Indian journal of clinical practice february 2015 by IJCP

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ISSN 0971-0876

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Volume 25, Number 9

February 2015, Pages 801â&#x20AC;&#x201C;900

Peer Reviewed Journal

American Family Physician

Cardiology

Critical Care

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Endocrinology

ENT

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Orthopedics

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

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

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

Volume 25, Number 9, February 2015 FROM THE DESK OF THE GROUP EDITOR-IN-CHIEF

806 Five Practices that should be Avoided by Cardiologists

KK Aggarwal

AMERICAN FAMILY PHYSICIAN

808 Evaluation and Treatment of Constipation in Children and Adolescents

Samuel Nurko, Lori A. Zimmerman

817 Practice Guidelines 821 Photo Quiz CARDIOLOGY

824 A Rare Association of Rheumatoid Arthritis with Ascending Aortic Aneurysm: A Case Report

Ravi Prakash Pandey, KD Singh, M Indurkar, Dharmendra Jain

CRITICAL CARE

828 Chickenpox Pneumonia with ARDS in a 46-year-old Immunocompetent Male

Kamal Kumar, Shivanjali Kumar

DERMATOLOGY

831 A Randomized Open Label Comparative Clinical Study of Synbiotic as an Add-on Therapy to Standard Treatment with Standard Treatment Alone in the Management of Patients with Eczema

T Meenakshi, R Nandini

839 Erythroderma: Epidemiology, Clinical Profile and Clinicopathological Correlation in 47 Patients

US Agarwal, Anshul Maheshwari, Sunil Kothiwala, Karuna Gupta, Arpita Jindal

ENDOCRINOLOGY

844 Primary Hyperparathyroidism with Chronic Pancreatitis: A Case Report

Achintya Pal, Avik Chakraborty, Arkadip Choudhury

847 Alternatives to Conventional Hormone Replacement Therapy for Postmenopausal Outcomes

Sippy Agarwal, Saurabh Agarwal, G Agarwal, Vivek Niranjan, PK Agarwal, Richa Goyal

ENT

Anand Gopal Bhatnagar Editorial Anchor

849 Bacteriology of Chronic Suppurative Otitis Media: A Preliminary Study at a Tertiary Hospital

Advisory Bodies Heart Care Foundation of India Non-Resident Indians Chamber of Commerce & Industry World Fellowship of Religions

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

Mirza Aneesa Afzal Beg, Irfan Iqbal, Imtiyaz Derweish

INTERNAL MEDICINE

854 Risk Factors Associated with Trimethoprim-sulfamethoxazole

and Ciprofloxacin Resistance Among Escherichia coli Strains Isolated from Community-acquired Urinary Tract Infection

Pottathil Shinu, Rajesh Bareja, Varsha A Singh, Monika Bansal, Manoj Goyal, Ruhi Bunger, Beena Jad, Avneet Singh Setia

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

861 To Compare Maternal Outcome in Registered (Booked) and Unregistered (Unbooked) Cases of Placenta Previa: A Prospective Study at a Tertiary Care Center of Northern India

Shaveta Jain, Pushpa Dahiya, Nitin Jain, Roopa Malik

866 Laparoscopic Resection of Large Cornual Pregnancy

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

Hasina Banu, Ju Wen Hui, Li Hui

870 Three Different Presentations of Ectopic Pregnancy in the Same Patient

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.

Madhupriya, Kundavi Shankar, Lakshmi Shanmugasundaram, Thankam R Varma

ORTHOPEDICS

874 Atypical Periosteal Osteoid Osteoma: A Case Report

SS Suresh, V Rani

PEDIATRICS

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

877 A Randomized, Double-blind, Placebo-controlled Study of Synbiotics (BIFILAC) in Children with Acute Diarrhea

Sabrina Harris Aydeross, Chidambaranathan S, Ramesh S

881 Severe Anemia and Hypothyroidism

Suprabha Shukla, Dillip Kumar Das, Jnanindra Nath Behera

EXPERT VIEW

884 Actions Necessary to Implement to Ensure Continuous Improvement...

Sunil Kumar Saggar

AROUND THE GLOBE

885 News and Views MEDILAW

889 Drugs and Ethical Advertising

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.

KK Aggarwal

INSPIRATIONAL STORY

893 Be a Good Friend LIGHTER READING

894 Lighter Side of Medicine

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FROM THE DESK OF THE GROUP EDITOR-IN-CHIEF

Dr KK Aggarwal

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

Five Practices that should be Avoided by Cardiologists ÂÂ Coronary CT angiography (CTA) should NOT be used as a 'screening' test in asymptomatic individuals

without clinical suspicion of coronary artery disease (CAD).

ÂÂ Cardiac stress testing is NOT indicated in asymptomatic individuals at low-risk of coronary events.

Noninvasive testing in patients with suspected CAD should be based on the assessment of their pre‐test probability of having disease determined from clinical evaluation (e.g., presence of symptoms and risk factors). Patients with an intermediate pre‐test probability (15‐ 85%) of having CAD should undergo stress testing.1 Coronary CTA may sometimes be considered as an alternative to rule out significant CAD in patients in the lower range of intermediate pre‐test probability.1 Neither stress testing nor coronary CTA is useful in patients with a low pre‐test probability of CAD.1,2 Asymptomatic patients may be further stratified by the risk of future CAD events using either the QRISK2, ASCVD or other validated scores. Patients who are categorized as having a 10‐year risk <10% will not benefit from stress testing or coronary CTA.3 Indiscriminate use of stress testing with imaging and coronary CTA expose patients to the risk of radiation and iodinated contrast, and the anxiety, costs and harms of the resulting downstream invasive testing and interventions, which may not be indicated. ÂÂ Annual cardiac stress testing should NOT be performed as part of routine follow‐up evaluation of

asymptomatic individuals or those with stable symptoms.

Periodic stress testing in asymptomatic individuals or patients with stable disease (i.e., testing not prompted by changes in symptom status) are considered inappropriate.3 The widely prevalent annual health check‐ups involving stress testing should be discouraged. ÂÂ Patients undergoing noncardiac surgery, who have moderate to good functional capacity (≥4 METs), OR

have no risk factors for CAD, should NOT undergo echocardiography or stress testing as part of routine pre‐operative evaluation.

Patients who are active and have moderate to good functional capacity (i.e., they can exercise ≥4 METs) and those without risk factors for CAD are unlikely to benefit from routine assessment of left ventricular or function stress testing.3 On the contrary, such an approach may cause more harm by delaying elective surgery. ÂÂ Patients presenting late (>72 hours) after ST-segment elevation myocardial infarction (STEMI) should NOT

have angioplasty for an occluded infarct related artery without evidence of ischemia or viability.

Patients with an occluded infarct related artery do not benefit from a strategy of systematic percutaneous coronary angioplasty performed after 72 hours of an STEMI.2 Decisions about revascularization should be made based on the presence of symptoms, evidence of ischemia/viability in the infarcted territory.

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FROM THE DESK OF THE GROUP EDITOR-IN-CHIEF REFERENCES 1. Task Force Members, Montalescot G, Sechtem U, Achenbach S, Andreotti F, Arden C, Budaj A, et al. 2013 ESC guidelines on the management of stable coronary artery disease: the Task Force on the management of stable coronary artery disease of the European Society of Cardiology. Eur Heart J 2013;34(38):2949-3003. 2. Authors/Task Force members, Windecker S, Kolh P, Alfonso F, Collet JP, Cremer J, Falk V, et al; Authors/Task Force members. 2014 ESC/EACTS Guidelines on myocardial revascularization: The Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS)Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J 2014;35(37):2541-619. 3. Wolk MJ, Bailey SR, Doherty JU, Douglas PS, Hendel RC, Kramer CM, et al; American College of Cardiology Foundation Appropriate Use Criteria Task Force. ACCF/AHA/ASE/ASNC/HFSA/HRS/SCAI/SCCT/SCMR/STS 2013 multimodality appropriate use criteria for the detection and risk assessment of stable ischemic heart disease: a report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, American Heart Association, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, and Society of Thoracic Surgeons. J Am Coll Cardiol 2014;63(4):380-406. ■■■■

Indian Journal of Clinical Practice, Vol. 25, No. 9, February 2015

807

AMERICAN FAMILY PHYSICIAN

Evaluation and Treatment of Constipation in Children and Adolescents SAMUEL NURKO, LORI A. ZIMMERMAN

ABSTRACT Childhood constipation is common and almost always functional without an organic etiology. Stool retention can lead to fecal incontinence in some patients. Often, a medical history and physical examination are sufficient to diagnose functional constipation. Further evaluation for Hirschsprung disease, a spinal cord abnormality, or a metabolic disorder may be warranted in a child with red flags, such as onset before one month of age, delayed passage of meconium after birth, failure to thrive, explosive stools, and severe abdominal distension. Successful therapy requires prevention and treatment of fecal impaction, with oral laxatives or rectal therapies. Polyethylene glycol–based solutions have become the mainstay of therapy, although other options, such as other osmotic or stimulant laxatives, are available. An increase in dietary fiber may improve the likelihood that laxatives can be discontinued in the future. Education is equally important as medical therapy and should include counseling families to recognize withholding behaviors; to use behavior interventions, such as regular toileting and reward systems; and to expect a chronic course with prolonged therapy, frequent relapses, and a need for close follow-up. Referral to a subspecialist is recommended only when there is concern for organic disease or when the constipation persists despite adequate therapy.

