Indian journal of clinical practice april 2015 by IJCP

Indexed with IndMED

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Volume 25, Number 11

April 2015, Pages 1001â&#x20AC;&#x201C;1100

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American Family Physician

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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 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

Volume 25, Number 11, April 2015 FROM THE DESK OF THE GROUP EDITOR-IN-CHIEF

1006 Hand, Foot and Mouth Disease

AMERICAN FAMILY PHYSICIAN

1007 Enuresis in Children: A Case-based Approach

Non-Resident Indians Chamber of Commerce & Industry World Fellowship of Religions

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

Drew C. Baird, Dean A. Seehusen, David V. Bode

1017 Practice Guidelines 1019 Photo Quiz CARDIOLOGY

1021 Dilated Cardiomyopathy in Young Adults (<40 Years): Clinical, Etiological and Echocardiographic Profile

Deepti Yadav, Lubna Zafar, Anjum Parvez, Asif Hasan

1029 Understanding Cardiomyopathy

Kamal Kumar, Shivanjali Kumar

COMMUNITY MEDICINE

1033 Trend and Pattern of Tuberculosis in Unnao District of North India by Nikshay

Devesh Prasad Mishra, Mili Mishra, Abhishek Gupta

1037 Vancomycin-resistant Staphylococcus aureus Isolates in a Tertiary Care Hospital in Punjab

Narinder B Kaur, Deepak Arora

1044 Clinical Profile of Patients of Nonorganophosphate and Nonorganochlorine Compounds Poisoning

Chandrakant M Raibhoge, AS Swami

1047 Reasons for Default Among Patients Receiving

Antitubercular Treatment in Eastern Uttar Pradesh

Praveen B Gautam, HN Chaudhary

CRITICAL CARE

1055 Current Trends of Sepsis in a Critical Care Unit of a Tertiary Hospital

Anand Gopal Bhatnagar Editorial Anchor Advisory Bodies Heart Care Foundation of India

KK Aggarwal

Minal Harde, Rakesh Bhadade, Rosemarie deSouza, Kavita Patil

DRUGS

1061 Comparative Efficacy and Tolerability of 2.5 mg S-amlodipine and 5 mg Amlodipine on Switchover from Amlodipine to S-amlodipine

Bhargav M Vyasa, Arun Maseeh, Devang Shah

INTERNAL MEDICINE

1066 NMDA Encephalitis - Rare Autoimmune Encephalitis

Zalak Malav Gadani, Malav Krushnakant Gadani

OBSTETRICS AND GYNECOLOGY

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

1068 Accidental Finding of Asymptomatic Tuberculosis of Uterine Cervix: A Case Report

DP Gupta, Ratna Prabha Gupta, Hem Prabha Gupta, RK Saxena, DK Saxena

1070 A Rare Case of Spontaneous Uterine Vessel Rupture of Unknown Etiology in Late Postpartum Period Diagnosed by CT Scan

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

Anita Kharat, Suman Kumari

1072 Chickenpox in Pregnancy: Not Rosy, Not Easy

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.

Vembu Radha, Ram Prakash Thirugnanasambandam, Narayanan Palaniappan

1076 To Evaluate Prognostic Value of Subchorionic Hematoma on Threatened Abortion

Saroj Singh, Anu Pathak, Kaustubh Srivastava, Nidhi Gupta, Shikha Singh, Hari Singh

IMAGES AND INVESTIGATIONS

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

1082 Multiple Cardiac Myxoma

Monika Maheshwari

EXPERT VIEW

1083 How Important a Risk Factor is Systolic Blood Pressure?

KK Aggarwal

AROUND THE GLOBE

1085 News and Views MEDILAW

1089 Ethical Doctor-Pharma Relationship

KK Aggarwal

LIGHTER READING

1094 Lighter Side of Medicine

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

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FROM THE DESK OF THE GROUP EDITOR-IN-CHIEF

Prof. Dr KK Aggarwal

Padma Shri, Dr BC Roy & National Science Communication Awardee Sr. Physician and Cardiologist, Moolchand Medcity President, Heart Care Foundation of India Group Editor-in-Chief, IJCP Group and eMedinewS

Hand, Foot and Mouth Disease

e have been seeing a rise in the number of cases of hand, foot and mouth disease in Delhi among school children. These may be mistaken for chicken pox. HAND, FOOT AND MOUTH DISEASE: SALIENT FACTS ÂÂ Hand, foot and mouth disease is a viral illness

most commonly caused by the Coxsackie virus A6.

ÂÂ Enteroviruses 71 (EV71) can also cause hand, foot

and mouth disease.

ÂÂ Both adults and children can develop this infection.

But young children below 5 years old are more susceptible.

ÂÂ It is a moderately contagious illness. ÂÂ The incubation period is 5 days. ÂÂ The illness begins with fever, which lasts for

24-48 hours.

ÂÂ Fever is followed by appearance of painful sores in

mouth. They begin as small red spots that blister and then often become ulcers. Tongue is involved.

ÂÂ There are peripherally distributed small tender

nonitchy rash with blisters on palms of the hands, and soles of feet and buttocks.

ÂÂ The sores hurt on touch and swallowing is difficult. ÂÂ There is proximal separation of nail from the nail

bed.

ÂÂ The virus is present in mucus from nose, saliva,

fluid from sores and traces of bowel movements.

ÂÂ The virus spreads in the first week of infection.

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Indian Journal of Clinical Practice, Vol. 25, No. 11, April 2015

ÂÂ The infection spreads from person to person by

direct contact with nasal discharge, saliva or blister fluid or from stool of infected persons.

ÂÂ The virus can persist in the stool for weeks. ÂÂ The illness is not transmitted to or from pets or

other animals.

ÂÂ The illness stays for 2-3 days. It is usually mild and

self-limited.

ÂÂ EV71

is associated with brain involvement (meningitis and encephalitis), lungs and the heart.

ÂÂ The patient remains infectious after the symptoms

have gone.

ÂÂ Test is not necessary. ÂÂ There is no specific treatment. ÂÂ Paracetamol tablet can be taken to relieve pain and

fever.

ÂÂ Aspirin is to be avoided in children. ÂÂ Dehydration should be avoided. ÂÂ Eat ice cream to numb the pain. ÂÂ Using mouthwashes or sprays that numb mouth. ÂÂ Regularly wash your hands with soap and water. ÂÂ Avoid exposure to infected person. ÂÂ Maintain touch hygiene to reduce your risk of

acquiring the infection.

ÂÂ During first week of illness, the child should be

kept in isolation.

ÂÂ Schools should be closed. ÂÂ There is no vaccine currently available.

AMERICAN FAMILY PHYSICIAN

Enuresis in Children: A Case-based Approach DREW C. BAIRD, DEAN A. SEEHUSEN, DAVID V. BODE

ABSTRACT Enuresis is defined as intermittent urinary incontinence during sleep in a child at least five years of age. Approximately 5% to 10% of all seven-year-olds have enuresis, and an estimated 5 to 7 million children in the United States have enuresis. The pathophysiology of primary nocturnal enuresis involves the inability to awaken from sleep in response to a full bladder, coupled with excessive nighttime urine production or a decreased functional capacity of the bladder. Initial evaluation should include a history, physical examination, and urinalysis. Several conditions, such as constipation, obstructive sleep apnea, diabetes mellitus, diabetes insipidus, chronic kidney disease, and psychiatric disorders, are associated with enuresis. If identified, these conditions should be evaluated and treated. Treatment of primary monosymptomatic enuresis (i.e., the only symptom is nocturnal bedwetting in a child who has never been dry) begins with counseling the child and parents on effective behavioral modifications. First-line treatments for enuresis include bed alarm therapy and desmopressin. The choice of therapy is based on the childâ&#x20AC;&#x2122;s age and nighttime voiding patterns, and the desires of the child and family. Referral to a pediatric urologist is indicated for children with primary enuresis refractory to standard and combination therapies, and for children with some secondary causes of enuresis, including urinary tract malformations, recurrent urinary tract infections, or neurologic disorders.

Keywords: Enuresis, urinary incontinence, urinalysis, counseling, behavioral modifications, desmopressin

nuresis, or nocturnal enuresis, is defined as urinary incontinence during sleep in a child five years or older.1 It affects 5% to 10% of all sevenyear-olds and an estimated 5 to 7 million children in the United States, and it is more common in boys.2-5 There is a spontaneous annual cure rate of 15%, although 2% to 3% of children have symptoms into adulthood.6 This article offers a case-based approach to the evaluation and management of monosymptomatic enuresis in children.

DEFINITIONS Enuresis can be subdivided into primary vs. secondary, or monosymptomatic vs. nonmonosymptomatic types. Primary enuresis refers to children who have never achieved six months of continuously dry nights. Secondary enuresis refers to children who previously

DREW C. BAIRD, MD, is the assistant program director and research director at the Family Medicine Residency Program at Carl R. Darnall Army Medical Center, Fort Hood, Tex. DEAN A. SEEHUSEN, MD, MPH, is chief of the Department of Family and Community Medicine at Eisenhower Army Medical Center, Fort Gordon, Ga. At the time the article was written, Dr. Seehusen was program director at the Family Medicine Residency Program, Fort Belvoir (Va.) Community Hospital. DAVID V. BODE, MD, is a staff adolescent medicine physician at the Family Medicine Residency Program at Eisenhower Army Medical Center. Source: Adapted from Am Fam Physician. 2014;90(8)560-568.

attained at least six months of nighttime dryness but who have relapsed. Secondary enuresis is more likely to occur with new psychosocial stressors or an underlying medical or behavioral condition.3 In monosymptomatic enuresis, the only symptom is nighttime bed-wetting. Enuresis is often primary and monosymptomatic.7 Nonmonosymptomatic enuresis involves daytime lower urinary tract symptoms (e.g., urgency, frequency, dribbling, incomplete emptying) or daytime incontinence, dysuria, or holding maneuvers (e.g., standing on tiptoes, crossing the legs, pressing the heel or hand into the perineum).6,8 This type of enuresis may suggest an overactive bladder, dysfunctional voiding, or more serious pathology. Children with nonmonosymptomatic enuresis, recurrent urinary tract infections, urinary tract malformations, previous pelvic surgeries, or neurologic disorders should be considered for referral to a subspecialist.9,10 ILLUSTRATIVE CASE: NOCTURNAL ENURESIS The mother of a five-year-old boy is concerned about his nightly bed-wetting. He has never achieved a consistent period of nighttime dryness. He has no daytime wetting, and he denies any dysuria or urgency. What information is needed to make a diagnosis?

Indian Journal of Clinical Practice, Vol. 25, No. 11, April 2015

1007

AMERICAN FAMILY PHYSICIAN Table 1. Key Questions from the Patient History in Children with Enuresis Question

Significance and clinical response

General history What is the childâ&#x20AC;&#x2122;s age?

Younger children are more likely to experience spontaneous resolution without therapy; children 5 to 7 years of age may be offered nonpharmacologic treatment if they are sufficiently motivated

Is the child bothered by enuresis?

If not, consider delaying treatment until child is motivated or reaches 7 years of age

Has there been a previous period of 6 months of nighttime dryness?

Suggests secondary nocturnal enuresis; investigate for psychosocial stressors and other comorbidities

Have any therapies been tried previously?

Failure of bed alarm therapy is often caused by inadequate compliance and may warrant a second attempt with proper counseling, or switching to desmopressin Consider subspecialist referral if the enuresis does not respond to an adequate trial of bed alarm therapy and desmopressin Obtain a bladder diary if not already done

Enuresis characteristics What is the frequency of enuresis (days per week and episodes per night)?

Enuresis occurring every night with multiple episodes per night has a less favorable prognosis

When during the night does enuresis occur?

A large void in the first hours of sleep is typical for primary monosymptomatic enuresis

Are nighttime absorbent underpants being soaked?

Suggests nocturnal polyuria; the child may be a good candidate for desmopressin therapy

Does the child have a large firstmorning void despite enuresis?

Suggests nocturnal polyuria; the child may be a good candidate for desmopressin therapy

What are the childâ&#x20AC;&#x2122;s daytime drinking habits, particularly in the afternoon and evening?

Improve habits with behavioral modification; polydipsia may indicate diabetes mellitus and should be excluded; psychogenic polydipsia is a contraindication to desmopressin

Comorbidities and complicating factors Does the child have daytime symptoms (e.g., incontinence, urgency, frequency, dribbling, incomplete emptying, straining, weak stream, leakage, holding maneuvers, voiding < 4 or > 7 times per day)?

Suggests nonmonosymptomatic enuresis and possibly overactive bladder, dysfunctional voiding, neurogenic bladder, or anatomic malformations

Does the child have dysuria?

Suggests possible urinary tract infection; perform urine culture

Have parents and child complete a bladder diary Daytime symptoms should be evaluated and treated first; consider subspecialist referral in severe cases

Does the child have a history of urinary Suggests lower urinary tract dysfunction or malformation, or neurogenic bladder; consider tract infections? subspecialist referral Does the child have constipation (< 4 stools per week, hard stools, fecal incontinence)?

May decrease functional bladder capacity; treat constipation first because enuresis may resolve afterward

Does the child have behavioral problems?

May be more resistant to treatment; consider further psychological evaluation if suspected

Does the child have polydipsia, polyuria, or weight loss?

Consider diabetes or kidney disease

Does the child snore or have daytime somnolence?

Suggests obstructive sleep apnea; consider polysomnography

Does the child have a history of motor or learning disabilities, or delayed development?

Not a contraindication to bed alarm therapy or desmopressin; consider subspecialist referral if there is a suggestion of an undiagnosed central nervous system disorder

If a behavioral disorder is present, treat simultaneously with enuresis; consider subspecialist referral

Cont'd...

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Indian Journal of Clinical Practice, Vol. 25, No. 11, April 2015

AMERICAN FAMILY PHYSICIAN ...Cont'd

Table 1. Key Questions from the Patient History in Children with Enuresis Question Are there psychosocial concerns?

Significance and clinical response Explore for possible contributing stressors; be mindful of signs and symptoms of maltreatment Assess family dynamic and whether family is supportive in treatment Avoid use of bed alarm therapy if there are concerns for punishment and negative reinforcement by family

Information from references 2, 6, 8, and 11 through 13.

Table 2. Common Comorbidities and Differential Diagnosis of Enuresis in Children Diagnosis

Prevalence

Clinical features

Constipation*

33% to 75% Encopresis, hard stools, infrequent bowel movements

Urinary tract infection

18% to 60% Fever, urinary frequency and/or urgency, urinary nitrites or leukocytes present

Obstructive sleep apnea

10% to 54% Adenoidal hypertrophy, snoring, daytime somnolence

Overactive bladder or dysfunctional voiding

Up to 41%

Attention-deficit/ hyperactivity disorder*

12% to 17% Inattentiveness, hyperactivity, impulsivity

Daytime symptoms including urgency, dribbling, incomplete emptying, straining, weak stream or leakage, urinary postponement or frequency (i.e., < 4 or > 7 voids per day), and holding maneuvers (e.g., standing on tiptoes, crossing the legs, pressing the heel or hand into the perineum)

*Associated with treatment resistance. Information from references 6 through 8, 11, 14, 15, and 17 through 22.

Evaluating Enuresis The pathophysiology of primary enuresis involves the inability to awaken from sleep in response to a voiding stimulus (i.e., a full bladder), coupled with excessive nighttime urine production or decreased functional capacity of the bladder.6 When evaluating a child with enuresis, physicians should ask about the frequency, timing, and volume of bed-wetting. They should also ask about daytime lower urinary tract symptoms, because these may not be volunteered by the child or parents who are focused on the bed-wetting. A sense of the childâ&#x20AC;&#x2122;s and parentsâ&#x20AC;&#x2122; concerns about the bed-wetting should be determined, as well as their motivation and desire for treatment. Table 1 provides a list of questions and the clinical responses to the answers.2,6,8,11-13 A bladder diary can be used to assess nighttime voiding patterns, urine output, and daytime drinking habits. Information from the bladder diary can assist in selecting treatment options and assessing response. An example of a bladder diary is available at http:// www.geisinger.org/services/jwch/ specialties/nephrology/pdf/3_day_voiding_diary.pdf. Risk factors for enuresis include younger age, male sex, black race, history of urinary tract infection, and a family history of enuresis.14,15 Obesity is also a likely risk factor.16 Low socioeconomic status is not consistently

associated with enuresis. Multiple conditions can present with enuresis, either causative or comorbid, and they can influence management and prognosis. Table 2 outlines the most common comorbidities and differential diagnosis.6-8,11,14,15,17-22 Other conditions that may be present include chronic kidney disease, diabetes mellitus, diabetes insipidus, neurogenic bladder, anorexia or other behavioral disorders, sickle cell disease, and hyperthyroidism.11,17 The physical examination should focus on identifying causes of secondary (nonmonosymptomatic) enuresis because findings are typically normal in primary enuresis. Genital and rectal examinations can help identify genitourinary malformations or constipation. These examinations may be considered if acceptable to the child and family, and if there are concerns for secondary enuresis. Neurologic examination should include inspection of the lumbosacral spine for signs of occult abnormalities (e.g., dimple, lipoma, hypertrichosis, sacral agenesis), or signs of spinal cord dysfunction, such as tight heel cords, or hammer or claw toes. There should also be an assessment of posturing through stressed gait or mirrored movements to evaluate for central nervous system abnormalities.6 Table 3 summarizes key elements of the physical examination for children with enuresis.2,6,8,11-13

Indian Journal of Clinical Practice, Vol. 25, No. 11, April 2015

1009

AMERICAN FAMILY PHYSICIAN Table 3. Key Findings from the Physical Examination in Children with Enuresis Finding

Significance and clinical response

Height and weight

Growth delay or failure to thrive may suggest an underlying disorder, including chronic kidney disease or diabetes mellitus; further evaluation of these conditions is warranted

Head, eyes, ears, nose, and throat Enlarged adenoids and tonsils

Consider obstructive sleep apnea if snoring and/or daytime somnolence is also present; consider treatment of sleep apnea first

Abdomen Enlarged bladder or kidneys

Suggest anatomic malformations; consider subspecialist referral

Hard stool in abdomen

Suggests constipation

Genitalia Physical abnormalities: hypospadias, meatal stenosis, phimosis, labial adhesions

Suggest urinary tract malformations; consider subspecialist referral

Signs of sexual abuse

Perianal and perineal excoriations and vulvovaginitis are concerning for sexual abuse and warrant further evaluation

Rectum Evidence of fecal soiling on undergarments

Suggests fecal incontinence and constipation

Poor anal sphincter tone

Suggests neurogenic bladder; consider subspecialist referral

Dimple, hair tuft, lipoma, or other finding above gluteal cleft

Suggests spinal dysraphism and neurogenic bladder; consider further evaluation and subspecialist referral

Nervous system (motor, strength, sensory, reflexes, gait) Gait abnormality, sensory deficit, abnormal reflexes in lower limbs, tight heel cords, hammer or claw toes

Suggest neurologic disorder; consider further evaluation and subspecialist referral

Information from references 2, 6, 8, and 11 through 13.

Diagnostic Studies A diagnostic and therapeutic approach to enuresis in children is provided in Figure 1.1-3,6,10,11,13,23,24 For monosymptomatic enuresis, urinalysis is sufficient for an initial laboratory evaluation. Glycosuria or proteinuria suggests diabetes or chronic kidney disease, and warrants further testing with measurement of serum glucose, blood urea nitrogen, and serum creatinine levels. A urine culture should be obtained if bacteria or white blood cells are present.3,9,23 Further diagnostic studies may be indicated for select patients when signs and symptoms suggest nonmonosymptomatic enuresis or an underlying medical condition. Renal ultrasonography can detect kidney disease or anatomic malformations, whereas bladder ultrasonography can evaluate for lower urinary tract malformations, bladder capacity, bladder wall thickness, and postvoid residual urine volume. In addition, bladder ultrasonography is useful in measuring rectal diameter when investigating for

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Indian Journal of Clinical Practice, Vol. 25, No. 11, April 2015

constipation. Magnetic resonance imaging is indicated if there is concern for occult spinal dysraphism or other central nervous system disorders. Voiding cystourethrography and urodynamic studies are more invasive diagnostic procedures that are rarely indicated in primary enuresis. They are generally reserved for moe complicated cases, and should be performed by subspecialists in enuresis.3,11 ILLUSTRATIVE CASE: PRIMARY MONOSYMPTOMATIC NOCTURNAL ENURESIS One year ago, primary enuresis was diagnosed in a sixyear-old girl. At the time, she was not concerned with her bed-wetting. After discussion with her parents, treatment was deferred until she expressed interest in staying dry at night. Now, her parents report that she has been reluctant to attend sleepovers because of her bed-wetting, and she has been increasingly interested in resolving her bed-wetting. What initial treatments are appropriate for this patient? When should referral be considered?

AMERICAN FAMILY PHYSICIAN Suggested Management Parents should be educated and reassured that primary monosymptomatic enuresis is a common condition that resolves spontaneously in most children. Therefore, parents of younger children may wish to defer treatment other than behavioral interventions, and the physician should support this decision. Counseling and positive reinforcement measures should be discussed.23 Comorbid conditions that can cause or contribute to enuresis should be identified and managed, because the child’s response to management may be impaired if other conditions are untreated. Constipation should be treated because enuresis may resolve spontaneously afterward. Obstructive sleep apnea in children is most often caused by enlarged tonsils and adenoids. It is diagnosed by polysomnography, and the primary treatment is adenotonsillectomy. Behavioral or psychiatric disorders should be treated simultaneously with enuresis. Studies suggest that treating attention-deficit/hyperactivity disorder may benefit children with concomitant enuresis, although further research is needed.3,9,24-26

Behavioral Interventions Simple behavioral interventions can be used as a starting point. Limiting fluid intake in the hours before bed is often encouraged, but has not been systematically studied. Waking the child at night to attempt to urinate; lifting the sleeping child onto the toilet and then waking him or her to urinate; bladder training (e.g., increasing bladder capacity by delaying urination for extended periods, pelvic floor and sphincter control exercises); and instituting reward systems, such as star charts, are all reasonable interventions that appear to be more effective than no treatment, but less effective than bed alarm therapy.27 However, the long-term effectiveness of these methods remains unclear.28 More complex behavioral interventions are more effective. Dry bed training involves a schedule of periodically waking the child to attempt to urinate, “cleanliness training” (having the child change the bedding in the event of an accident), and possible use of a bed alarm. Full-spectrum therapy is a more comprehensive approach that includes bed alarm therapy, cleanliness training, bladder training, and overlearning, which involves having the child drink extra at night after 14 consecutive dry nights are achieved. These interventions are more effective when

used in conjunction with a bed alarm, suggesting that much of their benefit is derived from the alarm.29 Negative consequences for wetting should be avoided.30

Bed Alarm Therapy Bed alarms are currently the most effective treatment available, and are considered first-line therapy for monosymptomatic enuresis.3,9,13,24,30 Many types of alarms are available, but no one type has been shown to be superior. Bed alarms include a moisture sensor, placed on the child’s undergarments or as a pad underneath the child, which is connected by wire or wirelessly to an alarm that signals a loud, acoustic stimulus when wetness is detected. The goal is for the child to awaken at the beginning of an enuresis episode, stop urinating temporarily, shut off the alarm, go to the toilet, and finish urinating. Alarms that give an electric shock are generally not acceptable to patients or parents. The patient’s and parents’ levels of motivation should be evaluated, because alarms are time intensive and not acceptable for everyone.28 Families who choose to try a bed alarm should commit to a minimum trial of three months. The alarm is usually an out-of-pocket expense, because many health insurance policies do not cover it. After a bed alarm is initiated, follow-up should occur at four weeks to assess for response and compliance, troubleshoot any technical difficulties, and answer any questions. If signs of response (e.g., smaller enurectic voids, fewer wet nights, child waking to the alarm, alarm going off later and less often) are evident within one to three months of use, then therapy should be continued until 14 consecutive dry nights are achieved.13 A Cochrane review of 13 trials with 576 patients comparing bed alarm therapy with no treatment or placebo found that the likelihood of treatment failure was much lower with bed alarm therapy than with the control therapy (relative risk = 0.38; 95% confidence interval [CI], 0.33 to 0.45). About one-half of these patients remained dry after discontinuation of alarms compared with almost none in the control group (relapse occurred in 45 of 81 in the treatment group vs. 80 of 81 in the control group). Overlearning is a beneficial addition to alarm training (relative risk = 1.92 for avoiding relapse; 95% CI, 1.27 to 2.92).30

Pharmacotherapy Pharmacotherapy should be limited to children seven years or older, and can be used if initial

Indian Journal of Clinical Practice, Vol. 25, No. 11, April 2015

1011

AMERICAN FAMILY PHYSICIAN Diagnostic and Therapeutic Approach to Enuresis in Children Child â&#x2030;Ľ 5 years presents with enuresis Patient history (Table 1) Is nighttime bed-wetting the only symptom? Yes Physical examination (Table 3) and urinalysis Are there any findings suggestive of an underlying behavioral or medical condition? No

Yes

Monosymptomatic enuresis Provide patient and parental counseling and reassurance on condition; instruct on behavioral interventions; consider obtaining a bladder diary Is the child interested in treatment?

Constipation: treat appropriately and reevaluate Acute urinary tract infection: treat with appropriate antibiotics History of urinary tract infections: consider imaging and subspecialist referral Psychiatric disorder: if suspected and complicating enuresis, consider concomitant treatment; refer to behavioral subspecialist, if indicated Dysfunctional voiding or urinary tract malformation: consider imaging and subspecialist referral Neurologic disorder: consider magnetic resonance imaging of lumbar spine and referral to subspecialist Diabetes mellitus, chronic kidney disease, or other underlying medical condition: consider serum glucose measurement, chemistries, and other laboratory studies; consider subspecialist referral Obstructive sleep apnea: consider referral for polysomnography

Nonmonosymptomatic enuresis Obtain bladder diary, if not already done; consider further laboratory and imaging studies, if warranted; refer to subspecialist

Select appropriate first-line therapy

Considerations for bed alarm therapy First-line therapy for children < 7 years Requires motivated child and parents with commitment to time and effort Parents may need to help child wake to bed alarm; may require sleeping in same room Continuous treatment is necessary Do not exclude children with learning disabilities or hearing impairments (vibratory alarms are available) Reasons to consider alternative therapy: Parents show signs of negativity or blame toward child; concern for presence of negative reinforcement Infrequent bed-wetting (< 1 to 2 nights per week)

Considerations for desmopressin therapy Preferred choice if child or parents desire rapid, short-term improvement Ideal for children with nocturnal polyuria May require titrating dose to effect Consider in children whose enuresis has not responded to alarm therapy Reasons to consider alternative therapy: Not as effective in children who have low nighttime urinary output or confirmed small bladder capacity Concern for poor compliance with nighttime fluid restriction

Continue treatment if signs of response are evident and no adverse effects For alarm therapy, consider discontinuing if 14 consecutive dry nights have been achieved For desmopressin Consider upward titration of dose if inadequate response If dry for 3 months, consider suspending treatment to see if child has achieved nighttime continence; if not, then continue treatment

Figure 1. Diagnostic and therapeutic approach to enuresis in children. Information from references 1 through 3, 6, 10, 11, 13, 23, and 24.

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No Physical examination (Table 3) and urinalysis Are there any findings suggestive of an underlying behavioral or medical condition?

Yes

No Reinforce behavioral interventions and follow up when child is motivated for treatment

Reassess at monthly intervals for Confirmation of monosymptomatic enuresis Signs of response (smaller enuretic voids, less frequent wet nights; if bed alarm is used, child is waking to alarm and alarm is going off less often) Compliance Adverse effects Satisfaction with treatment

Yes

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Consider combination therapy if inadequate response at 6 to 8 weeks Consider subspecialist referral if enuresis does not respond to either therapy or if there is new evidence of an underlying medical disorder or nonmonosymptomatic nocturnal enuresis

AMERICAN FAMILY PHYSICIAN nonpharmacologic therapy is unsuccessful or if families prefer medications as initial therapy. Medications are more convenient than behavioral or alarm therapy, but symptoms typically return after discontinuation.

worse adverse effect profile, including the potential for cardiac toxicity in the event of accidental overdose. Most children have recurrence after the discontinuation of tricyclic antidepressants.33

The most commonly used medications are desmopressin, tricyclic antidepressants (e.g., imipramine), and anticholinergics. Desmopressin is an analogue of antidiuretic hormone.

Other medications have been studied to a limited extent. Diclofenac and indomethacin improve enuresis, although neither is as effective as desmopressin.34

It is first-line therapy and the medication of choice, especially in children with nocturnal polyuria and normal bladder capacity.9,13 Desmopressin has a success rate of approximately 70%,23 which is similar to alarm therapy, but the risk of recurrence after discontinuation is higher with desmopressin. In a Cochrane review of two studies with 119 patients, the relative risk of enuresis recurring after discontinuing desmopressin was 1.42 (95% CI, 1.05 to 1.91) compared with alarm therapy. Patients treated with desmopressin have an average of 1.21 more dry nights per week (95% CI, 0.95 to 1.49) compared with placebo.31 Desmopressin is available as an oral tablet and is generally well tolerated; the intranasal form is no longer recommended in children because of the risks of water intoxication, hyponatremia, and seizures if accidentally overdosed or coupled with excessive nighttime fluid intake.1,3 Follow-up should occur at two to four weeks to assess response and any adverse effects. If no response is achieved at the starting dose of 0.2 mg, it may need to be titrated up to 0.6 mg to achieve dry nights. Desmopressin should be withheld periodically for a short time every three months to assess if nighttime continence has been achieved.2,6 It can also be used on an as-needed basis for events such as sleepovers or camps after an effective dosage is found. A newer, orally disintegrating desmopressin tablet (DDAVP Melt) is available in Canada and Europe, but not yet in the United States. It is more expensive than the swallowed desmopressin tablet, but may be more effective and preferable to patients. The 0.120-mg disintegrating tablet is the equivalent dose of the 0.2mg swallowed tablet starting dose.32 Tricyclic antidepressants are considered second-line pharmacotherapy for enuresis. Although they have similar effectiveness to desmopressin, they have a

Anticholinergics have been used alone or in combination with desmopressin for enuresis not responsive to initial therapies, but are associated with significant adverse effects. They are typically reserved for cases in which low bladder capacity is suspected.23 A wide variety of complementary and alternative medicine therapies have been studied in a limited number of small trials. A Cochrane review determined that there is currently insufficient evidence to recommend any of these therapies for the treatment of enuresis.35

Combination Therapy Combination therapy should be considered in the event of treatment failure. Only a few combination therapies have been systematically studied. Bed alarm therapy plus dry bed training is better than either intervention alone.29 A Cochrane review found that the evidence for alarm therapy plus pharmacotherapy is mixed,30 although expert guidelines suggest that if enuresis does not respond or only partially responds to alarm therapy after several months, desmopressin can be combined with alarm therapy.3,13 Almost one-half of patients whose enuresis did not respond to desmopressin became dry when longacting tolterodine, 4 mg nightly, was added.36 Limited evidence suggests that pseudoephedrine is effective when combined with ibuprofen or imipramine.37,38 Pelvic floor exercises do not appear to improve full-spectrum therapy.39 Table 4 compares various treatments for enuresis.27,29-31,33,34,40 Referral to a pediatric urologist is indicated for children with primary monosymptomatic or nonmonosymptomatic enuresis whose symptoms do not improve with standard therapies or who have evidence of urinary tract malformations or recurrent urinary tract infections. Secondary enuresis is typically caused by psychological issues or true urinary tract malformations, and should prompt a thorough workup.2,3,6,11,13,23,24

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AMERICAN FAMILY PHYSICIAN Table 4. Effectiveness of Enuresis Treatments Compared with Control Therapy Therapy

Likelihood of treatment failure*; RR (95% CI)

Likelihood of relapse; RR (95% CI)

Comments

Bed alarm30

0.39 (0.33 to 0.45) in 14 studies with 576 patients

0.57 (0.47 to 0.70) in 5 studies with 162 patients

No bed alarm was found to be superior, although alarms that woke the child (vs. parents) immediately (vs. delayed) were more effective Children preferred body-worn alarms over bed pad alarms Electric shock alarms had significant adverse effects Evidence favors alarm therapy over behavioral therapy, although the evidence is scant and of poor quality Alarm therapy tended to have lower failure and relapse rates than desmopressin and tricyclic antidepressants

Desmopressin (0.2 mg)31

0.84 (0.78 to 0.91) in 4 studies with 288 patients

Treatment failure or relapse in all 34 patients in 1 study

Doses of 0.1 mg, 0.4 mg, and 0.6 mg were also found to be effective Desmopressin was more effective than imipramine during treatment, but there were no comparison data on relapse There is not enough evidence to clarify whether desmopressin is better than oxybutynin Relapse rates are higher after desmopressin use compared with bed alarm therapy

Dry bed training (bed alarm plus parents as therapists at home)29

0.03 (0.00 to 0.42) in 1 study with 40 patients

0.22 (0.10 to 0.50) in 1 study with 40 patients

Studies of complex behavioral interventions, such as dry bed training and full-spectrum home training, without a bed alarm have not shown significant benefit

Imipramine variable dosing)33

0.77 (0.72 to 0.83) in 11 studies with 813 patients

0.98 (0.94 to 1.03) in 5 studies with 416 patients

25-mg nightly dosage resulted in fewer wet nights per week than the 10-mg dosage (2.83 vs. 3.69) Imipramine trended less effective than bed alarm therapy and desmopressin in several small studies of poor quality Significant cardiac toxicity is possible May cause anticholinergic adverse effects (e.g., dry mouth, constipation)

Oxybutynin (5 mg, three times daily)34

0.80 (0.52 to 1.24) in 1 study with 39 patients

1.13 (0.79 to 1.62) in 1 study with 23 patients

The addition of oxybutynin does not appear to improve the effect of desmopressin, although a subset of patients with restricted bladder capacity may benefit from this combination40 Combination therapy of oxybutynin and imipramine was more effective with fewer relapses than either therapy alone Anticholinergic adverse effects are common (e.g., dry mouth, constipation)

Reward systems27

0.84 (0.73 to 0.95) in 2 studies with 325 patients

Data not available

Reward systems varied between trials and there was no comparison of which reward system is superior Reward systems combined with lifting were also effective compared with control

Note: Control therapy: for bed alarm therapy‑no treatment, a nonfunctioning alarm, or placebo; for dry bed training‑no treatment; for rewards systems‑wait listing controls; for medications‑placebo. CI = Confidence interval; RR = Relative risk. *Failure to achieve 14 consecutive dry nights; lower relative risks are better. Information from references 27, 29 through 31, 33, 34, and 40.

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AMERICAN FAMILY PHYSICIAN REFERENCES 1. Nevéus T, von Gontard A, Hoebeke P, et al. The standardization of terminology of lower urinary tract function in children and adolescents: report from the Standardisation Committee of the International Children’s Continence Society. J Urol. 2006;176(1):314-324. 2. Nevéus T. Nocturnal enuresis-theoretic background and practical guidelines. Pediatr Nephrol. 2011;26(8): 1207-1214. 3. Tekgul S, Nijman RJ, Hoebeke P, Canning D, Bower W, von Gontard A. Diagnosis and management of urinary incontinence in childhood. 4th International Consultation on Incontinence, Committee 9. Health Publication Ltd; 2009. http://www.icsoffice.org/Publications/ICI_4/ filesbook/ Comite-9.pdf. Accessed April 4, 2012. 4. Byrd RS, Weitzman M, Lanphear NE, Auinger P. Bedwetting in US children: epidemiology and related behavior problems. Pediatrics. 1996;98 (3 pt 1):414-419. 5. Butler RJ, Heron J. The prevalence of infrequent bedwetting and nocturnal enuresis in childhood. A large British cohort. Scand J Urol Nephrol. 2008;42(3):257-264. 6. Vande Walle J, Rittig S, Bauer S, Eggert P, Marschall-Kehrel D, Tekgul S; American Academy of Pediatrics; European Society for Paediatric Urology; European Society for Paediatric Nephrology; International Children’s Continence Society. Practical consensus guidelines for the management of enuresis [published corrections appear in Eur J Pediatr. 2013;172(2):285, and Eur J Pediatr. 2012;171(6):1005]. Eur J Pediatr. 2012;171(6):971-983. 7. Kajiwara M, Inoue K, Kato M, Usui A, Kurihara M, Usui T. Nocturnal enuresis and overactive bladder in children: an epidemiological study. Int J Urol. 2006;13(1):36-41. 8. International Children’s Continence Society. Appendix 1: minimal primary evaluation protocol. 2012. http://i-c-c-s. org/standardisationdocuments/ (subscription required). Accessed March 30, 2012. 9. Abrams P, Andersson KE, Birder L, et al. Fourth International Consultation on Incontinence Recommendations of the International Scientific Committee: Evaluation and treatment of urinary incontinence, pelvic organ prolapse, and fecal incontinence. Neurourol Urodyn. 2010;29(1):213-240. 10. Franco I, von Gontard A, De Gennaro M. Evaluation and treatment of nonmonosymptomatic nocturnal enuresis: a standardization document from the International Children’s Continence Society. J Pediatr Urol. 2013;9(2):234-243.

