less meat and replace butter and cheese with products based on plant oils). The 2013 guidelines advised against routinely recommending eating oily fish for the sole purpose of preventing another MI. Patients should not be advised to take supplements containing beta-carotene.

ÂÂ Alcohol

consumption: Weekly consumption should be kept within safe limits (no >21 units of alcohol/week for men or 14 units/week for women) and to avoid binge drinking (more than 3 alcoholic drinks in 1-2 hours).

ÂÂ Physical activity: Regular physical activity should

be recommended to all people; they should be advised to be physically active for 20-30 minutes a day to the point of slight breathlessness.

*Senior Physician and Cardiologist Moolchand Medcity, New Delhi †Consultant Interventional Cardiologist Kolkata, West Bengal

to stop smoking and assistance should be provided for the same.

ÂÂ Weight

management: All patients who are overweight or obese should be advised and supported to achieve and maintain a healthy weight.

Drug therapy All patients who have had an acute MI should be treated with the following drugs: ÂÂ Angiotensin-converting enzyme (ACE) inhibitor:

ACE inhibitor should be started as soon as the patient is hemodynamically stable. Continue the ACE inhibitor indefinitely. The dose of ACE inhibitor should be titrated upwards at short intervals (every 12-24 hours) before the patient is discharged until it reaches the maximum tolerated dose. An ACE inhibitor and an angiotensin receptor blocker (ARB) should not be combined unless indicated. Those who are intolerant to ACE inhibitors should be treated with an ARB.

ÂÂ Dual antiplatelet therapy (aspirin plus a second

antiplatelet agent): Aspirin should be given to all people after an MI and continued indefinitely, unless contraindicated. Clopidogrel monotherapy is an alternative in those with aspirin hypersensitivity.

Ticagrelor in combination with low-dose aspirin is recommended for up to 12 months in adults with acute coronary syndrome (ACS). Anticoagulation should be continued and clopidogrel should be added to treatment in people who have had an MI, who have undergone percutaneous coronary intervention (PCI) with stents and who otherwise need anticoagulation.

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EXPERT VIEW ÂÂ b-blocker: b-blocker therapy should be initiated as

soon as possible after an MI. A b-blocker should be given for at least 12 months after an MI in people without left ventricular systolic dysfunction or heart failure.

ÂÂ Aldosterone antagonists: Acute MI patients with

signs of heart failure and left ventricular systolic dysfunction should be treated with an aldosterone antagonist approved for post-MI treatment within 3-14 days of the MI, preferably after ACE inhibitor therapy.

ÂÂ Statins: Statin therapy is recommended for adults

with clinical evidence of cardiovascular disease.

ÂÂ Calcium channel blockers (CCBs) should not be

given routinely to reduce cardiovascular risk after

an MI. For patients who are stable after an MI, CCBs may be given to treat hypertension or angina.

References 1. MI - secondary prevention. Secondary prevention in primary and secondary care for patients following a myocardial infarction. NICE Clinical Guideline 172.

Available from: guidance.nice.org.uk/cg172.

2. Booth JN 3rd, Levitan EB, Brown TM, Farkouh ME, Safford MM, Munter P. Effect of sustaining lifestyle modifications (nonsmoking, weight reduction, physical activity, and Mediterranean diet) after healing of myocardial infarction, percutaneous intervention, or coronary bypass (from the REasons for Geographic and racial differences in Stroke Study). Am J Cardiol 2014;113(12):1933-40.

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Around the Globe

News and Views ÂÂ Patients receiving chronic hemodialysis appear to

be at a significantly higher risk for death if they are prescribed b-blockers with a high dialyzability (atenolol, acebutolol or metoprolol) compared with b-blockers with a low dialyzability (bisoprolol or propranolol), suggests a retrospective cohort study published online October 30 in the Journal of the American Society of Nephrology.

ÂÂ Drainage

followed by urokinase instillation seems to be as effective as video-assisted thoracoscopic surgery (VATS) for treating septated parapneumonic empyema in children, suggests new study published online in Pediatrics.

ÂÂ A Maine judge has rejected the state’s desire to keep

least likely to survive a total joint replacement, suggests new research presented at the American College of Surgeons 2014 Clinical Congress.

a nurse in quarantine over Ebola fears. Instead, Judge Charles LaVerdiere ruled that Kaci Hickox, RN, should continue twice-daily direct active monitoring of her temperature and symptoms and coordinate any travel with state authorities so the monitoring can continue.

ÂÂ Older people with strabismus seem to be about

ÂÂ Rifaximin, a gut-targeted antibiotic for diarrhea-

ÂÂ A frailty index can successfully identify the patients

27% more likely than people without the condition to be injured by a fall, reported a new study published online in JAMA Ophthalmology.

ÂÂ A new study published online in the American

Journal of Gastroenterology has pointed that the location of diverticular disease in the colon may be a risk factor for irritable bowel syndrome (IBS).