Keywords: Constipation, functional, fecal impaction, oral laxatives, rectal therapies, dietary fiber

onstipation is one of the most common chronic disorders of childhood, affecting 1% to 30% of children worldwide.1 Constipation is responsible for 3% of all primary care visits for children and 10% to 25% of pediatric gastroenterology visits.2

Children with constipation cost the health care system three times as much as children without constipation,3 and the negative effect on quality of life often persists into adulthood.4 DEFINITION The Rome III criteria are the most accepted criteria for diagnosing childhood constipation (Table 1).5,6 However, the time duration does not need to be fulfilled to start therapy because there is evidence that early treatment favorably affects outcome.2

SAMUEL NURKO, MD, is director of the Motility and Gastrointestinal Disorders Center at Boston (Mass.) Children’s Hospital, and is an associate professor in the hospital’s Department of Medicine. LORI A. ZIMMERMAN, MD, is an attending physician in gastroenterology and nutrition in the Department of Medicine at Boston Children’s Hospital. Source: Adapted from Am Fam Physician. 2014;90(2):82-90.

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NORMAL DEFECATION PATTERNS Parents often worry that their child’s bowel movements are too infrequent. The number of bowel movements a child has in a day decreases with age and reaches adult frequencies during the preschool years.7,8 An infant averages three to four stools a day in the first week of life, two stools a day later in infancy and the toddler years, and once a day to every other day after the preschool years.9 Many healthy breastfed infants go several days or longer without a bowel movement.2 Thus, less frequent defecation patterns may be normal and must be considered in the context of stool caliber, associated symptoms, and physical examination findings. ETIOLOGY AND PATHOPHYSIOLOGY Outside of the neonatal period, childhood constipation is usually functional (i.e., there is no evidence of an organic condition).2,10 Functional constipation is most commonly caused by painful bowel movements that prompt the child to voluntarily withhold stool. To avoid the passage of another painful bowel movement, the child will contract the anal sphincter or gluteal muscles by stiffening his or her body, hiding in a corner, rocking back and forth, or fidgeting with each urge to defecate. Parents often confuse these withholding behaviors as

AMERICAN FAMILY PHYSICIAN straining to defecate. Withholding of stool can lead to prolonged fecal stasis in the colon with reabsorption of fluid, causing the stool to become harder, larger, and more painful to pass. Over time, as the rectum stretches to accommodate the retained fecal mass, rectal sensation decreases, and fecal incontinence may develop. This cycle commonly coincides with toilet training, changes in routine or diet, stressful events, illness, or lack of accessible toilets, or occurs in a busy child who defers defecation. FECAL INCONTINENCE Fecal incontinence is the voluntary or involuntary passage of feces in the underwear or in socially inappropriate places in a child with a developmental age of at least four years. It occurs in 1% to 4% of school-aged children and is almost always associated with underlying constipation.11 Fecal incontinence may also be associated with urinary incontinence. The pathophysiology of fecal incontinence is poorly understood. An interaction of behavioral and physiologic factors is thought to cause long-standing functional constipation with overflow incontinence.12 Families may incorrectly confuse fecal incontinence for diarrhea or lack of attention. Fecal incontinence often improves when the stool retention is treated.13

CLINICAL DIAGNOSIS A history and physical examination are usually sufficient to distinguish functional constipation from constipation caused by an organic condition.2,10 A medical history should include the familyâ&#x20AC;&#x2122;s definition of constipation and a careful review of the frequency, consistency, and size of stools; age at onset of symptoms; timing of meconium passage after birth; recent stressors; previous and active therapies; presence of withholding behaviors, pain, or bleeding with bowel movements; abdominal pain; fecal incontinence; and systemic symptoms (Table 2).2 The presence of withholding behaviors supports the diagnosis of functional constipation. Further evaluation may be warranted in children with red flags that might suggest an organic etiology (Table 3).2 Physical examination should include a review of growth parameters, an abdominal examination, an external examination of the perineum and perianal area, an evaluation of the thyroid and spine, and a neurologic evaluation for appropriate reflexes (cremasteric, anal wink, patellar). A digital examination of the anorectum is recommended to assess for perianal sensation, anal tone, rectum size, anal wink, and amount and consistency of stool in the rectum. However, in children with normal neonatal courses or clear withholding behaviors, or in whom trauma is suspected, the

Table 2. Components of a Medical History in the Evaluation of Childhood Constipation Components

Clinical significance

Frequency, consistency, and size of stools

Larger, hard stools may be a sign of withholding; normal bowel movement frequency associated with symptoms may indicate irritable bowel syndrome

Age of onset

Infants younger than one month with constipation have a relatively greater likelihood of an organic etiology

Pain or bleeding with passing stools

May suggest stools that are hard enough to produce fissures or that are associated with an allergy

Abdominal pain

It is important to see if pain is relieved or affected by defecation (may suggest irritable bowel syndrome); rule out other causes because abdominal pain is often misdiagnosed as being related to constipation

Timing of first bowel movement after birth

Lack of a bowel movement in first 48 hours suggests Hirschsprung disease

Fecal incontinence

Suggests fecal impaction

Withholding behaviors

Important contributor to constipation in younger children; behavior interventions may be beneficial

Systemic symptoms (e.g., fever, vomiting, weight loss, decreased appetite)

May indicate an organic etiology, such as Hirschsprung disease

Social history, including toilet training, stressors

May be associated with the onset of constipation

Review of current and previous therapies including diet, behavior, medications

It is important to ascertain how the patient has been treated previously and if medication dosages were appropriate

Assess adherence and effectiveness of previous and current treatments

It is important to understand factors that may influence the treatment outcome

Information from reference 2.

Indian Journal of Clinical Practice, Vol. 25, No. 9, February 2015

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AMERICAN FAMILY PHYSICIAN Table 3. Red Flags Suggesting an Organic Cause of Constipation in Children Red flags

Suggested diagnoses

Onset before one month of age

Congenital malformation of anorectum or spine, Hirschsprung disease, allergy, metabolic/endocrine condition

Delayed passage of meconium (more than 48 hours after birth)

Hirschsprung disease, cystic fibrosis, congenital malformation of anorectum or spine

Failure to thrive

Hirschsprung disease, malabsorption, cystic fibrosis, metabolic condition

Abdominal distension

Hirschsprung disease, impaction, neurenteric problem (e.g., pseudoobstruction)

Intermittent diarrhea and explosive stools

Hirschsprung disease

Empty rectum

Hirschsprung disease

Tight anal sphincter

Hirschsprung disease, anorectal malformations

Pilonidal dimple covered by tuft of hair

Spinal cord abnormality

Midline pigmentary abnormalities of lower spine

Spinal cord abnormality

Abnormal neurologic examination (absent anal wink, absent cremasteric reflex, decreased lower extremity reflexes and/or tone)

Spinal cord abnormality

Occult blood in stool

Hirschsprung disease, allergy

Extraintestinal symptoms (vomiting, fever, illappearance)

Hirschsprung disease, neurenteric problem

Gushing of stool with rectal examination

Hirschsprung disease

No history of withholding or soiling

Hirschsprung disease, neurenteric problem, spinal cord abnormality

No response to conventional treatment

Hirschsprung disease, neurenteric problem, spinal cord abnormality

Information from reference 2.

rectal examination may be deferred. A test for occult blood in the stool should be performed in all infants with constipation and in any child with constipation who has pain, failure to thrive, diarrhea, or a family history of colon cancer or polyps. The presence of a hard mass in the lower abdomen combined with a dilated rectum filled with hard stool indicates fecal impaction. Abdominal radiography is of limited value in diagnosing chronic constipation because it lacks interobserver reliability and accuracy.2,14,15 It should be reserved for specific clinical circumstances in which a rectal examination is unreasonable (e.g., in a child with a history of trauma) or the diagnosis is uncertain. DIFFERENTIAL DIAGNOSIS Table 4 outlines the differential diagnosis of constipation in children and the recommended diagnostic evaluations.2 The age of the patient must be carefully considered.

Young Infants The likelihood of an organic etiology for constipation is relatively greater in infants younger than six months, and particularly in those younger than three

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months. Hirschsprung disease must be considered in infants with delayed passage of meconium (more than 48 hours after birth) or other red flags, even in the setting of normal findings on barium enema examination. Hirschsprung disease is the most common cause of lower intestinal obstruction in neonates. A delayed diagnosis can result in enterocolitis, a potentially fatal complication that causes fever; abdominal distension; and explosive, bloody diarrhea.16 Patients with suspected Hirschsprung disease should be referred to a medical center with a pediatric gastroenterologist and surgeon for confirmatory testing with rectal suction biopsy. If Hirschsprung disease is excluded in an infant with delayed passage of meconium, cystic fibrosis and other anatomic malformations should be considered. The physical examination of a young infant should assess the position and patency of the anus and include a neurologic examination to evaluate for congenital anomalies of the anus and spine (e.g., anteriorly displaced anus, anal stenosis, imperforate anus, spina bifida, tethered cord). Breastfed infants require special consideration because in the absence of red flags or other medical issues, they require no further workup for infrequent bowel movements.