2010. http://www.nice.org.uk/guidance/CG111. Accessed August 13, 2014. 14. Shreeram S, He JP, Kalaydjian A, Brothers S, Merikangas KR. Prevalence of enuresis and its association with attention-deficit/hyperactivity disorder among U.S. children: results from a nationally representative study. J Am Acad Child Adolesc Psychiatry. 2009;48(1):35-41. 15. Gunes A, Gunes G, Acik Y, Akilli A. The epidemiology and factors associated with nocturnal enuresis among boarding and daytime school children in southeast of Turkey: a cross sectional study. BMC Public Health. 2009;9:357. 16. Weintraub Y, Singer S, Alexander D, et al. Enuresis—an unattended comorbidity of childhood obesity. Int J Obes (Lond). 2013;37(1):75-78. 17. Kanbur N, Pinhas L, Lorenzo A, Farhat W, Licht C, Katzman DK. Nocturnal enuresis in adolescents with anorexia nervosa: prevalence, potential causes, and pathophysiology. Int J Eat Disord. 2011;44(4):349-355. 18. Robson WL, Leung AK, Van Howe R. Primary and secondary nocturnal enuresis: similarities in presentation. Pediatrics. 2005;115(4):956-959. 19. McGrath KH, Caldwell PH, Jones MP. The frequency of constipation in children with nocturnal enuresis: a comparison with parental reporting. J Paediatr Child Health. 2008;44(1-2):19-27. 20. Bascom A, Penney T, Metcalfe M, et al. High risk of sleep disordered breathing in the enuresis population. J Urol. 2011;186(4 suppl):1710-1713. 21. Su MS, Li AM, So HK, Au CT, Ho C, Wing YK. Nocturnal enuresis in children: prevalence, correlates, and relationship with obstructive sleep apnea. J Pediatr. 2011;159(2):238-242.e1. 22. Okur M, Ruzgar H, Erbey F, Kaya A. The evaluation of children with monosymptomatic nocturnal enuresis for attention deficit and hyperactivity disorder. Int J Psychiatry Clin Pract. 2012;16(3):229-232. 23. Tekgül S, Riedmiller H, Dogan HS, et al. Guidelines on paediatric urology. European Association of Urology, European Society for Paediatric Urology, 2012. http:// www.uroweb.org/gls/pdf/21_Paediatric_Urology_LR%20 [correctie%20Hoebeke].pdf. Accessed March 11, 2012. 24. Neveus T, Eggert P, Evans J, et al. Evaluation of and treatment for monosymptomatic enuresis: a standardization document from the International Children’s Continence Society. J Urol. 2010;183(2): 441-447.

12. Robson WL. Clinical practice. Evaluation and management of enuresis. N Engl J Med. 2009;360(14):1429-1436.

25. Shreeram S, He JP, Kalaydjian A, Brothers S, Merikangas KR. Prevalence of enuresis and its association with attention-deficit/hyperactivity disorder among U.S. children: results from a nationally representative study. J Am Acad Child Adolesc Psychiatry. 2009;48(1):35-41.

13. National Institute for Health and Care Excellence. Nocturnal enuresis: the management of bedwetting in children and young people. NICE clinical guideline 111.

26. Williamson LB, Gower M, Ulzen T. Clinical case rounds in child and adolescent psychiatry: enuresis and ADHD in older children and an adolescent treated with stimulant

11. Ramakrishnan K. Evaluation and treatment of enuresis. Am Fam Physician. 2008;78(4):489-496.

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AMERICAN FAMILY PHYSICIAN medication: a case series. J Can Acad Child Adolesc Psychiatry. 2011;20(1):53-55.

desmopressin and tricyclics). Cochrane Database Syst Rev. 2012;(12):CD002238.

27. Caldwell PH, Nankivell G, Sureshkumar P. Simple behavioural interventions for nocturnal enuresis in children. Cochrane Database Syst Rev. 2013;(7):CD003637.

35. Huang T, Shu X, Huang YS, Cheuk DK. Complementary and miscellaneous interventions for nocturnal enuresis in children. Cochrane Database Syst Rev. 2011;(12):CD005230.

28. Nunes VD, O’Flynn N, Evans J, Sawyer L; Guideline Development Group. Management of bedwetting in children and young people: summary of NICE guidance. BMJ. 2010;341:c5399. 29. Glazener CM, Evans JH, Peto RE. Complex behavioural and educational interventions for nocturnal enuresis in children. Cochrane Database Syst Rev. 2004;(1):CD004668. 30. Glazener CM, Evans JH, Peto RE. Alarm interventions for nocturnal enuresis in children. Cochrane Database Syst Rev. 2005;(2):CD002911. 31. Glazener CM, Evans JH. Desmopressin for nocturnal enuresis in children. Cochrane Database Syst Rev. 2002;(3):CD002112. 32. Juul KV, Van Herzeele C, De Bruyne P, Goble S, Walle JV, Nørgaard JP. Desmopressin melt improves response and compliance compared with tablet in treatment of primary monosymptomatic nocturnal enuresis. Eur J Pediatr. 2013;172(9):1235-1242. 33. Glazener CM, Evans JH, Peto RE. Tricyclic and related drugs for nocturnal enuresis in children. Cochrane Database Syst Rev. 2003;(3):CD002117. 34. Deshpande AV, Caldwell PH, Sureshkumar P. Drugs for nocturnal enuresis in children (other than

36. Austin PF, Ferguson G, Yan Y, Campigotto MJ, Royer ME, Coplen DE. Combination therapy with desmopressin and an anticholinergic medication for nonresponders to desmopressin for monosymptomatic nocturnal enuresis: a randomized, double-blind, placebo-controlled trial. Pediatrics. 2008;122(5):1027-1032. 37. Gelotte CK, Prior MJ, Gu J. A randomized, placebo-controlled, exploratory trial of ibuprofen and pseudoephedrine in the treatment of primary nocturnal enuresis in children. Clin Pediatr (Phila). 2009;48(4):410-419. 38. Abedin Zadeh M, Moslemi MK, Kholaseh Zadeh G. Comparison between imipramine and imipramine combined with pseudoephedrine in 5-12-year-old children with uncomplicated enuresis: a double-blind clinical trial. J Pediatr Urol. 2011;7(1):30-33. 39. Van Kampen M, Lemkens H, Deschamps A, Bogaert G, Geraerts I. Influence of pelvic floor muscle exercises on full spectrum therapy for nocturnal enuresis. J Urol. 2009;182(4 suppl):2067-2071. 40. Montaldo P, Tafuro L, Rea M, Narciso V, Iossa AC, Del Gado R. Desmopressin and oxybutynin in monosymptomatic nocturnal enuresis: a randomized, double-blind, placebocontrolled trial and an assessment of predictive factors. BJU Int. 2012;110(8 pt B):E381-E386.

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Practice Guidelines ACIP RELEASES UPDATED RECOMMENDATIONS ON INFLUENZA VACCINATION TO INCLUDE THE 2014-2015 SEASON

he Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP) has released its yearly recommendations for routine influenza vaccination in the 2014-2015 season. Updates include information on antigenic composition of seasonal influenza vaccines available in the United States; concerns about dosing in children six months to eight years of age; and the preferred use of live attenuated influenza vaccine (LAIV), when available, in healthy children two to eight years of age. Any information not addressed in this updated report can be found in the ACIP’s 2013 recommendations. Ideally, vaccination should happen before influenza activity begins. It should be offered as soon as the vaccines are available (preferably by October) and should continue through influenza season. In children six months to eight years of age who need to have two doses of the influenza vaccine, the first dose should be given as soon as possible after the vaccine is available. The second dose should be given at least four weeks after the first dose. VACCINE DOSING IN CHILDREN SIX MONTHS TO EIGHT YEARS OF AGE Two approaches exist to establish influenza vaccine dosing in children six months to eight years of age for the 2014-2015 season; one takes into account only doses received since July 1, 2010, and the other relies on a known vaccination history before the 2010-2011 season. With the first approach, if the child had at least one dose of the 2013-2014 seasonal vaccine, or at least two doses since July 1, 2010, then he or she needs to have only one dose of the 2014-2015 seasonal vaccine. If the vaccination history is unknown, or the child did not receive at least one dose of the 2013-2014 seasonal vaccine or at least two doses since July 1, 2010, then two doses of the 2014-2015 vaccine are needed.

For the second approach, the vaccination history starting before July 1, 2010, must be available. If the child has received at least one dose of the 2013-2014 seasonal vaccine or at least two doses during any previous season, and at least one dose of a 2009 (HlN1)containing vaccine, then only one dose is needed for the 2014-2015 season. VACCINES AVAILABLE FOR THE 2014-2015 SEASON Influenza vaccines available in the United States will have the same vaccine virus strains in the 2014-2015 season as those in the 2013-2014 season. Trivalent vaccines will have hemagglutinin originating from an A/California/7/2009 (H1N1)-like virus, an A/Texas/50/2012 (H3N2)-like virus, and a B/ Massachusetts/2/2012-like (Yamagata lineage) virus. Quadrivalent vaccines will have these same antigens plus a B/Brisbane/60/2008-like (Victoria lineage) virus. Table 1 provides information on the influenza vaccines available in the United States for the 2014-2015 season. RECOMMENDATIONS

Considerations for Vaccination Persons at least six months of age should receive an influenza vaccination each year. If an acceptable preparation is available, this vaccination should not be postponed for a different preparation. If there are no contraindications or precautions, LAIV should be given to all healthy children two to eight years of age. If LAIV is not available, inactivated influenza vaccine (IIV) can be given instead. The upper age limit for this recommendation is eight years because of greater proven effectiveness of LAIV in this age group and to maintain programmatic consistency. The recommendation to give LAIV to all healthy children two to eight years of age should be put into effect for the 2014-2015 season; however, if this is not possible, it should occur no later than the 2015-2016 season. LAIV should not be given to persons with the following characteristics: ÂÂ Age younger than two years ÂÂ Age older than 49 years ÂÂ Contraindications stated in the package insert

Source: Adapted from Am Fam Physician. 2014;90(8):584-587.

for LAIV (age two to 17 years, taking aspirin or

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AMERICAN FAMILY PHYSICIAN products containing aspirin; allergic reactions to the vaccine or its components, or to any previously received influenza vaccine) ÂÂ Pregnancy ÂÂ Immunosuppression ÂÂ Egg allergy ÂÂ Age two to four years with asthma or wheezing

within the past 12 months

ÂÂ Influenza antiviral drug use in the past 48 hours.

Additionally, the LAIV package insert indicates that any person with asthma may have an increased risk of wheezing after receiving LAIV. The safety of LAIV in persons with other underlying medical conditions that may put them at risk of complications after influenza infection, such as hepatic, neurologic, hematologic, or metabolic disorders, has not been established. These underlying medical conditions, as well as asthma in persons at least five years of age, are precautions for LAIV use. LAIV should not be given if a person is taking care of another person with severe immunosuppression. If that person does choose to get LAIV, he or she should not have contact with the immunosuppressed person for seven days.

Vaccination in Persons with EGG Allergy Persons with egg allergy should still get the influenza vaccine if they have had only hives after having contact with or ingesting eggs. However, because of a lack of evidence regarding LAIV use in this population, IIV or trivalent recombinant influenza vaccine (RIV3, non–egg based) or IIV (traditional egg based) should be given instead of LAIV. If no other contraindications exist, RIV3 may be used in persons 18 to 49 years of age. IIV can also be used, but only if the vaccine is given

by a health care professional who knows how egg allergy presents. Additionally, persons with egg allergy receiving the vaccine should be monitored for at least 30 minutes after each dose to determine if there are any signs of an allergic reaction. Persons 18 to 49 years of age with egg allergy who have reported having more severe reactions to egg (e.g., angioedema, respiratory distress, light-headedness, emesis) or who have had to use epinephrine or any other type of emergency intervention can receive RIV3; however, they must have no other contraindications. If RIV3 is not available or if the patient is younger than 18 years or older than 49 years, IIV can be given. In this situation, the vaccine should be given by a health care professional who knows how to recognize and treat severe allergic reactions. Irrespective of the recipient’s allergy status, staff and equipment should be available to allow for immediate identification and management of allergic reactions. Persons who can eat lightly cooked eggs without having a reaction probably do not have an egg allergy, and those with a known egg allergy may be able to eat egg in baked products, such as bread, without having a reaction. These scenarios indicate that just because a person is able to ingest eggs without having a reaction, it does not rule out the possibility of an egg allergy. A consistent history of adverse reactions to eggs, combined with immunoglobulin E testing directed against egg proteins, can confirm an egg allergy. If there is no known history of exposure to egg, but egg allergy is still suspected, a physician with expertise in allergies should be consulted before vaccination. RIV3 may be used if the patient is 18 to 49 years of age. Previous severe allergic reaction to the influenza vaccine is a contraindication to future vaccination. Note: For complete article visit: www.aafp.org/afp.

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Photo Quiz CHRONIC ULCERATION ON THE LOWER EXTREMITY A 50-year-old man presented with an annular plaque located on the medial aspect of the left lower extremity. The lesion was painless, ulcerated, and indurated, and had been present for approximately one year. There was no history of trauma to the site. The patient lived most of his life in Southwest Asia, but had no other significant travel history. He was otherwise healthy. On physical examination, the patient had a large (3 Ă&#x2014; 6 cm) ulcer on his left lower extremity with a larger area of surrounding erythema (Figures 1 and 2). The ulcer was growing despite topical steroid treatment. More recently, a similar smaller ulceration appeared on the lateral aspect of his right lower extremity.

Figure 1.

Question Based on the patientâ&#x20AC;&#x2122;s history and physical examination findings, which one of the following is the most likely diagnosis? A. Atypical mycobacteria infection. B. Basal cell carcinoma. C. Cutaneous anthrax. D. Erythema induratum. E. Localized cutaneous leishmaniasis.

DISCUSSION The answer is E: localized cutaneous leishmaniasis. Lesions occur on exposed skin as a result of Leishmania infection after inoculation from a sandfly bite. Leishmania infections often occur in troops returning to the United States after serving in the Middle East or Southwest Asia. The initial manifestation of a pink papule enlarges into a nodule or plaque, eventually becoming a painless, indurated, annular ulcer. The lesion heals over months to years and leaves an atrophic, depressed scar. Localized cutaneous leishmaniasis is oriented

Source: Adapted from Am Fam Physician. 2014;90(8):571-572.

Figure 2.

along skin creases, and causes inflammatory satellite papules and induration beneath the lesion.1 Histopathology, culture, or polymerase chain reaction can be used to diagnose localized cutaneous leishmaniasis. Determining the species can guide treatment, but success is variable.2 Mycobacterium fortuitum, M. chelonae, and M. abscessus are considered rapid-growing, atypical mycobacteria. They can cause a large fluctuant abscess, which progresses to a solitary ulcerated, indurated lesion. These infections often occur after a penetrating injury or a surgical procedure in immunosuppressed patients. Diagnosis is made with mycobacterial cultures from skin lesions.3 Basal cell carcinoma is typically a pearly white, domeshaped papule with telangiectatic surface

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AMERICAN FAMILY PHYSICIAN Summary Table Condition

Causes

Characteristics

Atypical mycobacteria infection

Mycobacterium fortuitum, M. chelonae, M. abscessus

Large fluctuant abscess progressing to a solitary ulcerated, indurated lesion; often occurs at the site of a penetrating injury or surgery

Basal cell carcinoma

Associated with exposure to ultraviolet B light

Pearly white, dome-shaped papule with telangiectatic surface vessels or ulcer with indurated borders; located on the head and neck

Cutaneous anthrax

Bacillus anthracis

Painless, often pruritic papule that enlarges into a vesicle or bulla; black eschar and surrounding edema and erythema

Erythema induratum

Reaction associated with multiple infections, usually M. tuberculosis, Nocardia, Pseudomonas, and Fusarium; also associated with thrombophlebitis, hypothyroidism, rheumatoid arthritis, Crohn disease, and chronic lymphocytic leukemia

Crops of tender, violaceous nodules and plaques on the posterior lower extremities`

Localized cutaneous leishmaniasis

Leishmania parasite, transmitted by sandfly vector

Pink papule enlarges into a nodule or plaque, eventually becoming a painless, indurated, annular ulcer; usually occurs on exposed skin

vessels. It can also present as a pigmented, superficial, scaly plaque; an ulcer with indurated borders; or a yellow, firm, ill-defined mass (morpheaform). Most basal cell carcinomas occur on the head and neck. It is associated with exposure to ultraviolet B light. Diagnosis is by biopsy.4 Cutaneous anthrax is caused by Bacillus anthracis. It begins as a painless, often pruritic papule that enlarges into a vesicle or bulla within 24 hours. The vesicle becomes hemorrhagic, followed by ulcer formation with a painless black eschar. Marked edema and erythema develop, often with associated satellite vesicles. The eschar usually falls off within two weeks. Cutaneous anthrax spontaneously resolves in 90% of patients. Diagnosis is made by Gram stain or culture; a full-thickness punch biopsy should be obtained for histology, polymerase chain reaction testing, and immunochemistry studies.5 Erythema induratum, a form of nodular vasculitis, presents as crops of tender, violaceous nodules and plaques on the posterior lower extremities that evolve over several weeks. The lesions often ulcerate and drain. The disorder is overwhelmingly more common in women, usually in middle age. Erythema induratum is a reaction usually

associated with M. tuberculosis, Nocardia, Pseudomonas, and Fusarium infections; however, it can also be associated with thrombophlebitis, hypothyroidism, rheumatoid arthritis, Crohn disease, and chronic lymphocytic leukemia.6 REFERENCES 1. Kubba R, et al. Clinical diagnosis of cutaneous leishmaniasis (Oriental sore). J Am Acad Dermatol. 1987;16(6):1183-1189. 2. Ameen M. Cutaneous leishmaniasis: advances in disease pathogenesis, diagnostics and therapeutics. Clin Exp Dermatol. 2010;35(7):699-705. 3. Elston D. Nontuberculous mycobacterial skin infections: recognition and management. Am J Clin Dermatol. 2009;10(5):281-285. 4. Firnhaber JM. Diagnosis and treatment of basal cell and squamous cell carcinoma. Am Fam Physician. 2012;86(2):161-168. 5. Wenner KA, Kenner JR. Anthrax. Dermatol Clin. 2004;22(3):247-256. 6. Gilchrist H, Patteron JW. Erythema nodosum and erythema induratum (nodular vasculitis). Dermatol Ther. 2010;23(4):320-327.

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CARDIOLOGY

Dilated Cardiomyopathy in Young Adults (<40 Years): Clinical, Etiological and Echocardiographic Profile DEEPTI YADAV*, LUBNA ZAFAR†, ANJUM PARVEZ‡, ASIF HASAN#

ABSTRACT Dilated cardiomyopathy refers to a spectrum of heterogeneous myocardial disorders that lead to ventricular dilation and depressed myocardial contractility in the absence of abnormal loading conditions. It is the most common cause of the clinical syndrome of chronic heart failure and may affect young population also. In this observational study in patients of dilated cardiomyopathy <40 years of age, male-to-female ratio was 1.41:1. The most common type was idiopathic cardiomyopathy, followed by peripartum and ischemic cardiomyopathy. Dyspnea was the most common presenting symptom (100%) and basal crepitations were most common sign (85.71%). The mean ejection fraction was 26.08% and there was no correlation between ejection fraction and etiology of dilated cardiomyopathy. Mitral regurgitation was present in 41 (58.57%) patients.

Keywords: Cardiomyopathy, heart failure, dyspnea, mitral regurgitation

process with which they are associated like ischemic, alcoholic, peripartum, etc.2,3

The first group is based on anatomic description of chambers in systole and diastole thereby having dilated, restrictive and hypertrophic phenotypes in this category. The second category includes secondary cardiomyopathies i.e., those associated with known cardiac or systematic processes. These are referred to as specific cardiomyopathies named for the disease

Dilated cardiomyopathy is a disease of the heart muscle in which the heart chambers become enlarged or dilated. The left ventricle is affected most commonly, although the right ventricle can also be affected. The dilatation often becomes severe and the heart may become quite enlarged. As the function of the left and/or right ventricle worsens, signs and symptoms of heart failure may develop.

ardiomyopathy is a disease of the heart muscle that results from myriad insults, such as genetic defects, cardiac myocyte injury and infiltration of myocardial tissues. Cardiomyopathy is defined as “a heterogeneous group of diseases of the myocardium associated with mechanical and/or electrical dysfunction that usually exhibit inappropriate ventricular hypertrophy or dilatation and are due to a variety of causes that frequently are genetic.1 The 1995 World Health Organization (WHO) and International Society and Federation of Cardiology has classified cardiomyopathy into two categories.2

*Junior Resident †Assistant Professor ‡Associate Professor #Professor Dept. of Medicine JN Medical College, AMU, Aligarh, Uttar Pradesh Address for correspondence Dr Anjum Parvez Flat No. 2, IInd Floor, Royal Apartment Kelanagar, Civil Lines, Aligarh - 202 002, Uttar Pradesh E-mail: anjumparvez66@yahoo.com

Dilated cardiomyopathy is the most common cardiomyopathy, of which approximately two-third is still labeled as idiopathic.4,5 Dilated cardiomyopathy represents the final common pathway produced by a variety of ischemic, toxic, metabolic and immunological mechanisms damaging the heart muscle.6 Though, the initial insult to the myocardium may vary, pathophysiologic and clinical presentations are similar in all the varieties.

Dilated cardiomyopathy predominantly presents as congestive failure and account for approximately 25% of the cases of congestive heart failure.7 Incidence of dilated cardiomyopathy in adults is estimated to be between 5 and 8 per 1,00,000 persons per year, but the exact epidemiological data on dilated cardiomyopathy in India are lacking. This study was undertaken with the aim to study the clinical, etiological and echocardiographic correlations of dilated cardiomyopathy in young patients (<40 years).

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CARDIOLOGY MATERIAL AND METHODS

OBSERVATIONS AND RESULTS

The study was an observational cross-sectional study, which included 70 patients of dilated cardiomyopathy <40 years of age, attending Medicine or Cardiology OPD or admitted in Medicine Ward or Coronary Care Unit, at Jawaharlal Nehru Medical College and Hospital, AMU, Aligarh.

The study included 70 patients, of which 41 (58.57%) were males and 29 (41.42%) were females. Maximum number of patients were in the age group 35-40 years followed by age group 30-35 years being 23 (32.87%) and 17 (24.28%), respectively. Male-to-female ratio was 1.41:1, depicting a slight male predominance (Table 1).

Inclusion Criteria

Idiopathic cardiomyopathy was most common, seen in as many as 41.42% patients. Peripartum cardiomyopathy was the next common cause present

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Left ventricular ejection fraction (LVEF) 50% and below

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Age >12 years and <40 years.

Exclusion Criteria Patients with congenital heart disease, significant valvular heart disease, pericardial disease, cor pulmonale, hypertrophic cardiomyopathy, restrictive cardiomyopathy, hypertension and suspected druginduced cardiomyopathy were excluded from the study. The patients were enrolled in the study after obtaining informed consent. The clinical evaluation included symptom profile like dyspnea, palpitation, paroxysmal nocturnal dyspnea (PND), orthopnea, pedal edema and chest pain. Physical examination included signs like crepitations, jugular venous pressure (JVP), hepatomegaly, pedal edema, S3, S4 and murmurs. The patients underwent chest radiography, ECG and echocardiography, in addition to routine investigations like compete blood count, renal function tests, blood sugar, serum electrolytes, liver function tests, human immunodeficiency virus (HIV), thyroid profile. The echocardiographic criteria were based on the recommendations of the American Society of Echocardiography and American Heart Association.

Statistical Analysis Statistical analysis was performed using SPSS Versin 18.0 for Windows (Chicago, IL, USA). Continuous variables were expressed as mean and standard deviation (SD) and categorical variables were expressed as percentages. Differences between groups were determined with chi-square test for categorical variables and association between categorical variables was determined using chi-square association test. Analysis of variance (ANOVA) was used to compare more than two groups. Correlations between variables were tested with Pearson’s r-test. A two-sided p < 0.05 was considered significant.

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Table 1. Age and Sex Distribution of Patients (<40 Years) with Dilated Cardiomyopathy Age (years)

No. of males

No. of females

Total (%)

15-20

7.14

4.28

8 (11.42)

20-25

4.28

10 (14.28)

25-30

7.14

12 (17.14)

30-35

17.14

7.14

17 (24.28)

35-40

12.85

23 (32.87)

Total

58.57

41.42

Table 2. Etiological Profile of Patients (<40 Years) with Dilated Cardiomyopathy Type of dilated cardiomyopathy

No. of patients

Peripartum

27.14

Ischemic

Idiopathic

41.42

Miscellaneous

11.42

Peripartum Idiopathic

Ischemic Miscellaneous

11.42% 27.14%

41.42% 20%

Figure 1. Etiological profile of patients (<40 years) with dilated cardiomyopathy.

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CARDIOLOGY Table 3. Age Distribution in Patients (<40 Years) with Different Etiologies of Dilated Cardiomyopathy Age (years)

No. of patients No. of patients No. of patients No. of patients of peripartum of ischemic of idiopathic of miscellaneous cardiomyopathy (%) cardiomyopathy (%) cardiomyopathy (%) cardiomyopathy (%)

Total (%)

15-20

8 (11.42)

20-25

4 (5.71)

5 (7.14)

1 (1.42)

10 (14.28)

25-30

5 (7.14)

6 (8.57)

1 (1.42)

12 (17.41)

30-35

4 (5.71)

2 (2.85)

7 (1)

3 (4.28)

16 (22.85)

35-40

6 (8.57)

12 (17.14)

3 (4.28)

24 (34.28)

P < 0.0001.

Table 4. Sex Distribution in Patients (<40 Years) with Different Etiologies of Dilated Cardiomyopathy (Excluding Peripartum Cardiomyopathy) Sex

No. of patients of ischemic cardiomyopathy (%)

No. of patients of idiopathic cardiomyopathy (%)

No. of patients of miscellaneous cardiomyopathy (%)

Total (%)

Male

12 (17.14)

23 (32.85)

6 (8.57)

41 (80.39)

Female

2 (2.85)

6 (8.57)

2 (2.85)

10 (19.60)

P value

0.007

0.04

0.15

Peripartum

Ischemic

Idiopathic

Misc

Table 5. Symptom Profile of Patients (<40 Years) of Dilated Cardiomyopathy Symptoms

No. of patients

Shortness of breath

100

PND

42.85

No. of patients

8 6 4 2 0

15-20

20-25

25-30 Age (years)

30-35

47.14

52.85

Palpitation

24.28

Chest pain

14.28

35-40

Figure 2. Age distribution in patients (< 40 years) with different etiologies of dilated cardiomyopathy.

in 27.14% of patients. Nearly 20% patients were having ischemic cardiomyopathy. Rest were having miscellaneous cardiomyopathies like alcoholic, diabetic and hypothyroid cardiomyopathy (Table 2 and Fig. 1). Peripartum, ischemic and miscellaneous cardiomyopathy group had no patient in the age group 15-20 years. Twelve patients (17.14%) with ischemic cardiomyopathy were in the age group 35-40 years. Patients of idiopathic cardiomyopathy were almost evenly distributed among different age groups (Table 3 and Fig. 2). Mean age for peripartum, ischemic, idiopathic and miscellaneous cardiomyopathy were 26.12 years, 36.12 years, 20.87 years and 32.12 years, respectively.

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Orthopnea Pedal edema

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Ischemic cardiomyopathy was more common in males (n = 12) than females (n = 2). The same pattern was observed in subgroup of idiopathic cardiomyopathy, 23 males and 6 females. P value for ischemic, idiopathic and miscellaneous cardiomyopathy were 0.007, 0.04 and 0.15, respectively; indicating that there was statistically significant difference in sex distribution in ischemic and idiopathic cardiomyopathy (Table 4). All the patients were having dyspnea and more than half had pedal edema (52.85%) at presentation. Orthopnea and PND were present in 47.14% and 42.85%, respectively; other symptoms being palpitations and chest pain (Table 5 and Fig. 3). On clinical examination, at the time of presentation, 85.7% patients had basal crepitations. Pansystolic murmur at apex was seen in 58.57% of patients and JVP was raised in 57.14% (Table 6 and Fig. 4). The mean ejection fraction was 26.08%.

CARDIOLOGY

100

No. of patients

80 60 50 40

37 17

10 0

PND

Shortness of breath

Orthopnea Swelling Palpitation Chest pain over feet

37 30

30 20 10 0

Basal crepts Raised JVP Hepatomegaly Pedal edema

Symptoms

Signs

Pansyst murmur...

Figure 3. Symptom profile of the patients (<40 years) of dilated cardiomyopathy.

Figure 4. Physical signs in patients (<40 years) of dilated cardiomyopathy.

Table 6. Physical Signs in Patients (<40 Years) of Dilated Cardiomyopathy

Table 7. Echocardiographic Profile of Patients (<40 Years) with Dilated Cardiomyopathy

Signs

Parameter

No. of patients

Basal crepitations

85.71

Raised JVP

57.14

<30

55.71

Hepatomegaly

42.85

30-50

44.28

Pedal edema

52.85

LV dilation

100

Pansystolic murmur at apex

58.57

Mitral regurgitation

58.57

Ejection fraction (%)

Table 8. Distribution of Different Etiologies of Dilated Cardiomyopathy in Patients (<40 Years) According to Ejection Fraction Ejection fraction (%)

No. of patients of peripartum cardiomyopathy (%)

No. of patients of ischemic cardiomyopathy (%)

No. of patients of idiopathic cardiomyopathy (%)

No. of patients of miscellaneous cardiomyopathy (%)

Total (%)

15-20

4 (5.71)

2 (2.8)

4 (5.71)

1 (1.42)

11 (15.71)

20-25

6 (8.57)

3 (4.28)

8 (11.42)

2 (2.8)

19 (27.14)

25-30

2 (2.8)

5 (7.14)

9 (12.85)

30-35

2 (2.8)

5 (7.14)

10 (14.28)

2 (2.8)

19 (27.14)

35-40

5 (7.14)

2 (2.8)

3 (4.28)

12 (17.14)

Total

P value 0.57.

Table 9. Arrhythmias in Different Etiologies of Dilated Cardiomyopathy in Young Adults (<40 Years) Arrhythmia

No. of patients of peripartum cardiomyopathy (%)

No. of patients of ischemic cardiomyopathy (%)

No. of patients of idiopathic cardiomyopathy (%)

No. of patients of miscellaneous cardiomyopathy (%)

Present

5 (35.71)

10 (34.48)

2 (25)

Absent

9 (64.28)

19 (65.51)

6 (75)

Total

P value 0.03.

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CARDIOLOGY Thirty-nine patients had ejection fraction <30%, whereas remaining had ejection fraction between 30-50%. All the patients had left ventricular dilation. Mitral regurgitation was observed in 41 (58.57%) patients (Table 7). Mean ejection fractions for peripartum, ischemic, idiopathic and miscellaneous cardiomyopathy were 29.37%, 26.24%, 24.75% and 29.25%, respectively. The p value was 0.57 (nonsignificant); that means the difference in the ejection fraction between different etiologies of dilated cardiomyopathy was not statistically significant. This shows that ejection Peripartum

Ischemic

Idiopathic

Misc

No. of patients

10 8 6 4

15-20

30-35

20-25 25-30 Ejection fraction (%)

35-40

Figure 5. Distribution of different etiologies of dilated cardiomyopathy in young adults (<40 years) in different groups of ejection fraction.

Table 10. Association of Ejection Fraction with Mitral Regurgitation in Patients (<40 Years) of Dilated Cardiomyopathy Mitral regurgitation

No. of patients with EF <30%

No. of patients with EF 30-50%

Present

24 (61.53)

17 (54.83)

Absent

15 (38.46)

14 (45.16)

Total

MR+

No. of patients

20 15

MR-

24 17

10 5 0

EF <30%

EF 30-50% Mitral regurgitation

Figure 6. Association of ejection fraction with mitral regurgitation in patients (< 40 years) of dilated cardiomyopathy.

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Out of total 39 patients with ejection fraction <30%, 24 (61.53%) had mitral regurgitation, whereas 17 out of 31 (54.83%) patients with ejection fraction 30-50% were having mitral regurgitation. P value being 0.57 was statistically nonsignificant, implying that the presence of mitral regurgitation was not correlated with ejection fraction (Table 10 and Fig. 6). DISCUSSION

fraction in patients of dilated cardiomyopathy is not significantly correlated with different etiologies (Table 8 and Fig. 5). No arrhythmia was observed in patients of peripartum cardiomyopathy. Out of total 14 patients of ischemic cardiomyopathy, five patients (35.71%) had arrhythmias. In idiopathic cardiomyopathy 10 (34.48%) patients were having arrythmias. P value 0.03 implies that there was association between arrhythmias and different etiologies of dilated cardiomyopathy, with maximum arrhythmias seen in ischemic cardiomyopathy (Table 9).