Researchers noted that patients with diverticular disease in the left-side colon and bilaterally were 2.6-3.1 times more likely to also have IBS.

ÂÂ Egg freezing is ‘an invaluable option’ for female

cancer patients who want to preserve their fertility before undergoing potentially sterilizing chemotherapy, suggests new research presented at the American Society for Reproductive Medicine (ASRM) 2014 Annual Meeting.

ÂÂ Aortic valve replacement (AVR) can safely be used

to treat severe aortic stenosis in patients aged 90 years and older and is associated with a lowrisk of operative stroke and mortality, suggests a study published in The Annals of Thoracic Surgery.

ÂÂ Lyme carditis associated with Borrelia burgdorferi

infection was uncommon but was linked to two previously unsuspected cases of sudden cardiac death, as reported in the October 31 issue of the CDC’s Morbidity and Mortality Weekly Report.

ÂÂ Children conceived with the help of assisted

reproductive technologies are not at increased risk for common childhood cancers; however, the risk for rarer cancers remains unclear, suggests new research presented at the American Society for Reproductive Medicine 2014 Annual Meeting.

predominant IBS, can be safely and effectively used to retreat patients who have relapsed after already being treated with the drug, report investigators.

These are the findings from the TARGET 3 trial presented at the American College of Gastroenterology 2014 Annual Scientific Meeting.

ÂÂ The results of a new US study show that only 58%

of individuals with type 2 diabetes were started on metformin as their first oral glucose-lowering medication, despite the fact that this drug is widely recommended as the initial therapy of choice in numerous diabetes guidelines. The research is published October 27 in JAMA Internal Medicine.

ÂÂ A novel, noninvasive neurostimulator targeting

the vagus nerve improves on treatment of chronic cluster headaches over the current standard of care, according to a new study. “Patients who used this device for 6 minutes, two times per day had the number of cluster headache attacks reduced by 40% per week,” said lead author Eric J. Liebler, vice president of scientific, medical and governmental affairs for ElectroCore, LLC, based in Basking Ridge, New Jersey.

ÂÂ Men who lose chromosome Y in blood cells are

more likely to get cancer and to die younger, suggests a new study presented at the American Society of Human Genetics 2014 Annual Meeting.

ÂÂ In patients undergoing noncardiac surgery after

previous percutaneous coronary intervention (PCI) and stent implantation, the use of aspirin appears to be unrelated to the occurrence of a major cardiac adverse event, suggests a new study presented at

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Around the Globe the American Society of Anesthesiologists 2014 Annual Meeting. ÂÂ New American Heart Association (AHA)/American

Stroke Association (ASA) guideline on primary stroke prevention includes recommendations for new oral anticoagulants in patients with atrial fibrillation (AF), home blood pressure monitoring in patients with hypertension, smoking cessation, nonestrogen oral contraceptives for women experiencing migraine with aura, and the healthy Mediterranean diet for all patients. The updated guideline was published online October 28 in Stroke.

ÂÂ A child’s later-life intelligence may not be influenced

by parenting; instead it may be more dependent on genetics, suggests new research published in the journal Intelligence.

ÂÂ In children with poorly controlled asthma, once-

daily tiotropium delivered with the Respimat inhaler may improve lung function when added to inhaled corticosteroids, with no apparent change in adverse effects, suggests new research presented at CHEST 2014: American College of Chest Physicians Meeting.

ÂÂ Isolation of the most severely ill patients with Ebola

within the first few days of symptoms may be the key to ending the epidemic. A new mathematical model of the Ebola epidemic in Liberia reveals that a shift in the focus of public health efforts from case isolation and hygienic burial of the dead to the isolation of infected individuals before they progress into critical condition and the late phase of illness may slow disease transmission. (October 28 in the Annals of Internal Medicine.)

ÂÂ Swedish researchers have found that a high intake

of milk may be associated with higher mortality and fracture risks in women and higher mortality risk in men, but they caution against basing any dietary recommendations on their findings, which were published online October 28 in BMJ.

ÂÂ Weight loss following laparoscopic Roux-en-Y

gastric-bypass (RYGB) surgery is almost double that following adjustable gastric banding (AGB), suggested a large comparative study published online October 29 in JAMA Surgery.

ÂÂ Brodalumab appears safe and effective for treating

moderate-to-severe psoriasis, points a new 120week open-label extension study of a phase ΙΙ trial.

The study is published online in the Journal of the American Academy of Dermatology.

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ÂÂ A US Food and Drug Administration (FDA)

advisory panel voted in favor of a novel anticoagulant for the treatment of patients with atrial fibrillation (AF). The Cardiovascular and Renal Drugs Advisory Committee voted 9 to 1 in favor of approving edoxaban, a factor Xa inhibitor, for the prevention of stroke and non–centralnervous-system (CNS) systemic embolism in patients with nonvalvular AF.