AMERICAN FAMILY PHYSICIAN Table 4. Differential Diagnosis of Constipation in Children Conditions

Recommended diagnostic evaluation

Functional constipation

History and physical examination; no testing

Anatomic malformations of the colon and rectum Imperforate anus, anal or colonic stenosis, anteriorly displaced anus

Physical examination, barium enema

Spinal cord abnormalities Meningomyelocele, spinal cord tumor or trauma, tethered cord

Spinal magnetic resonance imaging, anorectal manometry, urodynamics

Metabolic conditions Hypothyroidism

Thyroid studies

Hypercalcemia, hyperkalemia

Serum calcium and potassium levels

Diabetes mellitus

Fasting glucose level

Diabetes insipidus

Serum and urine osmolarity

Neuropathic gastrointestinal disorders Hirschsprung disease, internal anal sphincter achalasia

Anorectal manometry, rectal suction biopsy

Visceral myopathy/neuropathy

Colonic manometry

Drug use/toxin exposure Opiates, phenobarbital, anticholinergics and attention-deficit/ hyperactivity disorder drugs, antacids and sucralfate antidepressants, antihypertensives

History, drug level

Lead toxicity

Lead level

Other systemic disorders Celiac disease

Tissue transglutaminase IgA, total IgA, endoscopy

Cystic fibrosis

Sweat test

Cow’s milk protein intolerance

Cow’s milk elimination

Connective tissue disorder, mitochondrial disorders

Special testing

Psychiatric disorders

Psychological and psychiatric evaluation

IgA = Immunoglobulin A. Information from reference 2.

Older Children

TREATMENT

Further evaluation is indicated in older children with red flags or with intractable constipation despite strict adherence to therapy. Laboratory studies may be performed to evaluate for systemic diseases, such as thyroid disease, other metabolic diseases, celiac disease, or lead toxicity. Motility studies (e.g., anorectal manometry) can assess for sphincter abnormalities, such as Hirschsprung disease or a nonrelaxing internal anal sphincter.

The treatment of functional constipation requires parental education, behavior interventions, measures to ensure that bowel movements occur at normal intervals with good evacuation, close follow-up, and adjustment of medication and evaluation as necessary. Algorithms for the evaluation and management of constipation in infants and older children are presented in Figures 1 and 2.2,10,19

Magnetic resonance imaging of the spine may be necessary to evaluate for a tethered cord, spinal cord tumor, or sacral agenesis.17 A trial of a cow’s milk–free diet may also be considered because constipation can be caused by intolerance to cow’s milk, especially in young children with anal fissures.2,18

Education is the first step in treatment. Educational materials for parents on constipation and fecal soiling are available at http:// www.gikids.org. It is important to explain that fecal incontinence occurs from involuntary overflow of stool and not from voluntary defiance. Behavior modification with regular toileting (for five to

Education and Behavior Modification

Indian Journal of Clinical Practice, Vol. 25, No. 9, February 2015

811

AMERICAN FAMILY PHYSICIAN Constipation in Infants Younger than Six Months Constipation

History, physical examination, occult blood testing

Delayed passage of meconium (more than 48 hours after birth)?

Yes

No Red flags? (Table 3)

Yes Referral for evaluation of possible organic etiologies (e.g., Hirschsprung disease, cystic fibrosis)

Exclusively breastfed (older than two weeks)?

Yes Most likely normal

Functional constipation

Treatment: Education and diet modification (e.g., fruit juice, such as prune; increased fluids; verification of formula preparation)

Effective?

Yes Maintenance therapy

Medication: Lactulose, sorbitol, polyethylene glycol solutions, occasional glycerin suppository

Effective?

Yes Maintenance therapy

No If therapy fails despite good adherence and education, refer for further evaluation

Figure 1. Algorithm for evaluation and management of constipation in infants younger than six months. Information from references 2, 10, and 19.

10 minutes) after meals combined with a reward system is often helpful. Parents should be encouraged to maintain a positive and supportive attitude throughout treatment and expect gradual improvement with occasional relapses. Although behavior modification and education are important, intensive behavior therapy does not seem to add to treatment success, except in rare cases in which the patient has underlying behavior

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problems.20 Biofeedback has not been shown to be effective in children with functional constipation.2,21

Dietary Changes Dietary changes are often advised in children with constipation.21 An increased intake of fluids and absorbable and nonabsorbable carbohydrates (e.g., sorbitol in prune, pear, and apple juice) can help

AMERICAN FAMILY PHYSICIAN Constipation in Children Six Months and Older

Table 5. Therapies for Disimpaction in Children Therapy

Constipation

Dosage

Oral History, physical examination

Osmotics

Red flags? (Table 3)

Yes Referral for further evaluation

Polyethylene glycol 3350*

1.5 g per kg per day

Polyethylene glycol solution*

25 mL per kg per hour via nasogastric lavage

Magnesium citrate

Functional constipation

< 6 years: 2 to 4 mL per kg per day 6 to 12 years of age: 100 to 150 mL per day

Fecal impaction?

> 12 years: 150 to 300 mL per day Stimulants Senna

Yes Initiate oral or rectal medications for disimpaction

6 to 12 years of age: 5 to 15 mL; 1 to 2 tablets per day

Effective?

Bisacodyl Yes

No Referral for further evaluation

2 to 6 years of age: 2.5 to 7.5 mL (8.8 mg per 5 mL); ½ to 1 ½ tablets (8.6 mg per tablet) per day

Lubricants Mineral oil

Functional constipation without impaction

Effective after two weeks?

Yes

Saline

5 to 10 mL per kg

Mineral oil

15 to 30 mL per year of age up to 240 mL

Phosphate soda

2 to 12 years of age: 66-mL enema (should not to be used in children < 2 years because of the risk of electrolyte abnormality)

No Reassess, reeducate, monitor treatment adherence, change medications

> 12 years: 133 mL Suppository (one per day)

Effective?

Yes Maintenance therapy

15 to 30 mL per year of age per day

Rectal agents Enemas (one per day)

Treatment: Education, behavior modification, diet modification, oral medications, close follow-up

Maintenance therapy

≥ 2 years: 5 to 15 mg (1 to 3 tablets) per day in a single dose

Bisacodyl

≥ 2 years: 5 to 10 mg (½ to 1 suppository)

Glycerin*

½ to 1 infant suppository; adult suppository for those older than 6 years

No Referral for further evaluation

Figure 2. Algorithm for evaluation and management of constipation in children six months and older. Information from references 2, 10, and 19.

soften stools, particularly in infants. The recommended dosage of prune juice for infants is 2 oz per day. It can be diluted with 2 oz of water for palatability. Studies have shown that children with constipation have a lower fiber intake than other children. An increased intake of dietary fiber may improve the likelihood that a child

Other Manual (used rarely; general anesthesia needed)

*May be used in infants < 1 year. Information from references 2, and 24 through 26.

will be able to discontinue laxative therapies.22 The addition of a probiotic (e.g., Lactobacillus GG) may be helpful in some children with functional constipation, although the studies are preliminary.23

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AMERICAN FAMILY PHYSICIAN Table 6. Maintenance Therapies for Children with Constipation Therapy

Dosage

Adverse effects

Polyethylene glycol 3350*†

0.5 to 0.8 g per kg up to 17 g per day

Anaphylaxis, flatulence

Lactulose†

1 mL per kg per day once or twice per day, single dose or in two divided doses

Abdominal cramps, flatulence

Magnesium hydroxide

< 2 years: 0.5 mL per kg per day

Infants are susceptible to magnesium overdose (hypermagnesemia, hyperphosphatemia, hypocalcemia)

Osmotics

2 to 5 years of age: 5 to 15 mL per day 6 to 11 years of age: 15 to 30 mL per day ≥ 12 years: 30 to 60 mL per day Medication may be given at bedtime or in divided doses Sorbitol (e.g., prune juice)†

1 to 3 mL per kg once or twice per day in infants

Similar to lactulose

1 month to 2 years of age: 1.25 to 2.5 mL (2.2 to 4.4 mg) at bedtime (< 5 mL per day); 8.8 mg per day

Idiosyncratic hepatitis, melanosis coli, hypertrophic osteoarthropathy, analgesic nephropathy

Stimulants Senna†

2 to 6 years of age: 2.5 to 3.75 mL (4.4 to 6.6 mg) or ½ tablet (4.3 mg) at bedtime (< 7.5 mL or 1 tablet per day) 6 to 12 years of age: 5 to 7.5 mL (8.8 to 13.2 mg) or 1 tablet (8.6 mg) at bedtime (< 15 mL or 2 tablets per day) > 12 years: 10 to 15 mL (26.4 mg) or 2 tablets (17.2 mg) at bedtime (< 30 mL or 4 tablets per day) Bisacodyl

> 2 years: 5 to 15 mg (1 to 3 tablets) once per day

Abdominal cramps, diarrhea, hypokalemia, abnormal rectal mucosa, proctitis (rare), urolithiasis (case reports)

Children: 5 to 15 mL per day

Lipoid pneumonia if aspirated, theoretical interference with absorption of fat-soluble substances, foreign body reaction in intestine

Lubricants Mineral oil

Adolescents: 15 to 45 mL per day

*First-line therapy. †May be used in infants < 1 year. Information from references 2, and 24 through 26.