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The study was conducted to evaluate the young patients (<40 years) who present with dilated cardiomyopathy with respect to their clinical, etiological and echocardiographic profile. The study included 70 patients, of which 41 were males and 29 were females, the male-to-female ratio being 1.41:1. Ahmad et al8 conducted a study that included 65.45% males and 34.54% females, with male-to-female ratio of 1.89:1. Recently in a study by Ganesh et al,9 there were 62% males and 38% females with male-to-female ratio 1.63:1. In our study, idiopathic cardiomyopathy was the most common dilated cardiomyopathy found in 29 (41.42%) patients, followed by peripartum cardiomyopathy in 19 (27.14%) patients and ischemic cardiomyopathy in 14 (20%) patients. Miscellaneous cardiomyopathies were least common, seen in only eight (11.42%) patients and included three patients each of diabetic and hypothyroid cardiomyopathy along with two patients of alcoholic cardiomyopathy. Jain et al10 in their study observed ischemic cardiomyopathy as the most common (37%) dilated cardiomyopathy followed by idiopathic cardiomyopathy (30%) and alcoholic cardiomyopathy (14.5%). Dilated cardiomyopathy was present in 7.8% and peripartum cardiomyopathy in 7% of study population. The difference in the etiological profile may be attributed to the younger patients included in our study, where ischemia and diabetes are relatively less

CARDIOLOGY common causes. In a study by Ganesh et al in which ischemic cardiomyopathy was not included, idiopathic cardiomyopathy was the most common cardiomyopathy present in 50% of patients, followed by alcoholic cardiomyopathy (22%), peripartum cardiomyopathy (14%) and diabetic cardiomyopathy (10%). Thyrotoxic and HIV-induced cardiomyopathy were seen in 2% of the study population. The mean age of presentation of patients with dilated cardiomyopathy in our study was 29.31 years, being 30.51 years for males and 27.62 years for females. The study conducted by Ahmad et al8 had mean age of presentation 52.9 ± 15.1 years in males and 51.3.9 ± 17.7 years in females. With respect to etiology, the mean age for peripartum, ischemic, idiopathic and miscellaneous cardiomyopathies were 26.12 years, 36.12 years, 20.87 years and 32.12 years, respectively. Singh et al11 reported the mean age for dilated cardiomyopathy as 64.4 years in males and 55.5 years in females. Jain et al10 found the mean age of presentation for patients with dilated cardiomyopathy as 42.6 ± 9.1 years. Mantziari et al12 reported the mean age of presentation for ischemic cardiomyopathy as 71.1 ± 8 years and for idiopathic cardiomyopathy as 56.7 ± 14.9 years. This study did not include other types of dilated cardiomyopathy. The mean age of peripartum cardiomyopathy was around 30 years in study by Ganesh et al.9 This discrepancy in the age is due to selection bias as our study included younger patients. Our study also observed statistically significant male predominance in ischemic and idiopathic cardiomyopathy. About 85.71% patients of ischemic cardiomyopathy were males and 16.66% females. Of idiopathic cardiomyopathy 79.31% were males and 20.68% females. Similar preponderance was observed by Mantziari et al,12 where there were 31% females and 69% males in idiopathic cardiomyopathy and 91% males and 9% females in ischemic cardiomyopathy. All the patients presented with dyspnea, with orthopnea and PND being present in 33 (47.11%) and 30 (42.85%) patients, respectively. Pedal edema was the second most common presentation, observed in 37 (52.85%) patients. Palpitations, mostly due to arrhythmias, were experienced by 17 patients (24.28%). Ten patients (14.28%) had chest pain. Most of these patients had ischemic cardiomyopathy. Jain et al10 reported dyspnea, pedal edema and orthopnea in 100% patients. Palpitations were present in 66.7% patients and PND in 53% patients. In a study by Ahmad et al,8 96.3% patients had breathlessness and 65.4% had palpitations. Pedal edema was seen in 56% patients

followed by orthopnea that was reported in 40% patients. On clinical examination, basal crepitations attributed to pulmonary edema secondary to left ventricular failure was observed in 85.71% of patients. Cardiac examination revealed pansystolic murmur secondary to mitral regurgitation in 58.57% of patients. Raised JVP as a result of right ventricular failure was seen in 40 patients (57.14%) and pedal edema in 52.85% patients. Hoskatti et al13 reported basal crepitations as the most common sign observed in 93.3% in their study population. Pedal edema was observed next (76.6%) followed by raised JVP (73.3%). Forty-six percent patients were having hepatomegaly and pansystolic murmur of functional mitral regurgitation. The mean ejection fraction was 26.08% in our study. Of the total 70 patients, 39 were having ejection fraction <30% and 31 had ejection fraction between 30-50%. Left ventricular dilation was observed in all the patients and functional mitral regurgitation in 58.57% patients. Singh et al,11 reported the mean ejection fraction of 30% and functional mitral regurgitation in 90% of the patients. Routray et al,14 observed mean ejection fraction of 35% and functional mitral regurgitation in 86% of the patients. In a study by Jain et al,10 mean ejection fraction was 29% and functional mitral regurgitation present in 67% of the patients. Ahmad et al,8 reported the mean ejection fraction of 30.05% and functional mitral regurgitation in 63.6% of the patients. Ganesh et al,9 reported that 58% of the patients had ejection fraction <30% and 42% patients had ejection fraction 30-50%. Functional mitral regurgitation was present in 62% of the patients. Depending on the etiologies of dilated cardiomyopathy, it was observed that the mean ejection fraction for peripartum cardiomyopathy was 29.37%, ischemic cardiomyopathy was 26.24% and for idiopathic cardiomyopathy was 24.75%. The p value of 0.57 was nonsignificant implying that the ejection fraction was not correlated with the different etiologies of dilated cardiomyopathy. This is compatible with Mantziari et al12 who reported mean ejection fraction for idiopathic cardiomyopathy of 28.7% ± 7.8% and for ischemic cardiomyopathy 27.8% ± 5.7%, with p value of 0.57; rest of the etiologies of dilated cardiomyopathy were not included in their study. In our study population, no arrhythmia was observed in patients of peripartum cardiomyopathy. However, arrhythmias were noticed in 35.71% patients of ischemic cardiomyopathy and 34.48% patients of idiopathic cardiomyopathy. P value 0.03 indicates that there is association between arrhythmias and different etiologies

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CARDIOLOGY of dilated cardiomyopathy, with maximum arrhythmias seen in ischemic cardiomyopathy. Mantziari et al12 reported atrial fibrillation in 16.7% patients of idiopathic cardiomyopathy and 15.2% of ischemic cardiomyopathy with p value of 0.859 indicating no difference in occurrence of atrial fibrillation in ischemic and idiopathic cardiomyopathy. The difference in observations may be because this study has considered only atrial fibrillation that too only in ischemic and idiopathic cardiomyopathy leaving other etiologies of dilated cardiomyopathy. CONCLUSION Dilated cardiomyopathy is a primary myocardial disease characterized by left ventricular dilation and impaired myocardial contractility. Studies have been conducted time and again to have better understanding of the etiology, clinical features and echocardiographic patterns of the disease in different populations. This study evaluated the parameters in patients of dilated cardiomyopathy who presented at a younger age (<40 years) and observed different clinical, etiologic and echocardiographic profile. Further studies with large sample size are needed to better delineate the profile of dilated cardiomyopathy in younger age group so that appropriate management planning can be done. REFERENCES 1. Maron BJ, Towbin JA, Thiene G, Antzelevitch C, Corrado D, Arnett D, et al; American Heart Association; Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; Council on Epidemiology and Prevention. Contemporary definitions and classification of the cardiomyopathies: an American Heart Association Scientific Statement from the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups;

and Council on Epidemiology and Prevention. Circulation 2006;113(14):1807-16. 2. Richardson. WHO report on classification cardiomyopathy. Br Heart J 1980;44:680-2.

3. Report of the WHO/ISFC task force on the definition and classification of cardiomyopathies. Br Heart J 1980;44(6):672-3. 4. Dec GW, Fuster V. Idiopathic dilated cardiomyopathy. N Engl J Med 1994;331(23):1564-75. 5. Felker GM, Shaw LK, O’Connor CM. A standardized definition of ischemic cardiomyopathy for use in clinical research. J Am Coll Cardiol 2002;39(2):210-8. 6. Brigden W. Uncommon myocardial diseases: the noncoronary cardiomyopathies. Lancet 1957;273(7007): 1179-84. 7. Hare JM. The etiologic basis of congestive heart failure. In: Atlas of Heart Failure. 5th edition, Colucci WS (Ed.), Springer: Philadelphia, Current Medicine Group 2008:p.29-56. 8. Ahmad S, Rabbani M, Zaheer M, Shirazi N. Clinical ECG and echocardiographic profile of patients with dilated cardiomyopathy. Indian J Cardiol 2005;8:25-9. 9. Ganesh N, Rampure DM, Rajashekarappa. Etiological study of dilated cardiomyopathy in a tertiary care hospital. J Pharm Biomed Sci 2014;4(10):910-3. 10. Jain A, Tewari S, Kapoor A, Kumar S, Garg N, Goel PK, et al. Clinical profile of dilated cardiomyopathy. Indian Heart J 2004;56:374-82. 11. Singh G, Nayyar SB, Bal BS, Arora P, Arora JS. Clinical profile of dilated cardiomyopathy - a study of 138 cases. JAPI 2002;50:1556. 12. Mantziari L, Ziakas A, Ventoulis I, Kamperidis V, Lilis L, Katsiki N, et al. Differences in clinical presentation and findings between idiopathic dilated and ischaemic cardiomyopathy in an unselected population of heart failure patients. Open Cardiovasc Med J 2012;6:98-105. 13. Hoskatti SC, Phadnis PK, Kalagate SB. Clinical profile of patients with dilated cardiomyopathy. JAPI 2007;23:67-74. 14. Routray SN, Behra M, Mishra TK, Pattnaik UK, Satapathy C, Nayak CR. Clinical profile and long-term follow-up of patients with dilated cardiomyopathy. JAPI 2002;50:1495-6.

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CARDIOLOGY

Understanding Cardiomyopathy KAMAL KUMAR*, SHIVANJALI KUMAR†

ABSTRACT Cardiomyopathies are a heterogeneous group of diseases of the myocardium associated with mechanical and/or electrical dysfunction that usually exhibit inappropriate ventricular hypertrophy or dilatation and are due to a variety of causes that frequently are genetic. Diagnosis is made primarily on 2-dimensional echocardiography and Doppler studies. The anatomical and functional characteristics of the heart diagnostic of dilated, hypertrophic, restrictive or arrhythmogenic right ventricular cardiomyopathy/dysplasia can be seen easily.

Keywords: Dilated cardiomyopathy, hypertrophic cardiomyopathy, restrictive cardiomyopathy, ARVD, echocardiography, doppler studies

ardiomyopathy has always been a medical enigma with its definitions changing from timeto-time. The term ‘Cardiomyopathy’ was coined by the World Health Organization (WHO)1 in 1980 for ‘heart muscle diseases of unknown cause’ where cardiac dysfunction caused by other known cardiovascular disease entities like hypertension, ischemic heart disease and valvular heart disease had been excluded. The WHO/International Society and Federation of Cardiology (ISFC) Task Force2 on the definition and classification of the cardiomyopathies took etiology and dominant pathophysiology into consideration and amended this definition in 1995. They defined cardiomyopathy as ‘diseases of the myocardium associated with cardiac dysfunction’ and divided it into several groups with multiple causes in each group. These are: ÂÂ

Dilated cardiomyopathy (DCM)

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Hypertrophic cardiomyopathy (HCM)

ÂÂ

Restrictive cardiomyopathy (RCM)

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Arrhythmogenic right ventricular cardiomyopathy/ dysplasia (ARVC/D)

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Unclassified cardiomyopathies.

*Senior Consultant †Consultant Heartline Hospital and Cardiac Cath Lab, Allahabad, Uttar Pradesh Address for correspondence Dr Kamal Kumar E-mail: drkamalkumar@rediffmail.com

The expert consensus panel of the American Heart Association (AHA) (2006)3 proposed that “Cardiomyopathies are a heterogeneous group of diseases of the myocardium associated with mechanical and/or electrical dysfunction that usually (but not invariably) exhibit inappropriate ventricular hypertrophy or dilatation and are due to a variety of causes that frequently are genetic. Cardiomyopathies either are confined to the heart or are a part of generalized systemic disorders, often leading to cardiovascular death or progressive heart failurerelated disability.” Thus, cardiomyopathy may be: ÂÂ

Primary - that involves only the heart

ÂÂ

Secondary - that involves the heart as well as other organ systems.

Cardiomyopathy may further be subdivided into: ÂÂ

Genetic-like HCM, ARVC/D, left ventricular non-compaction, PRKAG2 and Danon glycogen storage diseases, conduction defects, mitochondrial myopathies and ion channel disorders.

ÂÂ

Mixed - predominantly nongenetic; less commonly genetic like DCM and RCM.

ÂÂ

Acquired - that includes myocarditis, cardiomyopathy in infants of insulin-dependent diabetic mothers, stress-induced (takotsubo), peri-partum and tachycardia-induced cardiomyopathy.

In 2008, the European Society of Cardiology (ESC) working group on myocardial and pericardial diseases4 proposed a clinical approach to cardiomyopathy calling it: “A myocardial disorder in which the heart muscle is structurally and functionally sufficiently abnormal to explain the observed myocardial abnormality in

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CARDIOLOGY the absence of coronary artery disease, hypertension, valvular disease and congenital heart disease.”   The AHA and ESC classification systems emphasize the distinction between familial/genetic and nonfamilial/ nongenetic causes of cardiomyopathy and exclude heart disease secondary to coronary artery disease, valvular heart disease or congenital heart disorders. In addition, the ESC classification also excludes ion channelopathies. Despite these definitions, clinicians continued to use terms like ‘ischemic cardiomyopathy’ and ‘hypertensive cardiomyopathy’. The term ‘ischemic cardiomyopathy’ has been mentioned in the 2013 American College of Cardiology Foundation (ACCF)/ AHA heart failure guidelines, the 2010 Heart Failure Society of America guidelines and the 2008 Canadian Cardiovascular Society guidelines.5-8 Strictly speaking, these are not cardiomyopathies. IDENTIFICATION AND DIAGNOSIS OF CARDIOMYOPATHY Diagnosis is made primarily on 2-dimensional echocardiography and Doppler studies. The anatomical and functional characteristics of the heart diagnostic of dilated, hypertrophic, restrictive or ARVC/D can be seen easily. Computed tomography (CT) or magnetic resonance imaging (MRI) of the heart may at times be required to identify or localize scars, fibrosis, fatty infiltrations, aneurysms or other pathologies. Echocardiographic evaluation may reveal: ÂÂ

ÂÂ

Systolic dysfunction that is characterized by a decrease in myocardial contractibility. Widespread decrease in function or global reduction in contractibility results in reduced left ventricular ejection fraction (LVEF). Compensatory mechanisms come into play in an attempt to maintain cardiac output. Left ventricular enlargement results in a higher stroke volume and the stretched cardiac muscles contract more strongly in accordance with Starling’s law. Ultimately, these compensatory mechanisms are exceeded, cardiac output falls and physiologic manifestations of heart failure manifest. Systolic dysfunction is the hall mark of DCM. Diastolic dysfunction is characterized by abnormal left ventricular relaxation and filling accompanied by elevated filling pressures. Compared to systolic dysfunction, diastolic dysfunction is more difficult to identify on echocardiography. Tissue Doppler and Doppler assessment of transmitral flow and pulmonary venous flow are required for diagnosis. Diastolic dysfunction may be associated with systolic dysfunction.

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ÂÂ

Heart failure may sometimes be seen with normal or near-normal LVEF termed HF-PEF (heart failure with preserved ejection fraction) or HF-NEF (heart failure with normal ejection fraction).

ANATOMIC AND PHYSIOLOGIC CLASSIFICATION

Dilated Cardiomyopathy Dilated cardiomyopathy is a condition with dilatation and impaired contraction of either the left ventricle alone or of both ventricles. The EF (ejection fraction) is usually <40% with FS (fractional shortening) being <25%.1,2 The disease may or may not exhibit overt heart failure, has a high incidence of supraventricular and/or ventricular arrhythmias with a high-risk of sudden death. The disease usually presents between 20 to 60 years, but can occur even in children or older adults. It may present as overt heart failure with progressive effort dyspnea, orthopnea, paroxysmal nocturnal dyspnea or edema. It may also present as incidental detection of asymptomatic cardiomegaly, sudden arrhythmias, conduction disturbances, thromboembolism or sudden death.9,10 In more than half of the patients no cause is found and these are deemed to be idiopathic. Again more than half of these idiopathic cases have familial cardiomyopathy. Other causes include myocarditis, infiltrative disease of myocardium, peripartum cardiomyopathy, connective tissue disease and drugs like doxorubicin. Viral infections including human immunodeficiency virus (HIV) infection and gene mutations account for a large number of cases. DCM caused by ischemia and hypertension are not cardiomyopathies in the strictest terms according to the AHA/ESC definitions. The echocardiogram in DCM shows left ventricular cavitatory dilatation. The left ventricular cavity becomes more spherical compared to the normal ovoid shape; with normal or decreased muscle wall thickness, poor wall contraction and reduced inward systolic endocardial motion. Left atrial enlargement, right ventricular enlargement and dysfunction or dilatation of all four chambers may also be present.

Hypertrophic Cardiomyopathy Hypertrophic cardiomyopathy is a clinically heterogeneous disorder characterized by hypertrophy of the left and occasionally the right ventricle. In almost 60-70% of cases, it is caused by genetic mutation of one or more sarcomere genes as an autosomal dominant trait with incomplete penetrance.11 It also includes other conditions causing increased ventricular mass,

CARDIOLOGY but excludes loading conditions like hypertension or valve disease.12 It has a prevalence rate of about 1:500.13 Patients may be asymptomatic or may present with effort dyspnea, orthopnea, paroxysmal nocturnal dyspnea, chest pain, palpitations, syncope, edema or arrhythmias. Physical examination may be normal, have nonspecific abnormalities like a fourth heart sound, systolic murmurs caused by turbulent flow across areas with intracavitatory hypertrophy and obstructions. On echocardiography, one finds that the interventricular septum is more often involved compared to the left ventricular-free wall. Sometimes apical or concentric hypertrophy is present. The left ventricular volume may be normal or reduced. Diastolic dysfunction is usual and intracavitatory gradients may be demonstrated over areas of obstruction caused by hypertrophied myocardium. Myocyte hypertrophy and disarray are present on histological examination and this is maximum where the hypertrophy is greatest.14,15 HCM should be distinguished from ‘athlete’s heart’ where there is a physiological increase in left ventricular thickness, cavity size and mass in response to intensive exercise and endurance training. The hypertrophy seen in athletes is usually symmetrical. Wall thickness usually is about 12 mm though it may sometimes go up to 14-16 mm. Athletes are known to exhibit arrhythmias. Sinus bradycardia is extremely common. Arrhythmias associated with cardiomyopathy; however, are more serious and often lethal.16 Other causes include genetic diseases (Noonan’s syndrome), metabolic diseases like (Friedreichs ataxia, Pompe’s and AMP-kinase disorder), mitochondrial diseases and storage disorders (Fabry’s disease).

Restrictive Cardiomyopathy cardiomyopathy17

Restrictive is a condition with impaired filling of the ventricles during diastole. In most cases of RCM, the cause is idiopathic. It may be caused by familial infiltrative or noninfiltrative storage disorders, collagen disorders like scleroderma and frequently by endomyocardial fibrosis, which is very common in tropical countries. The clinical presentation of RCM is fairly similar to that of constrictive pericarditis. There are features of both systemic and pulmonary congestion. Common symptoms include edema, dyspnea, fatigue, weakness and exercise intolerance as the cardiac output fails to increase with exercise. Physical signs include features of right-sided heart failure viz. peripheral edema/anasarca, raised jugular venous pressure, tender hepatomegaly and ascites together with evidence of left-sided heart failure with basal crepts and pulmonary

congestion. A S3 gallop may sometimes be heard. On echocardiography, we get dilated atria with normal sized, nonhypertrophic ventricles, normal systolic function and impaired diastolic filling on Doppler assessment of transmitral flow. Cardiac MRI and endomyocardial biopsy may be required for a precise diagnosis. Measuring brain natriuretic peptide (BNP) levels may aid in differentiating from constrictive pericarditis and noncardiac dyspnea. Endocardial fibroelastosis, a condition distinct from endomyocardial fibrosis, is characterized by diffuse thickening of the left ventricular endocardium due to proliferation of elastic and fibrous tissue. Endocardial fibroelastosis is seen primarily in infants during the first year of life. It is probably a nonspecific response to cardiac injury caused by conditions like anoxia, viral infections, bacterial endocarditis, genetic defects, neonatal lupus or even carnitine deficiency. It may present either as a dilated form (DCM phenotype) or as left ventricular restriction (RCM phenotype). Dense echoes may be seen on the endocardial surfaces of the ventricles on echocardiography. Gadolinium-enhanced cardiac MRI may help in diagnosis, but endomyocardial biopsy is usually necessary for diagnosis.18

Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia Arrhythmogenic right ventricular cardiomyopathy/ dysplasia is a genetic disorder in which the myocardium of the right ventricle is replaced by fibrous and or fibrofatty tissue with very little residual myocardial cells. There is akinesia or dyskinesia of the right ventricle with global right ventricular dilatation in severe cases. Ventricular arrhythmias are the rule.19

Unclassified Cardiomyopathies The unclassified cardiomyopathies consist of disorders that do not fit into any of the categories described in the 2008 ESC classification. Included are: ÂÂ

Left ventricular noncompaction. A rare disease caused by prenatal arrest of compaction of the loose interwoven meshwork on the myocardial wall. There is formation of deep intratrabecular recesses that do not communicate with the epicardial arterial system, but fill directly from the ventricular cavity. It is associated with a very high incidence of heart failure, thromboembolism and ventricular arrhythmias.

ÂÂ

Stress-induced cardiomyopathy is also known as ‘takotsubo’ cardiomyopathy, broken heart syndrome or apical ballooning syndrome. It is caused by stress.

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CARDIOLOGY ÂÂ

Cardiomyopathy has been described in cirrhosis. Alcohol-induced cardiomyopathy is wellknown, but one may see cardiac dysfunction in cirrhosis independent of alcohol intake. The exact mechanism of causation is not very clear. Diastolic dysfunction of LV, left atrial enlargement, QT interval prolongation and electrical and mechanical dyssynchrony may be seen.20

REFERENCES 1. Report of the WHO/ISFC Task Force on the definition and classification of cardiomyopathies. Br Heart J 1980;44(6):672-3. 2. Richardson P, McKenna W, Bristow M, Maisch B, Mautner B, O’Connell J, et al. Report of the 1995 World Health Organization/International Society and Federation of Cardiology Task Force on the definition and classification of cardiomyopathies. Circulation 1996;93(5):841-2. 3. Maron BJ, Towbin JA, Thiene G, Antzelevitch C, Corrado D, Arnett D, et al; American Heart Association; Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; Council on Epidemiology and Prevention. Contemporary definitions and classification of the cardiomyopathies: an American Heart Association Scientific Statement from the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; and Council on Epidemiology and Prevention. Circulation 2006;113(14):1807-16. 4. Elliott P, Andersson B, Arbustini E, Bilinska Z, Cecchi F, Charron P, et al. Classification of the cardiomyopathies: a position statement from the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J 2008;29(2):270-6. 5. Elliott PM. Classification of cardiomyopathies: evolution or revolution? J Am Coll Cardiol 2013;62(22):2073-4. 6. Arnold JM, Liu P, Demers C, Dorian P, Giannetti N, Haddad H, et al; Canadian Cardiovascular Society. Canadian Cardiovascular Society consensus conference recommendations on heart failure 2006: diagnosis and management. Can J Cardiol 2006;22(1):23-45. 7. WRITING COMMITTEE MEMBERS, Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Drazner MH, et al; American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation 2013;128(16):e240-327. 8. Heart Failure Society of America, Lindenfeld J, Albert NM, Boehmer JP, Collins SP, Ezekowitz JA, Givertz MM,

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et al. HFSA 2010 Comprehensive Heart Failure Practice Guideline. J Card Fail 2010;16(6):e1-194. 9. Dec GW, Fuster V. Idiopathic dilated cardiomyopathy. N Engl J Med 1994;331(23):1564-75. 10. Abelmann WH, Lorell cardiomyopathy. J Am 1219-39.

BH. Coll

The challenge of Cardiol 1989;13(6):

11. Richard P, Charron P, Carrier L, Ledeuil C, Cheav T, Pichereau C, et al; EUROGENE Heart Failure Project. Hypertrophic cardiomyopathy: distribution of disease genes, spectrum of mutations, and implications for a molecular diagnosis strategy. Circulation 2003;107(17):2227-32. 12. Braunwald E, Seidman CE, Sigwart U. Contemporary evaluation and management of hypertrophic cardiomyopathy. Circulation 2002;106(11):1312-6. 13. M aron BJ, Gardin JM, Flack JM, Gidding SS, Kurosaki TT, Bild DE. Prevalence of hypertrophic cardiomyopathy in a general population of young adults. Echocardiographic analysis of 4111 subjects in the CARDIA Study. Coronary Artery Risk Development in (Young) Adults. Circulation 1995;92(4):785-9. 14. St John Sutton MG, Lie JT, Anderson KR, O’Brien PC, Frye RL. Histopathological specificity of hypertrophic obstructive cardiomyopathy. Myocardial fibre disarray and myocardial fibrosis. Br Heart J 1980;44(4):433-43. 15. Maron BJ, Wolfson JK, Roberts WC. Relation between extent of cardiac muscle cell disorganization and left ventricular wall thickness in hypertrophic cardiomyopathy. Am J Cardiol 1992;70(7):785-90. 16. Corrado D, Pelliccia A, Bjørnstad HH, Vanhees L, Biffi A, Borjesson M, et al; Study Group of Sport Cardiology of the Working Group of Cardiac Rehabilitation and Exercise Physiology and the Working Group of Myocardial and Pericardial Diseases of the European Society of Cardiology. Cardiovascular pre-participation screening of young competitive athletes for prevention of sudden death: proposal for a common European protocol. Consensus Statement of the Study Group of Sport Cardiology of the Working Group of Cardiac Rehabilitation and Exercise Physiology and the Working Group of Myocardial and Pericardial Diseases of the European Society of Cardiology. Eur Heart J 2005;26(5):516-24. 17. Kushwaha SS, Fallon JT, Fuster V. Restrictive cardiomyopathy. N Engl J Med 1997;336(4):267-76. 18. Ino T, Benson LN, Freedom RM, Rowe RD. Natural history and prognostic risk factors in endocardial fibroelastosis. Am J Cardiol 1988;62(7):431-4. 19. Basso C, Corrado D, Marcus FI, Nava A, Thiene G. Arrhythmogenic right ventricular cardiomyopathy. Lancet 2009;373(9671):1289-300. 20. Zardi EM, Abbate A, Zardi DM, Dobrina A, Margiotta D, Van Tassell BW, et al. Cirrhotic cardiomyopathy. J Am Coll Cardiol 2010;56(7):539-49.

COMMUNITY MEDICINE

Trend and Pattern of Tuberculosis in Unnao District of North India by Nikshay DEVESH PRASAD MISHRA*, MILI MISHRA†, ABHISHEK GUPTA†

ABSTRACT Tuberculosis (TB) remains a leading cause of morbidity and mortality in developing countries. Objectives: To study the trend and pattern of selected indicators in Unnao district by Nikshay. Material and methods: A descriptive study was conducted in Unnao district from January 2011 to September 2014. The secondary data of related TB indicators of Unnao district was obtained from District TB Center by means of Nikshay, web application format for case data collection. The information regarding sputum, smear report, type of TB and treatment outcomes of these patients were analyzed. Results: The new sputum-positive rate was found to be 107% (2011), 106% (2012), 97% (2013), 76% (1st Quarter 2014) and 77% (2nd Quarter 2014). The sputum conversion rate was found to be 92% (2011), 91% (2012), 92% (2013), 90% (1st Quarter 2014) and 92% (2nd Quarter 2014). The cure rate was found to be 87% (2011-2013), 85% (1st Quarter 2014) and 88% (2nd Quarter 2014). Conclusion: The district Unnao is on its way to achieve the targets of RNTCP by the year 2015.

Keywords: Conversion rate, cure rate, new sputum-positive, Nikshay, tuberculosis

uberculosis (TB) is as old as mankind and is mentioned in Vedas and Ayurvedic Samhitas. Caries spine has been found in Egyptian mummies in 3500 BC. Robert Koch demonstrated that it was caused by the bacillus, known as Mycobacterium tuberculosis (Koch’s bacillus).1 The World Health Organization (WHO) has identified 22 high-burden TB countries, which collectively contribute 80% of the global burden of TB.

standardized short-course in the 1980s, it was believed that TB would decline globally. Although, a declining trend was observed in most developed countries, this was not evident in many developing countries.3 In developing countries, about 7% of all deaths are attributed to TB, which is the most common cause of death from a single source of infection among adults.4 It is the first infectious disease declared by the WHO as a global health emergency.5

TB is responsible for 5% of all deaths worldwide and 9.6% of adult deaths in the 15-59 years old-economic productive age groups.2 TB kills more women worldwide than all causes of maternal mortality. The case fatality rate of TB is high; approximately 50% of untreated cases die of the disease.

In 2013, an estimated 9.0 million people developed TB and 1.5 million died from the disease; 3,60,000 of whom were human immunodeficiency virus (HIV)-positive. TB is slowly declining each year and it is 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 and efforts to combat it must be accelerated if 2015 global targets, set within the context of the Millennium Development Goals (MDGs), are to be met.6

TB remains a leading cause of morbidity and mortality in developing countries. With the discovery of chemotherapy in the 1940s and adoption of the

*Assistant Professor Dept. of TB and Chest †Assistant Professor Dept. of Community Medicine Hind Institute of Medical Sciences, Barabanki, Uttar Pradesh Address for correspondence Dr Mili Mishra C-1/64, Vikrant Khand, Gomtinagar, Lucknow - 226 010, Uttar Pradesh E-mail: drmili85@gmail.com

Revised National TB Control Program (RNTCP), since implementation, followed international guidelines for recording and reporting for TB Control Program with minor modifications. Epi-info-based EPI-CENTRE. Software was being used for the purpose of electronic data transmission from district level upwards. Initially, DOS version was in use and the program shifted to windows version in 2007.

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COMMUNITY MEDICINE However, the data available at district, state or national level was in aggregated form, with a lead time of >4 months, excluding private sector and neither could help much for TB burden estimation or individual case management or monitoring. To address this, Central TB Division (CTD) in collaboration with National Informatics Center (NIC) undertook the initiative to develop a case-based web online (cloud) application named Nikshay.7 This study was conducted with the objective to study the trend and pattern of selected indicators in Unnao district by Nikshay. MATERIAL AND METHODS The secondary data of selected TB indicators of Unnao district were obtained from District TB Center. The study was conducted from January 2011 to September 2014. It was a descriptive study done to assess the trend and pattern in patients registered under Nikshay, the web-based software. This software was launched in May 2012 and has following functional components.7 ÂÂ

Master management

ÂÂ

User details

ÂÂ

TB patient registration and details of diagnosis, directly observed treatment (DOT) provider, HIV status, follow-up contact tracing, outcomes

ÂÂ

Details of solid and liquid culture and drugsensitivity testing (DST), line probe assay (LPA), cartridge-based nucleic acid amplification test (CBNAAT) details

SMS alerts to program officers.

All the diagnosed cases of TB were taken as study population. The information regarding sputum smear report, type of TB and treatment outcomes of these patients were analyzed. In the process, the following technical indicators were calculated.

Technical Indicators Case finding and case management indicators: ÂÂ

Percentage of smear-positive among new TB cases

ÂÂ

Proportion of new smear positive cases put under DOTS

ÂÂ

Sputum conversion rate for new smear-positive TB cases at the end of intensive phase (IP)

ÂÂ

Percentage of new smear-positive cases who were cured.

The data were represented in tabular form after calculating percentages and later depicted in the form of graphs. RESULTS

ÂÂ

Drug-resistant TB patient registration with details

ÂÂ

Referral and transfer of patients

ÂÂ

Private health notification

ÂÂ

Mobile application for TB notification

ÂÂ

SMS alerts to patients on registration

facility

ÂÂ

registration

and

Table 1 shows year-wise new smear-positive, conversion rate and cure rate. The cure rate was found to increase from 87% in 2011 to 88% in 2014. The conversion rate was found to be 92% (2011), 91% (2012), 92% (2013), 90% (1st Quarter 2014) and 92% (2nd Quarter 2014). Figure 1 shows year-wise new sputum-positive case rates, sputum conversion rates and cure rates. The new sputum-positive rate was found to be 107% (2011), 106% (2012), 97% (2013), 76% (1st Quarter 2014) and 77% (2nd Quarter 2014). The sputum conversion rate was found to be 92% (2011), 91% (2012), 92% (2013), 90% (1st Quarter 2014) and 92% (2nd Quarter 2014). The cure rate was found to be 87% (2011-2013), 85% (1st Quarter 2014) and 88% (2nd Quarter 2014).

Table 1. RNTCP Achievement of Unnao District for the Year 2011, 2012, 2013 and I, II Qr 2014 Quarter and Year

Population

Target of NSP NSP (70%) achieved

Conversion rate (target is 90% of total registered)

Cure rate (target 85%)

Total register

Total converted

Conversion rate

Total registered

Total cure

Cure rate

2011

31,10,595

2,084

2,231

2,140

1,960

1,930

1,687

2012

31,66,586

2,120

2,251

2,192

2,001

2,231

1,950

2013

32,23,584

2,140

2,077

2,139

1,964

2,251

1,959

1st Quarter 2014

32,80,583

545

412

465

418

493

418

2nd Quarter 2014

32,80,583

545

599

412

380

593

524

NSP = New sputum-positive.

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COMMUNITY MEDICINE

NSP case rate (70%) 120

107

Percentage (%)

100

Sputum conversion rate (90%)

Cure rate (85%)

106 92

97 87

60 40 20 0

2011

2012

2013

1st Quarter 2014

2nd Quarter 2014

Year

Figure 1. Selected indicators of RNTCP in Unnao.

Table 2. MDR/XDR-TB Status in District Unnao as on 26-08-2014 (MDR Suspect Sputum Sample Sent from 24 March 2013 to 24 July 2014) MDR suspect

Diagnosed MDR Diagnosed MDR Refused to take positive negative treatment

260

170

Put on treatment

Died

Not willing to take treatment defaulted

XDR

Presently on treatment

6,000

Percentage (%)

5,000

5,039

4,887

4,433

4,000

4,174

4,146

2013

2014

3,000 2,000 1,000 0

2010

2011

2012 Year

Figure 2. Case notification in last 5 years (total registered cases) annual data of Unnao.

Table 2 depicts the multidrug-resistant (MDR)-TB status in Unnao district on 26-08-2014. It was found that out of 260 MDR suspects, 90 were diagnosed to be MDR positive and two were found to be extreme drugresistant (XDR) positive. Figure 2 shows the case notification from 2010 to 2014. Five thousand thirty-nine cases were notified in the

year 2010; 4,887 in 2011; 4,433 in 2012; 4,174 in 2013 and 4,146 in the year 2014. DISCUSSION The RNTCP in India has the objectives of achieving the following targets by the end of 2015: Early detection and treatment of at least 90% of estimated TB cases

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COMMUNITY MEDICINE in the community, including HIV-associated TB and successful treatment of at least 90% of all new TB patients, and at least 85% of all previously treated TB patients.8 The present study shows that the district has nearly achieved the targets of the RNTCP with respect to cure rate (88%) in the year 2014. However, the district is still lagging behind in new sputum-positive case detection rate (77%) for the year 2014. In the present study, the new smear-positive rate was found to be 107% (2011), 106% (2012), 97% (2013), 76% (1st Quarter 2014) and 77% (2nd Quarter 2014). According to Annual TB Report 2014, the national new smear-positive rate is 63% and 62% for the state of Uttar Pradesh.7 The sputum conversion rate was found to be 92% (2011), 91% (2012), 92% (2013), 90% (1st Quarter 2014) and 92% (2nd Quarter 2014). Similar findings were found in a study done by Bawri et al in which sputum conversion i.e., from smear-positive to smear-negative was found to be 92% at the end of 3 months of treatment.9 The Annual TB Report 2014, shows that the national TB sputum conversion rate is 90% and 91% for the state of Uttar Pradesh.7 In the present study, the cure rate was found to be 87% (2011-2013), 85% (1st Quarter 2014) and 88% (2nd Quarter 2014). The cure rate in a study done in the district of Meerut by Sanjay Gupta, the cure rate was found to be lower (80.5%) than the present study.10 CONCLUSION The district Unnao is on its way to achieve the targets of RNTCP by the year 2015. The cure rate was found to increase from 2011 to 2014. The new sputum-positive rate was found to be decrease progressively from 2011 to 2nd Quarter of the year 2014. The sputum conversion rate was found to follow almost a constant trend from 2011 to 2014.

Acknowledgments The authors express their thanks to Dr Rajendra Prasad, Senior District Tuberculosis Officer, Unnao and Dr Rishi Saxena, Deputy DTO, Unnao for providing valuable information on the selected TB indicators for the district Unnao.

REFERENCES 1. Dubos R, Dubos J. The white plague. Rutgers University Press: New Brunswick, New Jersey; 1987. Available from: http:// www.nature. com/nature/journal/v358/n6387/ abs/358538b0.html-33k. 2. World Health Organization. World Health Reports 1999. Making a difference: Report of Dir. Gen. WHO. Geneva: WHO; 1999. 3. Chadha VK. Progress towards millennium development goals for TB control in seven Asian countries. Indian J Tuberc 2009;56(1):30-43. 4. Kaye K, Frieden TR. Tuberculosis control: the relevance of classic principles in an era of acquired immunodeficiency syndrome and multidrug resistance. Epidemiol Rev 1996;18(1):52-63. 5. Kochi A. The global tuberculosis situation and the new control strategy of the World Health Organization. Tubercle 1991;72(1):1-6. 6. WHO Global TB report 2014. Available from: http://apps. who.int/iris/bitstream/10665/137094/1/9789241564809_ eng.pdf?ua=1. Accessed on 15th January, 2015. 7. TB India 2014. Annual Status Report. Reach the Unreached. Available from http://www.tbcindia.nic.in/pdfs/TB%20 INDIA%202014.pdf. Accessed on 15th January, 2015. 8. TB Statistics India. Available from: http://www.tbfacts. org/tb-india.html. Accessed on 5th January, 2015. 9. Bawri S, Ali S, Phukan C, Tayal B, Baruwa P. A study of sputum conversion in new smear positive pulmonary tuberculosis cases at the monthly intervals of 1, 2 & 3 month under directly observed treatment, short course (dots) regimen. Lung India 2008;25(3): 118-23. 10. Gupta S. A quantitative assessment of RNTCP in Meerut district of Uttar Pradesh. IJCP 2013;24(6):578-80.

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COMMUNITY MEDICINE

Vancomycin-resistant Staphylococcus aureus Isolates in a Tertiary Care Hospital in Punjab NARINDER B KAUR*, DEEPAK ARORA†

ABSTRACT Staphylococcus aureus is one of the most common causes of community and nosocomial infections. With the rapid global development of methicillin-resistant S. aureus (MRSA), there is an increased occurrence of MRSA isolates that are only susceptible to vancomycin. In May 1996, in Japan, the first S. aureus strain with reduced susceptibilities to vancomycin was reported later, eight cases of infection caused by vancomycin-intermediate S. aureus (VISA) were detected in the United State. The present study was carried out to know the prevalence of vancomycin-resistant enterococci (VRE) and S. aureus in our hospital and to determine their susceptibility to different antimicrobial agents.