ÂÂ Two newly identified genetic variants that influence

the LDL cholesterol response to statin therapy have been identified in a large analysis. Two single nucleotide polymorphisms (SNPs) at SORT1/ CELSR2/PSRC1 appear to be associated with an enhanced LDL cholesterol-lowering response with statin therapy, while a SNP at SLCO1B1 was associated with a smaller LDL cholesterol reduction in response to statin treatment. The report is published October 28 in Nature Communications.

ÂÂ A new study has shown that ‘Integrated Play

Groups,’ or IPGs, appear effective in teaching children with autism the skills they need to interact with their peers and engage in symbolic play such as pretending. The study is published in the Journal of Autism and Developmental Disorders.

ÂÂ Teens whose parents use guilt or withholding

have trouble working out disagreements well into adulthood, suggests a new study published online in Child Development.

ÂÂ Some food labels may not reliably list all possible

food allergens, according to the US FDA. The agency added that these ‘undeclared allergens’ are the leading cause of FDA-requested food recalls.

ÂÂ In view of the growing concern over Ebola virus,

which has claimed over 4,000 lives worldwide, the Indian Medical Association (IMA) is working on a training and awareness program for its members on tackling the outbreak of various viral diseases.

The program is envisaged to help medical fraternity to stay updated on the emerging and re-emerging viral diseases and equip them to face emergencies.

The scientific session of the 57th State conference of IMA’s Kerala chapter, scheduled to be held here from November 7-9, will set a framework of the program, IMA Kerala secretary AV Jayakrishnan said.

ÂÂ A recent multi-city survey conducted by Research

Pacific (commissioned by Tetra Pak) showcased that almost 70% of mothers aren’t too sure about the food that their child consumes. Roughly translated,

Around the Globe it means that one in every three mothers is unsure about the safety and quality of food that she gives to her child and family. Add to that, over 60% of mothers don’t really spend time reading labels, missing out on crucial ingredients that a growing child needs. The lack of awareness coupled with a growing concern about food freshness and purity certainly calls for alternative measures. Food laws in India do address the issue of purity but what we really need is a program which connects with people and educates them. ÂÂ For the first time, Australian doctors have

transplanted a heart that had stopped beating in what they say is a paradigm shift for organ donation: Victor Chang Institute executive director Professor Bob Graham said a newly developed technique would save 20-30% more lives. The doctors at Sydney’s St Vincent’s Hospital transplanted a heart that had stopped beating for 20 minutes. The heart was resuscitated with a new console and injected with a preservation solution that was developed by researchers at the hospital and the Victor Chang Cardiac Research after 12 years of work. Professor Graham told the ABC’s The World Today program that most hearts were donated by patients who were brain dead but kept alive using a ventilator, which meant their hearts were still beating when they were transplanted.

ÂÂ Doctor gets ebola infection: A doctor recently

back from West Africa is in isolation in New York City’s Bellevue Hospital after testing positive for Ebola. A second test to confirm the result will be done at the CDC’s labs in Atlanta, the agency said in a statement. The doctor, Craig Spencer, MD, had returned from Guinea Oct. 17 and had passed through the enhanced screening protocol in place at JFK airport. He had no fever or symptoms during his trip or at the time of arrival, the CDC said. A person’s body mass index (BMI) does not always correspond with body fat percentage or metabolic health, according to a study presented here at the 25th Annual Meeting of the North American Menopause Society (NAMS).

ÂÂ The biggest viral disease outbreak has nothing to

do with Ebola. It is Chikungunya virus, and it is sweeping the Americas. The primary symptoms are fever and polyarthralgia. “Chikungunya, in the Makonde language of Tanzania and Northern Mozambique, means that which bends over or dries up,” said Lyle Petersen, MD, from the US Centers for Disease Control and Prevention (CDC)

in Fort Collins, Colorado. Unlike the Dengue virus, where most infections are asymptomatic, 72-97% of people infected with the Chikungunya virus develop clinical symptoms. The incubation period is usually 3-7 days, with a range of 1-12 days, Dr Petersen reported at ID Week 2014. ÂÂ Treatment of diarrhea-predominant irritable bowel

syndrome (IBS-D) with rifaximin was associated with significant symptomatic improvements, and treatment could be successfully repeated if patients relapsed. In an open-label study known as TARGET 3 that included 2,579 patients, a total of 42% of patients responded to 2 weeks of treatment according to the FDA’s stringent criteria of at least a 30% reduction in pain and a 50% or greater decrease in the number of days with scores or 6 (loose) or 7 (watery) on the Bristol Stool Scale, according to Anthony Lembo, MD, of Harvard Medical School and Beth Israel Deaconess Medical Center in Boston, and colleagues. Among those initial responders, 36% never relapsed over 18-22 weeks of follow-up, which was ‘very important,’ co-author Mark Pimentel, MD said at the American College of Gastroenterology meeting.