Disimpaction When fecal impaction is present, disimpaction with oral or rectal medication is required before initiation of maintenance therapy. Oral medications are less invasive but require more patient cooperation and may be slower to relieve symptoms. A number of therapies are available (Table 5).2,24-26 The advent of polyethylene glycol–based solutions has changed the initial approach to constipation in children because they are effective, easy to administer, noninvasive, and well tolerated.27 Rectal therapies and polyethylene glycol are similarly

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effective in the treatment of fecal impaction in children.28 Although some evidence supports polyethylene glycol as first-line treatment, the overall data do not clearly demonstrate superiority of one laxative.29

Maintenance Therapy The goal of maintenance therapy is to avoid reaccumulation of stool by maintaining soft bowel movements, preferably occurring once a day. Given a robust placebo response, there is insufficient evidence to support the effectiveness of laxative therapies over placebo in the treatment of childhood constipation.30

AMERICAN FAMILY PHYSICIAN However, most studies show that the addition of laxatives is usually necessary and more effective than behavior modification alone.31 Although the use of enemas has been advocated in the past, recent studies have shown that the addition of enemas to oral laxative regimens does not improve outcomes in children with severe constipation.32 Table 6 summarizes maintenance therapies.2,24-26 Overall, polyethylene glycol achieves equal or better treatment success than other laxatives, such as lactulose or milk of magnesia,30,33,34 although it may be associated with more episodes of fecal incontinence.27 The dose of polyethylene glycol can be adjusted according to treatment response. Maintenance doses of medications need to be continued for several weeks to months after a regular bowel habit is established. Children who are toilet training should remain on laxatives until toilet training is well established. Stimulant laxatives (e.g., bisacodyl, sennosides) may be required in some children, although data on their use in children are limited. The lack of liquid formulations limits the practical use of stimulant laxatives in younger children. In the primary care setting, stimulant laxatives should be reserved for rescue therapy when an osmotic laxative is ineffective. Patients requiring constant administration of stimulant laxatives should be evaluated further. LONG-TERM PROGNOSIS Most children with functional constipation require prolonged treatment and have frequent relapses.19 Studies have shown that only 60% of children with constipation achieve treatment success after one year of therapy. Children with fecal incontinence or who are younger than four years at onset of constipation are particularly at risk of poor long-term outcomes.35 REFERRAL Referral to a pediatric gastroenterologist may be needed when a child with constipation has red flags for organic disease or the constipation is unresponsive to adequate therapy. Subspecialists may pursue newer medical therapies, such as lubiprostone, which acts on chloride channels in the intestine,36 or onabotulinumtoxin A injected into a nonrelaxing sphincter.37 Surgical therapies, such as antegrade colonic enemas, have also been shown to improve continence in children with intractable constipation.38 Motility testing often helps guide management in children with intractable constipation.19,39 Although most children have

functional constipation, it is important to reevaluate those who do not follow the expected course. Note: See for complete article visit: www.aafp.org/afp. REFERENCES 1. van den Berg MM, Benninga MA, Di Lorenzo C. Epidemiology of childhood constipation: a systematic review. Am J Gastroenterol. 2006;101(10):2401-2409. 2. Tabbers MM, Dilorenzo C, Berger MY, et al. Evaluation and treatment of functional constipation in infants and children: evidence-based recommendations from ESPGHAN and NASPGHAN. J Pediatr Gastroenterol Nutr. 2014;58(2):265-281. 3. Liem O, Harman J, Benninga M, Kelleher K, Mousa H, Di Lorenzo C. Health utilization and cost impact

of childhood constipation in the United States. J Pediatr. 2009;154(2):258-262.

4. Bongers ME, van Wijk MP, Reitsma JB, Benninga MA. Long-term prognosis for childhood constipation: clinical outcomes in adulthood. Pediatrics. 2010;126(1):e156-e162. 5. Rasquin A, Di Lorenzo C, Forbes D, et al. Childhood functional gastrointestinal disorders: child/adolescent. Gastroenterology. 2006;130(5):1527-1537. 6. Hyman PE, Milla PJ, Benninga MA, Davidson GP, Fleisher DF, Taminiau J. Childhood functional gastrointestinal disorders: neonate/toddler. Gastroenterology. 2006;130(5):1519-1526. 7. Tunc VT, Camurdan AD, Ilhan MN, Sahin F, Beyazova U. Factors associated with defecation patterns in 0-24-monthold children. Eur J Pediatr. 2008;167(12):1357-1362. 8. Corazziari E, Staiano A, Miele E, Greco L; Italian Society of Pediatric Gastroenterology, Hepatology, and Nutrition. Bowel frequency and defecatory patterns in children: a prospective nationwide survey. Clin Gastroenterol Hepatol. 2005;3(11):1101-1106. 9. Fontana M, Bianchi C, Cataldo F, et al. Bowel frequency in healthy children. Acta Paediatr Scand. 1989;78(5):682-684. 10. Bardisa-Ezcurra L, Ullman R, Gordon J; Guideline Development Group. Diagnosis and management of idiopathic childhood constipation: summary of NICE guidance. BMJ. 2010;340:c2585. 11. van der Wal MF, Benninga MA, Hirasing RA. The prevalence of encopresis in a multicultural population. Pediatr Gastroenterol Nutr. 2005;40(3):345-348. 12. van den Berg MM, Bongers ME, Voskuijl WP, Benninga MA. No role for increased rectal compliance in pediatric functional constipation. Gastroenterology. 2009;137(6):1963-1969. 13. Brazzelli M, Griffiths PV, Cody JD, Tappin D. Behavioural and cognitive interventions with or without other treatments for the management of faecal incontinence in children. Cochrane Database Syst Rev. 2011;(12): CD002240.

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AMERICAN FAMILY PHYSICIAN 14. Moylan S, Armstrong J, Diaz-Saldano D, Saker M, Yerkes EB, Lindgren BW. Are abdominal x-rays a reliable way to assess for constipation? J Urol. 2010;184 (4 suppl):1692-1698. 15. Pensabene L, Buonomo C, Fishman L, Chitkara D, Nurko S. Lack of utility of abdominal x-rays in the evaluation of children with constipation: comparison of different scoring methods. J Pediatr Gastroenterol Nutr. 2010;51(2):155-159. 16. Marty TL, Matlak ME, Hendrickson M, Black RE, Johnson DG. Unexpected death from enterocolitis after surgery for Hirschsprung’s disease. Pediatrics. 1995;96(1 pt 1): 118-121. 17. Rosen R, Buonomo C, Andrade R, Nurko S. Incidence of spinal cord lesions in patients with intractable constipation. J Pediatr. 2004;145(3):409-411. 18. Iacono G, Cavataio F, Montalto G, et al. Intolerance of cow’s milk and chronic constipation in children. N Engl J Med. 1998;339(16):1100-1104. 19. Nurko S. Advances in the management of pediatric constipation. Curr Gastroenterol Rep. 2000;2(3):234-240. 20. van Dijk M, Bongers ME, de Vries GJ, Grootenhuis MA, Last BF, Benninga MA. Behavioral therapy for childhood constipation: a randomized, controlled trial. Pediatrics. 2008;121(5):e1334-e1341. 21. Tabbers MM, Boluyt N, Berger MY, Benninga MA. Nonpharmacologic treatments for childhood constipation: systematic review. Pediatrics. 2011;128(4):753-761. 22. Maffei HV, Vicentini AP. Prospective evaluation of dietary treatment in childhood constipation: high dietary fiber and wheat bran intake are associated with constipation amelioration. J Pediatr Gastroenterol Nutr. 2011;52(1): 55-59. 23. Guerra PV, Lima LN, Souza TC, et al. Pediatric functional constipation treatment with Bifidobacterium-containing yogurt: a crossover, doubleblind, controlled trial. World J Gastroenterol. 2011;17(34):3916-3921. 24. Epocrates. http://www.epocrates.com. Accessed April 3, 2014. 25. Tschudy MM, Arcara KM; Johns Hopkins Hospital. Harriet Lane Handbook: A Manual for Pediatric House Officers. 19th ed. Philadelphia, Pa.: Elsevier; 2012. 26. Biggs WS, Dery WH. Evaluation and treatment of constipation in infants and children. Am Fam Physician. 2006;73(3):469-477. 27. Nurko S, Youssef NN, Sabri M, et al. PEG3350 in the treatment of childhood constipation: a multicenter, double-blinded, placebo-controlled trial. J Pediatr. 2008;153(2):254-261. 28. Bekkali NL, van den Berg MM, Dijkgraaf MG, et al. Rectal fecal impaction treatment in childhood constipation:

enemas versus high doses oral PEG. Pediatrics. 2009;124(6):e1108-e1115. 29. Pijpers MA, Tabbers MM, Benninga MA, Berger MY. Currently recommended treatments of childhood constipation are not evidence based: a systematic literature review on the effect of laxative treatment and dietary measures [published correction appears in Arch Dis Child. 2009;94(8):649]. Arch Dis Child. 2009;94(2): 117-131. 30. Candy D, Belsey J. Macrogol (polyethylene glycol) laxatives in children with functional constipation and faecal impaction: a systematic review. Arch Dis Child. 2009;94(2):156-160. 31. Loening-Baucke V. Prevalence, symptoms and outcome of constipation in infants and toddlers. J Pediatr. 2005;146(3):359-363. 32. Bongers ME, van den Berg MM, Reitsma JB, Voskuijl WP, Benninga MA. A randomized controlled trial of enemas in combination with oral laxative therapy for children with chronic constipation. Clin Gastroenterol Hepatol. 2009;7(10):1069-1074. 33. Thomson MA, Jenkins HR, Bisset WM, et al. Polyethylene glycol 3350 plus electrolytes for chronic constipation in children: a double blind, placebo controlled, crossover study [published correction appears in Arch Dis Child. 2008;93(1):93]. Arch Dis Child. 2007;92(11):996-1000. 34. Lee-Robichaud H, Thomas K, Morgan J, Nelson RL. Lactulose versus polyethylene glycol for chronic constipation. Cochrane Database Syst Rev. 2010;(7):CD007570. 35. van Ginkel R, Reitsma JB, Büller HA, van Wijk MP, Taminiau JA, Benninga MA. Childhood constipation: longitudinal follow-up beyond puberty. Gastroenterology. 2003;125(2):357-363. 36. Lembo AJ, Johanson JF, Parkman HP, Rao SS, Miner PB Jr, Ueno R. Long-term safety and effectiveness of lubiprostone, a chloride channel (ClC-2) activator, in patients with chronic idiopathic constipation. Dig Dis Sci. 2011;56(9):2639-2645. 37. Chumpitazi BP, Fishman SJ, Nurko S. Long-term clinical outcome after botulinum toxin injection in children with nonrelaxing internal anal sphincter. Am J Gastroenterol. 2009;104(4):976-983. 38. Siddiqui AA, Fishman SJ, Bauer SB, Nurko S. Long-term follow-up of patients after antegrade continence enema procedure. J Pediatr Gastroenterol Nutr. 2011;52(5): 574-580. 39. Nurko S. What’s the value of diagnostic tools in defecation disorders? J Pediatr Gastroenterol Nutr. 2005;41 (suppl 1):S53-S55.

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AMERICAN FAMILY PHYSICIAN

Practice Guidelines ACC/AHA RELEASE UPDATED GUIDELINE ON THE TREATMENT OF BLOOD CHOLESTEROL TO REDUCE ASCVD RISK Decades of research have demonstrated an association between high levels of low-density lipoprotein cholesterol (LDL-C) and an increased risk of atherosclerotic cardiovascular disease (ASCVD), including coronary heart disease, stroke, and peripheral arterial disease. Randomized controlled trials (RCTs) have found that treating with statins reduces ASCVD events. Based on these data, the Blood Cholesterol Expert Panel from the American College of Cardiology (ACC) and the American Heart Association (AHA) issued an updated evidence-based guideline in 2013 that addresses the use of fixed doses of cholesterol-lowering drugs (statins) to reduce the risk of ASCVD in adults 21 years and older. WHAT IS NEW IN THE GUIDELINE?

Four Statin Benefit Groups This updated guideline focuses on reducing the risk of ASCVD in four statin benefit groups: (1) persons with clinical ASCVD (i.e., acute coronary syndromes, or a history of myocardial infarction, stable or unstable angina, coronary or other arterial revascularization, stroke, transient ischemic attack, or peripheral arterial disease of atherosclerotic origin); (2) persons with primary elevations of LDL-C levels of 190 mg per dL (4.92 mmol per L) or greater; (3) persons with diabetes mellitus who are 40 to 75 years of age with LDL-C levels of 70 to 189 mg per dL (1.81 to 4.90 mmol per L) but without clinical ASCVD; and (4) persons without clinical ASCVD or diabetes who have LDL-C levels of 70 to 189 mg per dL and an estimated 10-year ASCVD risk of 7.5% or greater. The guideline identifies high- and moderate-intensity statin therapy for use in primary and secondary prevention (Table 1). Less evidence is available to support nonstatin therapy for ASCVD prevention.

Source: Adapted from Am Fam Physician. 2014;90(4):260-265.

New Perspective on Goals for LDL-C and/or Nonâ&#x20AC;&#x201C;HDL-C Levels The Expert Panel did not find evidence to support the use of specific LDL-C or nonâ&#x20AC;&#x201C;high-density lipoprotein cholesterol (HDL-C) target levels. Although many clinicians use target levels (e.g., LDL-C levels less than 70 mg per dL for secondary prevention and less than 100 mg per dL [2.59 mmol per L] for primary prevention), evidence has shown that using the maximum tolerated statin intensity in persons who will benefit reduces ASCVD events. No RCTs were identified that titrated drug therapy to a specific target level to improve ASCVD outcomes. Using LDL-C targets could lead to undertreating with evidence-based statin therapy or overtreating with nonstatin drugs that have not been shown to reduce ASCVD events in RCTs.

Global Risk Assessment for Primary Prevention The Pooled Cohort Equations are recommended to estimate the 10-year risk and lifetime risk of ASCVD in white and black adults, with the goal of identifying high-risk persons who will benefit from statin therapy. Before initiating statin therapy, physicians and patients should discuss potential benefits, adverse effects, drugdrug interactions, and patient preferences. The absolute risk reduction in ASCVD events associated with statin therapy can be estimated by multiplying the 10-year ASCVD risk by the anticipated relative risk reduction based on the intensity of the statin (roughly 30% for moderate intensity and 45% for high intensity). The net ASCVD risk-reduction benefit is approximately the number of potential ASCVD events prevented with statin therapy vs. the number of potential excess adverse effects. The Expert Panel acknowledges that persons 70 years or older may have the greatest potential for risk reduction with statin use, even without other risk factors. For example, for persons in this age group, the estimated 10-year risk is 7.5% or greater, which is a risk threshold for which a reduction in ASCVD events has been demonstrated in RCTs. Although evidence supports continuing the use of statins beyond 75 years of age in those already tolerating the drugs, limited data were available to support the initiation of statins for primary prevention in patients older than 75 years without clinical ASCVD.

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AMERICAN FAMILY PHYSICIAN Table 1. High-, Moderate-, and Low-Intensity Statin Therapy (Used in the RCTs Reviewed by the Expert Panel)* High intensity

Moderate intensity

Low intensity

Daily dosage lowers LDL-C by approximately ≥ 50% on average

Daily dosage lowers LDL-C by approximately 30% to 50% on average

Daily dosage lowers LDL-C by < 30% average

Atorvastatin, 40† to 80 mg

Atorvastatin, 10 (20) mg

Simvastatin, 10 mg

Rosuvastatin, 20 (40) mg

Rosuvastatin, (5) 10 mg

Pravastatin, 10 to 20 mg

Simvastatin, 20 to 40

mg‡

Lovastatin, 20 mg

Pravastatin, 40 (80) mg

Fluvastatin, 20 to 40 mg

Lovastatin, 40 mg

Pitavastatin, 1 mg

Fluvastatin XL, 80 mg Fluvastatin, 40 mg twice daily Pitavastatin, 2 to 4 mg Note: Specific statins and dosages noted in bold were evaluated in RCTs included in critical question 1, critical question 2, and the Cholesterol Treatment Trialists 2010 meta-analysis included in critical question 3 (see full guideline for details). All of these RCTs demonstrated a reduction in major cardiovascular events. Statins and dosages listed in italics are approved by the U.S. Food and Drug Administration but were not tested in the RCTs reviewed.

LDL-C = Low-density lipoprotein cholesterol; RCT = Randomized controlled trial. *Individual responses to statin therapy varied in the RCTs and should be expected to vary in clinical practice. There might be a biologic basis for a lessthan-average response. †Evidence

from one RCT only: down-titration if unable to tolerate atorvastatin, 80 mg, in Incremental Decrease through Aggressive Lipid Lowering study.

‡Although

simvastatin, 80 mg, was evaluated in RCTs, initiation of simvastatin, 80 mg, or titration to 80 mg is not recommended by the U.S. Food and Drug Administration because of the increased risk of myopathy, including rhabdomyolysis. Adapted with permission from Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129(25 suppl 2):S13.