Keywords: Community infections, nosocomial infections, VRE, VRSA

he emergence of organisms resistant to commonly used antimicrobial agents has reached global epidemic proportions. In particular, nosocomial pathogens with antimicrobial-resistant phenotypes are presenting significant clinical difficulties. These difficulties arise due to limited efficacious antimicrobial agents available to treat patients infected with these organisms. Two organisms, which currently represent major nosocomial pathogens include enterococci and Staphylococcus aureus. Both organisms exhibit antimicrobial-resistant phenotypes, which currently make clinical management difficult.1 S. aureus is one of the most common causes of community and nosocomial infections. It is the leading cause of osteomyelitis, infective arthritis, acute endocarditis, bacteremia and sepsis, nosocomial pneumonia and postsurgical wound infections. S. aureus must be considered one of the most significant pathogenic bacteria that clinicians will encounter.

*Assistant Professor Dept. of Microbiology AIMSR, Bathinda, Punjab †Associate Professor Dept. of Microbiology GGSMC, Faridkot, Punjab Address for correspondence Dr Deepak Arora Associate Professor Dept. SAAA Microbiology GGSMC, Faridkot, Punjab E-mail: drdeepakarora78@gmail.com

S. aureus produces a wide variety of exotoxins, including hemolysins that disruptred blood cells.2 With the rapid global development of methicillinresistant S. aureus (MRSA), there is an increased occurrence of MRSA isolates that are only susceptible to vancomycin. In May 1996, in Japan, the first S. aureus strain with reduced susceptibilities to vancomycin was reported. After the finding in Japan of the isolate with reduced vancomycin susceptibility, eight cases of infection caused by vancomycin-intermediate S. aureus (VISA) were detected in the United State. The relative increase in incidence of vancomycinresistant enterocci (VRE) and vancomycin-resistant S. aureus (VRSA) is worrisome, which made us to carry the present study.3 AIMS AND OBJECTIVES ÂÂ

To know the prevalence of VRE and S. aureus in our hospital.

ÂÂ

To determine their susceptibility to different antimicrobial agents.

MATERIAL AND METHODS The study was conducted in the Dept. of Microbiology, AIMSR, Bathinda. A total of 250 strains of enterococci and 250 strains of S. aureus, isolated from patients irrespective of age and sex, constituted the material for the present study.

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COMMUNITY MEDICINE Samples

Preparation of Inoculum

The following samples were included for the present study: ÂÂ

Urine

Standard control strains of S. aureus ATCC 25923 was also inoculated into peptone water and standardized as mentioned above.7

ÂÂ

Pus and pus swab

INTERPRETATION OF RESULT

ÂÂ

Blood

ÂÂ

Cerebrospinal fluid (CSF) and other body fluids

ÂÂ

Stool

ÂÂ

Sputum and throat swabs

ÂÂ

High vaginal swabs (HVS) (only for S. aureus).

Staphylococci were isolated and identified by standard microbiological procedures4 and were tested for antimicrobial susceptibility by modified Stokes diskdiffusion method5 to commonly used antimicrobial agents and also to vancomycin disk (30 mg) by KirbyBauer disk-diffusion method.6 Processing of various samples was done according to the guidelines. Identification of S. aureus was done according to culture characteristics, microscopic examination and biochemical reactions.

Antibiotic Susceptibility Testing All identified isolates of S. aureus were put to antimicrobial susceptibility testing by Kirby-Bauer disk-diffusion method7 to vancomycin (30 mg) disk (Hi-media) and by modified Stokes disk-diffusion method8 to routinely used antibiotics (in house prepared). Potency of various antimicrobial agents used was:7 ÂÂ

Penicillin - 10 mg

ÂÂ

Tetracycline - 10 mg

ÂÂ

Erythromycin - 5 mg

ÂÂ

Cefazolin - 30 mg

ÂÂ

Cotrimoxazole - 25 mg

ÂÂ

Cefuroxime - 30 mg

ÂÂ

Amikacin - 30 mg

ÂÂ

Clindamycin - 2 mg

ÂÂ

Nitrofurantoin - 50 mg

ÂÂ

Gentamicin - 10 mg

Preparation of Plates Mueller-Hinton agar (MHA) was used for antibiotic sensitivity testing. It was commercially available and was supplied by Hi-media.7

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Indian Journal of Clinical Practice, Vol. 25, No. 11, April 2015

For S. aureus:8 Organisms for which the vancomycin zone diameters were ≥15 mm were considered susceptible. All VRSA were tested for antimicrobial susceptibility by modified Stokes disk-diffusion method for following antimicrobial agents with their disk content in brackets. ÂÂ

Minocycline - 30 mg

ÂÂ

Trimethoprim-sulfamethoxazole - 1.25/25 mg

ÂÂ

Quinupristin-dalfopristin - 15 mg

ÂÂ

Chloramphenicol - 30 mg

ÂÂ

Rifampin - 5 mg

ÂÂ

Linezolid - 30 mg

ÂÂ

Clindamycin - 2 mg

ÂÂ

Ampicillin + sulbactam - 10/10 mg

OBSERVATIONS A total of 250 isolates each of enterococci and staphylococci were isolated from various clinical samples - urine, pus and pus swabs, blood, CSF and other body fluids, sputum and throat swabs, high vaginal swabs and stool. The organisms were identified on the basis of unstained and stained smear examination, culture characteristics and biochemical tests. The isolated organisms were tested against various antimicrobial agents representative from all clinically important classes by modified Stokes disk-diffusion method and vancomycin (30 mg) disk by Kirby-Bauer disk-diffusion method. Table 1 shows the distribution of S. aureus in various clinical samples with maximum number in pus and pus swabs (57.6%) followed by blood (12.4%) and sputum and throat swabs (10.4%). Table 2 shows the distribution of S. aureus in various age groups. The majority of S. aureus were isolated from 21 to 30 years age group (19.2%) and that too from pus and pus swabs, and in case of blood samples majority of S. aureus were isolated from 0 to 1 years age group (38.7%). Table 3 shows the sex distribution of S. aureus in various samples and the rate of isolation, which was

COMMUNITY MEDICINE seen in case of pus and pus swabs (66%) and the organism most commonly isolated from pus and pus swabs along with S. aureus was Psuedomonas spp. The minimum mixed cultures were seen in case of stool, CSF and other body fluids. Table 6 shows the sensitivity pattern of S. aureus to antibiotics commonly used for S. aureus. The maximum resistance was seen to

more in males (53.2%) than in females (46.8%). Table 4 shows that the rate of isolation of S. aureus was more from indoor patients (69.2%) as compared to outdoor patients (30.8%). Table 5 shows the prevalence of occurrence of concomitant organisms along with S. aureus in various clinical samples. The infection was polymicrobial in 144 (57.6%) cases. The maximum mixed cultures were

Table 1. Distribution of S. aureus among Various Clinical Samples Samples

Number (n)

Percentage (%)

Pus and pus swabs

144

57.6

Blood

12.4

Sputum and throat swabs

10.4

High vaginal swab

6.8

Urine

5.6

CSF and other body fluids

3.6

Stool

3.6

Total

250

100

Table 2. Distribution of S. aureus in Clinical Samples in Various Age Groups Pus and pus swabs (n = 144) (%)

Blood (n = 31) (%)

Sputum and throat swabs (n = 26) (%)

High vaginal swab (n = 17) (%)

Urine (n = 14) (%)

CSF and other body fluids (n = 9) (%)

Stool (n = 9) (%)

Total number of isolated S. aureus n (%)

0-1

2 (1.3)

12 (38.7)

0 (0)

4 (44.4)

18 (7.2)

2-10

26 (18)

4 (12.9)

0 (0)

5 (55.5)

35 (14)

11-20

23 (16)

5 (16.1)

4 (15.3)

2 (11.7)

0 (0)

36 (14.4)

21-30

23 (16)

2 (6.45)

2 (7.6)

11 (64.7)

10 (71.4)

0 (0)

48 (19.2)

31-40

17 (11.8)

5 (16.1)

3 (11.5)

3 (17.6)

0 (0)

1 (11.1)

0 (0)

29 (11.6)

41-50

18 (12.5)

3 (9.6)

6 (23)

1 (5.8)

2 (14.2)

2 (22.2)

0 (0)

32 (12.8)

51-60

28 (19.4)

0 (0)

2 (7.6)

0 (0)

1 (7.1)

5 (55.5)

0 (0)

36 (14.4)

7 (4.8)

0 (0)

9 (34.6)

0 (0)

1 (7.1)

1 (11.1)

0 (0)

18 (7.2)

Age groups (years)

>60

Table 3. Distribution of S. aureus in Both Sexes Samples (n = 250)

Male

Female

Pus and pus swabs (n = 144)

Blood (n = 31)

Sputum and throat swabs (n = 26)

High vaginal swab (n = 17)

Urine (n = 14)

Table 4. Distribution of S. aureus According to Outdoor and Indoor Patients Samples (n = 250)

Outdoor n (%)

Indoor n (%)

Pus and pus swabs (n = 144)

50 (34.7)

94 (65.2)

Blood (n = 31)

7 (22.5)

24 (77.4)

Sputum and throat swabs (n = 26)

9 (34.6)

17 (65.3)

High vaginal swab (n = 17)

2 (11.7)

15 (88.2)

CSF and other body fluids (n = 9)

Urine (n = 14)

6 (42.8)

8 (57.1)

Stool (n = 9)

CSF and other body fluids (n = 9)

2 (22.2)

7 (77.7)

133 (53.2%)

117 (46.8%)

Stool (n = 9)

1 (11.1)

8 (88.8)

Total

77 (30.8)

173 (69.2)

Total

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COMMUNITY MEDICINE Table 5. Prevalence of Concomitant Organisms along with S. aureus in Various Clinical Samples Pus and pus swabs (n = 144)

Blood (n = 31)

Sputum and throat swabs (n = 26)

High vaginal swab (HVS) (n = 17)

Urine (n = 14)

CSF and other body fluids (n = 9)

Stool (n = 9)

Total

Escherichia coli

Klebsiella spp.

Organisms

Enterobacter spp.

Citrobacter spp.

Acinetobacter spp.

Pseudomonas spp.

Enterococcus spp.

95 (66%)

13 (42%)

12 (46.1%)

6 (35.2%)

8 (57.1%)

5 (55.5%)

144 (57.6%)

Total

Table 6. Antimicrobial Resistance (%) of S. aureus by Disk-diffusion Test Pus and pus swabs (n = 144) (%)

Blood (n = 31) (%)

Sputum and throat swabs (n = 26) (%)

High vaginal swab (n = 17) (%)

Urine (n = 14) (%)

CSF and other body fluids (n = 9) (%)

Stool (n = 9) (%)

Total (%)

Penicillin

122 (84.7)

15 (48.3)

20 (76.9)

11 (64.7)

10 (71.4)

7 (77.7)

9 (99.9)

77.6

Tetracycline

113 (78.4)

18 (69.2)

11 (64.7)

7 (77.7)

80.1

Erythromycin

94 (65.2)

11 (35.4)

14 (53.8)

9 (52.9)

10 (71.4)

4 (44.4)

6 (66.6)

59.2

Cefazolin

82 (56.9)

4 (12.9)

13 (50)

5 (29.4)

10 (71.4)

3 (33.3)

5 (55.5)

48.8

Antibiotics

Cotrimoxazole

133 (92.3)

22 (84.6)

13 (76.4)

13 (92.8)

9 (100)

90.4

Cefuroxime

74 (51.3)

13 (41.9)

10 (38.4)

6 (35.2)

11 (78.5)

6 (66.6)

4 (44.4)

49.6

Amikacin

78 (54.1)

10 (32.2)

7 (26.9)

3 (17.6)

8 (57.1)

3 (33.3)

44.8

Clindamycin

82 (56.9)

6 (19.3)

2 (7.6)

2 (11.7)

8 (57.1)

2 (22.2)

41.6

Nitrofurantoin

8 (57.1)

57.1

Gentamicin

20 (64.5)

6 (66.6)

Table 7. Vancomycin (30 mg) Sensitivity of Isolated S. aureus Zone diameter (mm) >15 mm

No. of isolates

Resistance (%)

250

cotrimoxazole (90.4%), followed by tetracycline (80.1%) and penicillin (77.6%). The minimum resistance was seen to clindamycin (41.6%) followed by amikacin (44.8%) and cefazolin (48.8%). Table 7 shows the sensitivity of all the 250 S. aureus isolates to vancomycin and it was seen that all of them showed zone diameter >15 mm.

of VRE and VRSA organisms in our hospital. In our study, 250 isolates each of enterococci and S. aureus were isolated from various clinical specimens. These specimens included blood, urine, pus and pus swabs, sputum and throat swabs, stool, CSF and body fluids (pleural fluid, ascitic fluid, synovial fluid) and high vaginal swabs.

DISCUSSION

Antimicrobial-resistant bacteria are the cause of numerous clinical problems worldwide. Although, the development of some resistance is the inevitable result of clinical use of antimicrobials, the extent of resistance and the variety of resistance mechanisms that are now relatively common among bacteria are truly astounding.9

The present study was carried out in the Dept. of Microbiology, AIMSR, Bathinda to ascertain the prevalence and antimicrobial susceptibility pattern

Two organisms, which currently represent major nosocomial pathogens include enterococci and S. aureus. Both organisms exhibit antimicrobial-resistant

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COMMUNITY MEDICINE phenotypes, which currently make clinical management difficult.1 S. aureus has long been recognized as a major pathogen of hospital-acquired infections. Over the last decade, MRSA strains have become endemic in hospitals worldwide. In addition, it is now the incipient community pathogen in many geographical regions. MRSA is important because, in addition to being methicillin-resistant, most strains are also resistant to other b-lactam antibiotics, with the exception of glycopeptide antibiotics. In 1980s, because of widespread occurrence of MRSA, empiric therapy for staphylococcal infections (particularly nosocomial sepsis) was changed to vancomycin in many healthcare institutions. Vancomycin use in the United States also increased during this period because of the growing numbers of infections with Clostridium difficile and coagulase-negative staphylococci (CoNS) in healthcare institutions. Thus, the early 1990s have shown a discernible increase in vancomycin use. As a consequence, selective pressure was established that eventually led to the emergence of strains of S. aureus and other species of staphylococci with decreased susceptibility to vancomycin and other glycopeptides. In 1997, the first strain of S. aureus with reduced susceptibility to vancomycin and teicoplanin was reported from Japan. Shortly after, two additional cases were reported from United States. However, first clinical isolate of VRSA was reported from United States in 2002.10 In the present study, the distribution of 250 isolates of S. aureus by site of isolation included 144 (57.6%) from pus and pus swabs: 31 (12.4%) from bloodstream; 26 (10.4%) from sputum and throat swabs; 17 (6.8%) from high vaginal swabs; 14 (5.6%) from urinary tract; 9 (3.6%) from CSF and other body fluids and 9 (3.6%) from stool. Comparable results were seen in a study conducted by Rajaduraipandi et al, they reported prevalence of S. aureus in clinical specimens as pus (31.1%), tissue exudates (11.1%), blood (9.7%), catheter tip (8.5%), sputum/throat swabs (6.4%), bed sore (5.2%), semen (3.7%), pleural/synovial fluid (3.3%).11 In another study conducted by Anbumani and colleagues, prevalence of S. aureus in various clinical samples was (34.9%) wound, (30.6%) pus, (15.6%) blood, (5.9%) high vaginal swabs, (3.1%) drain tip, (3.1%) ear swab.12 According to study conducted by Assadullah and colleagues, the prevalence of MRSA in various clinical samples was reported as pus (35.2%), urine (20%) and blood (17.1%).13

However, in a report prepared by Brett and colleagues, the rate of isolation of S. aureus from various clinical specimens was wound, abscess, skin (80.6%), ear (7.5%), nose, sputum, throat, tracheal aspirate (4.3%), eye (3.6%), urine, genital, urethra (1.7%), blood and sterile aspirates (1.2%).14 In the present study, the maximum rate of isolation was in the age group of 20-30 years and isolation rate was equally distributed among males (53.2%) and females (46.8%). Similarly, in a study conducted by Moran and colleagues, patients were in 20-60 years of age group, median age was 42 years and men made up 77% of study.15 Also, in a study conducted by Egido and colleagues, the age range was 1-49 years, median age was 23 years and rate of isolation was 56.3% in males and 43.8% in females.16 However, in the study conducted by Charlebois and colleagues, the age distribution was 18-29 years (6.2%), 30-39 years (26.4%), 40-49 years (40.8%), 50-77 years (26.6%). Males constituted 68.4% and females 31.6% from whom isolates were isolated.17 In a study by Brett and colleagues, isolates were obtained from all age groups 1-10 years (25%), 11-20 years (11%), 21-30 years (10%), 31-40 years (9%), 41-50 years (10%), 51-60 years (8%), 61-70 years (8%), 81-90 years (7%), >91 years (4%).14 In the present study, rate of isolation of S. aureus from indoor patients was 69.2% and from outdoor patients was 30.8%. As we know that most important risk factor for acquisition of VRSA is from patients colonized with VRE and mode of spread is nosocomial, so there are more chances of detection of VRSA in hospitalized patients. Also, most of the VRSA isolates were also resistant to methicillin and in a study conducted by Moran and colleagues 81.8% of MRSA isolates were from admitted patients.15 In the present study, staphylococcal infections were polymicrobial in 57.6% cases and maximum rate of mixed cultures was seen in pus and pus swabs (66%). In the present study, the antimicrobial susceptibility testing of S. aureus to commonly used antibiotics in the laboratory revealed that maximum resistance was seen with cotrimoxazole (90.4%) followed by tetracycline (80.1%), penicillin (77.6%), gentamicin (65%), erythromycin (59.2%), nitrofurantoin (57.1%), cefuroxime (49.6%), cefazolin (48.8%), amikacin (44.8%), clindamycin (41.6%). In a study conducted by Alzwaini, the rate of resistance of S. aureus to various antibiotics was benzylpenicillin

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COMMUNITY MEDICINE (98%), amoxicillin (91%), cephalothin (74%), cloxacillin (72%), ampicillin (70%), cefotaxime (70%), gentamicin (63%), chloramphenicol (50%). Similarly in a study conducted by Bataineh, the percentage resistance of S. aureus to various antimicrobials was penicillin (92%), oxacillin (59%), amoxiclav (57%), tetracycline (42%), erythromycin (31%), gentamicin (30%), cephalothin (29%), clindamycin (15%).18

ÂÂ

Total 250 strains each of S. aureus were isolated in pure culture from various specimens and identified by standard microbiological procedures and were tested for antimicrobial susceptibility by modified Stokes disk-diffusion method to commonly used antibiotics and also to vancomycin (30 mg) by Kirby-Bauer disk-diffusion method.

ÂÂ

Another study conducted by Charlebois and colleagues, showed that the percentage resistance to various antimicrobials was erythromycin (35.3%), trimethoprim-sulfamethoxazole (13.2%), tetracycline (5.4%), clindamycin (2.4%), ciprofloxacin (1.8%).17

Majority of isolates of S. aureus were isolated from pus and pus swabs (57.6%) followed by blood (12.4%), sputum and throat swabs (10.4%), high vaginal swabs (6.8%), urine (5.6%), CSF and other body fluids (3.6%) and stool (3.6%).

ÂÂ

Maximum rate of isolation was in the age group 21-30 years and isolation rate was almost equal in males (53.2%) and females (46.8%).

ÂÂ

Majority of S. aureus were isolated from indoor patients (69.2%).

ÂÂ

Polymicrobial infection was noted in 144 (57.6%) of the isolates.

ÂÂ

On antimicrobial susceptibility testing, maximum resistance was seen with cotrimoxazole (90.4%) followed by tetracycline (80.1%), penicillin (77.6%), gentamicin (65%), erythromycin (59.2%), nitrofurantoin (57.1%), cefuroxime (49.6%), cefazolin (48.8%), amikacin (44.8%) and clindamycin (41.6%).

ÂÂ

On testing, the isolates to vancomycin, no isolate of S. aureus was found to be resistant to vancomycin.

ÂÂ

To conclude, incidence of infections due to S. aureus is high in indoor patients and they are resistant to commonly used antibiotics, but their resistance to vancomycin is low, so strict measures should be taken i.e., hospital infection control measures and prudent use of vancomycin to prevent the rise of VRSA.

According to von Eiff and colleagues, the resistance of S. aureus was reported as penicillin (73.5%), erythromycin (16%), oxacillin (13.5%), ciprofloxacin (11%), gentamicin (10.7%), clindamycin (7.7%), teicoplanin (0%).19 In a study conducted by Mohanty and colleagues, the antimicrobial sensitivity of urinary S. aureus isolates was amikacin (47.65%), ciprofloxacin (47.65%), ampicillin (28.57%), rifampicin (19%) and nitrofurantoin (9.52%).20 In the present study, all of the S. aureus strains were sensitive to vancomycin, they have shown zone diameter >15 mm with vancomycin disk of 30 mg. So, prevalence of VRSA in our hospital is 0%. Similar results were seen in the study conducted by von Eiff and colleagues; all the strains were sensitive to vancomycin and teicoplanin (100% sensitivity).19 Also Hanumanthappa and colleagues found that all S. aureus strains were uniformly sensitive to vancomycin.21 Other studies conducted in India by Rajaduraipandi and colleagues,11 Tiwari and colleagues,10 Vidhani and colleagues,22 Anbumani and colleagues,12 Saxena and colleagues,23 Mohanty and colleagues,20 found that 100% isolates of S. aureus were sensitive to vancomycin.

REFERENCES

Similarly, in a study conducted by Tiwari and colleagues, out of 783 strains of S. aureus, (0.25%) were found to be resistant to vancomycin (0.25%).10 On the contrary, in a study conducted by Bataineh prevalence of VRSA was 3.5%.18

1. MacKinnon M. Vancomycin-resistant enterococci and vancomycin-resistant Staphylococcus aureus: Heralding the end of antibiotic era? Dalhousie Med J 1998;26(1): 33-44.

SUMMARY AND CONCLUSIONS

3. Rapp RP, Grim S. A rational approach to vancomycin resistance issues. Ind J Clin Pract 2004;14(10): 18-24.

ÂÂ

This study entitled “Prevalence of Vancomycinresistant S. aureus” was conducted in the Dept. of Microbiology, AIMSR, Bathinda with the main objective of assessing the prevalence of VRE and VRSA in our hospital and their antimicrobial susceptibility pattern.

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2. Bellmore NY. Clinical Microbiology Review. 2nd edition, Wisteria 1998:p.6.

4. Collee JG, Marr W. Culture of bacteria. In: Mackie and McCartneys Practical Medical Microbiology. 14th edition, Collee JG, Marmion BP, Fraser AG, Simmons A (Eds.), Churchill Livingstone Publishers: Edinburgh EHI3AF, New York 1996:p.245-73.

COMMUNITY MEDICINE 5. Aggarwal KC. Antibiotic sensitivity by disc diffusion method. Standardization and interpretation. Ind J Path Bact 1974;17:149-50. 6. Viallonova PA. National Committee for Clinical Laboratory Standards. Performance standards for antimicrobial susceptibility testing. Supplemental Tables M100-S10 (M2), 2000:p. 22-7. 7. Miles RS. Laboratory control of antimicrobial therapy. In: Mackie and McCartney, Practical Medical Microbiology. 14th edition, Collee JG, Marmion BP, Fraser AG, Simmons A (Eds.), Longman Singapore Publishers Ltd.: Singapore 1996:p.151-78. 8. Laboratory detection of vancomycin-intermediate/ resistant Staphylococcus aureus (VISA/VRSA). Centre for Disease Control and Prevention. Available from: http// www.cdc.gov/ncidod/dhqp/ar_visavrsa_labFAQ.html. 9. Pfaller MA, Jones RN, Marshall SA, Coffman SL, Hollis RJ, Edmond MB, et al. Inducible amp C beta-lactamase producing gram-negative bacilli from blood stream infections: frequency, antimicrobial susceptibility, and molecular epidemiology in a national surveillance program (SCOPE). Diagn Microbiol Infect Dis 1997;28(4):211-9. 10. Tiwari HK, Sen MR. Emergence of vancomycin resistant Staphylococcus aureus (VRSA) from a tertiary care hospital from northern part of India. BMC Infect Dis 2006;6:156. 11. Rajaduraipandi K, Mani KR, Panneerselvam K, Mani M, Bhaskar M, Manikandan P. Prevalence and antimicrobial susceptibility pattern of methicillin resistant Staphylococcus aureus: a multicentre study. Indian J Med Microbiol 2006;24(1):34-8. 12. Anbumani N, Wilson AA, Kalyani J, Mallika M. Prevalence of methicillin-resistant Staphylococcus aureus in a tertiary referral hospital in Chennai, South India. Ind J Pract Doct 2006-08-2006-09;3(4). 13. Assadullah S, Kakru DK, Thoker MA, Bhat FA, Hussain N, Shah A. Emergence of low level vancomycin resistance in MRSA. Indian J Med Microbiol 2003;21(3):196-8. 14. Brett M. Antimicrobial susceptibility of Staphylococcus aureus in New Zealand in 1999: A report prepared for the

Ministry of Health as part of 1998/1999 Contract (Project 8). pg.:1-21. 15. Moran GJ, Amii RN, Abrahamian FM, Talan DA. Methicillin-resistant Staphylococcus aureus in communityacquired skin infections. Emerg Infect Dis 2005;11(6): 928-30. 16. Egido JM, Barros ML. Preliminary study of communityacquired Staphylococcus aureus infection in Manaus Hospital, Amazonia Region, Brazil. Rev Soc Bras Med Trop 2003;36(6):707-9. 17. Charlebois ED, Bangsberg DR, Moss NJ, Moore MR, Moss AR, Chambers HF, et al. Population-based community prevalence of methicillin-resistant Staphylococcus aureus in the urban poor of San Francisco. Clin Infect Dis 2002;34(4):425-33. 18. Bataineh HA. Resistance of Staphylococcus aureus to vancomycin in Zarqa, Jordan. Pak J Med Sci 2006;22(2): 144-8. 19. von Eiff C, Reinert RR, Kresken M, Brauers J, Hafner D, Peters G. Nationwide German multicenter study on prevalence of antibiotic resistance in staphylococcal bloodstream isolates and comparative in vitro activities of quinupristin-dalfopristin. J Clin Microbiol 2000;38(8): 2819-23. 20. Mohanty S, Dhawan B, Gadepalli RS, Lodha R, Kapil A. Case report vancomycin-resistant Enterococcus faecium VanA phenotype: first documented isolation in India. Southeast Asian J Trop Med Public Health 2006;37(2): 335-7. 21. Hanumanthappa AR, Chandrappa NR, Rajasekharappa MG. Prevalence of methicillin resistant Staphylococcus aureus in Karnataka. Indian J Pathol Microbiol 2003;46(1):129-32. 22. Vidhani S, Mehndiratta PL, Mathur MD. Study of methicillin resistant S. aureus (MRSA) isolates from high risk patients. Indian J Med Microbiol 2001;19(2):13-6. 23. Saxena S, Singh K, Talwar V. Methicillin-resistant Staphylococcus aureus prevalence in community in the east Delhi area. Jpn J Infect Dis 2003;56(2):54-6.

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ACIP Updates Recommendations, Adds 9-Valent HPV Vaccine The Advisory Committee on Immunization Practices (ACIP) recommends the 9-valent human papillomavirus vaccine (9vHPV; Gardasil 9, Merck) as one of three HPV vaccines that can be used for routine vaccination, according to a report published in the March 26 issue of Morbidity and Mortality Weekly Report. The US Food and Drug Administration approved 9vHPV in December 2014, and, as reported by Medscape Medical News, the European Medicines Agency just recommended approval this week.

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COMMUNITY MEDICINE

Clinical Profile of Patients of Nonorganophosphate and Nonorganochlorine Compounds Poisoning CHANDRAKANT M RAIBHOGE*, AS SWAMI†

ABSTRACT Objectives: 1) To study the clinical profile of patients of nonorganophosphate and nonorganochlorine compounds poisoning. 2) To study the clinical manifestations and outcome of different poisonings. Material and methods: Patients of nonorganophosphate and nonorganochlorine compounds poisoning admitted over 24 months in a tertiary care hospital were studied for clinical profile and outcome. Results: Among 155 patients, 37.4% of patients were between 3rd and 4th decade and 29.03% of patients were between 1st and 2nd decade. Eighty-one patients were male and 74 were females. There was no significant difference according to gender (p = 0.838). About 92.09% were due to suicidal intention and 5.16 were accidental in nature; 1.93% occurred under the influence of alcohol. The route of exposure was oral in all patients (100%). About 26.45% were manual laborers, 23.87% were housewives, 21.29% were farmers and 18.06% were students. Most common poisoning was rodenticide poisoning (49.03%); 6.38% patients (13) died (p = 0.822). Conclusions: There was no significant gender difference. The route of exposure was oral in all. The most common poisoning was rodenticide poisoning. The most common intention was suicidal and most patients survived.

Keywords: Organophosphate, organochlorine, oral, suicidal, rodenticide

oison is a substance that causes damage or injury to the body and endangers one’s life due to its exposure by means of ingestion, inhalation or contact.1 Worldwide various agents such as agrochemicals, drugs or environmental agents are used as poisoning agents.2 Worldwide intentional poisoning is one of the important causes for mortality and morbidity.3

World Health Organization (WHO) estimates that 0.3 million people die every year due to various poisoning agents.4 It has been estimated that, in India 5-6 persons per 1,00,000 of population die due to acute poisoning every year.5 Poisoning is the fourth common cause of mortality in India.6 Acute pesticide poisoning is one of the most common causes of intentional deaths worldwide.7 High doses of analgesics, tranquilizers and antidepressants are the commonly used agents

*Assistant Professor †Junior Resident III Dept. of Medicine Government Medical College, Latur, Maharashtra Address for correspondence Dr Chandrakant M Raibhoge 41-A Mantri Nagar, Sutmill Road, Latur - 413 512, Maharashtra E-mail: cmraibhoge@gmail.com

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for intentional poisoning in industrialized countries.8 In advanced countries, it has been observed that poisoning deaths are mainly due to cleansing agents, detergents, paracetamol, carbon monoxide and other cosmetic products.9 In Asian region, agriculture pesticides are used in for self-poisoning particularly in rural areas with a fatality rate of 10-20%.10 Majority of pesticide exposure is seen more in middle- and low-income countries due to increased use of agrochemicals in agricultural sector.11 Studies have revealed that pesticides are the commonly used poisoning agents for intentional poisoning in India.12 As agriculture is a major profession in the rural part of India, farmers stock the pesticides to eradicate the weeds and pests. Due to easy availability of the pesticides, they are commonly used by the individuals to end their life in stressful situations. Pattern of poisoning in a region depends on various factors, which include availability and access to the poison, socioeconomic status of an individual, cultural and religious influences, etc. Against this background, the present study was undertaken to know spectrum and clinical profile of patients of acute poisoning due to various nonorganophosphate and nonorganochlorine compounds.

COMMUNITY MEDICINE AIMS AND OBJECTIVES ÂÂ

ÂÂ

To study the clinical profile of patients of nonorganophosphate and nonorganochlorine compounds poisoning. To study the clinical manifestations and outcome of different poisonings.

MATERIAL AND METHODS This study was conducted in 155 patients of nonorganophosphate and nonorganochlorine compounds poisoning admitted in a tertiary care hospital during a study period of 24 months. This study was observational and patients were selected at one time with help of inclusion criteria. RESULTS It was found that 37.41% of patients were in between 2nd and 3rd and 29.03% of patients were in between 1st and 2nd decade. Eighty-one percent were males and 74 were females. P = 0.838 suggests that there was no significant difference in incidence of poisoning according to gender in each of age groups. Most of poisonings (92.09%) were due to suicidal intention and 5.16% were accidental in nature. About 1.93% of total poisonings occurred under the influence of alcohol. The mode of exposure was oral in all (100%) patients. About 26.45% patients were manual laborers, 23.87% were housewives, 21.29% were farmers and 18.06% were students. Most common poisoning was due to rodenticides, n = 76 (49.03%) followed by drug overdosages, n = 27 (17.41%) followed by herbicides, n = 14 (9.03%). Average duration of hospital stay was 3.3 days and average duration of ICU stay was 2.3 days. Total, n = 37 (23.87%) patients required ICU care. Most (82.58%) patients survived. Overall mortality was n = 13 (8.38%). As p = 0.822, gender was not making any significant effect on mortality. Maximum mortality was due to rodenticides, n = 11 out of 76 cases (14.47%) followed by herbicides, n = 2 out of 14 cases (14.28%). Rodenticide poisoning was seen in n = 76 (49.03%) patients of which 53.94% were females and 46.05% were males. Most common symptoms were vomiting in 100% and abdominal pain in 92.10%, palpitation in 39.47%, respiratory distress in 21.05% patients. Liver function tests were deranged in 44.73% of patients and prothrombin time was deranged in 39.47% patients. Renal function tests were deranged in 10.52% patients.

Arrhythmias were seen in 15.78% patients; 26.31% patients required ICU care and mechanical ventilation was required in 18.42% patients. Mortality was highest with rodenticide poisoning, with overall mortality of 14.47%. It was 100% with aluminum phosphide group with yellow phosphorus group showing 66.66% mortality and zinc phosphide group showing 14.70% mortality. In our study, there were total 14 patients (9.03%) with herbicide intoxication. Out of these 35.71% had consumed parquet dichloride, 28.57% had consumed glyphosate, 21.42% had consumed oxyfluorfen, 14.28% had consumed 2,4-dimethylamine salt. DISCUSSION In India, as agriculture is the main occupation, insecticides and other agrochemical fertilizers are used to a greater extent and the poisoning with such products are more common.13 According to various studies, organophosphate forms the commonest poisoning agent.14,15 Information available in our country is limited, with regard to acute poisoning in adults, including hospitalized patients. CONCLUSIONS In this study, total 155 patients of nonorganophosphate and nonorganochlorine compounds poisoning were studied over a period of 24 months. ÂÂ

Eighty-one patients were males and 74 patients were females.

ÂÂ

There was no significant difference in incidence of poisoning according to gender in each of age groups.

ÂÂ

Most of poisonings were due to suicidal intention.

ÂÂ

Most common poisoning was due to rodenticide, drug overdosages and herbicides.

ÂÂ

The route of exposure was oral in all patients.

ÂÂ

Mean duration of hospital stay was 3.3 days and mean duration of ICU stay was 2.3 days.

ÂÂ

Most patients (82.58%) survived. Overall mortality was 8.38%, gender is not making any difference.

REFERENCES 1. Thomas WF, John HD, Willium RH. Stedman’s Medical Dictionary. 28th edition, Lippincott Williams and Wilkins: New York 2007:p.2004.

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COMMUNITY MEDICINE 2. Hempstead K. Manner of death and circumstances in fatal poisonings: evidence from New Jersey. Inj Prev 2006;12 Suppl 2:ii44-ii48. 3. Eddleston M, Phillips MR. Self poisoning with pesticides. BMJ 2004;328(7430):42-4. 4. Thundiyil JG, Stober J, Besbelli N, Pronczuk J. Acute pesticide poisoning: a proposed classification tool. Bull World Health Organ 2008;86(3):205-9. 5. Narayana Reddy KS. Toxicology, general consideration. In: Essentials of Forensic Medicine and Toxicology. Narayana Reddy KS (Ed.), Suguna Devi: Hyderabad, Inc. 2010:p.446-65. 6. Unnikrishnan B, Singh B, Rajeev A. Trends of acute poisoning in south Karnataka. Kathmandu Univ Med J (KUMJ) 2005;3(2):149-54. 7. Konradsen F, Dawson AH, Eddleston M, Gunnell D. Pesticide self-poisoning: thinking outside the box. Lancet 2007;369(9557):169-70. 8. McClure GM. Suicide in children and adolescents in England and Wales 1970-1998. Br J Psychiatry 2001;178:469-74. 9. Gargi J, Tejpal HR, Chanana A, Rai G, Chaudhary R. A retrospective autopsy study of poisoning in the Northern

region of Punjab. J Punjab Acad Foren Med Toxicol 2008;8(2):17-9. 10. Marecek J. Culture, gender, and suicidal behavior in Sri Lanka. Suicide Life Threat Behav 1998;28(1):69-81. 11. Dash SK, Raju AS, Mohanty MK, Patnaik KK, Mohanty S. Sociodemographic profile of poisoning cases. J Indian Acad Foren Sci 2005;27(3): 133-8. 12. Srinivas Rao Ch, Venkateswarlu V, Surender T, Eddleston M, Buckley NA. Pesticide poisoning in south India: opportunities for prevention and improved medical management. Trop Med Int Health 2005;10(6): 581-8. 13. Aaron R, Joseph A, Abraham S, Muliyil J, George K, Prasad J, et al. Suicides in young people in rural southern India. Lancet 2004;363(9415):1117-8. 14. Adlakha A, Philip PJ, Dhar KL. Organophosphorus and carbamate poisoning in Punjab. J Assoc Physicians India 1988;36(3):210-2. 15. Jaiprakash H, Sarala N, Venkatarathnamma SS, Kumar TN. Analysis of different types of poisoning in a tertiary care hospital in rural South India. Food Chem Toxicol 2011;49(1):248-50.