ÂÂ Two short treatment regimens for tuberculosis

failed to match the standard 6 months of therapy in efficacy. Both experimental regimens substituted a fourth-generation fluoroquinolone antibiotic for one of the drugs used in standard treatment, according to separate reports in the Oct. 23 issue of the New England Journal of Medicine.

ÂÂ World Health Organization (WHO) released data

that the incidence of TB is falling globally, although owing to better information gathering - the actual numbers are about half a million cases higher than previously thought. The UN agency said its data confirm that incidence of the disease is declining at about 1.5% a year and the mortality rate has dropped 45% since 1990. But, because of more accurate data collection, the WHO said it now estimated that about 9 million people developed TB in 2013 and 1.5 million people died from the disease. The agency estimated that 37 million lives were saved between 2000 and 2013 through effective diagnosis and treatment. “However, given that most deaths from TB are preventable, the death toll from the disease is still unacceptably high,” the WHO said in its Global Tuberculosis Report 2014.

ÂÂ The US Food and Drug Administration (FDA) has

approved a once-daily combination of dapagliflozin and metformin hydrochloride extended-release for

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Around the Globe the treatment of adults with type 2 diabetes. The once-daily oral tablet is the first in the United States to combine the sodium glucose cotransporter-2 inhibitor dapagliflozin with the biguanide extended-release (XR) metformin hydrochloride.

It is indicated for use as an adjunct to diet and exercise in adults in whom treatment with both dapagliflozin and metformin is appropriate ÂÂ Withdrawing inhaled corticosteroids (ICS) from

patients with severe chronic obstructive pulmonary disease (COPD) does not lead to an increased rate of exacerbations, suggests a new study presented at CHEST 2014. Based on their findings, the authors suggest that ICS may be successfully withdrawn in patients receiving dual bronchodilator therapy with a long-acting muscarinic antagonist (LAMA) and a long-acting beta-agonist (LABA).

ÂÂ Moderately

suppressing thyroid-stimulating hormone (TSH) after treatment for differentiated thyroid cancer may be the best strategy, suggest new findings presented at the American Thyroid Association meeting. Moderate TSH suppression was associated with better overall survival and disease-free survival versus aggressive suppression.

ÂÂ The drug D-cycloserine appears to be no more

effective than placebo when used with a computerbased cognitive training program for relieving persistent ear ringing in patients with tinnitus in a small clinical study, but patients did report fewer cognitive difficulties. The study is published online in the journal JAMA Otolaryngology-Head & Neck Surgery.

ÂÂ Omega 3 and 6 fatty acids supplementation can

help children and adolescents who have the inattentive subtype of ADHD called ADD, suggest researchers at the Sahlgrenska Academy, University of Gothenburg, Sweden.

ÂÂ Binge drinking during adolescence can have lasting

effects on brain function, suggests a new study published in The Journal of Neuroscience.

ÂÂ The American Academy of Neurology and the

American Association of Neuromuscular and Electrodiagnostic Medicine have issued a new guideline for the diagnosis and management of patients with limb-girdle or distal muscular dystrophies. The guideline, published in the October 14 issue of Neurology, highlights the importance of genetic testing to identify specific types of dystrophy.

ÂÂ The genotype of primary gastrointestinal stromal

tumors (GIST) of gastric origin may help predict the risk of relapse and, thereby, identify patients for adjuvant therapy with imatinib, suggests a new analysis published online in Clinical Cancer Research.

ÂÂ Dr Ashley C Mays from Wake Forest Baptist

Health in Winston-Salem, North Carolina has come up with a new model that accurately predicts the need for gastrostomy tube placement in patients undergoing surgery of the upper aerodigestive tract. The data are published online in JAMA Otolaryngology Head and Neck Surgery.

ÂÂ Obese patients who have plastic surgery to remove

ÂÂ Scratching an itch causes the brain to release

the mood-regulating and pain-controlling neurotransmitter serotonin which has the effect of intensifying the itch sensation, suggests a new study published online in Neuron.

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excess skin after bariatric surgery may be more apt to keep the weight off than those who don’t, suggests a new study presented at the annual conference of the American Society of Plastic Surgeons in Chicago.

mediLAW

Real Consent and not Informed Consent Applicable in India (Part III) KK Aggarwal

question of taking her mother’s consent for radical surgery did not arise. Therefore, such consent by mother cannot be treated as valid or real consent.

Further a consent for hysterectomy, is not a consent for bilateral salpingo-oophorectomy.”

Can the consent for stenting be taken from the nonspouse relatives of the patient?

No, consent for stenting cannot be taken from the nonspouse accompanying relatives of the patient, unless the patient is minor, mentally challenged or incapacitated.