Safety Considerations, Biomarkers, and Noninvasive Tests RCT results identified safety concerns in persons taking statins. To maximize safety in men and in women who are not pregnant or nursing, physicians should select the appropriate statin and dose based on patient characteristics, ASCVD risk level, and potential for adverse effects. Characteristics that predispose patients to adverse effects from statin therapy include, but are not limited to, the following: multiple or serious comorbidities, such as impaired renal or hepatic function; a history of previous statin intolerance or muscle disorders; unexplained elevated levels of alanine transaminase greater than three times the upper limit of normal; patient characteristics or concomitant use of medications that affect statin metabolism; and age older than 75 years. See Table 8 in the full guideline for additional safety recommendations. For persons who do not fall into one of the four statin benefit groups, other factors may be considered when making treatment decisions, including a primary LDL-C level of 160 mg per dL (4.14 mmol per L) or greater, or other evidence of genetic hyperlipidemias; family history of premature ASCVD before 55 years of age in a first-degree male relative or before 65 years of age in a first-degree female relative; high-sensitivity C-reactive

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protein level of 2 mg per L (19.05 nmol per L) or greater; coronary artery calcium score of 300 Agatston units or greater, or being in the 75th percentile or greater for age, sex, and ethnicity; ankle-brachial index less than 0.9; or elevated lifetime risk of ASCVD. STATIN RECOMMENDATIONS The Expert Panel’s treatment recommendations are divided into several major categories and are summarized in Table 2. An algorithm for determining appropriate statin therapy for patients who are candidates for treatment is presented in eFigure A. Specific classes of recommendation, levels of evidence, and their definitions are available in the full guideline.

Treatment Targets There are no recommendations for or against specific target levels for LDL-C or non–HDL-C in the primary or secondary prevention of ASCVD.

Secondary Prevention In men and women up to 75 years of age who have clinical ASCVD, high-intensity statin therapy should be initiated unless contraindicated. For persons with clinical ASCVD in whom high-intensity statin therapy

AMERICAN FAMILY PHYSICIAN Table 2. Summary of Major Recommendations for the Treatment of Blood Cholesterol to Reduce ASCVD Risk in Adults Regularly monitor adherence to lifestyle and drug therapy with lipid and safety assessments

Encourage heart-healthy lifestyle habits for all individuals Initiate or continue appropriate intensity of statin therapy

Assess adherence, response to therapy, and adverse effects within 4 to 12 weeks following statin initiation or change in therapy (COE = I; LOE = A)

Clinical ASCVD* Age ≤ 75 years and no safety concerns: high-intensity statin (COE = I; LOE = A)

Measure fasting lipid levels (COE = I; LOE = A)

Age > 75 years or safety concerns: moderate-intensity statin (COE = I; LOE = A)

Do not routinely monitor alanine transaminase or creatine kinase levels unless symptomatic (COE = IIa; LOE = C)

Primary prevention: primary LDL-C ≥ 190 mg per dL (4.92 mmol per L) Rule out secondary causes of hyperlipidemia (see Table 6 in full guideline)

Screen and treat type 2 diabetes according to current practice guidelines; heart-healthy lifestyle habits should be encouraged to prevent progression to diabetes (COE = I; LOE = B)

Age ≥ 21 years: high-intensity statin (COE = I; LOE = B) Achieve at least a 50% reduction in LDL-C (COE = IIa; LOE = B)

Anticipated therapeutic response: approximately ≥ 50% reduction in LDL-C from baseline for high-intensity statin and 30% to < 50% for moderate-intensity statin (COE = IIa; LOE = B)

Consider LDL-C–lowering nonstatin therapy to further reduce LDL-C (COE = IIb; LOE = C) Primary prevention: persons 40 to 75 years of age with diabetes mellitus and with LDL-C of 70 to 189 mg per dL (1.81 to 4.90 mmol per L)

yy Insufficient evidence for LDL-C or non–HDL-C treatment targets from RCTs

Moderate-intensity statin (COE = I; LOE = A) Consider high-intensity statin when ≥ 7.5% 10-year ASCVD risk using the Pooled Cohort Equations† (COE = IIa; LOE = B)

yy For those with unknown baseline LDL-C, an LDL-C < 100 mg per dL (2.59 mmol per L) was observed in RCTs of high-intensity statin therapy

Primary prevention: persons 40 to 75 years of age without diabetes and with LDL-C of 70 to 189 mg per dL

Less than anticipated therapeutic response:

Estimate 10-year ASCVD risk using the risk calculator based on the Pooled Cohort Equations† in those not receiving a statin; estimate risk every 4 to 6 years (COE = I; LOE = B)

yy Reinforce improved adherence to lifestyle and drug therapy (COE = I; LOE = A) yy Evaluate for secondary causes of hyperlipidemia if indicated (see Table 6 in full guideline) (COE = I; LOE = A)

To determine whether to initiate a statin, engage in a clinician-patient discussion of the potential for ASCVD risk reduction, adverse effects, drug-drug interactions, and patient preferences (COE = IIa; LOE = C) Reemphasize heart-healthy lifestyle habits and address other risk factors yy ≥ 7.5% 10-year ASCVD risk: moderate- or high-intensity statin (COE = I; LOE = A) yy 5% to < 7.5% 10-year ASCVD risk: consider moderate-intensity statin (COE = IIa; LOE = B) yy Other factors may be considered‡: LDL-C ≥ 160 mg per dL (4.14 mmol per L), family history of premature cardiovascular disease, high-sensitivity C-reactive protein ≥ 2 mg per L (19.05 nmol per L), coronary artery calcium score ≥ 300 Agatston units, anklebrachial index < 0.9, or elevated lifetime ASCVD risk (COE = IIb; LOE = C) Primary prevention when LDL-C < 190 mg per dL and age < 40 or > 75 years, or < 5% 10-year ASCVD risk Statin therapy may be considered in select individuals‡ (COE = IIb; LOE = C)

yy Increase statin intensity, or if on maximally tolerated statin intensity, consider addition of nonstatin therapy in select high-risk individuals§ (COE = IIb; LOE = C) Regularly monitor adherence to lifestyle and drug therapy every 3 to 12 months after adherence has been established; continue assessment of adherence for optimal ASCVD risk reduction and safety (COE = I; LOE = A) In individuals intolerant of the recommended intensity of statin therapy, use the maximally tolerated intensity of statin (COE = I; LOE = B) If there are muscle or other symptoms, establish that they are related to the statin (COE = IIa; LOE = B) For specific recommendations on managing muscle symptoms, see Table 8 in full guideline

Statin therapy is not routinely recommended for individuals with New York Heart Association class II to IV heart failure or who are receiving maintenance hemodialysis ASCVD = Atherosclerotic cardiovascular disease; COE = Class of recommendation||; HDL-C = High-density lipoprotein cholesterol; LDL-C = Low-density lipoprotein cholesterol; LOE = Level of evidence¶; RCTs = Randomized controlled trials. *Clinical ASCVD includes acute coronary syndromes, or a history of myocardial infarction, stable or unstable angina, coronary or other arterial revascularization, stroke, transient ischemic attack, or peripheral arterial disease presumed to be of atherosclerotic origin.

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AMERICAN FAMILY PHYSICIAN †Estimated

10-year or “hard” ASCVD risk includes first occurrence of nonfatal myocardial infarction, coronary heart disease death, and nonfatal and fatal stroke as used by the Risk Assessment Work Group in developing the Pooled Cohort Equations (see http://my.americanheart.org/cvriskcalculator and http://www.cardiosource.org/science-and-quality/practice-guidelines-and-quality-standards/2013-prevention-guideline-tools.aspx).

‡These

factors may include primary LDL-C ≥ 160 mg per dL or other evidence of genetic hyperlipidemias; family history of premature ASCVD with onset before 55 years of age in a first-degree male relative or before 65 years of age in a first-degree female relative; high-sensitivity C-reactive protein ≥ 2 mg per L; coronary artery calcium score ≥ 300 Agatston units or ≥ 75th percentile for age, sex, and ethnicity (for additional information, see http:// www.mesa-nhlbi.org/CACReference.aspx); ankle-brachial index < 0.9; or lifetime risk of ASCVD. Additional factors that may aid in individual risk assessment may be identified in the future. §High-risk

individuals include those with clinical ASCVD, an untreated LDL-C ≥ 190 mg per dL suggesting genetic hypercholesterolemia, or diabetes.

||Classes

of recommendation: I = procedure or treatment should be performed or administered; IIa = it is reasonable to perform procedure or administer treatment; IIb = procedure or treatment may be considered. ¶Levels of evidence: A = multiple populations evaluated (data derived from multiple randomized clinical trials or meta-analyses); B = limited populations evaluated (data derived from a single randomized trial or nonrandomized studies); C = very limited populations evaluated (only consensus opinion of experts, case studies, or standard of care).

is contraindicated but would otherwise be used, or in persons with characteristics predisposing to statinassociated adverse effects, moderate-intensity statins should be the second option, if tolerated. When initiating moderate- or high-intensity statin therapy in persons older than 75 years who have clinical ASCVD, it is reasonable to evaluate for potential risk-reduction benefits, adverse effects, and drug-drug interactions. Patient preferences should also be considered. Continuation of statin therapy is reasonable in persons who tolerate it.

Primary Prevention in Persons 21 Years or Older With LDL-C Level of 190 mg per dL or Greater Persons who have LDL-C levels of 190 mg per dL or greater, or triglyceride levels of 500 mg per dL (5.65 mmol per L) or greater should be assessed for secondary causes of hyperlipidemia. Persons 21 years or older who have LDL-C levels of 190 mg per dL or greater should be treated with statin therapy. Highintensity statins should be used unless contraindicated. If high-intensity statins are not tolerated, the maximum tolerated intensity should be used. In persons with untreated LDL-C levels of 190 mg per dL or greater, statin therapy may be intensified to achieve a minimum 50% LDL-C reduction. When maximum intensity of statin therapy is reached, a nonstatin may be added to further reduce LDL-C levels. Potential benefits, adverse events, drug-drug interactions, and patient preferences should be considered.