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Guidelines: Tempered Response to Incidental CT Findings Best New guidelines from the American Gastroenterological Association (AGA) suggest that incidental pancreatic cysts should not undergo aggressive evaluation. The AGA found there is little high-quality evidence to inform the decision to aggressively evaluate this type of incidental finding. Moreover, reports in support of aggressive evaluation are primarily retrospective and do not directly evaluate reduced mortality from pancreatic adenocarcinoma as the key outcome. “The AGA has taken a bold and welcome stand in backing away from more aggressive previous recommendations,” writes Russell P. Harris, MD, MPH, from the University of North Carolina in Chapel Hill, in a commentary on the new guidelines published online March 25 in the Annals of Internal Medicine. He also notes that incidental findings can lead to a cascade of decisions that involve possible risks and benefits.

Roseroot may have Potential as Alternative Treatment for Depression A herb used in traditional European folk medicine for over 3,000 years could be a potential treatment option for depression, according to the results of a new study. The study, published in Phytomedicine, was led by Dr Jun J Mao, an associate professor of family medicine, community health and epidemiology at the Perelman School of Medicine of the University of Pennsylvania. Rhodiola rosea, also referred to as roseroot, has been used in traditional folk medicine to promote work endurance, increase longevity and promote resistance to several health conditions including fatigue, altitude sickness and depression.

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COMMUNITY MEDICINE

Reasons for Default Among Patients Receiving Antitubercular Treatment in Eastern Uttar Pradesh PRAVEEN B GAUTAM*, HN CHAUDHARY†

ABSTRACT Objectives: To study the reasons for nonadherence to antituberculosis treatment (ATT) in Eastern Uttar Pradesh. Methods: This retrospective analysis was done among cohort of 670 patients attending BRD Medical College, Gorakhpur during 2014. Defaulters were interviewed using semi-structured questionnaire to elicit reasons of treatment default. Statistical analysis was done by using Chi-square test. Results: Out of the total 670 patients enrolled in the study, 87 (16.35%) pulmonary, 7 (6.08%) extrapulmonary and 2 (8.69%) both pulmonary as well extrapulmonary defaulted ATT. Overall default rate was 14.32%. Major reasons for treatment interruption were early improvement (24.19%), high cost of treatment (16.12%) and ATT-induced side-effects (11.29%). Maximum treatment interruption occurred between second and third month of ATT. More than one reason was often reported for discontinuation of treatment. Conclusion: Noncompliance was found to be mainly due to early improvement, high cost of treatment and side-effects of medicine. So, information on disease and treatment should be intensified and appropriate to the level of education of population, in order to promote adherence to treatment and counter the spread of multidrug-resistant tuberculosis.

Keywords: Noncompliance, antituberculosis treatment

uberculosis (TB) remains one of the major public health concern in the South-East Asia region. The region accounts for 39% of the global burden of TB in terms of incidence and India alone accounts for 26% of the world’s TB cases.1 Though, India is the second-most populous country in the world, onefourth of the global TB cases occur in India annually. In 2012, out of the estimated global annual incidence of 8.6 million TB cases, 2.3 million were estimated to have occurred in India.2 World Health Organization (WHO) has recommended directly observed treatment, short-course (DOTS) strategy for global TB control, which is accepted worldwide.3 Direct observation and regular home visit by treatment providers are provision to increase treatment completion under DOTS. Based on DOTS strategy India’s Revised National Tuberculosis Control

*Senior Resident †Professor and Head Dept. of TB and Chest BRD Medical College, Gorakhpur, Uttar Pradesh Address for correspondence Dr Praveen B Gautam H No.: 727, Anand Vihar Colony, Rapti Nagar, Gorakhpur - 273 003, Uttar Pradesh E-mail: pravingautom12@gmail.com

Program (RNTCP) was launched in 1997. Though treatment completion rate reported by RNTCP is satisfactory, recently there is growing concern of emergence of drug-resistant strains of TB bacillus. Incomplete antituberculosis treatment (ATT) is the reason for emergence of multidrug-resistant strains of TB bacillus that emerged in the early 1990s, extensively drug-resistant strains emerged in 2006 and totally drug-resistant strains emerged in 2012 in India.4 Further poor adherence to treatment leads to emergence of multidrug-resistant bacilli, so ensuring compliance is of utmost importance to control TB and halt the multidrug-resistant TB epidemic at its beginning. So, there is continuing need to sustain and further intensify the action being undertaken to reduce default. The focus must remain on dealing with important reasons of default and timely retrieval of patients who interrupt treatment. The aim of this study was to study the reasons for nonadherence to ATT in Eastern Uttar Pradesh. METHODS The present study was conducted over a 6-month period from March to August 2014 and consisted of an analysis of the data of pulmonary as well as extrapulmonary indoor and outdoor TB patients of

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COMMUNITY MEDICINE BRD Medical College, Gorakhpur, Uttar Pradesh. After obtaining consent, patients were interviewed using a semi-structured questionnaire. Information recorded in the questionnaire included personal data, sociodemographic data, past and present history of ATT and reasons for discontinuation of antitubercular treatment.

Definition (Defaulter) As per RNTCP guidelines defaulter is defined as “a patient who, any time after registration has not taken antitubercular drugs for 2 months or more consecutively”. Patients who gave a history of treatment interruption as defined above were enrolled for the study. All these patients were then interviewed in detail using a pretested semi-structured questionnaire. In addition to the personal and sociodemographic data, treatment history was recorded in detail. Statistical analysis was performed by using the Chisquare test and a ‘p’ value of <0.05 was considered as significant. RESULTS The study was conducted among patients of BRD Medical College, Gorakhpur, who were admitted and attended OPD in the Dept. of TB and Chest. A total 670 patients suffered from TB; among these 670 TB patients, 96 (14.32%) were found to have history of ATT interruption and were included in the study. Biosocial characteristics of the patients were studied and the effect of various factors on patient’s compliance to treatment was observed. In present study, (Table 1) 78 (16.95%) males 18 (8.5%) females defaulted. The highest number of defaulters were in the age group of 25-45 years, 69 (18.5%) and 15 (11.71%) defaulters were in the age of >45 years, while 12 (7.4%) were <25 years of age. On analyzing the religion, 76 (14.84%) of the defaulters were Hindus and 16 (12.30%) Muslims, while 4 (14.28%) others (i.e., Christian, Sikh) defaulted. As regards marital status, 34 (12.97%) married patients had history of treatment interruption, while 62 (15.19%) other patients (unmarried, widow, divorced) defaulted. On analyzing the effect of education and occupation level, 59 (22.69%) illiterate and 37 (9.0%) literate patients had history of noncompliance to treatment, respectively, while 58 (21%) laborers, 18 (12.32%) unemployed, 15 (8.33%) house wives and 5 (7.3%) employed defaulted,

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respectively. On analyzing the effect of smoking, 35 (16.27%) patients who were smokers defaulted, while 61 (13.4%) patients who were nonsmokers defaulted. Among 760 patients, 87 (16.35%) pulmonary, 7 (6.08%) extrapulmonary and 2 (8.69%) both pulmonary as well as extrapulmonary defaulted. Eighty-one of the patients interviewed had no comorbidities and the 15 patients had history of comorbidities (e.g., diabetes mellitus, hypertension). Among the 96 patients interviewed, 51 (53.12%) had defaulted treatment only once and Table 1. Factors Associated with Noncompliance to Treatment Factors

Total no. of patients (n = 670)

Noncompliance (%) (n = 96)

P value

<25

162

12 (7.40)

<0.05

25-45

380

69 (18.15)

>45

128

15 (11.71)

Male

460

78 (16.95)

Female

210

18 (8.5)

Hindu

512

76 (14.84)

Muslim

130

16 (12.30)

Others

4 (14.28)

Married

262

34 (12.97)

Others

408

62 (15.19)

Illiterate

260

59 (22.69)

Literate

410

37 (9.0)

Smokers

215

35 (16.27)

Ex or nonsmokers

455

61 (13.40)

Employed

5 (7.35)

Laborer

276

58 (21.01)

Housewives

180

15 (8.33)

Unemployed

146

18 (12.32)

Pulmonary

532

87 (16.35)

Extrapulmonary

115

7 (6.08)

Both

2 (8.69)

Age (in years)

Sex <0.05

Religion NS

Marital status NS

Education level <0.05

Smoking NS

Occupation <0.01

Type of disease <0.05

COMMUNITY MEDICINE Table 2. Reasons for Default (186) Reasons

No. of patient who interrupted treatment (n = 186)

Percentage (%)

Early improvement

24.19

High cost of treatment

16.12

ATT-induced side-effect

11.29

Alcoholism

10.75

No improvement or deterioration

8.6

Advised to stop treatment by physician

6.98

Unaware about long duration of treatment

6.45

Long distance travel to center

5.91

Lack of faith in treatment

4.30

Personal reasons

5.37

Family problem

3.22

2.15

Went to village Total

186

32 (33.3%) had interrupted treatment twice, while rest of the patients had interrupted treatment more than two times (i.e., three or four). Thus, the 96 patients included in the study had interrupted treatment 157 times. Among 157 treatment interruption episodes, 102 (64.96%) occurred when the prescribing source of ATT was private practitioner, 50 (31.84%) took place, while on treatment under DOTS therapy and remaining 5 (3.18%) interruption took place, while on non-DOTS treatment from a government source. Among the 96 patients interviewed, 38 (39.58%) stated only one reason for defaulting their treatment, 34 (35.4%) number of patients stated two reasons and 16 (16.66%) and 8 (8.33%) gave three and four reasons, respectively. Thus, 186 responses for treatment interruption were obtained from 96 patients. Maximum interruption were found to occur between second and third month of antitubercular treatment and 61 (64%) had defaulted treatment by the end of second month. On analyzing the reasons of default among defaulters (Table 2), early improvement following medication were found to be the most common reason 45 (24.19%). Next important reasons were high cost of treatment and ATT-induced side-effects (16.12% and 11.29%, respectively). Alcoholism, no relief of symptoms and stop treatment advised by physician

were other important reasons behind the default (10.75%, 8.6%, 6.98%, respectively). Some other reasons such as unaware about long duration of treatment, long distance travel to center, lack of faith and personal problems were also found to be important reasons for treatment interruption (6.45%, 5.91%, 4.30% and 5.37%, respectively). DISCUSSION Among the 670 TB patients, both indoor and outdoor during the study period, 96 (14.32%) had history of treatment interruption, of which 90.62% patients had pulmonary TB while 7.29% had extrapulmonary and 2.08% both pulmonary as well extrapulmonary TB. In the present study, out of 157 treatment interruption, 102 (64.96%) interruption occurred on private treatment, while 50 (31.84%) interruption took place on DOTS and remaining 3.18% treatment interruption occurred on non-DOTS government treatment. This emphasizes the need to provide DOTS to all as it is the only path to minimize treatment interruption. In our study, default to treatment was found to be more in the 25-45 years age group of patients (18.15%), while good compliance to treatment was observed among <25 years (7.40% default). It also observed in the study conducted by Chandrasekaran et al.5 Kumar et al6 observed maximum default in 35-44 years age group (25.4%), followed by the patients aged above 45 years (18.1%). Further comparatively more default in the 25-45 years of age group is mainly due to the subjects being economically productive members of the family, which led then away from the treatment rather than to stay away from work and hence earning. Another risk factor for default is sex, males defaulted (16.95%) more as compared to females (8.5%). More default among males is supposed to be due to their being on job, while in contrast DOTS center are present in most of the localities, so females can visit the center regularly. Similar result were also found in study of Jaggarajamma et al7 in which 24% and 8%, male and female defaulted, respectively. Another risk factor for default is education, illiterate defaulted more as compared to literate (22.69% vs 9.0%). Similar results were also found by Jaggarajamma et al.7 Person involved in various occupation, especially the laborers (21%) default more as compared to housewives, unemployed (students, retired) and employed. Mittal et al8 also observed more default among businessman (30.6%) and laborer (18.2%) class of patients. While few others did not find any association

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COMMUNITY MEDICINE between patientâ&#x20AC;&#x2122;s occupation and treatment default.5 The main reason behind the difference in compliance among person with occupation seems to be loss of wages and lack of time. In our study, 64% patients had interrupted treatment by the end of second month and other studies have also reported that maximum number of patients interrupted their treatment by the end of second or third month. Kaona et al9 reported up to 39% patients stopped taking their medication within the first 2-month of commencing treatment. Oliveira et al10 from Brazil also found that there were 43.3% defaulters in the first 2-month of treatment. The present study identified early improvement following medication as the most common reason of default. So, the most common reason was a feeling of early improvement as stated by 45 patients (24.19%). Kaona et al9 also found that 29.8% of TB patients interrupted treatment once they start feeling better. In other survey by Tissera at Colombo Chest Clinic, relief from symptoms (13%) emerged as the most common reason for treatment interruption.11 The next most common reason for default was high cost of treatment cited by 30 (16.12%) patients in our study. This was exclusively reported by patients who took ATT from outside the government sources (i.e., purchase their medicine from the market). It is thus necessary that all TB patients should be registered under DOTS for treatment, as to reduce the number of interruption occurring due to high cost of treatment. Third common reason for default was ATT-induced sideeffects, as stated by 21 (11.29%) patients in the present study. Wares et al12 found the most common reason for stopping treatment being the adverse effects of ATT. A study from Bihar and West Bengal reported that improvement in symptoms (40% and 56%), intolerance to drugs (20% and 9%) and other illness causes in some patients.13 Oâ&#x20AC;&#x2122;Boyle et al14 have also reported similar finding. Alcohol consumption is well-known risk for non-adherence.15 In the present study, 20 (10.75%) patients blamed alcoholism as the reason for their treatment interruption and 35 (16.27%) patients stated smoking as reason treatment default. Jakubowiak et al16 have found alcohol use to be the second commonest reason (30%) for treatment default. Sophia et al17 stated smoking is at times associated with alcoholism, it can also predict poor treatment adherence. Sixteen (8.6%) patients stopped treatment due to no improvement and 12 (6.45%) patients defaulted because they were unaware about long duration of treatment. Mittal et al8 also have similar finding 11 (5.91%) patients had default

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treatment due to long distance of travel to their DOTS center and 5.37% patients interrupted treatment due to domestic problem. In a study by Chatterjee et al13 the most common reason for default was distance from the treatment center. Mishra et al18 reported that the risk of nonadherence to treatment was significantly associated with cost of travel to the TB treatment facility. CONCLUSION There were many reasons often reported for discontinuation of treatment and maximum interruption were found in the end of second and third month. The default could be a result of inadequate pre-treatment health education and counseling and poor defaulter tracing mechanism resulting from overworked healthcare personnel, feeling better after medication for a while and socioeconomic factors including inadequate food and opportunity costs. Multiple factors influence default. Keeping in mind all the important reasons of default, initial counseling by the health personnel explaining the treatment plan before starting of the treatment, periodic motivation of patient, increased number of DOTS centers and prompt action to tackle any problem will enhance compliance. Adequate health education and information about TB has been demonstrated to be most effective when given as one to one counseling. Such measures are likely to increase the therapeutic success rate, impacting on global disease burden attributable to TB and thus multidrug-resistant TB can be decreased. REFERENCES 1. World Health Organization. Tuberculosis Control in the South-East Asia Region, Annual Report 2014. 2. Revised National TB Control Programme Annual Status Report. TB India, 2014. 3. World Health Organization. The origins of DOTS. Research for action: Understanding and controlling TB in India, 2000. 4. Coghlan A. Totally drug-resistant TB at large in India. New Scientist Health January 12, 2012. 5. Chandrasekaran V, Gopi PG, Subramani R, Thomas A, Jaggarajamma K, Narayanan PR. Default during the intensive phase of treatment under DOTS programme. Indian J Tuberc 2005;52:197-202. 6. Kumar M, Singh JV, Srivastava AK, Verma SK. Factors affecting the noncompliance in directly observed short course chemotherapy in Lucknow District. Indian J Community Med 2002;27(3):114-7.

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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

COMMUNITY MEDICINE 7. Jaggarajamma K, Sudha G, Chandrasekaran V, Nirupa C, Thomas A, Santha T, et al. Reasons for non-compliance among patients treated under Revised National Tuberculosis Control Programme (RNTCP), Tiruvallur district, South India. Indian J Tuberc 2007;54(3):130-5. 8. Mittal C, Gupta S. Noncompliance to DOTS: How it can be decreased. Indian J Community Med 2011;36(1):27-30. 9. Kaona FA, Tuba M, Siziya S, Sikaona L. An assessment of factors contributing to treatment adherence and knowledge of TB transmission among patients on TB treatment. BMC Public Health 2004;4:68. 10. Oliveira VL, da Cunha AJ, Alves R. Tuberculosis treatment default among Brazilian children. Int J Tuberc Lung Dis 2006;10(8):864-9. 11. Tissera WAA. Non-compliance with anti-tuberculous treatment at Colombo Chest Clinic. NTI Bulletin 2003;39:5-9. 12. Wares DF, Singh S, Acharya AK, Dangi R. Non-adherence to tuberculosis treatment in the eastern Tarai of Nepal. Int J Tuberc Lung Dis 2003;7(4):327-35. 13. Chatterjee P, Benerjee B, Dutt D, Pati RR, Mullick A. A comparative evaluation of factors and reasons for defaulting in tuberculosis treatment in the states of

West Bengal, Jharkhand and Arunachal Pradesh. Indian J Tuberc 2003;50:17-21. 14. O’Boyle SJ, Power JJ, Ibrahim MY, Watson JP. Factors affecting patient compliance with anti-tuberculosis chemotherapy using the directly observed treatment, short-course strategy (DOTS). Int J Tuberc Lung Dis 2002;6(4):307-12. 15. World Health Organization. Disease specific reviews. Adherence to long-term therapies: evidence for action. 2003:123-8. 16. Jakubowiak WM, Bogorodskaya EM, Borisov SE, Danilova ID, Lomakina OB, Kourbatova EV. Social support and incentives programme for patients with tuberculosis: experience from the Russian Federation. Int J Tuberc Lung Dis 2007;11(11):1210-5. 17. Sophia V, Balasangameswara VH, Jagannatha PS, Saroj VN, Kumar P. Default among tuberculosis patients treated under DOTS in Bangalore city: a research for solution. Indian J Tuberc 2003;50:185-95. 18. Mishra P, Hansen EH, Sabroe S, Kafle KK. Adherence is associated with the quality of professional-patient interaction in directly observed treatment short-course, DOTS. Patient Educ Couns 2006;63(1-2):29-37.

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Guide Stresses BCG for Bladder Maintenance after Induction Although there have been no major changes to the current version of the National Comprehensive Cancer Network (NCCN) guidelines for bladder cancer, several key existing recommendations have been strengthened, according to the chair of the guidelines committee. “The three (changes) that come most to mind are new adjuvant chemotherapy in the setting of muscleinvasive bladder cancer just prior to cystectomy; strengthening the recommendation for maintenance BCG (Bacillus Calmette-Guérin) for patients who receive induction BCG for nonmuscle invasive bladder cancer and strengthening, at least in our minds, the recommendation to combine chemotherapy with radiation for those undergoing bladder-preservation therapy for muscle-invasive bladder cancer,” Peter E Clark, MD, from the Vanderbilt-Ingram Cancer Center in Nashville, Tennessee, said in an interview with Medscape Medical News.

Valganciclovir may Curb CMV, EBV in Living Kidney Donors Antiviral prophylaxis with valganciclovir in living kidney donors may reduce transmission of cytomegalovirus (CMV) and Epstein-Barr virus (EBV), a pilot study suggests."Giving a kidney is one of the greatest gifts, and yet, some of the kidneys come with viruses like CMV or EBV that can have devastating effects in kidney transplant recipients," Dr Priya S Verghese, a pediatrician at the University of Minnesota, told Reuters Health by email.

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CRITICAL CARE

Current Trends of Sepsis in a Critical Care Unit of a Tertiary Hospital MINAL HARDE*, RAKESH BHADADE†, ROSEMARIE DESOUZA‡, KAVITA PATIL#

ABSTRACT Background: Sepsis is an increasingly common cause of morbidity and mortality, mainly in critically ill patients. Aim: To study patients with sepsis admitted in Medical Intensive Care Unit (MICU) with respect to clinical, biochemical, hematological parameters, mortality and factors influencing mortality. Settings and design: It was a prospective observational study done in the MICU of a tertiary care teaching public hospital. Methodology: Consecutive 100 patients admitted in MICU meeting, the criteria for sepsis were studied. Results: Out of 100 patients, mortality was 52%. Diabetes mellitus (27 patients) and hypertension (19 patients) were the most common comorbid illnesses. Lungs (28 patients), renal (20 patients) and abdomen (12 patients) were the commonest sources of infection. Central nervous system (CNS) 85.7% and renal 65% source of infection resulted in highest mortality. Significant predictors of mortality in patients with sepsis were multiorgan dysfunction syndrome (MODS) with septic shock, higher total leukocyte count (TLC), lower serum albumin, calcium (Ca2+), magnesium (Mg2+) levels, higher serum creatinine, hyperglycemia, severe acidosis, raised C-reactive protein, low glasgow coma scale (GCS) score and high APACHE II score. Conclusion: Patients with comorbid illness had 2.3 times higher mortality than those without it. Lungs, renal and abdomen were the common sources of infection. Serum albumin, Ca2+, Mg2+ were independent markers of sepsis. Predictors of mortality in patients with sepsis were degree of sepsis, glycemic control, GCS and APACHE II score.

Keywords: Sepsis, sepsis markers, mortality in sepsis

epsis is a major healthcare problems, with rising incidence and high mortality. Over 18 million cases of severe sepsis occur worldwide each year.1,2 Sepsis has been reported to be the most common cause of death in the noncoronary intensive care units.2

Different stages of sepsis form a continuum and as it progresses to septic shock, multiorgan dysfunction syndrome (MODS) sets in and patients often succumb despite aggressive therapy.3 Vital to the successful management of sepsis is ability to rapidly diagnose so as to prevent further progression. The trends of sepsis may differ significantly from place to place,

because of rising incidence, new etiologies, changing demographics and the increased use of more potent and broad-spectrum antibiotics, immunosuppressive agents. Hence to reduce mortality associated with sepsis, there is constant search of various parameters that can predict the onset and severity of sepsis and define prognosis. In the present study, we sought to assess the current trends of sepsis in our Medical Intensive Care Unit (MICU) with respect to causes, various biochemical, hematological and clinical parameters, indicators of organ dysfunction and correlation and prediction of mortality. MATERIAL AND METHODS

*Associate Professor Dept. of Anesthesiology †Assistant Professor ‡Professor #Registrar Dept. of Medicine Topiwala National Medical College and BYL Nair Ch. Hospital Mumbai, Maharashtra Address for correspondence Dr Minal Harde Flat no. 15, B-Wing, Anand Bhavan, Nair Hospital Mumbai Central, Mumbai - 11, Maharashtra E-mail: minalharde@gmail.com

It was a prospective observational study done in the MICU of a tertiary care teaching, public hospital. We aimed to study patients with sepsis admitted in MICU, with respect to clinical, biochemical, hematological parameters, mortality and factors influencing mortality. After Institute’s Ethics Committee approval, 100 consecutive patients with sepsis admitted in MICU in the 1 year study period meeting the criteria for sepsis as defined by American College of

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CRITICAL CARE Chest Physicians/Society of Critical Care Medicine Consensus Conference Committee, were enrolled in the study.4 Sepsis was defined as systemic response to infection manifested by two or more of the following conditions as a result of infection, T >38째C or <36 째C, HR >90 beats/min, RR >20 breaths/min or PaCO2 <32 mmHg, WBC count >12,000/mm3 or <4,000/mm3 or >10% immature forms.4 We excluded patients <18 years of age, post surgical sepsis and with hematological disorders from the study. Patients were assessed, investigated, and treated according to surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock, which is the existing practice.5,6 The management strategy was individualized for each patient appropriate

for the disease condition and was the sole prerogative of the treating physician. Appropriate antibiotics according to prevalent sensitivity patterns and changed as per culture sensitivity pattern.7 Main interventions done in MICU were central venous line insertion, endotracheal intubation, ventilatory support, blood and blood products transfusion and hemodialysis. After the valid written informed consent, the following data was recorded: Demographic and vital parameters, diagnosis, indication for admission to MICU, the Acute Physiology and Chronic Health Evaluation (APACHE) II score on admission, glasgow coma scale (GCS) score. Investigations namely complete blood count, liver function tests, renal function tests, serum electrolytes i.e., sodium, potassium, calcium,

Table 1. Characteristics of the Study Population-based on Parameter and Statistical Significance Parameter

Mortality (%)

Mortality in Nos.

P value

Most common comorbid illness Diabetes mellitus (DM)

74.1

Hypertension (HT)

78.9

Organ failure

Renal failure

Cardiac failure

Hepatic failure

20 out of 27 pts. DM 15 out of 19 with HT 84 out of 100 had at least one organ failure

0.007 0.009 1.46 x 1/105

Source of infection with highest mortality Central nervous system Renal source

85.7

6 out of 7 with CNS infections

13 out 20 with renal infections

MODS with septic shock

74.3

TLC count of >40,000/mm3 on Day 1/death

100

Severe acidosis (pH<7.15)

82.4

Serum albumin <2 mg/dL on day of discharge/death

26 out of 35 pts. with MODS & septic shock

0.255 0.00053 0.0007

14 out of 17 pts with acidosis

0.0071

9 out of 10 with hypoalbuminemia

0.021

Serum calcium <9 mg/dL

53.5

46 out of 86 pts. with hypocalcemia

0.033

Serum magnesium level <1.6 mg/dL

59.7

40 out of 67 pts. with hypocalcemia

0.047

Serum creatinine on Day 1

0.013

3-6 mg/dL

66.7

16 out of 24 pts.

>6 mg/dL

57.9

11 out of 19 pts.

Random blood glucose level 70-100 mg/dL

28.6

6 out of 21 pts.

>250 mg/dL

85.7

6 out of 7 pts.

0.088

C-reactive protein on Day 1 8-10 mg/dL

100

>10 mg/dL

71.4

5 out of 7 pts.

GCS <6 on Day 1

100

APACHE II >24 on Day 1

100

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0.0065 5.36E-08 1.24E-07

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Statistical Analysis Outcome of each patient was classified as either discharged or expired. Data thus obtained was tabulated and statistically analyzed, using multivariate logistic regression analysis of significance and Pearsonâ&#x20AC;&#x2122;s Chi-square test with the help of SPSS version 15. Using Medcalc software with type 1 error Alfa as 0.05 proportion and type 2 error beta as 0.2 proportion and taking null hypothesis value as 35% and proportion of mortality from past record in various study as 52%, minimum required sample was 64 for this study; however, we enrolled 100 patients over 1 year.

Comorbidities among the case DM HT

19 11

Chronic liver disease CRF/renal disease

10 8 7

COPD/Asthma 5

TB IHD

Hypothyroidism

3 0

Percentage (%)

Figure 1. Distribution of comorbid illnesses among the cases. Source of infection among the cases Pulmonary

Renal

Other

Abdominal

Skin and soft tissue CNS Pulmonary + Renal CNS + Skin and soft tissue Skin and soft tissue + Pulmonary Skin and soft tissue + Renal

RESULTS

17%

12% 10%

20%

7% 3% 28% 1% 1% 1%

Figure 2. Source of infection in patients with sepsis. Outcome by GCS among cases Expired 100

Survived

100

83.3

80 Percentage (%)

We enrolled 100 consecutive patients with sepsis; highest incidence of sepsis was seen in the age group of 30-50 years (37 patients). Male-to-female ratio was 60:40. Overall mortality was 52%. Females had a slightly higher mortality (57.5%) than males (48.3%). Diabetes mellitus (DM) (27 patients) and hypertension (HT) (19 patients) were the most common comorbid illnesses, chronic liver disease, chronic renal disease, pulmonary disease, ischemic heart disease (IHD) and hypothyroidism constituting the rest (Fig. 1). Lungs (28 patients), kidneys and urinary tract (20 patients) and abdomen (12 patients) were the commonest sources of infection in patients with sepsis (Fig. 2). Central nervous system (CNS) and renal source of infection resulted in highest mortality, 85.7% (6 out of 7 patients with CNS infections) and 65% (13 out of 20 patients with renal infections), respectively. Observation and statistical significance of various parameters in the study population is summarized in Table 1. Patients with DM had 3.7 times higher mortality (74.1%, 20 out of 27 patients with DM) than others and patients with HT had 4.5 times higher mortality (78.9%, 15 out of 19 patients with HT) than others. Renal failure occurred in 61% patients, cardiac failure in 36% and hepatic failure in 29% patients. Eighty-four patients had organ failure associated with sepsis (21 patients with 1, 30 patients with 2, 24 patients with 3 and 9 patients with 4 organ failures). Mean values of the following parameters were as follows: Serum

Others Comorbidities

phosphates, magnesium, random blood sugar, arterial blood gas (ABG), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), blood culture, need for ventilatory support, inotropic support, cardiac failure, hepatic failure, renal failure, duration of MICU stay till either the patient was discharged from MICU or expired.

73.7

70 60 50 40 30

10 0

26.3

16.7

20 0 3-6

6-9

9-12

12-15

GCS

Figure 3. Correlation between GCS and mortality.

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CRITICAL CARE GCS 1

APACHE II score 1

100

80 Sensitivity: 69.2 Specificity: 91.7 Criterion: ≤10

Sensitivity

Sensitivity: 59.6 Specificity: 95.8 Criterion: >21

0 0 0

100

100-Specificity

Figure 4. GCS ≤10 was predictive of higher mortality with sensitivity of 69.2% and specificity of 91.7% (area under the curve = 0.808). Outcome by APACHE II score among cases Expired Survived 100 100 100

100 90

76.3

Percentage (%)

80 69.2

70 60

52.4

50 40 30

47.6

30.8 23.7

20 10 0

6-12

12-18

18-24 24-30 APACHE II score

30-36

36-42

Figure 5. Correlation between APACHE II score and mortality.

calcium - 8.029, serum magnesium - 1.44, ESR - 71.67, CRP - 5.585 mg/L, GCS - 10.99, APACHE II score - 19.42. There was progressive increase in mortality, as GCS score decreased to <6 in patients with sepsis (Figs. 3 and 4). With APACHE II score >24 on Day 1 mortality was 100% (Figs. 5 and 6). DISCUSSION We studied consecutive 100 patients (60:40 males: females) of sepsis admitted in MICU of a tertiary care teaching public hospital. Overall mortality in our study was 52% and various published studies quoting a range of 28-50%.1,2,8-10 High incidence of sepsis was seen in the age group of 30-50 years (37 patients). The mortality

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Figure 6. APACHE II score >21 was predictive of higher mortality with sensitivity of 59.6% and specificity of 95.8% (area under the curve = 0.837).

was found to be progressively higher in older patients, age >70 years having 72.7% (8 out of 11 patients) mortality. This finding was consistent with the Sepsis Occurrence in Acutely ill Patients (SOAP) study.9 Seventy-three percent patients had some underlying comorbid illness along with sepsis. The high rate of associated comorbidity was due to large number of complicated referral cases coming to our hospital. The presence of comorbid illness significantly (2.3 times) increased mortality, with 57.5% in those with comorbid illness and 37% in those without comorbid illness. DM (27 patients) and HT (19 patients) were the most common comorbid illnesses among the patients with sepsis, with chronic liver disease, chronic renal disease, pulmonary disease, ischemic heart disease (IHD) and hypothyroidism constituting the rest. Patients with DM had 3.7 times higher mortality (74.1%) than others and patients with HT had 4.5 times higher mortality (78.9%) than others. This was statistically significant (p = 0.007, 0.009, respectively). This finding was consistent with the findings of other studies.10-12 Thus, even the common comorbid illnesses like DM and HT increases the mortality associated with sepsis. The most frequent organ dysfunctions were renal (61), respiratory (60), and circulatory (36) and 84 patients had organ failure associated with sepsis (21 with 1, 30 with 2, 24 with 3 and 9 with 4 organ failures). Significantly higher mortality was found in patients with more number of organ failures (p = 1.46 × 1/105). Lungs (28 patients), kidneys and urinary tract (20 patients) and abdomen (12 patients) were the commonest sources of infection in patients with sepsis. CNS (85.7%) and renal (65%) source

CRITICAL CARE of infection resulted in highest mortality. Guidet et al have found higher mortality with abdominal, respiratory or cardiovascular source of infection, whereas lower respiratory tract as focus of sepsis was associated with worse outcome in study by Degoricija et al.8,11 MODS with septic shock (35 patients) had highest mortality of 74.3%, followed by MODS (28 patients) 60.7% and severe sepsis 30%. Degree of sepsis was found to have significant correlation with mortality, with higher degree of sepsis resulting into higher mortality (p = 0.00053). This correlation of mortality with degree of sepsis echoed in many studies.1,3,12 Mortality was significantly high in patients who had total leukocyte count (TLC) either <4,000 or >40,000 on Day 1 or progressively higher TLC (p = 0.0007). A decrease in serum albumin concentrations is mediated by alterations in vascular permeability and redistribution; patients develop a capillary leak syndrome and serum albumin concentration decreases.13 In our study, mortality was significantly high (88.9%) among patients who had lowest serum albumin (<2 mg/dL) and patients who had persistently low serum albumin in spite of treatment (p = 0.021). There is a strong correlation between the serum concentration of albumin and increased mortality, morbidity and prolonged ICU or hospital stay in patients with sepsis.13-15 In the present study, mortality was significantly higher (56.5%) in patients who had lower serum calcium (<9 mg/dL) (p = 0.033). Studies have shown that hypocalcemia, especially ionized hypocalcemia is common in critically ill patients, including patients with sepsis and it is an independent adverse prognostic factor for mortality.16,17 Higher serum creatinine value on Day 1 was significantly associated with mortality (p = 0.013). Patients with creatinine of 3-6 mg/dL had mortality of 66.7% and patients with creatinine >6 mg/dL had mortality of 57.9%. Studies have mentioned mortality of 60-80% among patients with sepsis and acute renal failure (ARF).14,18 The mechanism of hyperglycemia in sepsis patients is multifactorial and there is association between glucose variability and mortality.19-21 Lowest mortality (28.6%) was found among patients who had blood glucose levels between 70-100 mg/dL. Progressively higher mortality was found among patients with persistent hyperglycemia as well as hypoglycemia in spite of treatment. Although mortality in our study was lowest with tight control (70-100 mg/dL) but is difficult to maintain. Various authors have suggested a target blood glucose level of 140-180 mg/dL in septic patients instead of tight glycemic control as it puts

septic patients at increased risk of hypoglycemia.19-21 High mortality was found among patients with severe acidosis (pH <7.15) and persistent acidosis in spite of treatment (82.4%) (p = 0.0071). Gutierrez et al have shown that lactic acidosis in sepsis patients on Day 1 is an independent adverse prognostic marker for mortality.22 Although serum lactate level is a better marker, we have considered pH as a surrogate marker for acidosis due to nonavailability of serum lactate determination in our hospital. Esen et al had mentioned hypomagnesemia is associated with increased morbidity and mortality in ICU patients with sepsis.23 In our study, mortality was significantly higher (59.7%, 40 patients expired out of 67) among patients with low serum magnesium levels (<1.6 mg/dL) (p = 0.047). ESR being a marker of ongoing inflammation is expected to rise in patients with sepsis. Higher mortality was found among patients with higher ESR. Patients with ESR of 50-100 had mortality of 65.5% whereas patients with ESR of >100 had mortality of 59.4%. However, this was not statistically significant. Circulating levels of CRP have been shown as useful indicator of sepsis in ICU patients and its increasing concentrations is correlated with increased risk of organ failure and death.24 In the current study, patients who had CRP between 8 to 10 mg/L on Day 1 had significantly high mortality (p = 0.0065). Highest mortality (100%) was found among patients with lowest GCS score (3 to 6) (p = 5.36 E-08). Also, there was progressive increase in mortality as GCS value decreases in patients with sepsis. On statistical analysis, GCS value â&#x2030;¤10 was predictive of high mortality with sensitivity of 69.2% and specificity of 91.7% (area under the curve = 0.808) (Fig. 3). Various studies have found that GCS on admission in sepsis patients is an independent predictor of mortality.25 Higher mortality was found among patients with progressively higher APACHE II score on Day 1 (p = 1.24 Ă&#x2014; 1/107). On statistical analysis, APACHE II score >21 was predictive of high mortality with sensitivity of 59.6% and specificity of 95.8% (area under the curve = 0.837) (Fig. 4). APACHE II is the most appropriate model for comparisons of mortality rates in different ICUs and higher score correlates with poor prognosis in patients with sepsis.25,26 Limitation of this study was it may underestimate the incidence of sepsis in population as it was cohort study limited to ICU patients. The trends of sepsis may differ considerably from place-to-place, which warrants multicentric further studies. We could not measure lactate levels because of nonavailability.