The MCI Code of Ethics Regulation, 2002 state: “MCI: 7.16: Before performing an operation the physician should obtain in writing the consent from the husband or wife, parent or guardian in the case of minor, or the patient himself as the case may be. In an operation which may result in sterility the consent of both husband and wife is needed.”

In a case decided by Supreme Court of India, SCI, Civil Appeal No. 1949 of 2004, 16.01.2008, Samira Kohli vs Dr. Prabha Manchanda and Anr, B.N. Agrawal, P.P. Naolekar and R.V. Raveendran, JJ, the following was observed: “45. The Respondent next contended that the consent given by the appellant’s mother for performing hysterectomy should be considered as valid consent for performing hysterectomy and salpingooophorectomy. The appellant was neither a minor, nor mentally challenged, nor incapacitated. When a patient is a competent adult, there is no question of someone else giving consent on her behalf.

There was no medical emergency during surgery.

The appellant was only temporarily unconscious, undergoing only a diagnostic procedure by way of laparoscopy. The respondent ought to have waited till the appellant regained consciousness, discussed the result of the laparoscopic examination and then taken her consent for the removal of her uterus and ovaries. In the absence of an emergency and as the matter was still at the stage of diagnosis, the

What is negligent nondisclosure?

Negligent nondisclosure cases are typical negligence cases. There are four elements that must be shown:1 ÂÂ

Duty: The duty is the requirement that a physician act as a minimally competent, similarly trained, reasonable physician in similar circumstances would act when disclosing information.

ÂÂ

Breach of duty: Failure to meet the minimal standard of care.

ÂÂ

Injury is the harm that befalls the patient.

ÂÂ

A causal relationship between the breach and the harm is shown when the patient reasonably declares that he would have refused to undergo the procedure had he known the true nature of the risks.

If all four elements are proven the physician is liable for the tort of negligent nondisclosure. The proof typically lies in the testimony of the plaintiff’s expert witness, who must present the following information:2 ÂÂ

Define the duty: The details that constitute an appropriate informed consent discussion.

ÂÂ

Identify the breach: The details that were wrongly omitted.

ÂÂ

Clarify the harm: The injuries that were suffered.

ÂÂ

Identify alternatives: The alternatives that a reasonable patient might have selected instead are defined. These may include a different procedure, a different physician or a different facility.

The plaintiff then adds that he or she, being a reasonable patient, would have refused to consent to the procedure.

References Senior Physician and Cardiologist, Moolchand Medcity, New Delhi Member, Ethics Committee, Medical Council of India

1. Ey RM. “Cause of Action Against Physician for Failure to Obtain Patient’s Informed Consent,” 5 Causes of Action § 1 (Updated September 2010).

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mediLAW 2. Miller-McGee v. Washington Hosp. Center, 920 A.2d 430, 440 (D.C. 2007).

Can the consent be taken a few days before the procedure?

ÂÂ

The physician should document that the patient understood the concepts as discussed, and agreed to proceed.

ÂÂ

In addition, the physician should document that the patient was provided with appropriate literature, the patient had the opportunity to ask questions, and that those questions were answered.

ÂÂ

The standard consent document means little, particularly in its generic form. The real work of obtaining informed consent is documented in office or in hospital notes.

ÂÂ

Documentation is particularly important when patients refuse intervention. The physician must note in the record the specific risks associated with delay or refusal which were disclosed.

ÂÂ

When informed consent cannot be obtained due to an emergency situation or diminished capacity due to intoxication, trauma or disease, physicians must document in the written record what facts were considered in determining the patient’s ability to process information and make reasonable decisions.

Recall of informed consent is not affected by the timing of obtaining informed consent before any procedure.

Evidence Sixty patients scheduled for colonoscopy or esophagogastroduodenoscopy were enrolled in a prospective, randomized study. Each patient received informed consent 24-72 hours or immediately before the procedure, and follow-up occurred 1-3 days post procedure. There was no statistically significant difference in recall of informed consent or the individual elements of informed consent (indication, risks, benefits, alternatives) between the two groups.

The study concluded that recall of informed consent is similar whether consent is obtained immediately or several days before endoscopic procedures.

Reference 1. Elfant AB, Korn C, Mendez L, et al. Recall of informed consent after endoscopic procedures. Dis Colon Rectum 1995;38(1):1-3.

Is there a need to take consent for doing echo on a female patient?

How is consent documented?

ÂÂ

If you are a female echocardiographer and the patient has come to you for an echo, there is an implied consent.

ÂÂ

If you are a female echocardiographer and the patient is a referred patient in your name, there is an implied consent.

ÂÂ

If you are a female echocardiographer and the patient is a referred patient by the hospital you need only to explain the procedure including exposure of the relevant portions of the chest and ensuring privacy and absence of male members in the room.

ÂÂ

If you are a male echocardiographer and the patient has come to you for an echo or referred to you by name, there is an implied consent but you should maintain privacy and ensure presence of a female member in the room.