Primary Prevention in Persons with Diabetes and LDL-C Level of 70 to 189 mg per dL Persons 40 to 75 years of age who have diabetes should start or continue moderate-intensity statin therapy. In those with 7.5% or greater estimated 10-year ASCVD risk, high-intensity statin therapy is reasonable, unless

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contraindicated. In persons younger than 40 years or older than 75 years, potential benefits, adverse events, drug-drug interactions, and patient preferences should be considered when deciding to initiate, continue, or intensify statin therapy.

Primary Prevention in Persons without Diabetes and with LDL-C Level of 70 to 189 mg per dL The Pooled Cohort Equations should be used to estimate the 10-year ASCVD risk in persons without clinical ASCVD to guide initiation of statin therapy. In persons 40 to 75 years of age without clinical ASCVD or diabetes and with an estimated 10-year ASCVD risk of 7.5% or greater, moderate- to high-intensity statin therapy should be used. If the 10-year risk of ASCVD is 5% to less than 7.5%, treatment with a moderateintensity statin is reasonable. Before initiating statin therapy, it is reasonable for clinicians and patients to engage in a discussion about the potential for ASCVD risk-reduction benefits, adverse events, drugdrug interactions, and patient preferences. Persons with LDL-C less than 190 mg per dL who do not fall into a statin benefit group or for whom risk-based treatment is uncertain, other factors may be used to inform treatment decision making. Statin therapy may be considered after evaluating for potential benefits, adverse events, drug-drug interactions, and patient preferences.

Heart Failure and Hemodialysis There are no recommendations on initiating or discontinuing statin therapy in patients with New York Heart Association class II through IV ischemic systolic heart failure or in patients on maintenance hemodialysis. Note: See for complete article visit: www.aafp.org/afp.

AMERICAN FAMILY PHYSICIAN

Photo Quiz ENLARGING, PAINFUL NODULE UNDER THE TOENAIL A 19-year-old woman presented with a slowly enlarging, painful nodule under her left great toenail that appeared two years earlier. She had attempted to remove part of the nodule on her own, but it grew back. She did not have a history of trauma to the area, but she noted increased pain when she wore tight or high-heeled shoes. The patient was a track athlete, and the pain of the nodule caused her to miss a season of competition. The physical examination revealed a tender 5-mm Ă&#x2014; 5-mm nodule under the medial side of the distal nail plate (Figure 1). The nodule was firm and displaced the nail plate upward. There was distal onycholysis, but no destruction of the overlying nail plate. No other toes were affected.

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

Figure 1.

A. Acral-lentiginous melanoma. B. Glomus tumor. C. Pyogenic granuloma. D. Subungual exostosis. E. Verruca vulgaris (common wart). SEE THE FOLLOWING PAGE FOR DISCUSSION.

Source: Adapted from Am Fam Physician. 2014;89(10):793-794.

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AMERICAN FAMILY PHYSICIAN DISCUSSION The answer is D: subungual exostosis. Subungual exostosis is a tender, epithelialized, slowly growing papule or nodule most common in children and young adults. The benign osteocartilaginous tumor occurs on the distal phalanx of a digit, usually on the great toe, under or adjacent to the nail plate.1 The nail plate is displaced but not altered. Subungual exostosis is thought to be caused by repetitive trauma or chronic infection.1 Because of the similar appearance to other conditions, subungual exostosis is often misdiagnosed. To narrow the differential diagnosis of a suspicious subungual mass, fine-detail radiography is recommended before biopsy. In this case, the radiograph was diagnostic of exostosis, which was continuous with the underlying cortex and medullary space (Figure 2). Recurrence is uncommon with proper surgical debridement of the base.2 Although acral-lentiginous melanomas are uncommon, they account for most melanomas in persons with darker skin.3 They present as irregularly shaped, pigmented macules or papules on the palm, sole, or nail bed. Amelanotic melanomas are unpigmented papules but can also present as nail dystrophy.3 Subungual pigment that extends proximal or lateral to the nail fold is called Hutchinson sign and should be biopsied to rule out a melanoma.4 Summary Table Condition

Characteristics

Acral-lentiginous Irregularly shaped, pigmented macules melanoma or papules on the palm, sole, or nail bed; pigment often extends beyond the proximal nail fold Glomus tumor

Painful, erythematous subungual papule or nodule; affects the distal nail plate; a vertical red band (erythronychia) often presents from the proximal to distal nail; sensitive to cold and pressure

Pyogenic granuloma

Tender vascular papules or nodules that bleed or erode easily; sudden appearance and rapid growth

Subungual exostosis

Tender, epithelialized, slowly growing papule or nodule; nail plate is displaced but not altered

Verruca vulgaris (common wart)

Hyperkeratotic, rough papule with irregular surface; alters normal skin lines; red or brown dots (thrombosed capillary loops)

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Figure 2. Radiograph showing exostosis that is continuous with the underlying cortex and medullary space.

Patients with a glomus tumor often present with pain in the digit. Glomus tumors are erythematous papules or nodules that grow from the glomus body, a specialized smooth muscle that links arterioles and venules.3 These lesions occur subungually, altering the distal nail plate and causing pain in response to cold and pressure. A vertical red band (erythronychia) often presents from the proximal to distal nail. Pyogenic granulomas are tender vascular papules or nodules that bleed or erode easily. They appear suddenly and grow rapidly over a period of weeks, usually after a minor injury.4 Common sites for these lesions are fingers, lips, mouth, trunk, and toes.3 Verrucae are hyperkeratotic, rough papules with an irregular surface that occur in skin infected with human papillomavirus. The papules alter the normal skin lines and often contain characteristic red or brown dots (thrombosed capillary loops).3 Periungual verrucae can be especially resistant to treatment.4 REFERENCES 1. Turan H, Uslu M, Erdem H. A case of subungual exostosis. Indian J Dermatol Venereol Leprol. 2012;78(2):186. 2. De Berker DA, Langtry J. Treatment of subungual exostoses by elective day case surgery. Br J Dermatol. 1999;140(5):915-918. 3. Wolff K, Johnson RS, Suurmond D, Fitzpatrick TB, eds. Fitzpatrickâ&#x20AC;&#x2122;s Color Atlas and Synopsis of Clinical Dermatology. 5th ed. New York, NY: McGraw-Hill; 2005. 4. Usatine R, et al., eds. The Color Atlas of Family Medicine. New York, NY: McGraw-Hill; 2009.

CARDIOLOGY

A Rare Association of Rheumatoid Arthritis with Ascending Aortic Aneurysm: A Case Report RAVI PRAKASH PANDEY*, KD SINGH†, M INDURKAR‡, DHARMENDRA JAIN#

ABSTRACT Rheumatoid arthritis (RA) is an inflammatory immune system disorder that is associated with a higher level of morbidity and mortality than found in the general population, mainly because of cardiovascular diseases. Here we report a case of a 70-year-old male, who was a known case of RA since past 12 years and presented to the outpatient department of our tertiary care center with complaints of difficulty in swallowing, blood tinged sputum and breathlessness. Patient was diagnosed as a case of ascending aortic aneurysm. A possibility of a rare association between RA and ascending aortic aneurysm has been highlighted in the ensuing case report.

Keywords: Aortic aneurysm, cardiovascular diseases, inflammatory disorder, rheumatoid arthritis

heumatoid arthritis (RA) is the commonest inflammatory polyarthritis seen in clinical practice. The prevalence of RA is about 0.5-1% in industrialized nations with 5-50 cases per 1,00,000 populations annually. It predominantly occurs in females and elderly people. In India, prevalence of RA was found to be 0.5-0.75%.1,2 RA primarily affects joints; however, it also affects other organ in 15-25% of individuals.3 Much less appreciated is the fact that what hurts in RA is the joint, but what kills is the ‘heart’. Over the years, cardiovascular disease (CVD) has emerged as a major cause of morbidity and mortality in RA. It can cause a spectrum of CVDs viz. myocardial infarction, valvular dysfunctions and possibly aortic aneurysm.4,5 Here we report one such case of ascending aortic aneurysm in association with RA.