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CRITICAL CARE In conclusion, from the experience of the present study, we put forth the following: Mortality in ICU patients with sepsis was 52%. Patients with comorbid illness had 2.3 times higher mortality than those without it, with DM and HT being the most common comorbid illnesses. As the number of organ failure increased so did the mortality. Lungs, renal and abdomen were the common sources of infection. CNS and renal source of infection, MODS with septic shock lead to highest mortality. Serum albumin, Ca2+ and Mg2+ were independent markers of sepsis. Persistent ARF and persistent acidosis in spite of treatment were associated with significant mortality. Higher mortality was found in patients with hyperglycemia as well as hypoglycemia, hence tolerable glycemic control should be the policy in medical ICU. GCS and APACHE II score on Day 1 were found to be good predictors of mortality in patients with sepsis. REFERENCES 1. Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med 2001;29(7):1303-10. 2. Mayr FB, Yende S, Angus DC. Epidemiology of severe sepsis. Virulence 2014;5(1):4-11. 3. Munford RS. Severe sepsis and septic shock. In: Harrison’s Principles of Internal Medicine. 17th edition, Fauci AS, Kasper DL (Eds.), McGraw-Hill: New York 2008:p.1695-702. 4. Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest 1992;101(6):1644-55. 5. Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med 2013;39(2):165-228. 6. Levy MM, Rhodes A, Phillips GS, Townsend SR, Schorr CA, Beale R, et al. Surviving Sepsis Campaign: association between performance metrics and outcomes in a 7.5-year study. Intensive Care Med 2014;40(11):1623-33. 7. Ferrer R, Martin-Loeches I, Phillips G, Osborn TM, Townsend S, Dellinger RP, et al. Empiric antibiotic treatment reduces mortality in severe sepsis and septic shock from the first hour: results from a guideline-based performance improvement program. Crit Care Med 2014;42(8):1749-55. 8. Degoricija V, Sharma M, Legac A, Gradiser M, Sefer S, Vucicević Z. Survival analysis of 314 episodes of sepsis in medical intensive care unit in university hospital: impact of intensive care unit performance and antimicrobial therapy. Croat Med J 2006;47(3):385-97.

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9. Vincent JL, Sakr Y, Sprung CL, Ranieri VM, Reinhart K, Gerlach H, et al. Sepsis in European intensive care units: results of the SOAP study. Crit Care Med 2006;34(2):344-53. 10. Blanco J, Muriel-Bombín A, Sagredo V, Taboada F, Gandía F, Tamayo L, et al. Incidence, organ dysfunction and mortality in severe sepsis: a Spanish multicentre study. Crit Care 2008;12(6):R158. 11. Guidet B, Aegerter P, Gauzit R, Meshaka P, Dreyfuss D. Incidence and impact of organ dysfunctions associated with sepsis. Chest 2005;127(3):942-51. 12. Angus DC, Wax RS. Epidemiology of sepsis: an update. Crit Care Med 2001;29(7 Suppl):S109-16. 13. Margarson MP, Soni NC. Changes in serum albumin concentration and volume expanding effects following a bolus of albumin 20% in septic patients. Br J Anaesth 2004;92(6):821-6. 14. Trimarchi H, Nozieres C, Cámpolo Girard V, Lombi F, Smith C, Young P, et al. Acute kidney injury in severe sepsis. Medicina (B Aires) 2009;69(3):321-6. 15. Balakrishnan I, Crook P, Morris R, Gillespie SH. Early predictors of mortality in pneumococcal bacteremia. J Infect 2000;40(3):256-61. 16. Forsythe RM, Wessel CB, Billiar TR, Angus DC, Rosengart MR. Parenteral calcium for intensive care unit patients. Cochrane Database Syst Rev 2008;(4):CD006163. 17. Zaloga GP. Ionized hypocalcemia during sepsis. Crit Care Med 2000;28(1):266-8. 18. Schrier RW, Wang W. Acute renal failure and sepsis. N Engl J Med 2004;351(2):159-69. 19. Ali NA, O’Brien JM Jr, Dungan K, Phillips G, Marsh CB, Lemeshow S, et al. Glucose variability and mortality in patients with sepsis. Crit Care Med 2008;36(8):2316-21 20. Hirasawa H, Oda S, Nakamura M. Blood glucose control in patients with severe sepsis and septic shock. World J Gastroenterol 2009;15(33):4132-6. 21. NICE-SUGAR Study Investigators, Finfer S, Chittock DR, Su SY, Blair D, Foster D, Dhingra V, et al. Intensive versus conventional glucose control in critically ill patients. N Engl J Med 2009;360(13):1283-97. 22. Gutierrez G, Wulf ME. Lactic acidosis in sepsis: another commentary. Crit Care Med 2005;33(10):2420-2. 23. Esen F, Telci L. Magnesium in the ICU: Sine qua non. Intensive Care Medicine Annual Update 2008;12:491-501. 24. Bastos PG, Sun X, Wagner DP, Wu AW, Knaus WA. Glasgow Coma Scale score in the evaluation of outcome in the intensive care unit: findings from the Acute Physiology and Chronic Health Evaluation III study. Crit Care Med 1993;21(10):1459-65. 25. Bossink AW, Groeneveld J, Hack CE, Thijs LG. Prediction of mortality in febrile medical patients: How useful are systemic inflammatory response syndrome and sepsis criteria? Chest 1998;113(6):1533-41. 26. Livingston BM, MacKirdy FN, Howie JC, Jones R, Norrie JD. Assessment of the performance of five intensive care scoring models within a large Scottish database. Crit Care Med 2000;28(6):1820-7.

DRUGS

Comparative Efficacy and Tolerability of 2.5 mg S-amlodipine and 5 mg Amlodipine on Switchover from Amlodipine to S-amlodipine BHARGAV M VYASA*, ARUN MASEEH*, DEVANG SHAH†

ABSTRACT Objectives: To evaluate the tolerability and efficacy of S-amlodipine 2.5 mg with amlodipine 5 mg upon switching the patients from amlodipine to S-amlodipine for treatment of hypertension. Methods: This study was a prospective, open-label, randomized, parallel-group and comparative study. Two hundred outdoor patients (98 women and 102 men) with mean age 51.32 ± 11.20 years with mild-to-moderate hypertension became a part of this study after taking informed consent from them. All the patients enrolled were already taking treatment with amlodipine 5 mg o.d. One hundred patients were continued on amlodipine 5 mg o.d. and evaluated for a period of 8 weeks, whereas the remaining 100 were switched on to S-amlodipine 2.5 mg o.d. and evaluated for 8 weeks. Student’s t-test was used for statistical analysis. Results: The mean systolic blood pressure (SBP) at baseline was 138.24 ± 5.81 as compared to 133.06 ± 3.95 (p < 0.05) and mean diastolic blood pressure (DBP) at baseline was 90.64 ± 3.60 as compared to 86.97 ± 2.62 (p = 0.15) at the end of 8 weeks in amlodipine group. The mean SBP at baseline was 133.16 ± 6.04 as compared to 128.2 ± 3.99 (p < 0.05) and mean DBP at baseline was 88.68 ± 3.46 as compared to 86.16 ± 2.42 (p = 0.15) at the end of 8 weeks in S-amlodipine group. Although, both the treatment groups showed significant reduction in the mean DBP and SBP, the DBP reduction was not statistically significant between the two treatment groups. Conclusions: S-amlodipine 2.5 mg was equivalent in its efficacy with better tolerability when switched from amlodipine 5 mg for treatment of hypertension. S-amlodipine may be an appropriate substitute for patients intolerant to amlodipine.

Keywords: Amlodipine, S-amlodipine, switch

alcium channel blockers (CCBs) are the main stay of antihypertensive therapy. Amlodipine, being a dihydropyridine possesses good efficacy in terms of lowering of blood pressure (BP) in vasculatures. But studies suggest that racemic mixture of amlodipine causes more arteriodilation compared to veinodilation, which may lead to side-effects such as peripheral edema. S-amlodipine, being a pure isomer of racemic amlodipine, claims to have superiority in terms of tolerability in management of hypertension. Structurally, amlodipine is a chiral calcium antagonist which is a racemic mixture of R-enantiomer and S-enantiomer in similar

*Dept. of Pharmacology JJT University, Vidyanagari, Rajasthan †Consulting Physician and Cardiologist Sanjivani Hospital, Ahmedabad, Gujarat Address for correspondence Bhargav M Vyasa D/301, Ashutosh Apartments, B/h St. Xaviers’ Loyola School Naranpura, Ahmedabad - 380 013, Gujarat E-mail: bmvyasa_1986@yahoo.co.in

ratio. S-amlodipine, also known as levamlodipine or levo-amlodipine, is a pharmacologically active monomer of amlodipine. Studies which evaluated the receptor binding and configuration analysis came to the conclusion that out of the two isomers only S-enantiomer and not the R-enantiomer binds and blocks L-type of voltage-gated calcium channels.1 This calcium antagonistic action resides with S-amlodipine only. Hence, S-amlodipine is 1,000-folds more active than R-amlodipine. Studies in rats with condition of spontaneous high BP suggest that R-amlodipine does not lower the BP at all while S-amlodipine lowers the BP effectively. And selective usage of S-amlodipine alone will confer extra longer duration of action than the mixture. S-amlodipine augments pharmacokinetic advantages of amlodipine.2 A systemic plasma clearance of isomers may play a crucial role in observation of enantioselectivity of amlodipine.3 Use of isolated S-amlodipine, the pharmacologically active isomer of amlodipine instead of the racemic mixture, could be of immense benefit as the required dose and systemic

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DRUGS toxicity can be reduced. In the Indian clinical scenario, many patients complain of side-effects with relation to daily use of amlodipine. We need to evaluate whether these patients will be benefited if they are switched over to S-amlodipine. Hence, the current study was conducted to compare the efficacy and tolerability of S-amlodipine with that of the racemic mixture of amlodipine in patients with hypertension. The prime intention was to compare the efficacy of S-amlodipine 2.5 mg once a day with amlodipine 5 mg once a day for treatment of hypertension upon switching patients from amlodipine to S-amlodipine. Secondary objective was to assess the tolerability of the drug S-amlodipine on switching patients from amlodipine. METHODS A prospective, open-label, randomized, parallel and comparative study in 200 patients, who had hypertension and were already on treatment with amlodipine 5 mg. Amlodipine was replaced by S-amlodipine if BP was controlled by amlodipine. If BP was not controlled by amlodipine and/or combination then S-amlodipine was replaced by amlodipine and dose escalation was done until target BP was achieved. If patient was on a combination with amlodipine e.g., amlodipine (5 mg) + Drug X (YY mg), amlodipine (5 mg) was replaced with S-amlodipine (2.5 mg) + Drug X (YY mg). Patients were divided randomly into two groups. Group A (100 patients) was prescribed amlodipine 5 mg once-daily and Group B (100 patients) was prescribed S-amlodipine 2.5 mg once-daily. Outdoor patients who had been on treatment for mildto-moderate hypertension with drug amlodipine 5 mg once a day were enrolled in this study. The study was conducted in accordance with the ethical principles of the current Declaration of Helsinki. Subjects signed informed consent prior to the study enrollment. And due permission for conduction of these experiments was obtained, from the independent ethics committee. Primary outcome measure was to evaluate the efficacy of drug S-amlodipine 2.5 mg once a day with drug amlodipine 5 mg once a day upon switching the patients who had been on drug amlodipine 5 mg to S-amlodipine 2.5 mg for the treatment of hypertension. Secondary outcome measure was to check the intensity of treatment emergent adverse event (TEAE) and tolerability of S-amlodipine.

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Indian Journal of Clinical Practice, Vol. 25, No. 11, April 2015

Inclusion Criteria ÂÂ Age: 18-75 years of males and females both inclusive at screening. ÂÂ Body mass index (BMI) between the range of 18 and 35 kg/m2. ÂÂ At least 40 kg of body weight at the time of screening and before enrollment. ÂÂ Male or female patients who were already on treatment with amlodipine 5 mg for stage 1 and/or stage 2 hypertension. Exclusion Criteria ÂÂ Hypersensitivity. ÂÂ Secondary hypertension. ÂÂ Episodic hypertensive emergency within 6 months prior to enrollment. ÂÂ Previous history of hypotension, syncope, fainting or collapse. ÂÂ Severe coronary artery disease and history of percutaneous coronary intervention or coronary artery bypass graft or myocardial infarction within last 12 months prior to enrollment. ÂÂ Symptoms of angina within 6 months prior to enrollment. Demographic characteristics of patients at the start of treatment are shown in Table 1. RESULTS

Efficacy of Evaluation In amlodipine (5 mg) group: The average systolic BP (SBP) (in mmHg) at baseline was 138.24 ± 5.81 as compared to 133.06 ± 3.95 at the end of 8 weeks. The average diastolic BP (DBP) (in mmHg) at baseline was 90.64 ± 3.596 as compared to 86.97 ± 2.62 at the end of 8 weeks. In S-amlodipine (2.5 mg): The average SBP (in mmHg) at baseline was 133.16 ± 6.04 as compared to 128.2 ± 3.99 at the end of 8 weeks. The average DBP (in mmHg) at baseline was 88.68 ± 3.46 as compared to 86.16 ± 2.42 at the end of 8 weeks. Although, both the treatment groups showed significant reduction in the average SBP and DBP, the DBP reduction was not found to be statistically significant between two treatment groups (Table 2).

Subgroup Efficacy Analysis: On the Basis of Age The study population were divided and evaluated on the basis of age i.e., younger patients (age ≤55 years) and elder patients (age >55 years).

DRUGS Younger Patients (Age ≤55 Years) In amlodipine (5 mg) group: The average SBP at baseline was 138.20 as compared to 132.80 at the end of 8 weeks. The average DBP at baseline was 91.67 as compared to 87.20 at the end of 8 weeks. Table 1. Demographic Characteristics of Patients at the Start of Treatment

Elder Patients (Age >55 Years)

Patients on amlodipine (n = 100)

Patients on S-amlodipine (n = 100)

Male

Female

Min

Max

Mean

51.78

51.32

11.14

11.20

Min

153

152

Max

176

Mean

163.54

161.62

138

5.11

4.81

136

Gender

Age

Height (cm)

In amlodipine (5 mg) group: The average SBP at baseline was 138.30 as compared to 133.40 at the end of 8 weeks. The average DBP at baseline was 89.10 as compared to 86.50 at the end of 8 weeks. In S-amlodipine (2.5 mg) group: The average SBP at baseline was 133.79 as compared to 129.05 at the end of 8 weeks. The average DBP at baseline was 89.68 as compared to 86.84 at the end of 8 weeks. Both the treatment groups showed significant reduction in the average SBP and DBP after 8 weeks of treatment (Figs. 1 and 2).

140 Mean SBP (mmHg)

Parameters

In S-amlodipine (2.5 mg) group: The average SBP at baseline was 132.77 as compared to 127.68 at the end of 8 weeks. The average DBP at baseline was 88.06 as compared to 85.74 at the end of 8 weeks. Both the treatment groups showed significant reduction in the average SBP and DBP after 8 weeks of treatment (Table 3).

Weight (kg) Min

Max

Mean

64.3

66.22

5.30

5.34

Min

18.42

20.8

Max

29.05

31.62

Mean

24.06

25.33

2.15

2.13

138.30 136.30

132

130.42

130

129.05

128 126 124

BMI

133.40

133.79

134

AM SAM

Baseline

After 4 weeks

After 8 weeks

138.30 133.79

136.30 130.42

133.40 129.05

Figure 1. Reduction in average SBP in elder patients after 8 weeks (age >55 years). AM = Amlodipine; SAM = S-amlodipine.

Table 2. Decrease in Mean SBP and DBP Amlodipine (n = 100)

S-amlodipine (n = 100)

Baseline

After 4 weeks

After 8 weeks

Baseline

After 4 weeks

After 8 weeks

138.24 ± 5.81

135.56 ± 4.72

133.06 ± 3.95

133.16 ± 6.04

130.16 ± 4.88

128.2 ± 3.99

(p < 0.05)

88.8 ± 2.97

86.97 ± 2.62

87.32 ± 2.82

86.16 ± 2.42

(p < 0.05)

(p = NS)

(p < 0.05)

(p = NS)

75.4 ± 2.85

73.95 ± 2.80

73.76 ± 2.94

71.76 ± 2.73

SBP Mean ± SD DBP Mean ± SD

90.64 ± 3.60

88.68 ± 3.46

Pulse Mean ± SD

76.8 ± 3.12

74.84 ± 3.21

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DRUGS On the Basis of BMI The study population were divided and evaluated on the basis of BMI determined by the World Health Organization (WHO) criteria as normal and overweight/obese category. The BMI of normal category was <25 kg/m2, whereas the BMI for overweight/obese category was ≥25 kg/m2.

Normal BMI (<25 kg/m2) In amlodipine (5 mg) group: The average SBP at baseline was 138.76 ± 6.98 as compared to 133.12 ± 4.06 at the end of 8 weeks. The average DBP at baseline was

Mean DBP (mmHg)

90 89 88

88.00 87.20

86.84 86.50

86 85 84 AM SAM

In S-amlodipine (2.5 mg) group: The average SBP at baseline was 132.61 ± 3.97 as compared to 128.61 ± 1.99 at the end of 8 weeks. The average DBP at baseline was 88.87 ± 2.99 as compared to 85.83 ± 1.65 at the end of 8 weeks. Both the treatment groups showed significant reduction in the average SBP and DBP after 8 weeks of treatment (Table 4). Overweight and Obese BMI (≥25 kg/m2) In amlodipine (5 mg) group: The average SBP at baseline was 137.13 ± 3.08 as compared to 132.88 ± 2.82 at the end of 8 weeks. The average DBP at baseline was 90 ± 4.64 as compared to 87.375 ± 3.79 at the end of 8 weeks.

89.68 89.10

90.94 ± 3.95 as compared to 86.71 ± 3.02 at the end of 8 weeks.

Baseline

After 4 weeks

After 8 weeks

89.10 89.68

87.20 88.00

86.50 86.84

Figure 2. Reduction in average DBP in elder patients after 8 weeks (age >55 years).

In S-amlodipine (2.5 mg) group: The average SBP at baseline was 133.63 ± 4.22 as compared to 127.85 ± 2.43 at the end of 8 weeks. The average DBP at baseline was 88.52 ± 1.85 as compared to 86.44 ± 1.36 at the end of 8 weeks. Both the treatment groups showed significant reduction in the average SBP after 8 weeks of treatment, whereas reduction in DBP in amlodipine group was nonsignificant after 8 weeks as compared to significant reduction in S-amlodipine group (Figs. 3 and 4).

Table 3. Reduction in Average SBP and DBP in Younger Patients (Age ≤55 Years) Reduction in BP on the basis of age (≤55 years), n = 122 Amlodipine (n = 60)

S-amlodipine (n = 62)

Baseline

After 4 weeks

After 8 weeks

Baseline

After 4 weeks

After 8 weeks

138.2 ± 5.94

135.07 ± 4.12 (p < 0.05)

132.8 ± 2.51 (p < 0.05)

132.77 ± 3.86

130 ± 2.38 (p < 0.05)

127.68 ± 1.91 (p < 0.05)

91.67 ± 3.97

89.87 ± 3.50 (p < 0.05)

87.2 ± 3.25 (p < 0.05)

88.06 ± 1.79

86.90 ± 1.67 (p < 0.05)

85.74 ± 1.32 (p < 0.05)

SBP Mean ± SD DBP Mean ± SD

Table 4. Reduction in Average SBP and DBP in Patients with Normal BMI (<25 kg/m2) Reduction in BP based on BMI (normal BMI <25 kg/m2), n = 114 Amlodipine (n = 68)

S-amlodipine (n = 46)

Baseline

After 8 weeks

Baseline

After 8 weeks

138.76 ± 6.98

133.12 ± 4.06 (p < 0.05)

132.61 + 3.97

128.61 ± 1.99 (p < 0.05)

90.94 ± 3.95

86.71 ± 3.02 (p < 0.05)

88.87 ± 2.99

85.83 ± 1.65 (p < 0.05)

SBP Mean ± SD DBP Mean ± SD

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DRUGS Safety Evaluation

Reduction in SBP based on BMI (Overweight and Obese BMI ≥25 kg/m2), n = 86 (AM - 32, SAM - 54)

Pedal edema by treatment in both groups as shown in Table 5. Occurrence of pedal edema was 26% in amlodipine group, whereas 12% in S-amlodipine group. However, severity of edema was mild in nature in both the groups, which subsided on discontinuation of the drug.

138 Mean SBP (mmHg)

136

137.13

134 132

133.63

132.88

130 128

DISCUSSION

127.85

126 124 122

SAM

137.13

133.63

SBP after 8 weeks 132.88

127.85

SBP baseline

Figure 3. Reduction in average SBP in patients with overweight and obese BMI (≥25 kg/m2).

Reduction in SBP based on BMI (Overweight and Obese BMI ≥25 kg/m2), n = 86 (AM - 32, SAM - 54) 91 Mean DBP (mmHg)

90.00

89 88 87

88.52 87.38 86.54

86 85 84

SAM

DBP baseline

90.00

88.52

DBP after 8 weeks

87.33

86.44

Figure 4. Reduction in average DBP in patients with overweight and obese BMI (≥25 kg/m2).

Table 5. Incidence of Adverse Effects Severity

Amlodipine (n = 100)

S-amlodipine (n = 100)

Mild

Moderate

Severe

Amlodipine is a well-proven therapy for mild-tomoderate hypertension. This study was aimed to determine the effectiveness of S-amlodipine compared to conventional drug amlodipine for treatment of hypertension. The amlodipine dose used in the present study was a therapeutic dose of 5 mg and a corresponding half strength of S-amlodipine was used. In both the treatment groups, there was a significant reduction in the BP, although the difference between two treatment groups was not found to be statistically significant. Treatment with amlodipine is usually associated with side-effect of pedal edema. It was observed in the current study that S-amlodipine group reported less incidence of pedal edema compared to amlodipine group over a period of 8 weeks upon switching from amlodipine. Hence, based on the above findings, it may be concluded that 2.5 mg daily dose of S-amlodipine has a better effect on BP of the patients with lesser incidence of side-effects. Further, long-term studies may confirm the better safety profile of S-amlodipine as compared to amlodipine. REFERENCES 1. Goldmann S, Stoltefuss J, Born L. Determination of the absolute configuration of the active amlodipine enantiomer as (-)-S: a correction. J Med Chem 1992;35(18):3341-4. 2. Chirality today and tomorrow’s way of treatment. Available from: http://www.chiralemcure.com/docs/ Chirality%20Booklet.pdf. Accessed on 14th April, 2013. 3. Laufen H, Leitold M. Enantioselective disposition of oral amlodipine in healthy volunteers. Chirality 1994;6(7):531-6.

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Indian Journal of Clinical Practice, Vol. 25, No. 11, April 2015

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INTERNAL MEDICINE

NMDA Encephalitis - Rare Autoimmune Encephalitis ZALAK MALAV GADANI*, MALAV KRUSHNAKANT GADANI†

ABSTRACT N-methyl-d-aspartate (NMDA) encephalitis is a rare, lethal but highly curable form of autoimmune encephalitis. This syndrome has been predominantly described in young females with a constellation of symptoms, including personality changes, autonomic dysfunction and neurologic decompensation. It is commonly associated with mature ovarian teratomas. It is caused by formation of systemic antibodies against NR1 subunit of NMDA receptors. I describe a case report with a classic presentation of antiNMDA receptor encephalitis in a young patient with no identifiable tumor, who had behavioral abnormalities for which she consulted psychiatrist. Her behavioral abnormalities failed to improve with antipsychotics, in fact symptoms were progressive in nature. Subsequently, she was diagnosed to have NMDA encephalitis.

Keywords: NMDA encephalitis, autoimmune encephalitis, ovarian teratomas, behavioral abnormalities

he syndrome of anti-NMDAR (N-methyl-daspartate receptor) encephalitis was first characterized in 2007.1 Initially, described as a paraneoplastic syndrome affecting young women with ovarian teratomas. In male, <5% of cases are associated with teratoma, while in female, 20-57% cases are associated with teratoma. Anti-NMDAR encephalitis is associated with mediastinal teratomas, sex-cord stromal tumors, smallcell lung cancer and testicular teratomas.2 Antibodies formed against neoplastic cells cross-react with native NMDARs leading to destruction or down-regulation.2 NMDARs are found throughout the central nervous system (CNS), mediating a role in synaptic transmission and plasticity. NR1 and NR2 subtypes bind glycine and glutamate, respectively. NR1 and NR2 heteromers predominate within the hippocampus, with less intense reactivity described in the forebrain, basal ganglia, spinal cord and cerebellum.2,3 Serum concentration of autoantibodies is 10 times more than cerebrospinal fluid (CSF) suggestive of systemic

*Assistant Professor AMC MET Medical College, Maninagar, Ahmedabad, Gujarat †Dept. of Neurology Dr Jivaraj Mehta Hospital, Ahmedabad, Gujarat Address for correspondence Dr Zalak Malav Gadani E/16, Siddhidarshan Apartment, Opp. Seema Hall Anand Nagar Road, Satellite, Ahmedabad - 380 015, Gujarat E-mail: drzalak83@gmail.com

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production of antibodies and diffusion through disrupted blood-brain barrier. High incidence is found in patients with age <30 years. Median age of affection is 21 years. Women affected more commonly than men. Clinical features are divided into prodromal, initial stage and progressive stage. ÂÂ

Prodromal symptoms include headache, upper respiratory symptoms, flu-like symptoms. Prodromal stage lasts for weeks to months.

ÂÂ

Initial stage consists of behavioral changes in form of increased agitation, paranoia, psychosis, violent behavior. Other manifestations include seizure, rhythmic movements of lips and mouth with leg and hand movements, impaired cognition, memory deficit, speech problems.

ÂÂ

Progressive stage consists of autonomic dysfunction, hypoventilation, cerebellar ataxia, hemiparesis, catatonia and loss of consciousness.

Treatment includes surgical removal of ovarian teratoma or other tumors and prompt and aggressive immunotherapy. Some patients appear to respond rapidly to intravenous immunoglobulin and methylprednisolone. Other therapeutic options include cyclophosphamide, anti-CD20 monoclonal antibodies (rituximab) and plasma exchange, mainly in more severe/persistent cases.4,5 The outcome improves following removal of a teratoma, if present, in combination with immunotherapy. Relapses have been noted in approximately 25% of young patients and seem to occur while tapering immunotherapy, as well as in cases without teratoma in those with high titers of anti-NMDAR antibodies in the CSF.6 Follow-up

INTERNAL MEDICINE evaluation should include neurologic and psychiatric examinations, ultrasound and magnetic resonance imaging (MRI) of the pelvis and abdomen, and measurements of the levels of anti-NMDAR antibodies’ titers in serum and CSF. CASE REPORT A 16-year-old female patient had behavioral abnormalities in form of increased agitation, violent behavior, not taking food properly since last 2-3 months. She had also history of episodic events of not recognizing her parents, which lasted for 5-10 minutes. Patient had past history of enteric fever 1 year back. She consulted psychiatrist and antipsychotic drugs were started. Irritability subsided after antipsychotics, but new symptoms in form of tremors and stiffness of hands and episodes of tonic posturing with unresponsiveness and up-rolling of eyeball emerged. For that, patient was advised to take neurophysician opinion. On examination, patient was vitally stable. CNS examination was suggestive of bradykinesia and postural tremors. Rest of the CNS examination and other system examinations were insignificant. Patient was advised complete blood count (CBC), erythrocyte sedimentation rate (ESR), creatinine, serum glutamic pyruvic transaminase (SGPT), serum ammonia level, electroencephalogram (EEG), creatinine phosphokinase (CPK) total, human immunodeficiency virus (HIV), antineutrophilic antibody (ANA), antiphospholipid antibody (APLA), lupus anticoagulants, thyroid function test, antithyroid antibodies, CSF examination, NMDA antibodies, voltage-gated potassium channel (VGKC) antibodies, MRI brain and computed tomography (CT) abdomen and pelvis for ovarian teratoma. Her CBC, ESR, SGPT, creatinine, serum ammonia level, CPK total, thyroid function tests were within normal limits. ANA, APLA, lupus anticoagulant were negative. CSF examination and EEG were within normal limits. MRI brain was suggestive of mild asymmetrical prominence of temporal horn of right lateral ventricle. Anti-NMDAR antibody was positive. CT scan of thorax, abdomen and pelvis was negative for tumor. Patient was treated with short-course of steroid pulse therapy (1g of methylprednisolone for 5 days). Patient gradually improved. DISCUSSION Anti-NMDAR encephalitis is an under-recognized syndrome. This clinical case presentation with symptoms resembling acute psychosis is consistent with

the diagnosis of anti-NMDAR encephalitis. In above described case report, clinical impression was subacute encephalopathy. Differential diagnosis includes: ÂÂ

Infective or post-infective encephalitis

ÂÂ

Autoimmune or paraneoplastic encephalitis

ÂÂ

Metabolic encephalopathy.

Features favoring the diagnosis of NMDA encephalitis are female gender, young age and behavioral abnormalities mimicking psychiatric illness. High level of serum anti-NMDA antibodies are also in favor of diagnosis. Although, the whole body scan was negative for tumor, NMDA encephalitis can be found without such association especially in female. Still regular periodic scan or imaging required is for detection of, in future development of teratoma. CONCLUSION In conclusion, this anti-NMDA encephalitis case reported was consistent with those reported in the literature, except for the fact that association with tumor could not be found. Clinicians should keep this condition in mind, especially when assessing patients with recent onset of psychiatric symptoms unresponsive to antipsychotic treatment. REFERENCES 1. Dalmau J, Tüzün E, Wu HY, Masjuan J, Rossi JE, Voloschin A, et al. Paraneoplastic anti-N-methyl-d-aspartate receptor encephalitis associated with ovarian teratoma. Ann Neurol 2007;61(1):25-36. 2. Dalmau J, Gleichman AJ, Hughes EG, Rossi JE, Peng X, Lai M, et al. Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol 2008;7(12):1091-8. 3. Tüzün E, Zhou L, Baehring JM, Bannykh S, Rosenfeld MR, Dalmau J. Evidence for antibody-mediated pathogenesis in anti-NMDAR encephalitis associated with ovarian teratoma. Acta Neuropathol 2009;118(6):737-43. 4. Dalmau J, Lancaster E, Martinez-Hernandez E, Rosenfeld MR, Balice-Gordon R. Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis. Lancet Neurol 2011;10(1):63-74. 5. Graus F, Dalmau J. Paraneoplastic neurological syndromes: diagnosis and treatment. Curr Opin Neurol 2007;20(6):732-7. 6. Florance NR, Davis RL, Lam C, Szperka C, Zhou L, Ahmad S, et al. Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis in children and adolescents. Ann Neurol 2009;66(1):11-8.

Indian Journal of Clinical Practice, Vol. 25, No. 11, April 2015

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OBSTETRICS AND GYNECOLOGY

Accidental Finding of Asymptomatic Tuberculosis of Uterine Cervix: A Case Report DP GUPTA*, RATNA PRABHA GUPTA†, HEM PRABHA GUPTA‡, RK SAXENA#, DK SAXENA#

ABSTRACT A 48-year-old lady was admitted to Era’s Lucknow Medical College on 12th September 2014, as a case of fibroid uterus with menorrhagia. She also give history of having taken antitubercular treatment 40 years ago. Her total hysterectomy with bilateral salpingo-oophorectomy was done. Histopathological report showed secretory endometrium with adenomyosis with leiomyoma uterus with tubercular cervicitis. Both tubes and ovaries were unremarkable.

Keywords: Cervix, asymptomatic tuberculosis, rare

ncidence of gynecological tuberculosis varies with social status and patient’s environment. Tuberculosis is common in the reproductive age of 20-40 years. Cervical tuberculosis is 0.1-0.65% of all gynecological cases. Five to 10% among the patients with infertility. With prevalence of human immunodeficiency virus (HIV), the incidence of gynecological tuberculosis is rising. Affection of fallopian tuberculosis is 95-100%, uterine endometrium accounts for 50-60% and ovarian cases are reported in 20-30% cases. Tuberculosis of the vulva and vagina are very rare.

CASE HISTORY This patient, Mrs X was admitted from OPD of Era’s Lucknow Medical College, Lucknow on 12th September 2014. Her presenting symptoms were heavy menstrual bleeding for last 4 years and also pain in abdomen for last 2 days. She had two children, both by lower segment cesarean section (LSCS). Last delivery occurred 18 years ago. In the past history, she gave history of

having taken antitubercular treatment 40 years ago for pulmonary tuberculosis. She also gave history of bronchial asthma and history of hypersensitivity to penicillin, perinorm and stemetil. She used to have normal cycles and average bleeding, but since last 4 years, she is having excessive menstrual bleeding with normal cycles. On examination, nothing abnormal was detected during general and systemic examination. On per vaginal examination, uterus was enlarged to about 10 weeks size and firm in consistency. Fornices were clear. Per speculum cervix looked normal except a nabothian cyst. INVESTIGATION Hematological values were normal. Renal function tests, chest X-ray and viral markers were all within normal limits. Ultrasonography (USG) showed enlarged uterus (90 × 60 × 75 mm), endometrial thickness was 4 mm, multiple small myomas were present in the myometrium. She had total hysterectomy with bilateral salpingo-oophorectomy on 17-9-2014.

Histopathological Report *Associate Professor Dept. of Radiology †Ex-Associate Professor ‡Professor Dept. of Obstetrics and Gynecology #Assistant Professor Dept. of Radiology Era’s Lucknow Medical College, Lucknow, Uttar Pradesh Address for correspondence Dr DP Gupta MIG-2 Napier Road - Part II, LDA Colony Thakurganj, Lucknow - 226 003, Uttar Pradesh E-mail: dp_gupta2007@yahoo.co.in

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Gross-uterus enlarged to 10 weeks size. Both tubes, ovaries looked normal. Microscopic report revealed secretory endometrium with adenomyosis with leiomyoma with tubercular cervicitis with nabothian cyst. Both tubes and ovaries were unremarkable. Cervix on microscopic examination showed infiltration with chronic inflammatory cells, foci of Langhan’s giant cells and granuloma. The cervix was diagnosed as tubercular cervicitis with nabothian cysts.

OBSTETRICS AND GYNECOLOGY DISCUSSION

SUGGESTED READING

Genital tuberculosis is common in the reproductive age that is 20-40 years in a developing country like India. It accounts for tuberculosis in at least 14 million women in the reproductive age.

1. Chowdhury NN. Overview of tuberculosis of the female genital tract. J Indian Med Assoc 1996;94(9):345-6, 361.

It is the most common cause of infertility in women in this age group (5-16%). Genital organs most frequently affected include endometrium (50-60%), fallopian tubes (95-100%) and ovaries (20-30%). Tuberculosis of the cervix is rare and accounts for 0.1-0.65% of all cases. The actual incidence might be under reported due to the asymptomatic presentation and also due to lack of investigation facility and also ignorance of the fact that cervix can also be affected by the disease. Pelvic organs are infected from a primary focus, usually the lung by hematogenous spread or by lymphatics and the cervix gets infected as a part of this process or by direct extension from the upper genital tract. In rare cases, cervical tuberculosis may be a primary focus introduced by a infected partner with tuberculous epididymis or other genitourinary disease. It has also been suggested that sputum used as a sexual lubricant in open cases may cause tuberculosis.

2. Carter JR. Unusual presentations of genital tract tuberculosis. Int J Gynaecol Obstet 1990;33(2):171-6. 3. Parikh FR, Nadkarni SG, Kamat SA, Naik N, Soonawala SB, Parikh RM. Genital tuberculosis - a major pelvic factor causing infertility in Indian women. Fertil Steril 1997;67(3):497-500. 4. Singh S, Gupta V, Modi S, Rana P, Duhan A, Sen R. Tuberculosis of uterine cervix: a report of two cases with variable clinical presentation. Trop Doct 2010;40(2):125-6. 5. Guié P, Iovenitti P, N’guessan K, Tegnan J, Koffi K, Carta G, et al. Tuberculosis of the cervix and infertility: report of a rare case. Clin Exp Obstet Gynecol 2008;35(2):149-50. 6. Sachan R, Patel ML, Gupta P, Verma AK. Genital tuberculosis with variable presentation: a series of three cases. BMJ Case Rep 2012;2012. pii: bcr2012006665. 7. Samantaray S, Parida G, Rout N, Giri SK, Kar R. Cytologic detection of tuberculous cervicitis: a report of 7 cases. Acta Cytol 2009;53(5):594-6. 8. Agarwal J, Gupta JK. Female genital tuberculosis - a retrospective clinico-pathologic study of 501 cases. Indian J Pathol Microbiol 1993;36(4):389-97. 9. Paprikar M, Biswas M, Bhattacharya S, Sodhi B, Mukhopadhya I. Tuberculosis of cervix. MJAFI 2008;64:297-8.