ÂÂ

If you are a male echocardiographer and a patient comes to you for an echo you must take an informed consent, ensure privacy and presence of a female member in the room.

ÂÂ

Never touch the skin of the chest area with fingers.

Always apply jelly with the bottle knob.

Patients may not accurately remember all the facts disclosed in a discussion. Thus, a physician must document the content of informed consent sessions. ÂÂ

The informed consent discussion and its documentation should be done by the physician who will be performing the procedure.

ÂÂ

Delegating the responsibility to obtain consent to someone else does not absolve the physician of liability if that consent session is incomplete or ineffective.

ÂÂ

The physician should note the date and time of the written summary of what was said and to whom.

Presence of relatives, friends or support staff such as nurses or interpreters should be noted.

ÂÂ

All elements of the discussion should be reduced to writing: Diagnosis, proposed treatment with its risks and benefits, and alternative treatments with their risks and benefits.

ÂÂ

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It is not sufficient to state that “the risks and benefits were discussed” without further description of the specifics.

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Echo etiquette (etiquette-based medicine)

mediLAW realities in medical and healthcare in India. But if medical practitioners and private hospitals become more and more commercialized, and if there is a corresponding increase in the awareness of patient’s rights among the public, inevitably, a day may come when we may have to move towards Canterbury. But not for the present.”

What is the extent of information to be disclosed in taking consent for percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG)?

In a case decided by Supreme Court of India, SCI, Civil Appeal No. 1949 of 2004, 16.01.2008, Samira Kohli vs Dr. Prabha Manchanda and Anr, B.N. Agrawal, P.P. Naolekar and R.V. Raveendran, JJ, the following was observed: “Lord Bridge however made it clear that when questioned specifically by the patient about the risks involved in a particular treatment proposed, the doctor’s duty is to answer truthfully and as fully as the questioner requires. He further held that remote risk of damage (referred to as risk at 1 or 2%) need not be disclosed but if the risk of damage is substantial (referred to as 10% risk), it may have to be disclosed.

Lord Scarman, in minority, was inclined to adopt the more stringent test laid down in Canterbury.”

The Court further observed that in India we may not follow the stringent consent as is the practice in the west.

“33. We may note here that courts in Canada and Australia have moved towards Canterbury standard of disclosure and informed consent - vide Reibl v. Hughes (1980) 114 DLR (3d.) 1 decided by the Canadian Supreme Court and Rogers v. Whittaker 1992 (109) ALR 625 decided by the High Court of Australia. Even in England there is a tendency to make the doctor’s duty to inform more stringent than Bolam’s test adopted in Sidaway. Lord Scarman’s minority view in Sidaway favouring Canterbury, in course of time, may ultimately become the law in England. A beginning has been made in Bolitho v. City and Hackney HA 1998 1 AC 232 and Pearce v. United Bristol Healthcare NHS Trust 1998 (48) BMLR 118.

We have however, consciously preferred the ‘real consent’ concept evolved in Bolam and Sidaway in preference to the ‘reasonably prudent patient test’ in Canterbury, having regard to the ground

“22. The stringent standards regarding disclosure laid down in Canterbury, as necessary to secure an informed consent of the patient, was not accepted in the English courts. In England, standard applicable is popularly known as the Bolam test, first laid down in Bolam v. Friern Hospital Management Committee [1957] 2 All.E.R. 118.

McNair J., in a trial relating to negligence of a medical practitioner, while instructing the Jury, stated thus: (i) A doctor is not negligent, if he has acted in accordance with a practice accepted as proper by a responsible body of medical men skilled in that particular art. - Putting it the other way round, a doctor is not negligent, if he is acting in accordance with such a practice, merely because there is a body of opinion that takes a contrary view. At the same time, that does not mean that a medical man can obstinately and pig-headedly carry on with some old technique if it has been proved to be contrary to what is really substantially the whole of informed medical opinion. (ii) When a doctor dealing with a sick man strongly believed that the only hope of cure was submission to a particular therapy, he could not be criticized if, believing the danger involved in the treatment to be minimal, did not stress them to the patient. (iii) In order to recover damages for failure to give warning the plaintiff must show not only that the failure was negligent but also that if he had been warned he would not have consented to the treatment.”

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INSPIRATIONAL Story

Our Lives are Better Left to Chance…

M

y family and I recently attended a Sweet 15.

In the Hispanic culture, it is more traditionally known as a Quinceanera. I wanted to share with you some special moments that I witnessed that day.

I saw a moment during the church service, a mother’s true love for her daughter. Mom stood up and shared some special thoughts of what she described as her strong-willed daughter. As she began to speak, her voice began to shake. She spoke with pure conviction of the bond they shared with one another. Everyone in the church began to feel the true love they had for one another. If mom had only kept talking, I believe all the parents, especially the moms in attendance would have been in tears.