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Risk for Preterm Delivery Higher among Mothers Born Preterm Women who were themselves born prematurely are more likely to give birth prematurely than women born full-term, a study published online April 3 in Obstetrics & Gynecology suggests. “The present study indicates that the risk of preterm delivery is significantly higher in women who were preterm themselves,” the authors write. “Moreover, this risk presents a dose-response relationship with more preterm women being at a greater risk of preterm delivery.”

Maternal Mortality Largely Preventable, Large Study Shows The top five causes of maternal mortality in California are cardiovascular disease, pre-eclampsia or eclampsia, hemorrhage, venous thromboembolism and amniotic fluid embolism, according to a recent study. The researchers also found that 41% to 70% of these cases might be preventable. Elliott K. Main, MD, from California Maternal Quality Care Collaborative, Stanford University, Palo Alto, and the Department of Obstetrics and Gynecology, California Pacific Medical Center, San Francisco, and colleagues report their findings in the April issue of Obstetrics & Gynecology.

Indian Journal of Clinical Practice, Vol. 25, No. 11, April 2015

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OBSTETRICS AND GYNECOLOGY

A Rare Case of Spontaneous Uterine Vessel Rupture of Unknown Etiology in Late Postpartum Period Diagnosed by CT Scan ANITA KHARAT*, SUMAN KUMARIâ&#x20AC;

ABSTRACT Rupture of uterine vessels, in the postpartum period, after vaginal delivery, is a very rare condition. Although, it presents with acute hemorrhage and is associated with high mortality, much less evidence and information are available on its etiology and pathogenesis. Our case presented very late; 34 days after normal vaginal delivery. Only few cases of ruptured uterine vessels, similar to this case, are reported in literature; however, they presented during labor or immediately after delivery. We report a case of a 32-year-old patient who had a spontaneous vaginal delivery in a private nursing home with initial uneventful puerperium; rupture of uterine vessels with hemoperitoneum occurred 34th day postpartum. CT scan done on 34th day postpartum revealed leakage from uterine artery and exploratory laparotomy found massive hemoperitoneum and large blood clots in the abdominal cavity with active bleeding from ruptured uterine artery. The patient was actively managed by performing hysterectomy and internal iliac artery ligation. The significance of the under-reported case lies in its rarity, its delayed presentation and clinically occult presentation.

Keywords: Acute hemorrhage, ruptured uterine vessels, hemoperitoneum, CT scan, laparotomy

CASE REPORT A 32-year-old female, P3L3, 34 days postpartum, presented to Terna Medical College OPD with complaints of fever and weakness with hemoglobin (Hb) - 4.6 g and was admitted in the medicine department. Gynecological consultation was done for pain in abdomen on and off since 3-4 days. Pain worsened with movement. She had past history of pulmonary tuberculosis few years back for which she was treated for 6 months. Her general examination revealed: Temperature afebrile, pulse - 92/min, blood pressure (BP) - 106/90 mmHg, moderate degree of anemia, bilateral pedal edema. On abdominal examination, tenderness in epigastric region and ascitis was noted; speculum

*Associate Professor â&#x20AC; Assistant Professor Dept. of Obstetrics and Gynecology Terna Medical College and Hospital, Nerul, Navi Mumbai, Maharashtra Address for correspondence Dr Anita Kharat 102/Jaysoham Apartment Sant Ramdas Road, Mulund (E), Mumbai - 400 081 E-mail: dranitakharat@gmail.com

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examination was normal. Sonography of abdomen and pelvis was advised; sonography was suggestive of gross ascitis and right pleural effusion. Uterus was of normal postpartum size and had retained placental bits, so patient was transferred to gynecology department for management. In view of postpartum status with retained placental bits, a provisional diagnosis of puerperal sepsis secondary to retained products of conception (RPOC) was made. Disseminated intravascular coagulation (DIC) profile was sent for evaluation and was found to be deranged. Higher antibiotics were started. Check curettage was planned after correction of DIC profile. As patient was not bleeding actively and she had a deranged coagulation profile, injection methotrexate was considered for RPOC. On second day of admission, she developed high BP (140/100 mmHg) for which labetalol and amlodipine were started. Ascitic fluid was sent for adenosine deaminase (ADA) evaluation and cytology. Till then five pints of packed cell and eight pints of fresh-frozen plasma had been transfused. With the uncertainty of diagnosis, contrast CT abdomen was advised. Her routine blood reports were traced. Blood urea nitrogen and serum creatinine were found to be raised. CT scan with contrast

OBSTETRICS AND GYNECOLOGY was done which suggested gross hemoperitoneum, hepatomegaly and left uterine artery leak; decision for exploratory laparotomy was taken. Surgical unit and ICU were kept on standby. The patient was taken for the exploratory laparotomy. A vertical midline incision was made. Approximately 2 litres of hemoperitoneum and a large blood clot were evacuated. A small erosion on posterior wall of the uterus was seen and there was active bleeding from left uterine artery. No other abnormality was detected. Uterine artery was secured and ligated. Prophylactically, bilateral internal iliac arteries were also ligated. Postoperative period was uneventful. Patient was kept in the hospital for 15 days for close monitoring. Patient was discharged after postoperative Day 15.

Missed Diagnosis Initially, the patient presented with occult clinical features. Presenting at 34th day postpartum with the chief complaints of fever was the reason of taken the complaints being taken casually. Role of CT scan: In this case, CT scan was done which detected hemoperitoneum with uterine vessel leak. This helped to diagnose the case and confidently make the decision of exploratory laparotomy. DISCUSSION Secondary postpartum hemorrhage occurring 24 hours after delivery is rare. Causes include arteriovenous malformations, aneurysm of uterine artery, rupture of pelvic vessels. Spontaneous rupture of uterine

vessels leading to hemoperitoneum is a life-threatening condition with the mortality rate 47% as reported by Steinberg et al. After excluding common causes, pelvic angiography or CT scan may be performed. Although, angiography is the gold standard for vascular pathology, CT scan can confirm the diagnosis and help to rule out other more common pathologies. Uterine artery embolization is a safe and effective option for secondary hemorrhage due to uterine artery leak due to preservation of reproductive function. Our patient had completed her family and also due to limited resources at our setup, the best we could do in emergency was radical surgery. So, hysterectomy with bilateral uterine and internal artery ligation was done. A high index of suspicion is warranted for the diagnosis of rupture of uterine artery and a timely diagnosis can decrease the morbidity and mortality associated with it. SUGGESTED READING 1. Ginsburg KA, Valdes C, Schnider G. Spontaneous uteroovarian rupture during pregnancy: three case report and review of the literature. Obstet Gynecol 1987;69 (3 Pt 2):474-6. 2. Steinberg LH, Goodfellow C, Rankin L. Spontaneous rupture of the uterine artery in pregnancy. Br J Obstet Gynaecol 1993;100(2):184. 3. Polat P, Suma S, Kantarcy M, Alper F, Levent A. Color Doppler US in the evaluation of uterine vascular abnormalities. Radiographics 2002;22(1):47-53.

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Blood Test may Help Clinicians Rule Out CAD in Women The age/sex/gene-expression score (ASGES) test known as Corus CAD (CardioDx) appears easy to incorporate and effective in excluding obstructive coronary artery disease (CAD) in middle-aged women with chest pains— saving them from having to undergo further, and possibly invasive, testing, new research suggests. Combined analysis of more than 300 women from the Investigation of a Molecular Personalized Coronary Gene Expression Test on Primary Care Practice Pattern (IMPACT-PCP) and Investigation of a Novel Gene Expression Test for Diagnosis of Obstructive Coronary Artery Disease (REGISTRY I) studies who presented to primary care with symptoms considered “stable yet suggestive of obstructive CAD” showed that those who had a lower ASGES were significantly less likely to be referred for further cardiac evaluation than those with an elevated score (P < 0.0001).

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Chickenpox in Pregnancy: Not Rosy, Not Easy VEMBU RADHA*, RAM PRAKASH THIRUGNANASAMBANDAM†, NARAYANAN PALANIAPPAN‡

ABSTRACT The incidence of chickenpox ranges from 1 to 5 cases/10,000 pregnancies. It becomes a disease of great concern among the pregnant population, since they are at a higher risk of developing complications. Here we report three cases of chickenpox in pregnancy. All three patients were seen in a span of 6 months. They all had classical lesions namely fluid-filled vesicles all over the abdomen. They were all treated with antiviral medications. All of them delivered by vaginal delivery. Expected maternal complications like pneumonia, hepatitis and encephalitis were not encountered in our patients. All three newborns were vaccinated. Thus, all three cases were uncomplicated and had a successful outcome.

Keywords: Chickenpox, pregnancy, complications

regnant women are particularly susceptible to a number of infectious diseases, whose management is made complex by pregnancy. Even if chickenpox does not pose a great risk to the expectant mother, it can impact fetal and neonatal development, thus posing a treatment challenge to physicians.1 This infection can be widely seen in developing countries, especially in tropical countries.2

with higher mortality. Pregnant women who contract varicella in the last trimester are at a higher risk of severe pneumonia and mortality. The management of chickenpox in pregnancy is of important concern to clinicians as it may cause intrauterine death or severe diseases (congenital or fetal varicella syndrome) depending on the time of maternal infection. Here we report three cases of varicella in pregnancy.4

Chickenpox is a common viral infection presenting with fever and discrete vesicular lesions. Incidence of varicella in pregnancy is calculated to be 2-3/1000 pregnancies.3 For the mother, the risk of severe illness is greatest after mid-pregnancy when she is relatively immunocompromised. For the fetus, the risk of congenital infection is greatest when maternal infection occurs in the first or second trimester.

CASE REPORT

The diagnosis of chickenpox in pregnancy is mainly limited to the clinical history and symptoms as no other diagnostic tool is necessary. Complications commonly encountered in pregnancy are pneumonia, hepatitis and encephalitis, and they are associated

*Associate Professor †Intern ‡Professor Dept. of Obstetrics and Gynecology Sri Ramachandra Medical College, Porur, Chennai, Tamil Nadu Address for correspondence Dr Narayanan Palaniappan Professor Dept. of Obstetrics and Gynecology Sri Ramachandra Medical College, Porur, Chennai, Tamil Nadu E-mail: npalaniappan@hotmail.com

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Three antenatal cases diagnosed with chickenpox presented to us at term gestation. All three patients had active lesions all over the body. Dermatologist opinion was sought and they were put on tablet acyclovir 800 mg five times a day for 7 days. They were isolated and supportive management was given. Two patients were induced with prostaglandin 2 gel at 40 weeks owing to prolonged pregnancy and oligoamnios respectively, while the third patient went into labor spontaneously. All three patients delivered normally. All three patient’s basic investigations were normal except for elevated total counts. They were discharged uneventfully without any anticipated complications. All three of the newborns were vaccinated with active immunization. Both mother and newborns are on follow-up. DISCUSSION Chickenpox is a viral infection which is highly contagious in nature. This disease is considered as an important infectious disease in any surveillance program. It is particularly seen in tropical countries.5 In chickenpox, it becomes our prime concern to

OBSTETRICS AND GYNECOLOGY identify the infection as early as possible, so that any maternal-fetal complication can be prevented. There appears to be no difference in the clinical presentation of the infection in the pregnant population. The onset of the infection is heralded by acute onset of high fever, which may last for 7 days as it is a viral infection. It is usually seen as a respiratory illness.5 As seen in our cases, the women had fever for a few days prior to the onset of any other symptoms. The characteristic skin lesion seen in chickenpox appears 1-2 days after the fever subsides. The identification of a disease is by its trademark symptoms or its pattern. In a similar way, the vesicular lesion is the only symptom, which defines chickenpox infection. In all our three cases, it was seen that they had multiple vesicles all over the abdomen. The identification of the condition as early as possible is important because of the effect of the virus in different trimesters of the pregnancy. It will help the clinicians to be better prepared for any complications that may arise and help in providing better care to the patient thereby achieving the goal of delivering a healthy baby with a healthy mother. Infection in the first trimester, has higher risk of teratogenicity like varicella embryopathy, hydrocephalus, meningocele and clubfeet.6 The virus is usually transmitted vertically. Fetal varicella syndrome is another consequence that has been reported in infected mothers.3 However, it is unclear if the infection itself would lead to miscarriage in the first trimester.6 If the mother were to contract the disease during her third trimester, the chance of the baby developing neonatal chickenpox is high. At the time of safe confinement, all pregnant women should be explained about scheduling an eye check-up for the newborn since the possibility of the occurrence of eye defects like microphthalmia, chorioretinitis and cataracts is high and they cannot be detected easily before birth. In our case reports, it is seen that all three women have contracted the disease only in the third trimester, while their first and second trimesters were uneventful. Thereby, the chance of occurrence of teratogenic consequences and fetal varicella syndrome is ruled out. There was also no need for an eye examination for the newborns, since the mothers had contracted the disease only in the third trimester. If contracted during the last trimester, there is a higher chance of complications in the mother. The infection if contracted between 28 and 36 weeks, the virus will be present in the maternofetal circulation, but not cause

any symptoms. It may become active in neonatal life causing shingles. The probability of the newborn being infected and being born with chickenpox is high if the mother contracts the disease after 36 weeks.7 The virus can be transmitted through the transplacental route or the ascending vaginal or from direct contact with the vesicular lesions during or after delivery. It will manifest in the newborn within 12 days of life.8 A detailed history will help in identifying the source of contact and establish the other symptoms that she had during the course of the disease. Serology may be used in case of doubt, wherein an infected patient will have immunoglobulin M (IgM) antibody.9 However, though the mother has been identified as an infected person, the need for fetal imaging is a must since the mother is normally anxious about the possible risks to the fetus. The ultrasound is the most important tool for establishing the presence of infection in the baby in the form of findings suggestive of congenital varicella infection such as intrauterine growth restriction, microcephaly, ventriculomegaly, the presence of echogenic foci in the fetal liver and circular scarring and deformities of the limbs.10 All three fetuses had no ultrasonographically detectable deformities. The maternal complications of chickenpox in pregnancy include pneumonia, hepatitis and encephalitis.8 While the onset of pneumonia is preceded by symptoms such as tachypnea and dyspnea, the onset of encephalitis will be preceded by headache and photophobia. The presence of pneumonia can be made severe if there is a superadded bacterial infection. The infected mother should always be counseled to seek medical care if she experiences any of the above-mentioned symptoms. Varicella pneumonia is considered a medical emergency, which may lead to ventilatory compromise and death. The management of the condition is the most important concern for obstetricians due to the fact that two lives are at stake. The two drugs commonly in use today are acyclovir and valcyclovir. Acyclovir is a category B drug in use, since the benefits far outweigh the risks in the case of the pregnant population. However, the use of the drug should be in a cautious manner if the pregnant woman has chickenpox before completion of 20 weeks of gestation. If the drug is administered at the initial stages its potency against the virus is increased.11 The dosage of the drug is 800 mg orally 5 times daily for 7 days or valacyclovir 1,000 mg orally 3 times daily for 7 days. Intravenous acyclovir is the choice in case the pregnant woman develops complications mentioned above with the dosage being 10 mg/kg

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OBSTETRICS AND GYNECOLOGY every 8 hours for 10 days. In obese patients, ideal body weight should be used to calculate the dose of acyclovir.12 There is also the inevitable question in the mind of an obstetrician about the use of the chickenpox vaccine in such patients. Though, the use of vaccination is an option that can be considered for women either in the antepartum or postpartum period, it should be kept in mind that the administration of the vaccine is of no use once the disease has been established in the pregnant woman.6 As suggested all our three patients were treated with acyclovir for the duration of 5 days, which improved their symptoms markedly with none of the patients going in for complications. We also did not have to worry about the teratogenicity of the drug since all three women were in their third trimester. The newborn must be kept away from the mother until all her lesions have crusted and dried. The use of immunoglobulins or antiviral drugs is recommended for infants. According to the green top guidelines of the Royal College of Obstetricians and Gynecologists (RCOG), the isolation of these patients is mandatory, since chickenpox is a communicable disease that is transmitted by droplets. All the healthcare workers involved in the treatment of the mother must be made aware of the patientâ&#x20AC;&#x2122;s status. If they are unsure of their immune status a serology test will help. If nonimmune then they are advised to get vaccinated. The potential risks of nonimmunization have to be explained to all healthcare workers. The mode of delivery is not a major source of conflict unless the mother contracts chickenpox just before term or if there is a need for an emergency delivery of the baby during her infective period. The risk of transmission is high if the onset of chickenpox in the mother occurs up to 7 days before or after delivery.13 Delivery is normally avoided for a period of 7 days to help the infant receive antibodies passively from the mother. If there is an urgent need for the delivery then the infant may be given intravenous immunoglobulin and observed up to a period of 28 days for signs of disease. All the three patients were delivered only after the infectious period settled down, which reduced the chance of neonatal varicella. All said and done there is no better way than prevention in the eradication of the concern in obstetricians towards patient care. Hence, every clinician must be aware of the preventive measures that are commonly in use. The presence of a multidisciplinary team consisting of an obstetrician, dermatologist, infectious disease

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consultant, neonatologist and a radiologist would help the mother to receive the best care possible and would also relieve the primary obstetrician of the pressure involved in treating such patients. Though, there is a specific vaccine available today for chickenpox, its use is not recommended routinely unless the woman is in a highly endemic area as a part of pre-pregnancy care. It should never be administered during pregnancy.14 Most of the patients of reproductive age will be immune to varicella, and they are not at a risk of infection. The use of immunoglobulins will be useful if the woman has previously has had no exposure to chickenpox and if her levels of varicella-zoster immunoglobulin G (VZ-IgG) are negative. In case the patient is unsure of her immunization status then her serology test will be a good indicator of her VZ-IgG levels. If the patient has not been exposed to chickenpox previously, the patient has to be counseled against exposure to individuals who have acute infection. The infants exposed to chickenpox are advised to be given immunoglobulins and treated with acyclovir with the help of a neonatologist. In our case, none of the infants had neonatal chickenpox and hence all three mothers were advised to have their babies vaccinated with the chickenpox vaccine. CONCLUSIONS Hence chickenpox in pregnancy can lead to a variety of complications in the mother and fetus. Early diagnosis, prompt treatment by a multidisciplinary team approach can lead to a good maternofetal outcome. Though all our three patients had an excellent outcome, managing chickenpox in pregnancy is not always rosy and easy. REFERENCES 1. Adler H, Lambert JS. Clinical focus: infections in pregnancy. Hosp Pract (1995) 2014;42(2):108-24. 2. Wiwanitkit V. Chicken pox in pregnancy: an obstetric concern. Indian J Dermatol 2010;55(4):313-5. 3. Enders G, Miller E, Cradock-Watson J, Bolley I, Ridehalgh M. Consequences of varicella and herpes zoster in pregnancy: prospective study of 1739 cases. Lancet 1994;343(8912):1548-51. 4. Sauerbrei A. Varicella-zoster virus infections in pregnancy. Intervirology 1998;41(4-5):191-6. 5. Asano Y. Clinicopathologic understanding and control of varicella-zoster virus infection. Vaccine 2008;26(50):6487-90. 6. Pastuszak AL, Levy M, Schick B, Zuber C, Feldkamp M, Gladstone J, et al. Outcome after maternal varicella infection in the first 20 weeks of pregnancy. N Engl J Med 1994;330(13):901-5.

OBSTETRICS AND GYNECOLOGY 7. Sauerbrei A, Wutzler P. Herpes simplex and varicellazoster virus infections during pregnancy: current concepts of prevention, diagnosis and therapy. Part 2: Varicella-zoster virus infections. Med Microbiol Immunol 2007;196(2):95-102. 8. Ghosh S, Chaudhuri S. Pregnancy and varicella infection: a resident’s quest. Indian J Dermatol Venereol Leprol 2013;79(2):264-7.

11. Wagstaff AJ, Faulds D, Goa KL. Acyclovir. A reappraisal of its antiviral activity, pharmacokinetic properties and therapeutic efficacy. Drugs 1994;47(1):153-205. 12. Swingler GH. Chickenpox. BMJ Clin Evid 2007 Aug 1;2007. pii: 0912.

9. McGregor JA, Mark S, Crawford GP, Levin MJ. Varicella zoster antibody testing in the care of pregnant women exposed to varicella. Am J Obstet Gynecol 1987;157(2):281-4.

13. Miller E, Cradock-Watson JE, Ridehalgh MK. Outcome in newborn babies given anti-varicella-zoster immunoglobulin after perinatal maternal infection with varicella-zoster virus. Lancet 1989;2(8659): 371-3.

10. Petignat P, Vial Y, Laurini R, Hohlfeld P. Fetal varicella-herpes zoster syndrome in early pregnancy: ultrasonographic and morphological correlation. Prenat Diagn 2001;21(2):121-4.

14. Shrim A, Koren G, Yudin MH, Farine D; Maternal Fetal Medicine Committee. Management of varicella infection (chickenpox) in pregnancy. J Obstet Gynaecol Can 2012;34(3):287-92.

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Mother's Smoking may Affect Girl’s Lifetime Reproductive Health Girls whose mothers smoked while pregnant entered puberty at a younger age in a new Australian study. Since early menstruation is linked to higher risk of uterine, endometrial and breast cancers later in life, the researchers say maternal smoking could set up daughters for health problems even before they're born.

Vitamin D Linked with Depression in Women Otherwise healthy college-aged women with low levels are more likely to be depressed. Another day, another study on depression and vitamin D. This one found a relationship between the vitamin and depression in otherwise healthy young women in the Pacific Northwest. Vitamin D levels were measured over a 5-week period, and were found to be common - 42% had vitamin D deficiency (<30 nm/mL) at Week 1 and 46% at Week 5.

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To Evaluate Prognostic Value of Subchorionic Hematoma on Threatened Abortion SAROJ SINGH*, ANU PATHAK†, KAUSTUBH SRIVASTAVA‡, NIDHI GUPTA#, SHIKHA SINGH#, HARI SINGH†

ABSTRACT Objectives: To evaluate cases of threatened abortion by serial ultrasonography to detect subchorionic hematoma characteristics and progression with an aim to prognosticate pregnancy outcome. Material and methods: This was a prospective study involving antenatal women of 14 weeks or less presenting with vaginal bleeding. A total of 477 patients were enrolled and cases with subchorionic hematoma (56) were followed up with serial sonograms till 24 weeks of gestation. Hematoma volume, size, site, fetal cardiac activity, relative size with respect to gestational sac, symptom regression and outcome were monitored. Results: The mean gestational age of hematoma group was 9.4 weeks. Sixty percent of cases had an anterior location of hematoma with the mean volume being 29 ± 8.4 cc. Fifty-two percent cases showed progressive decrease in size with complete resolution of hematoma, while 10% had an increase in size. Cases with relative size <20% mostly had a favourable outcome (48%) and cases with relative size >50% showed equivocal results. Conclusion: Subchorionic hemorrhage is significantly associated with increased risk of spontaneous abortion. Neither position nor size was related to the outcome. An early gestational age at diagnosis and relative size >50% may be considered a risk factor for poor outcomes.

Keywords: Threatened abortion, ultrasonography, subchorionic hematoma characteristics, pregnancy outcome

bstetricians are faced with a major dilemma while managing cases of first trimester bleeding per vaginum, and a diagnosis of subchorionic hematoma, which is one of the most common sonographic abnormalities with live embryos, often causes women a lot of concern, particularly when it is accompanied by vaginal bleeding. Available clinical methods leave much to be desired about status of gestation, whether it is viable and requires prolonged conservative treatment or fetus has undergone irreparable damage warranting evacuation of uterine contents.

First trimester bleeding occurs in 5-25% of all pregnancies.1 Half of the women who experience vaginal bleeding will continue their pregnancies, and the other half will experience an abortion. Possible causes of

*Professor and Head †Lecturer ‡Junior Resident #Associate Professor Dept. of Obstetrics and Gynecology SN Medical College, Agra, Uttar Pradesh Address for correspondence Dr Kaustubh Srivastava 2/107, Viram Khand, Gomtinagar, Lucknow - 226 010, Uttar Pradesh E-mail: proudaquarian@gmail.com

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bleeding include subchorionic hemorrhage, embryonic demise, anembryonic pregnancy, incomplete abortion, ectopic pregnancy and gestational trophoblastic disease.2 Other nonobstetric causes of bleeding are cervicitis, vaginitis, cystitis, genital trauma, cervical cancer, polyps and hemorrhoids. Subchorionic hematoma, initially described by Mantoni and Pedersen3 in 1981, appears to have gained some prominence lately. The exact etiology of intrauterine hematomas remains unclear, but pre-existing medical conditions, autoimmune diseases and immunological factors have been associated with intrauterine hematoma.4 The present study was conducted in the Dept. of Obstetrics and Gynecology in SN Medical College, Agra with the aim to evaluate cases with first trimester bleeding with ultrasound proven subchorionic hematoma and to find out the possible relationship of pregnancy outcome to hematoma volume, site and hematoma size relative to gestational sac. MATERIAL AND METHODS This was a prospective study including a total of 477 antenatal cases of gestational age <14 weeks, presenting with vaginal bleeding.

OBSTETRICS AND GYNECOLOGY The study protocol was approved by the Ethics and Research Committee of the Institutional Review Board and women who agreed to participate in the study completed a written informed consent form. Ultrasonic assessment was done in all the cases.

Inclusion Criteria ÂÂ

An intrauterine live pregnancy.

ÂÂ

Gestational age between 5 and 14 weeks.

ÂÂ

A crown-rump length of >4 mm.

ÂÂ

The existence of cardiac activity.

Exclusion Criteria ÂÂ

Nonviable or nonvisible embryos.

ÂÂ

Pathologic features, including fibroids, polyps and uterine malformations.

ÂÂ

Those who underwent elective termination of pregnancy.

Antenatal women presenting with vaginal bleeding between 5 and 14 weeks’ gestation were made to undergo routine antenatal examinations. Ultrasonographic assessment was undertaken with emphasis on crownrump length, gestational sac characteristics (gestational sac diameter, regularity of sac, turgidity, yolk sac) cardiac activity, presence or absence of hematoma, position of the hematoma (subchorionic retroplacental, both), location of the hematoma (anterior, posterior, fundal, corpus) size of hematoma relative to gestational sac diameter. Local examination, per abdominal examination and per speculum examination were carried out to rule out causes of bleeding apart from subchorionic hematoma. All routine investigations were carried out and documented. All women were subjected to same treatment. ÂÂ

Bed rest

ÂÂ

Folic acid supplementation

ÂÂ

Progesterone therapy.

All patients with live fetuses with continued fetal heart activity were re-evaluated at 7- to 10-day intervals initially till the bleeding resolved.

OBSERVATIONS Out of the 477 patients observed over the study period. Subchorionic hematoma was detected in 56 cases out of which four patients had absent cardiac activity at presentation hence were not followed up. One hundred seven patients were found to have a live fetus, but absence of any subchorionic hemorrhage. After counseling and informed consent, the patients were divided into two groups: ÂÂ

Group A: Subchorionic hematoma present with a viable fetus.

ÂÂ

Group B: Subchorionic hematoma absent with a viable fetus.

After accounting for a loss of follow-up, at the time of analysis 50 cases of Group A and 100 cases of Group B were available. RESULTS Cases in both the groups matched well-regarding age, parity, marital status, educational status and socioeconomic status. The incidence of subchorionic hematoma in population presenting with features of threatened abortion was calculated to be 56 of 477 (11.74%). ÂÂ

Mean gestational age of hematoma group was 9.4 weeks and study group was 7.2 weeks.

ÂÂ

Both groups were comparable with regard to maternal age, smoking history and medical and reproductive history (Table 1).

ÂÂ

In hematoma group, the mean duration of bleeding at presentation was 1042.2 ± 653.68 minutes and 1036.2 ± 633.68 minutes in control group.

ÂÂ

Subchorionic hematoma were found in 50 cases. Ninety percent cases of the study group were of gestational age <10 weeks at initial presentation and 10% cases of study group were of gestational age 10-14 weeks.

ÂÂ

Rest and progesterone therapy were very effective in symptom regression. Eighty-six percent patients had complete resolution of complaints by 3rd follow-up visit. Eight percent patients with severe symptoms (heavy vaginal bleeding with abdominal pain) had unfavourable outcomes. There was no significant correlation between symptoms viz. vaginal bleeding and abdominal pain with pregnancy outcome.

ÂÂ

Sixty-five percent patients presented with a volume of subchorionic hematoma <20 cc, followed by 20% cases

And further repeated sonograms were obtained at an interval of 2 weeks until: ÂÂ

The subchorionic bleeding resolved and the pregnancy continued

ÂÂ

Until the pregnancy ended in abortion

ÂÂ

Until 24 weeks of gestational age whichever is earlier.

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OBSTETRICS AND GYNECOLOGY 16 cases (32%) demonstrated a decrease in size of subchorionic hematoma, while five cases (10%) showed an increase in hematoma size (Figs. 1 and 2).

of hematoma volume 20-50 cc and 16% cases with hematoma volume >50 cc at first visit (Table 2). ÂÂ

ÂÂ

Majority of patients (50%) presented with a relative size of gestational sac (mean hematoma diameter, mean gestational sac diameter) <20%, followed by 15 cases (30%) having relative size 20-50% and 10 cases (20%) with relative size >50%.

ÂÂ

A spontaneous abortion rate of 14% in hematoma population was observed, which is significantly higher than that in control group (6%) (Table 3).

ÂÂ

In our present study, we have observed 21.8% and 16.6% abortion rate in cases presenting with gestational age <10 weeks and >10 weeks, respectively.

ÂÂ

Majority of subchorionic hematoma were anteriorly located (60%), followed by posterior (24%), fundal (10%) and isthmic (6%) in location (Table 4).

ÂÂ

By the 3rd follow-up visit, a majority 26 patients (52%) showed complete resolution of hematoma,

Table 1. Associated Obstetric and Medical Complicating Factors Study Group A

Control Group B

No.

History of previous termination of pregnancy

Previous spontaneous abortion

Although an absolute size of hematoma >60 cc appeared to be associated with a uniformly adverse outcome in our study, but in most of the studies, including ours, the estimated volume of the hematoma did not correlate with the outcome of the pregnancy when statistically analyzed.

Multiparity

90 80

Previous perinatal death

Smoking/tobacco consumption

History of chronic hypertension

History of gestational diabetes

Table 2. Outcome with Respect to Size of Subchorionic Hematoma with Relation to Gestational Sac Size and Absolute Volume Normal outcome (Pregnancy continued) No.

Adverse outcome (Abortion) No.

P value

60 50 40 30 20 10

Relative size 19

20-50%

>50%

>0.5

Volume (in cc) of subchorionic hematoma at first visit <20 cc

81.25

18.75

20-50 cc

>50 cc

<20%

20-50%

<50%

Figure 1. Ultrasound findings at follow-up visit (% regression in size of hematoma).

Table 3. Comparative Outcome of Both Groups at Follow-up Visits Outcome

Study Group A

Control Group B

No.

Normal

Adverse

Normal

Adverse

Normal

Adverse

First follow-up

<20%

Ist follow-up 2nd follow-up 3rd follow-up

P = 0.22.

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Percentage (%)

No.

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Indian Journal of Clinical Practice, Vol. 25, No. 11, April 2015

Second follow-up

Third follow-up

P = 0.03.

OBSTETRICS AND GYNECOLOGY Table 4. Outcome of Cases at Follow-up with Relation to Site of Subchorionic Hematoma Position

Anterior Posterior

Fundal

Corpus

No.

P value

First follow-up Continued

Aborted

0.1

Second follow-up Continued

Aborted

0.1

Third follow-up Continued

Aborted

0.1

DISCUSSION Subchorionic hematoma was first described by Mantoni and Pedersen in 1981 as “an echo-free area between the membranes and the uterine wall. Since then, innumerable studies have been done on the same till date, which focus on its clinical significance. Subchorionic bleeds increase the chances of pregnancy complications, particularly miscarriage and preterm delivery, a possibility of fetal growth problems prompting early delivery with potential for adverse neurologic and physical outcomes. It has been suggested that a localized accumulation of blood causes mechanical uterine irritation and therefore stimulates contractions. Another possible mechanism for the preterm uterine activity is bacterial colonization of the hematoma and endotoxin-release with subsequent prostaglandin synthesis.

Figure 2. Ultrasonographic images showing from top to bottom progressive regression in size of subchorionic hematoma at 9 weeks, 11 weeks and complete resolution at 13 weeks of gestation. ÂÂ

Subchorionic hematoma with a relative size of hematoma <50% were found to have a better prognosis compared to those having a relative size of hematoma >50%, but the result is statistically insignificant (Table 2).

Early studies of subchorionic hemorrhages focused on very selected populations (i.e., women with threatened abortion or recurrent miscarriage) and reported incidences that varied between 2% and 22% (Table 5). Possible reasons for the discrepancy in these rates include variable patient populations, a wide range of gestational ages and lack of a standard definition of intrauterine hematomas. Nagy et al5 calculated a net incidence of subchorionic hematoma to be 3.1% in the general obstetric population, but this figure is much higher in high-risk cases as evidenced by other studies concentrating on patients with threatened abortion, 20% (Goldstein 1983), 4-48% (Pearlstone 1993) and 18% (Adelusi 1996).

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OBSTETRICS AND GYNECOLOGY Table 5. Earlier Studies of Subchorionic Hemorrhages Author (year)

No. of patients

Hematoma frequency (%)

Spontaneous abortion rate (%)

Mantoni (1981)

2 (17)

Goldstein (1983)

2 (20)

Sauerbrei (1986)

3 (10)

Abu-Yousef (1987)

12 (57)

Ball (1996)

317

1.3

16 (7)

Tower (2001)

6 (15)

Present study

477

14%

In the present study, the incidence of subchorionic hematoma in population presenting with features of threatened abortion was calculated to be 11.74%. Subchorionic hematoma were found in 50 cases. Ninety percent cases of the study group were of gestational age <10 weeks at initial presentation and 10% cases of study group were of gestational age 10-14 weeks. Sixty-five percent patients presented with a volume of subchorionic hematoma <20 cc, followed by 20% cases of hematoma volume 20-50 cc and 16% cases with hematoma volume >50 cc at first visit. Published opinions on the clinical significance of the volume of intrauterine hematomas are controversial. Several authors have attempted to relate the size of the hematoma directly to pregnancy outcome and to determine whether this factor has predictive significance. In most of the studies, including ours, the estimated volume of the hematoma did not correlate with the outcome of the pregnancy.6 Perhaps, it is the presence or absence of a hematoma as a marker of the integrity of placentation and not its size that is important. A meta-analysis by Kyser et al7 reported a 93% abortion rate with a hematoma volume >60 mL. Sauerbrei and Pham8 also found that for volumes <60 mL, the outcomes tended to be favourable, concluding that subchorionic hematoma is a significant factor in abortion with relation to the volume of hematoma. Although an absolute size of hematoma >60 cc appeared to be associated with a uniformly adverse outcome in our study, but the estimated volume of the hematoma did not correlate with the outcome of the pregnancy when statistically analyzed. The significance of relative volume of the hematoma (volume of hematoma divided by volume of estational sac)

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was explored by Sauerbrei and Pham8 in 1986. For a relative volume <0.4, the outcome tended to be favourable. This study noted the relative volume of the hematoma to be a major prognostic factor related to pregnancy outcome preceded in significance by the absolute volume of the hematoma. Cases with subchorionic hematoma with a relative size of hematoma <50% were found to have a better prognosis compared to those having a relative size of hematoma >50%. The study observed a preponderance of anterior location of subchorionic hematoma. No significant association could be made out in the results on basis of site of hematoma and pregnancy outcome. CONCLUSION Net rate of spontaneous abortion in hematoma group was found to be much higher than that of control population. We can conclude that presence of subchorionic hemorrhage is associated with a significantly increased risk of spontaneous abortion. Moreover, an early gestational age at diagnosis of subchorionic hematoma was associated with higher abortion rate (21.8% vs 16.6%) and may be considered a risk factor for poor outcomes. However, relief in symptoms of threatened abortion is a welcome sign. This was found to be statistically significant on analysis. Lower hematoma volumes <20 cc are predictive of positive pregnancy outcomes, whereas an absolute hematoma volume >60 cc was found to be associated with uniformly poor prognosis. This result did not come out to be statistically significant (p = 0.6). Cases with subchorionic hematoma with a relative size of hematoma <50% were found to have a better prognosis compared to those having a relative size of hematoma >50%, but the result is statistically insignificant (p > 0.5). There was no significant correlation between the site of hematoma and pregnancy outcome. Our study suggests that the presence of a first trimester subchorionic hematoma may be a useful sign to identify a population of patients at greater risk for adverse pregnancy outcome. But, we must acknowledge the limitations of our sample and duration of study and suggest a larger study with more frequent follow-up visits with emphasis on follow-up till ultimate outcome- abortion or delivery, to refuse and reaffirm effectiveness of subchorionic hematoma as a predictor of outcome in cases presenting with threatened abortion.

OBSTETRICS AND GYNECOLOGY REFERENCES 1. Leite J, Ross P, Rossi AC, Jeanty P. Prognosis of very large first-trimester hematomas. J Ultrasound Med 2006;25(11):1441-5. 2. Deutchman M, Tubay AT, Turok D. First trimester bleeding. Am Fam Physician 2009;79(11):985-94. 3. Mantoni M, Pedersen JF. Intrauterine haematoma. An ultrasonic study of threatened abortion. Br J Obstet Gynaecol 1981;88(1):47-51. 4. Alijotas J, Izquierdo M, Serra B, Cusido MT, Ribera M, Carrera JM. Antinuclear autoantibodies, complement level, hypergammaglobulinemia and spontaneous intrauterine hematoma in pregnant women. Am J Reprod Immunol 2003;50(1):1-6.

5. Nagy S, Bush M, Stone J, Lapinski RH, Gardó S. Clinical significance of subchorionic and retroplacental hematomas detected in the first trimester of pregnancy. Obstet Gynecol 2003;102(1):94-100. 6. Børlum KG, Thomsen A, Clausen I, Eriksen G. Long-term prognosis of pregnancies in women with intrauterine hematomas. Obstet Gynecol 1989;74(2):231-3. 7. Kyser KL. Meta-analysis of subchorionic hemorrhage and adverse pregnancy outcomes. Proc Obstet Gynecol 2012;2(4):4. 8. Sauerbrei EE, Pham DH. Placental abruption and subchorionic hemorrhage in the first half of pregnancy: US appearance and clinical outcome. Radiology 1986;160(1):109-12.

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Ovarian Reserve Testing Useful in Some Situations, ACOG Says Ovarian reserve testing should be performed when women older than 35 years have not conceived after 6 months of trying and with women who are at heightened risk for diminished ovarian reserve, such as cancer survivors, according to an opinion by the American College of Obstetrics and Gynecologists’ Committee on Gynecologic Practice. The opinion, published in the January 2015 issue of Obstetrics & Gynecology, also advises clinicians to let such women know that their “window of opportunity” to conceive may be narrow and to encourage them to attempt to conceive “sooner rather than later.” However, none of the tests available predict failure to conceive, the authors emphasize

Key Substance Identified that Protects Against Preterm Birth Researchers at UT South-western Medical Center have identified hyaluronon (HA) as a critical substance made by the body that protects against premature births caused by infection. Preterm birth from infection is the leading cause of infant mortality in many countries according to the World Health Organization. The findings of the study, recently published in the Journal of Clinical Investigation, are the first to identify the specific role that HA plays in the reproductive tract.”We found that HA is required to allow the epithelial lining of the reproductive tract to serve as the first line of defense against bacterial infections,” said senior author Dr Mala Mahendroo, an Associate Professor in the Department of Obstetrics and Gynecology’s Cecil H. and Ida Green Center for Reproductive Biology Sciences. “Because of this action, HA offers cervical protection against the bacterial infections that cause 25-40% of preterm births in women.”

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IMAGES AND INVESTIGATIONS

Multiple Cardiac Myxoma MONIKA MAHESHWARI

45-year-old man presented in casualty with complain of progressive breathlessness and syncopal attacks since 1 month. On physical examination, his pulse was 80/minute regular, blood pressure 100/70 mmHg with raised jugular venous pressure (JVP) (prominent a wave and steep y descent) and bilateral pitting pedal edema. On cardiopulmonary auscultation, there was reduced air entry in both lung fields. S1 was loud and widely split. There was a audible holosystolic murmur at left sternal border and a low-pitched mid-diastolic murmur at the apex. Electrocardiogram revealed sinus rhythm with low voltage QRS complexes. Transthoracic echocardiography demonstrated multiple intracardiac masses obstructing right and left ventricular inflow/ outflow tracts (Fig. 1). Finally, cardiac magnetic resonance (CMR) was done, which confirmed multiple cardiac myxomas and patient underwent surgical removal at higher center. Primary tumors of the heart are rare across all age groups, with a reported prevalence of 0.001-0.03% in autopsy series. The diagnosis of primary cardiac tumors is frequently challenging because of vague symptoms. This elusiveness often results in a delay in the diagnosis of disease. Fortunately, the more widespread use of noninvasive and relatively sensitive imaging modalities such as echocardiography, computed tomography (CT), CMR facilitate the identification of cardiac lesions. Myxomas are usually located in either

Associate Professor Jawaharlal Nehru Hospital, Ajmer, Rajasthan E-mail: opm11@rediffmail.com

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Figure 1. TTE showing multiple intracardiac masses obstructing right and left ventricular inflow/outflow tracts. the left or right atrium of the heart; about 86% occur in the left atrium. Myxomas are typically pedunculated, with a stalk that is attached to the interatrial septum in fossa ovalis region. Because pedunculated myxomas are somewhat mobile, symptoms may only occur when the patient is in a particular position. Although histologically benign, untreated myxoma can lead to an peripheral embolism, arrhytmias, pulmonary edema and intracardiac obstruction. Hence once diagnosed, they should be surgically resected to reduce mortality.

EXPERT VIEW

How Important a Risk Factor is Systolic Blood Pressure? KK AGGARWAL

t has been shown in cross-sectional and longitudinal population studies that systolic blood pressure (SBP) increases with age, while diastolic blood pressure (DBP) rises until 50 years of age and then levels off or even slightly decreases. Consequently, with increasing age there is a shift from diastolic pressure to systolic pressure and then to pulse pressure as the predominant predictor of cardiovascular risk.1

Both observational studies and clinical trial data suggest that poor SBP control is largely responsible for the unacceptably low rates of overall BP control.2 In 1969, the Framingham Heart Study first noted that systolic hypertension was related to increased cardiovascular risk.3 Staessen et al found that a 10 mmHg rise in systolic hypertension was correlated with a 10% increase in all fatal and nonfatal cardiovascular complications. DBP, on the other hand, was inversely correlated with total and cardiovascular mortality.4,5 In the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) and Controlled Onset Verapamil Investigation of Cardiovascular End Points (CONVINCE) trial, DBP control rates exceeded 90%, but SBP control were considerably less (60-70%).6,7 Poor SBP control has also been partly related to physician attitudes. A multi-ethnic population sample of adults at or above 40 years old was surveyed, by random digit phone dialling in a major metropolitan area, regarding BP measurement and hypertension awareness and treatment status. The survey concluded that community physicians do not give equal weight to SBP >140 mmHg as to DBP >90 mmHg in diagnosing hypertension and intensifying treatment. A visit-level analysis indicated that when DBP >90 mmHg, physicians intensified drug therapy 24% of the time, but intensification actions occurred in only 4% of visits when SBP <140 mmHg and DBP

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

<90 mmHg.8 Observational epidemiologic studies and randomized controlled trials have demonstrated that SBP is an independent and strong predictor of risk of cardiovascular and renal disease. The association between SBP and risk of coronary heart disease, stroke and end-stage renal disease is continuous, graded and independent.9 Elevated SBP is even more associated with cardiovascular morbidity and mortality than DBP.10 Clinical trials have demonstrated that control of isolated systolic hypertension reduces total mortality, cardiovascular mortality, stroke and heart failure events.11-13 Hence, greater emphasis must clearly be placed on managing systolic hypertension in order to check the rising burden of cardiovascular and renal disease. REFERENCES 1. Nawrot T, Den Hond E, Thijs L, Staessen JA. Isolated systolic hypertension and the risk of vascular disease. Curr Hypertens Rep 2003;5(5):372-9. 2. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, et al; National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; National High Blood Pressure Education Program Coordinating Committee. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA 2003;289(19):2560-72. 3. Kannel WB. Elevated systolic blood pressure as a cardiovascular risk factor. Am J Cardiol 2000;85(2):251-5. 4. Staessen JA, Gasowski J, Wang JG, Thijs L, Den Hond E, Boissel JP, et al. Risks of untreated and treated isolated systolic hypertension in the elderly: meta-analysis of outcome trials. Lancet 2000;355(9207):865-72. 5. Tin LL, Beevers DG, Lip GY. Systolic vs diastolic blood pressure and the burden of hypertension. J Hum Hypertens 2002;16(3):147-50. 6. Cushman WC, Ford CE, Cutler JA, Margolis KL, Davis BR, Grimm RH, et al; ALLHAT Collaborative Research Group. Success and predictors of blood pressure control in diverse North American settings: the antihypertensive

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EXPERT VIEW and lipid-lowering treatment to prevent heart attack trial (ALLHAT). J Clin Hypertens (Greenwich) 2002;4(6): 393-404. 7. Black HR, Elliott WJ, Neaton JD, Grandits G, Grambsch P, Grimm RH Jr, et al. Baseline Characteristics and Early Blood Pressure Control in the CONVINCE Trial. Hypertension 2001;37(1):12-18. 8. Hyman DJ, Pavlik VN, Vallbona C. Physician role in lack of awareness and control of hypertension. J Clin Hypertens (Greenwich) 2000;2(5):324-30. 9. He J, Whelton PK. Elevated systolic blood pressure as a risk factor for cardiovascular and renal disease. J Hypertens Suppl 1999;17(2):S7-13. 10. Duprez D. Treatment of isolated systolic hypertension in the elderly. Expert Rev Cardiovasc Ther 2012;10(11): 1367-73.

11. Kostis JB, Davis BR, Cutler J, Grimm RH Jr, Berge KG, Cohen JD, et al. Prevention of heart failure by antihypertensive drug treatment in older persons with isolated systolic hypertension. SHEP Cooperative Research Group. JAMA 1997;278(3):212-6. 12. SHEP Cooperative Research Group. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). JAMA 1991;265(24):3255-64. 13. Staessen JA, Thijs L, Fagard R, O’Brien ET, Clement D, de Leeuw PW, et al. Predicting cardiovascular risk using conventional vs ambulatory blood pressure in older patients with systolic hypertension. Systolic Hypertension in Europe Trial Investigators. JAMA 1999;282(6): 539-46.

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AROUND THE GLOBE

News and Views ÂÂ Getting on the scale every day may boost enthusiasm

for healthy behaviors and lead to greater weight loss, suggests a new US study published online in the Journal of the Academy of Nutrition and Dietetics.

ÂÂ Warming human monocytes to a febrile-range

temperature, rather than normal body temperature, may reverse the effects of hypothermia, suggests a new study published online in Annals of Surgery.

ÂÂ Studies evaluating the performance of hybrid

obese children and adolescents, suggests a crosssectional study published online in the Journal of Allergy and Clinical Immunology. ÂÂ Adding an electroencephalography (EEG)-based

biomarker to standard clinician judgment may improve the accuracy of the diagnosis of attentiondeficit/hyperactivity disorder (ADHD) and reduce the likelihood of overdiagnosis, suggests new research published online in Brain and Behavior.

imaging using simultaneous PET/MRI for the staging of both primary and recurrent pelvic malignancies indicate that the integrated approach could be a valuable diagnostic modality in both settings, points new research presented at the European Congress of Radiology (ECR) 2015.

ÂÂ Prostatic artery embolization provides excellent

ÂÂ Cesarean section can be lifesaving for a pregnant

exercise-induced bronchoconstriction (EIB) treated with inhaled bronchodilators revealed that the selfreports of respiratory changes did not correlate with changes in airway caliber. The findings are published online in Medicine & Science in Sports & Exercise.

woman in cardiac arrest and her baby, but only when done promptly and effectively, suggest UK researchers in a 24-step protocol published online in Emergency Medicine Journal.

ÂÂ A new study suggests that loneliness and social

isolation seem to be risk factors for all ages for early mortality. The study is published online in Perspectives on Psychological Science.

ÂÂ The High Value Care Task Force of the American

College of Physicians (ACP) recommends against screening for coronary heart disease (CHD) in asymptomatic, low-risk adults with resting or stress electrocardiography, stress echocardiography or stress myocardial perfusion imaging. The statement was published online March 16 in the Annals of Internal Medicine.

ÂÂ Researchers from China have reported significantly

positive results from folic-acid supplementation for prevention of cardiovascular events. The China Stroke Primary Prevention Trial (CSPPT) showed that daily treatment of 10 mg enalapril plus 0.8 mg of folic-acid for 4.5 years in adults with hypertension but without a history of MI reduced the risk of first stroke (the primary outcome) by 21% compared with taking enalapril alone. The findings were presented at the American College of Cardiology (ACC) 2015 Scientific Sessions.

ÂÂ Metabolic syndrome and insulin resistance appear

to contribute to the pathogenesis of asthma in

symptom control in men with lower urinary tract symptoms related to benign hyperplasia, suggests a new study presented at the European Congress of Radiology 2015.

ÂÂ A study conducted in athletes suspected of having

ÂÂ The US Food and Drug Administration (FDA) has

cleared for marketing the Simpliciti ultra short-stem shoulder system for arthroplasty in patients with limited shoulder function and severe pain resulting from osteoarthritis or traumatic arthritis. The device is a total shoulder arthroplasty system that minimizes bone removal and soft-tissue disruption associated with use of long-stem devices.

ÂÂ Contrary to previous studies, the antimetabolite

mitomycin does not seem to be associated with an increase in complication rates in trabeculectomy, suggests a study published online in JAMA Ophthalmology.

ÂÂ A novel device that stimulates the vestibular

system may benefit patients with Parkinson’s disease, particularly those with balance and gait problems, suggests a preliminary study published in the journal Brain Stimulation.

ÂÂ In just 10 days, restricting the amount of fructose

children consumed through sugary drinks and juices resulted in dramatic reductions in liver fat, suggested new research presented at The Endocrine Society annual meeting.

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AROUND THE GLOBE ÂÂ Racial/ethnic minority children residing in low-

resource areas may benefit the most from schoolbased opportunities for moderate-to-vigorous physical activity (MVPA), suggests a new study from researchers at Washington University School of Medicine and St Louis Public Schools. The study is published in Preventing Chronic Disease.

ÂÂ Patients who survive an MI may be at significant

risk for overall and specific types of cancer, suggests a study presented in a poster at the American College of Cardiology (ACC) 2015 Scientific Sessions.

ÂÂ At a late-breaking clinical-trial session at the

American College of Cardiology (ACC) 2015 Scientific Sessions, investigators from the first and second Open-Label Study of Long-Term Evaluation Against LDL-C (OSLER-1 and OSLER-2) reported that evolocumab plus standard therapy reduced LDL cholesterol by 61% after 11 months of use vs. standard therapy alone.

ÂÂ A research has concluded that our genome

comprise of genes that are not passed down from our ancestors. These genes might get incorporated in human genome through horizontal transfer from species like bacteria.

ÂÂ A UN led campaign for tobacco free-world - Experts

have proposed UN to lead the efforts for attaining a world free of tobacco. It has been estimated that a world without tobacco can be achieved in less than 3 decades.

ÂÂ A study has found cochlear implants to benefit

cognitive function in elderly with impaired hearing. Improvement in cognitive tests scores were observed after the use of implant. The device activates the auditory nerve in the ear.

ÂÂ Lindioil, an olive oil extract of indigo naturalis, is an

effective treatment for psoriatic nails, suggests new research published online in JAMA Dermatology.

ÂÂ Patients report no significant difference in 2-year

outcomes for surgical vs nonsurgical treatment of displaced upper arm fractures, pointed a UK randomized controlled trial published in the March 10 issue of JAMA.

ÂÂ A prospective observational study published online

March 12 in the Journal of the American Society of Nephrology suggests that across all stages of kidney disease, the risk for adverse pregnancy outcomes increases.

ÂÂ A new study provides the strongest evidence that

anticholinergic drugs may increase the risk for dementia in older adults. The study is published online in JAMA Internal Medicine on January 26.

ÂÂ Updated

best practice recommendations for the emergency treatment of acute-onset, severe hypertension during pregnancy and the postpartum period, by the American College of Obstetricians and Gynecologists Committee on Obstetric Practice, include the addition of nifedipine as a first-line therapy. The updated opinion is published in the February issue of Obstetrics & Gynecology.

ÂÂ On a 10% protein diet, diabetic adults exhibited

increased sensitivity to insulin suppression of proteolysis, but inadequate stimulation of protein synthesis, resulting in a lower net nitrogen balance than patients who ate a 17% protein diet, pointed a new study published in Clinical Nutrition. The study thus suggests that it is especially important for people with type 2 diabetes to eat enough protein.

ÂÂ In a new study, researchers found an association

between the use of erectile dysfunction (ED) drugs after radical prostatectomy and biochemical recurrence. The study was published in the February issue of the Journal of Urology.

ÂÂ New Canadian public-health guidelines on obesity

than other men and even women smokers, suggests a new study published online in the Annals of the American Thoracic Society.

strongly recommend that primary-care clinicians measure body mass index (BMI) and offer structured behavioral weight-loss interventions to obese adults at high risk for type 2 diabetes. The guidelines are published online January 26 in CMAJ.

ÂÂ Men with acromegaly that is not controlled by

ÂÂ Obesity and overweight are known risk factors for

ÂÂ Male smokers have a greater risk for osteoporosis

surgery and somatostatin receptor ligands (SRLs) may do better with clomiphene citrate (CC) added to the current treatment, reveals a new study published online in the Journal of Clinical Endocrinology & Metabolism.

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developing renal cell carcinoma (RCC); however, a new validation data analysis has confirmed that excess weight in patients with RCC may be beneficial. Researchers noted that those with a higher body mass index (BMI) were more likely

AROUND THE GLOBE to have a higher overall survival, longer time to treatment failure and better tumor shrinkage when compared with patients with normal or lower BMI. The findings were presented at the 2015 Genitourinary Symposium. ÂÂ A new study suggests that spider venom could lead

to a more effective treatment for those who suffer from chronic pain. HD1a has been identified in the venom of a species of spider called Haplopelma doriae that blocks the human NaV1.7 pathway, thus having strong potential as an effective painkiller in humans. The findings are published online March 4 in the British Journal of Pharmacology.

ÂÂ Higher levels of fluoride in drinking water

appear to be associated with an increased risk for hypothyroidism in a new study from England in the Journal of Epidemiology and Community Health, raising concerns about the validity of community fluoridation of water as a safe public-health measure. In particular, when a comparison was drawn between the West Midlands, a completely fluoridated area (0.7 mg/L or more) and Greater Manchester, a nonfluoridated area (0.3 mg/L or less), nearly twice the risk for hypothyroidism was detected in the West Midlands.

ÂÂ Chronic kidney disease (CKD) rates are estimated

to rise substantially during the next 20 years, with more than half of individuals aged 30 to 64 years likely to be affected, reports a simulation study published in the March 2015 issue of the American Journal of Kidney Disease.

ÂÂ The first biosimilar product in the United States

has been approved by the US Food and Drug Administration. The product approved is the recombinant colony-stimulating factor filgrastimsndz which has several clinical uses, including aiding recovery from neutropenia in cancer patients undergoing chemotherapy.

ÂÂ A new study suggests that concussion is associated

with reduced cerebral blood flow, which recovers in most individuals within a few weeks. The findings were published online in JAMA Neurology on March 2.

ÂÂ Adults and children must cut the amount of sugar

they consume by as much as half and even more to lower risk of obesity and tooth decay, suggests the World Health Organization.

ÂÂ Long-term use of bisphosphonates is associated

with a reduced risk of developing type 2 diabetes,

suggests a new study published online in The Journal of Clinical Endocrinology & Metabolism. ÂÂ A new, long-term study of a hepatitis E vaccine has

found that it is 86.8% effective and the immunity may last for at least 4.5 years. The findings are published in the March 5 issue of the New England Journal of Medicine.

ÂÂ The

investigational pituitary-hormone–related protein (PTHrP) analog abaloparatide significantly reduces fractures in high-risk postmenopausal women with osteoporosis, suggests a key phase 3 study presented at the annual meeting of the Endocrine Society, ENDO 2015.

ÂÂ Repeated intravitreal injections of ranibizumab

for diabetic macular edema (DME) may lead to sustained elevation of intraocular pressure (IOP), suggest the results from the Diabetic Retinopathy Clinical Research Network, published online in JAMA Ophthalmology.

ÂÂ In patients with relapsed or refractory urothelial

carcinoma, the antitumor activity of paclitaxel chemotherapy plus the targeted agent pazopanib is significant, suggest data presented at the Genitourinary Cancers Symposium 2015.

ÂÂ The US Food and Drug Administration (FDA)

has approved isavuconazonium sulfate, a new antifungal for the treatment of adults with invasive aspergillosis and invasive mucormycosis, rare, but potentially life-threatening infections.

ÂÂ Combining

a conventional disease-modifying antirheumatic drug (DMARD) with a tumor necrosis factor inhibitor (TNFi) seems more effective than a TNFi alone in patients with ankylosing spondylitis (AS) or undifferentiated spondyloarthritis (uSpA), suggested a nationwide prospective study published online in the Annals of the Rheumatic Diseases. However, experts caution that the beneficial effect might not be large enough to justify changing current treatment guidelines.

ÂÂ Menopausal hormone replacement therapy does

not appear to affect mortality either positively or negatively, suggests a new systematic review and meta-analysis presented at the Endocrine Society’s annual meeting, ENDO 2015.

ÂÂ A meta-analysis of 62 studies revealed that

diabetes and prediabetes increased risk for conversion from mild cognitive impairment (MCI) to Alzheimer’s dementia and all-cause dementia. In addition, metabolic syndrome, low dietary folate,

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AROUND THE GLOBE the presence of any neuropsychiatric symptoms and having depressive symptoms all predicted dementia conversion in patients with various forms of MCI, while consumption of a Mediterranean diet decreased risk. The findings are published online in the American Journal of Psychiatry. ÂÂ Vegetarians appear to be at lower risk for

colorectal cancer than nonvegetarians, suggests new research. Investigators noted that those who consumed a vegetarian diet had a 22% lower risk for all colorectal cancers than those who ate meat. The study was published online March 9 in JAMA Internal Medicine.

ÂÂ A study revealed that an intranasal formulation of

oxytocin cut food consumption by an average of 122 kcal in a single-meal test involving 25 healthy men of varying body mass indexes. The results were presented March 8 at the annual meeting of the Endocrine Society, ENDO 2015.

ÂÂ The

anti-interleukin-5 monoclonal antibody, reslizumab, reduces asthma exacerbations in patients with inadequately controlled asthma with elevated blood eosinophil counts, suggest results from two duplicate phase 3 trials published online in The Lancet Respiratory Medicine.

ÂÂ New research suggests that the lower a woman’s

vitamin D levels are as she transitions to menopause, the greater is her risk of sustaining a nontraumatic fracture. The findings are published online in the Journal of Clinical Endocrinology and Metabolism.

ÂÂ Patients who continue to take proton pump

inhibitors (PPIs) after a first episode of Clostridium difficile infection may be at increased risk of recurrence, suggest new findings published online in JAMA Internal Medicine.

ÂÂ Family history is a significant risk factor for breast

cancer, especially in women who have first-degree relatives with the disease. The risk might be even higher if there is a first-degree relative with prostate cancer, suggests a new study published online March 9 in Cancer.

Advisory Committee reported that ATX-101 (deoxycholic acid) injection for improvement in the appearance of moderate-to-severe convexity or fullness associated with submental fat in adults is safe and effective. ÂÂ In postmenopausal women with osteoporosis,

the third generation selective estrogen receptor modulator (SERM) bazedoxifene seems to protect against new vertebral fractures across 7 years, suggest new data from a randomized controlled trial published online in the journal Menopause.

ÂÂ In HIV-infected patients on modern antiretroviral

therapy (ART), postoperative death rates are low and influenced as much by age and nutritional status as immune system function (CD4 cell counts), points new research published online in JAMA Surgery.

ÂÂ Gout was associated with a 24% lower risk

for Alzheimer’s disease (AD) in a populationbased study published online in the Annals of the Rheumatic Diseases.

ÂÂ Readmissions within 90 days of hospitalizations

for severe sepsis are common, suggests a research letter published in the March 10 issue of JAMA. However, just more than 40% of the readmissions were for diagnoses that could potentially be prevented or treated early to avoid hospitalization.

ÂÂ DNA from bacterial species normally found in the

intestinal tract was present in blood samples from some patients with plaque psoriasis during disease flares, researchers reported in an article published online March 11 in JAMA Dermatology.

ÂÂ A modified Mediterranean diet with local foods

may be easier for some people to stick with and also result in weight loss, suggests a new study from Germany published online in the European Journal of Clinical Nutrition.

ÂÂ For patients with hepatocellular carcinoma who

short naps might partly offset that effect, suggests a small study published online in the Journal of Clinical Endocrinology and Metabolism.

meet the Milan criteria, rates of disease-free and overall survival are similar after treatment with surgical resection or radiofrequency ablation, reported a European study presented at the European Congress of Radiology 2015.

ÂÂ A US Food and Drug Administration (FDA) advisory

ÂÂ High-dose corticosteroids increase the risk of

ÂÂ Getting too little sleep is linked to poor health, but

committee unanimously voted to recommend approval of a new injectable to help reduce double chin. The Dermatologic and Ophthalmic Drugs

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organ damage in patients with systemic lupus erythematosus (SLE), suggests a large cohort study published online in Lupus Science and Medicine.

MEDILAW

Ethical Doctor-Pharma Relationship KK AGGARWAL

Have you violated the MCI Act Clause 6.8.1? a. Did you take any gift from any pharmaceutical or allied healthcare industry and their sales people or representatives? b. Did you accept any travel facility inside the country or outside, including rail, air, ship, cruise tickets, paid vacations, etc. from any pharmaceutical or allied healthcare industry or their representatives for self and family members for vacation or for attending conferences, seminars, workshops, CME program, etc. as a delegate/chairperson/faculty/speaker? c. If yes, what was the fee charged? d. If not, what was the reason to accept the invitation? e. Did you accept individually any hospitality like hotel accommodation for self and family members under any pretext? f. Did you receive any cash or monetary grants from any pharmaceutical and allied healthcare industry for individual purpose in individual capacity under any pretext? g. Did you receive any funding for medical research, study, etc. h. If yes, through which institutions? i.

Was the ethics committee involved?

Are you affiliated with any pharmaceutical and allied healthcare industries in advisory capacities, as consultants, as researchers, as treating doctors or in any other professional capacity?

k. Is this association disclosed in your IT return?

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

l. Have you endorsed any drug or product of the industry publically? m. Did you violate IMS Act? i.

Were you involved in promoting any food for children up to 2 years?

ii. Did you indulge in promotion of infant foods before the age of 6 months? iii. Did you display notice in a hospital, nursing home, chemist shop, etc. for promoting these products? iv. Did you receive any payments/gifts from such companies? v. Did you receive funds from such companies for organizing seminars, meeting, conferences, contest, fee of educational course, sponsoring for projects, research work or tours?

What is the punishment for violation of doctorpharma relationship? The punishment for violation of doctor-pharma relationship is decided on a case-to-case basis by the MCI as per Chapter 8 of the Code of Ethics Regulations, 2002. The nature of punishment may range from censure, warning to suspension. 8: Punishment and Disciplinary Action. 8.1: It must be clearly understood that the instances of offenses and of professional misconduct which are given above do not constitute and are not intended to constitute a complete list of the infamous acts which calls for disciplinary action, and that by issuing this notice the MCI and or State Medical Councils are in no way precluded from considering and dealing with any other form of professional misconduct on the part of a registered practitioner. Circumstances may and do arise from time to time in relation to which there may occur questions of professional misconduct which do not come within any of these categories. Every care should be taken that the code is not violated in letter or spirit. In such instances as in all others, the MCI and/or State Medical Councils have to consider and decide upon the facts brought before the MCI and/or State Medical Councils.

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MEDILAW 8.2: It is made clear that any complaint with regard to professional misconduct can be brought before the appropriate Medical Council for Disciplinary action. Upon receipt of any complaint of professional misconduct, the appropriate Medical Council would hold an enquiry and give opportunity to the registered medical practitioner to be heard in person or by pleader. If the medical practitioner is found to be guilty of committing professional misconduct, the appropriate Medical Council may award such punishment as deemed necessary or may direct the removal altogether or for a specified period, from the register of the name of the delinquent registered practitioner. Deletion from the Register shall be widely publicised in local press as well as in the publications of different Medical Associations/Societies/Bodies. 8.3: In case the punishment of removal from the register is for a limited period, the appropriate Council may also direct that the name so removed shall be restored in the register after the expiry of the period for which the name was ordered to be removed. 8.4: Decision on complaint against delinquent physician shall be taken within a time limit of 6 months. 8.5: During the pendency of the complaint the appropriate Council may restrain the physician from performing the procedure or practice which is under scrutiny. 8.6: Professional incompetence shall be judged by peer group as per guidelines prescribed by Medical Council of India.

Is endorsement by the Association same as endorsement by a doctor? The answer is no. Under the MCI Ethics Regulation 2009 6.8, code of conduct for doctors and professional associations of doctors for their relationship with pharmaceutical and allied healthcare industry, the code of endorsement is described under Sub-section H. “h) Endorsement: A medical practitioner shall not endorse any drug or product of the industry publically. Any study conducted on the efficacy or otherwise of such products shall be presented to and/or through appropriate scientific bodies or published in appropriate scientific journals in a proper way.” As per this regulation a medical practitioner shall not endorse, which means that whenever a product is endorsed, his or her name has to appear before or after the endorsement. For example, a doctor endorsing that “A coke a day is not harmful to health: Dr X”. If

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the same endorsement does not carry his or her name, then it is not an endorsement by a medical practitioner for example “A coke a day is not harmful to health: Indian Doctors Association.” In the first case, the endorsement is by medical practitioner and in the second, the endorsement is by an association. Even though in the second case, the endorsement was signed by one of the office bearers, it does not mean that he is endorsing it as medical practitioner as he is not giving his or her name. There is also a loophole in clause H; the words “any study conducted on the efficacy or otherwise of such products shall be presented to and/or through appropriate scientific bodies or published in appropriate scientific journals in a proper way”, mean if somebody has carried out a study, for example “whether one coke a day is harmful to the body or not” and if the inference of the study is that “one coke a day is not harmful” and if the same study is published by the association in its own journal or presented in one of its own conference, it gets relief from the endorsement clause. In such case, the company can quote “A coke a day is not harmful to health: Journal of India Doctors Association.”

What is the check list for a default doctor-pharma relationship? ÂÂ Name of the Doctor ÂÂ Age ÂÂ Sex ÂÂ Address ÂÂ State Medical Council Registration No. ÂÂ Medical Council of India Registration No. ÂÂ Email Address What is the income tax rule about doctor-pharma relationships? Freebies to associations of doctors is in violation of IMC Act regulations. The Central Board of Direct Taxes (CBDT) issued a circular (as below) for the inadmissibility of expenses incurred in providing freebies by phamaceutical and allied health sector industry. CBDT Circular No.: 5/2012 [F. NO. 225/142/2012-ITA. II], dated 1-8-2012 a. “Section 37(1) of the Income Tax Act, 1961 - business expenditure - allowability of - inadmissibility of expenses incurred in providing freebies to medical practitioner by

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MEDILAW pharmaceutical and allied health sector industry. It has been brought to the notice of the Board that some pharmaceutical and allied health sector industries are providing freebies to medical practitioners and their professional associations in violation of the regulations issued by Medical Council of India (the ‘Council’) which is a regulatory body constituted under the Medical Council Act, 1956. b. The Council in exercise of its statutory powers amended the Indian Medical Council (Professional Conduct, Etiquette and Ethics) Regulations, 2002 (the regulations) on 10-122009 imposing a prohibition on the medical practitioner and their professional associations from taking any Gift, Travel facility, Hospitality, Cash or monetary grant from the pharmaceutical and allied health sector industries. c. Section 37(1) of Income Tax Act provides for deduction of any revenue expenditure (other than those failing under Sections 30 to 36) from the business Income if such expense is laid out/expended wholly or exclusively for the purpose of business or profession. However, the explanation appended to this sub-section denies claim of any such expense, if the same has been incurred for a purpose which is either an offence or prohibited by law. Thus, the claim of any expense incurred in providing above mentioned or similar freebies in violation of the provisions of Indian Medical Council (Professional Conduct, Etiquette and Ethics) Regulations, 2002 shall

be inadmissible under Section 37(1) of the Income Tax Act being an expense prohibited by the law. This disallowance shall be made in the hands of such pharmaceutical or allied health sector industries or other assessee which has provided aforesaid freebies and claimed it as a deductible expense in its accounts against income. d. It is also clarified that the sum equivalent to value of freebies enjoyed by the aforesaid medical practitioner or professional associations is also taxable as business income or income from other sources as the case may be depending on the facts of each case. The Assessing Officers of such medical practitioner or professional associations should examine the same and take an appropriate action. This may be brought to the notice of all the officers of the charge for necessary action.” Comments: The same is also a misconduct in MCI Act.

What is adultery? IPC 497: Adultery: Whoever has sexual intercourse with a person who is and whom he knows or has reason to believe to be the wife of another man, without the consent or connivance of that man, such sexual intercourse not amounting to the offence of rape, is guilty of the offence of adultery, and shall be punished with imprisonment of either description for a term which may extend to 5 years, or with fine, or with both. In such case, the wife shall not be punishable as an abettor. (Comments: This Code is important for medical professionals not only as doctors but also for their personal life as it defines adultery in detail).

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LIGHTER READING

THE BURNT BISCUITS When I was a kid…my mom liked to make food for breakfast and for dinner every now and then. And I remember one night in particular when she had made dinner after a long, hard day at work. On that evening so long ago, my mom placed a plate of eggs, sausage and extremely burned biscuits in front of my dad. I remember waiting to see if anyone noticed! Yet all my dad did was reach for his biscuit, smile at my mom and ask me how my day was at school.

HUMOR

INSPIRATIONAL STORY

Lighter Side of Medicine

You know…life is full of imperfect things…… and imperfect people. I’m not the best at hardly anything and I forget birthdays and anniversaries just like everyone else. What I’ve learned over the years is that learning to accept each other’s faults – and choosing to celebrate each other’s differences – is one of the most important keys to creating a healthy, growing and lasting relationship.

MR SMITH IS DEAD A law firm receptionist answered the phone in the morning after the firm’s senior partner had passed away unexpectedly. “Is Mr Smith there?” asked the client on the phone. “I’m very sorry, but Mr Smith passed away last night,” the receptionist answered. “Is Mr Smith there?” repeated the client. The receptionist was perplexed. “Perhaps you didn’t understand me I’m afraid Mr. Smith passed away last night.” “Is Mr Smith there?” asked the client again. “Ma’am, do you understand what I’m saying?” said the exasperated receptionist. “Mr Smith is DEAD!” “I understand you perfectly,” the client sighed. “I just can’t hear it often enough.”

QUOTES

I don’t remember what I told him that night, but I do remember watching him smear butter and jelly on that biscuit and eat every bite! When I got up from the table that evening, I remember hearing my mom apologize to my dad for burning the biscuits. And I’ll never forget what he said: “Honey, I love burned biscuits.” Later that night...I went to kiss Daddy good night and I asked him if he really liked his biscuits burned. He wrapped me in his arms and said, “Your Mom put in a hard day at work today and she’s real tired...And besides - a little burnt biscuit never hurt anyone!”

pass me a biscuit and yes…the burnt one will do just fine. Life is too short to wake up with regrets.

“And in the end, it’s not the years in your life that count. It’s the life in your years.” – Abraham Lincoln

Dr. Good and Dr. Bad SITUATION: A patient with Mediclaim was advised to get admitted in a 5-bedded hospital.

It does not matter

Go to a 15-bedded hospital

We could extend this to any relationship. In fact, understanding is the base of any relationship, be it a husband-wife or parent-child or friendship! “Don’t put the key to your happiness in someone else’s pocket…keep it in your own.” So please

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©IJCP Academy

Learn to take the good, the bad and the difficult parts of your life and take them for what they are worth. Because in the end, a burnt biscuit isn’t a deal-breaker!

LESSON: Mediclaim requires admission in hospital with minimum 15 beds (in C-Towns, it can be 10-bedded).

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

– –

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

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

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

–

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

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

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

Confidence intervals for the measurements should be provided wherever appropriate.

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

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Discussion –

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

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

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

Do not use clips/staples on photographs and artwork.

–

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

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

Books

5. Special requests _____________________________

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

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. –

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The legend must include enough information to permit interpretation of the figure without reference to the text.

Indian Journal of Clinical Practice, Vol. 25, No. 11, April 2015

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

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