There was another moment, one that made me believe of a daddy’s love for his little girl. This took place at the reception. You need to first paint a picture in your mind of how special it must be for a father to dance his last dance, if you will, with his little girl.

The young girl looked especially beautiful that day, almost magical in her long white dress. Her cheeks looked like roses and her blue eyes like flowers. The curls in her hair bounced as she walked in the room.

You could see her sparkle as she walked along to the middle of the dance floor. She looked like Cinderella and daddy like Prince Charmin standing there holding her hand.

“The Dance” by Garth Brooks began to play and the magic unfolded as they held each other and began to

dance. As the dad held his young daughter, they looked like they were dancing on air. Her dress swayed from side to side as he held her tight. How special this must have felt to be in her daddy’s arms that night.

The song finally came to an end and it was time for daddy to let go…but he couldn’t. He stood there big and strong, as his body began to shake, and then broke down as he began to cry. It was a very special moment.

Here was this giant of a man, towering over his young child, but yet with the innocence of a baby he fought hard to hold back his tears. He held his little girl by her arms as he leaned over and gave her a big kiss on her forehead. He embraced her as he wiped the tears streaming down his face.

As I stood there watching all this happen, I felt a big lump in my throat and I quickly began to share his pain. It made me sad but yet, at the same time, it made me happy. This is what it was all about. Daddy had always been there for his little girl.

As Garth Brooks sang his last note, I could feel dad “looking back on the times he shared” just like the song was saying. Daddy kissed her again and then his little girl turned and walked away.

Hug you children every day and tell them you love them. Time stands still for no one. One day you’ll be looking back and your memories will seem nothing more than a dream.

――

“A total commitment is paramount to reaching the ultimate in performance.” ―Tom Flores “Whether you believe you can do a thing or believe you can’t, you are right.” ―Henry Ford “If we wait until our lives are free from sorrow or difficulty, then we wait forever. And miss the entire point.” ―Dirk Benedict

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lighter reading

That Darned Cat

Tomatoes

A man absolutely hated his wife’s cat and decided to get rid of him 1-2 day by driving him 20 blocks from his home and leaving him at the park. As he was getting home, the cat was walking up the driveway. The next day he decided to drive the cat 40 blocks away. He put the beast out and headed home. Driving back up his driveway, there was the cat! He kept taking the cat further and further and the cat would always beat him home. At last he decided to drive a few miles away, turn right, then left, past the bridge, then right again and another right until he reached what he thought was a safe distance from his home and left the cat there. Hours later the man calls home to his wife: “Jen, is the cat there?”

“Yes”, the wife answers, “why do you ask?”

Frustrated, the man answered, “Put that darned cat on the phone. I’m lost and need directions!”

A small boy was looking at the red ripe tomatoes growing in the farmer’s garden. “I’ll give you my two pennies for that tomato,” said the boy pointing to a beautiful, large, ripe fruit hanging on the vine.

After shopping for most of the day, a couple returns to find their car has been stolen. They go to the police station to make a full report. Then, a detective drives them back to the parking lot to see if any evidence can be found at the scene of the crime. To their amazement, the car has been returned. There is an envelope on the windshield with a note of apology and two tickets to a music concert. The note reads, ‘I apologize for taking your car, but my wife was having a baby and I had to hot-wire your ignition to rush her to the hospital.

Please forgive the inconvenience. Here are two tickets for tonight’s concert of Garth Brooks, the country-and-western music star.’ Their faith in humanity restored, the couple attend the concert and return home late. They find their house has been robbed. Valuable goods have been taken from though out the house, from basement to attic. And, there is a note on the door reading, ‘Well, you still have your car. I have to put my newly born kid through college somehow, don’t I?’

The small boy pointed to a smaller green one, “Will you take two pennies for that one?”

“Yes,” replied the farmer, “I’ll give you that one for two cents.”

“OK,” said the lad, sealing the deal by putting the coins in the farmer’s hand, “I’ll pick it up in about a week.”

“Inventing is the mixing of brains and materials.

The more brains you use, the less materials you need.”

–Charles F Kettering

Dr. Good and Dr. Bad Situation: A patient on aspirin was to go for nonvascular surgery.

Stop aspirin fir 2 days

Stop aspirin for 7 days

©IJCP Academy

SMART THIEF

“No,” said the farmer, “I get a dime for a tomato like that one.”

QuoteS

LAUGH-A-WHILE

Lighter Side of Medicine

Lesson: Based on POISE-2, we recommend discontinuing aspirin about 7 days before noncardiovascular surgery.

KK Aggarwal

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Indian Journal of Clinical Practice strongly disapproves of the submission of the same articles simultaneously to different journals for consideration as well as duplicate publication and will decline to accept fresh manuscripts submitted by authors who have done so.

The boxed checklist will help authors in preparing their manuscript according to our requirements. Improperly prepared manuscripts may be returned to the author without review. The checklist should accompany each manuscript.

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– –

The covering letter should explain if there is any deviation from the standard IMRAD format (Introduction, Methods, Results and Discussion) and should outline the importance of the paper.

Principal/Senior author must sign the covering letter indicating full responsibility for the paper submitted, preferably with signatures of all the authors.

Articles must be accompanied by a declaration by all authors stating that the article has not been published in any other Journal/Book. Authors should mentioned complete designation and departments, etc. on the manuscript.

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

–

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

–

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

Note: Please keep a copy of your manuscript as we are not responsible for its loss in the mail. Manuscripts will not be returned to authors.

Title page Should contain the title, short title, names of all the authors (without degrees or diplomas), names and full location of the departments and institutions where the work was performed,

596

Indian Journal of Clinical Practice, Vol. 25, No. 6, November 2014

name of the corresponding authors, acknowledgment of financial support and abbreviations used.

– The title should be of no more than 80 characters and should represent the major theme of the manuscript.

A subtitle can be added if necessary.

– A short title of not more than 50 characters (including inter-word spaces) for use as a running head should be included.

– The name, telephone and fax numbers, e-mail and postal addresses of the author to whom communications are to be sent should be typed in the lower right corner of the title page.

– A list of abbreviations used in the paper should be included. In general, the use of abbreviations is discouraged unless they are essential for improving the readability of the text.

Summary – The summary of not more than 200 words. It must convey the essential features of the paper.

– It should not contain abbreviations, footnotes or references.

Introduction – The introduction should state why the study was carried out and what were its specific aims/objectives.

Methods – These should be described in sufficient detail to permit evaluation and duplication of the work by others.

– Ethical guidelines followed by the investigations should be described.

Statistics The following information should be given: – The statistical universe i.e., the population from which the sample for the study is selected.

– Method of selecting the sample (cases, subjects, etc. from the statistical universe).

– Method of allocating the subjects into different groups.

– Statistical methods used for presentation and analysis of data i.e., in terms of mean and standard deviation values or percentages and statistical tests such as Student’s ‘t’ test, Chi-square test and analysis of variance or non-parametric tests and multivariate techniques.

–

Confidence intervals for the measurements should be provided wherever appropriate.

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

Discussion –

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

References These should conform to the Vancouver style. References should be numbered in the order in which they appear in the texts and these numbers should be inserted above the lines on each occasion the author is cited (Sinha12 confirmed other reports13,14...). References cited only in tables or in legends to figures should be numbered in the text of the particular table or illustration. Include among the references papers accepted but not yet published; designate the journal and add ‘in press’ (in parentheses). Information from manuscripts submitted but not yet accepted should be cited in the text as ‘unpublished observations’ (in parentheses).

At the end of the article the full list of references should include the names of all authors if there are fewer than seven or if there are more, the first six followed by et al., the full title of the journal article or book chapters; the title of journals abbreviated according to the style of the Index Medicus and the first and final page numbers of the article or chapter. The authors should check that the references are accurate. If they are not this may result in the rejection of an otherwise adequate contribution.

Examples of common forms of references are: Articles Paintal AS. Impulses in vagal afferent fibres from specific pulmonary deflation receptors. The response of those receptors to phenylguanide, potato S-hydroxytryptamine and their role in respiratory and cardiovascular reflexes.

Q. J. Expt. Physiol. 1955;40:89-111.

Figures – Two complete sets of glossy prints of high quality should be submitted. The labelling must be clear and neat.

– All photomicrographs should indicate the magnification of the print.

– Special features should be indicated by arrows or letters which contrast with the background.

– The back of each illustration should bear the first author’s last name, figure number and an arrow indicating the top. This should be written lightly in pencil only. Please do not use a hard pencil, ball point or felt pen.

– Color illustrations will be accepted if they make a contribution to the understanding of the article.

–

Do not use clips/staples on photographs and artwork.

–

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

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

Books

5. Special requests _____________________________

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

6. Suggestions for reviewers (name and postal address)

Articles in Books

2.____________ 2.________________

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

3.____________ 3.________________

4.____________ 4.________________

Tables –

These should be typed double spaced on separate sheets with the table number (in Roman Arabic numerals) and title above the table and explanatory notes below the table.

Legends – These should be typed double spaces on a separate sheet and figure numbers (in Arabic numerals) corresponding with the order in which the figures are presented in the text.

–

The legend must include enough information to permit interpretation of the figure without reference to the text.

Indian 1.____________Foreign 1.________________

7. All authors’ signatures________________________ 8.

Corresponding author’s name, current postal and e-mail address and telephone and fax numbers __________________________________________

Online Submission Also e-Issue @ www.ijcpgroup.com For Editorial Correspondence

Dr KK Aggarwal

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

Indian Journal of Clinical Practice, Vol. 25, No. 6, November 2014

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