*Assistant Professor Dept. of Medicine †Assistant Professor Dept. of Medicine (Cardiology) ‡Professor Dept. of Medicine SS Medical College, Rewa, Madhya Pradesh #Assistant Professor Dept. of Cardiology Institute of Medical Sciences, Banaras Hindu University (BHU) Varanasi, Uttar Pradesh Address for correspondence Dr Dharmendra Jain Assistant Professor, Dept. of Cardiology C-2, New Medical Enclave, Naria, BHU, Varanasi - 05, Uttar Pradesh

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CASE REPORT A 72-year-old male, nonsmoker, presented to the outpatient department of our tertiary care hospital with complaints of difficulty in swallowing, blood tinged sputum, palpitation and breathlessness since 1½ months. Patient was a known case of RA since last 12 years. He had a negative history for hypertension, diabetes mellitus, ischemic heart disease and chronic obstructive pulmonary disease. On general examination, patient was average built with radial deviation at the wrist and bony deformity in digits of hands and feet (Fig. 1). No sign of pallor, cyanosis, clubbing, icterus, edema and lymphadenopathy was present. Patient was conscious, well-oriented to time, place and person. Vital parameters were as follows: Patient was afebrile, respiratory rate (14/min), pulse rate (90/min), irregular, high volume, collapsing with apex pulse deficit of 12. Blood pressure in right and left upper limb supine position was 128/50 mmHg and 120/40 mmHg and right and left lower limb was 170/60 mmHg and 156/50 mmHg, respectively. Cardiovascular (CVS): On inspection, apex impulse was seen over left 6th intercostal space 1.5 cm lateral to the mid-clavicular line. On palpation, apex beat was felt in the same space with hyperdynamic character. On auscultation, S1 was variable in intensity in aortic, pulmonary, tricuspid and mitral area, respectively with soft S2. A decrescendo diastolic murmur extending up to late diastole was heard to the right of sternum which was soft-high-pitched and blowing, best appreciated

CARDIOLOGY A

Figure 1. Various type of bony deformity in both hand and feet in above mentioned patient.

Figure 3. ECG showing LVH with strain pattern with underlying AF (A,B) and rhythm strip (B).

Figure 2. Chest X-ray PA view showing cardiomegaly with LV type of apex.

during expiration and leaning forward. Other systemic examinations were unremarkable. Routine investigations were within normal limits. RA factor was strongly positive (296 IU/mL). Chest X-ray PA view was suggestive of cardiomegaly with left ventricular (LV) type of apex (Fig. 2). ECG showed LV hypertrophy (LVH) with LV strain pattern with underlying atrial fibrillation (Fig. 3). 2D-echocardiography (TTE) of the patient revealed grossly dilated ascending aorta (diameter ~7.11 cm) with nonrheumatic severe AR with mild AS with moderate left ventricle systolic dysfunction

Figure 4. TTE showing gross dilation of ascending aorta (Diameter ~ 7.11cm) and associated severe aortic regurgitation.

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CARDIOLOGY the intima, which can occur in normal individuals and focussed on observations in the tunica media and tunica adventitia. They concluded that the observed changes were greater in patients with RA and that they could represent an inflammatory state that promotes the development of arteriosclerosis and the formation of aneurysms by decreasing the resistance of the arterial wall. Aortic aneurysm can also be the result of medial dysfunction induced by chronic inflammation and accelerated by prolonged corticosteroid therapy.8 Figure 5. TTE showing various images around aortic valve revealing aortic regurgitation along with its severity.

(left ventricular ejection fraction [LVEF] = 35.24%) (Figs. 4 and 5). Tricuspid aortic valve (unequal cusp) with annuloaortic ectasia with effacement of sinotubular junction was present. Mild-to-moderate mitral regurgitation was also present. DISCUSSION Aneurysm of aorta is an abnormal dilatation of aorta in all the three layers of aortic wall. The basic defect is destruction of the elastic fibers in the tunica media, which are replaced by fibrosis. The association between RA and loss of elasticity of aorta is principally due to inflammatory changes and structural alteration such as smooth muscle hypertrophy and changes in intracellular matrix characterized by an increase in collagen and decrease in elastin. Smooth muscle cells can produce bioapatite (they express osteoblastic markers under inflammatory conditions), which causes calcification of the aortic tunica media. Perivascular inflammation and cellular infiltration around the vasa vasorum have been, observed to result in ischemia.6 Moreover, in RA, a type of peripheral neuropathy caused by necrotizing vasculitis of the vasa vasorum has been reported. Elderly onset RA has been associated with poorer prognosis, as manifested by persistent disease activity, more frequent systemic association and more rapid functional decline. Patients having high titers of rheumatoid factor have more aggressive disease activity as compared to seronegative patients. Hollan et al7 studied changes in the aortic wall (i.e., inflammatory changes) in specimens obtained following coronary artery revascularization surgery and compared findings in patients with and without RA. They excluded patients with infiltration close to

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Vasulitis occurs in less than 1% of patients with RA and usually only in those with severe deforming RA and high titers of rheumatoid factor. Large vessel involvement with aortitis occurs in 5% of patients with rheumatoid vasculitis. Aneurysm formation secondary to rheumatoid vasulitis is extremely rare and then usually affects the aortic root and ascending aorta.9 Although initially, the vasculitis was attributed to occlusive vascular disease associated with giant cell arteritis (which corresponds to the current understanding of RA, principally with regard to coronary arteries), it was subsequently clear that inflammatory changes in the aorta associated with high blood pressure can also lead to the formation of an aneurysm and dissection.10,11 In the past aortic aneurysm has been reported with several connective tissue disorders like Marfanâ&#x20AC;&#x2122;s syndrome, Ehler-Danlos syndrome and systemic lupus erythematosus. CONCLUSION Involvement of ascending aorta in RA is very rare. Such massive aneurysm along with valvular dysfunction has been rarely reported in literature. Thus, the above case report highlights the possibility of a massive aneurysm being attributed to the long-standing inflammatory changes and structural alteration brought to the great vessel by RA. REFERENCES 1. Chopra A, Patil J, Billempelly V, Relwani J, Tandle HS; WHO-ILAR COPCORD Study. WHO International League of Associations from Rheumatology Community Oriented Program from Control of Rheumatic Diseases. Prevalence of rheumatic diseases in a rural population in western India: a WHO-ILAR COPCORD Study. J Assoc Physicians India 2001;49:240-6. 2. Malaviya AN, Kapoor SK, Singh RR, Kumar A, Pande I. Prevalence of rheumatoid arthritis in the adult Indian population. Rheumatol Int 1993;13(4):131-4. 3. Turesson C, Oâ&#x20AC;&#x2122;Fallon WM, Crowson CS, Gabriel SE, Matteson EL. Extra-articular disease manifestations in

CARDIOLOGY rheumatoid arthritis: incidence trends and risk factors over 46 years. Ann Rheum Dis 2003;62(8):722-7. 4. Hadda V, Handa R, Aggarawal P, Lakshmy R, Kumar U, Pandey RM. Disease activity and lipids in rheumatoid arthritis: a prospective. Indian J Rheumatol 2007;2(4): 137-40. 5. Handa R, Chaurasia A, Hari S, Kumar U, Gupta R. Endothelial cell dysfunction in rheumatoid arthritis. Ann Rheum Dis 2007;66(Suppl II):67.

8. Ohara N, Miyata T, Sato O, Oshiro H, Shigematsu H. Aortic aneurysm in patients with autoimmune diseases treated with corticosteroids. Int Angiol 2000;19(3):270-5. 9. Modi P, Suvarna K, Cooper GJ. Images in cardiology. Descending thoracic aortic aneurysm in rheumatoid arthritis. Heart 2000;84(2):122.

6. Yildiz M. Arterial distensibility in chronic inflammatory rheumatic disorders. Open Cardiovasc Med J 2010;4:83-8.

10. He R, Guo DC, Estrera AL, Safi HJ, Huynh TT, Yin Z, et al. Characterization of the inflammatory and apoptotic cells in the aortas of patients with ascending thoracic aortic aneurysms and dissections. J Thorac Cardiovasc Surg 2006;131(3):671-8.

7. Hollan I, Scott H, Saatvedt K, Prayson R, Mikkelsen K, Nossent HC, et al. Inflammatory rheumatic disease and smoking are predictors of aortic inflammation: a controlled study of biopsy specimens obtained at coronary artery surgery. Arthritis Rheum 2007;56(6):2072-9.

11. Gonzalez-Gay MA, Garcia-Porrua C, Piñeiro A, PegoReigosa R, Llorca J, Hunder GG. Aortic aneurysm and dissection in patients with biopsy-proven giant cell arteritis from northwestern Spain: a population-based study. Medicine (Baltimore) 2004;83(6):335-41.

■■■■

Walking 2,000 Steps Extra Lower Cardiovascular Risk Walking 20 minutes at a moderate pace each day is associated with improved cardiovascular outcomes in patients with impaired glucose tolerance, according to a study in The Lancet. People who walked 2,000 steps more per day at baseline had a 10% lower risk of cardiovascular death, paralysis or heart attack during an average follow-up of 6 years according to Thomas Yates, PhD, of the University of Leicester in England, and colleagues. And those who increased the amount they walked by 2,000 steps per day from baseline to 1 year had a similar reduction in risk of cardiovascular events. The findings from NAVIGATOR trial support both the promotion of increased ambulatory activity, and the avoidance of decreased ambulatory activity irrespective of the starting level, as important targets in the prevention of chronic disease.

Longer Chest Pain Equals Bigger MI Risk Patients with acute myocardial infarction have longer duration of chest pain than those without a myocardial infarction. Patients with chest pain of short duration, less than 5 minutes, are unlikely to have an acute infarction and have a good prognosis at 30 days. A single-center study showed that only 8.9% of the patients received a final diagnosis of acute MI, and these patients had a significantly longer duration of chest pain compared with the rest of the cohort (120 vs 40 minutes) according to Carlos Calle-Muller, MD, of Henry Ford Hospital in Detroit, and colleagues. Those who had chest pain lasting less than 5 minutes always had a good outcome, with no acute MIs or deaths within 30 days, as reported in the September issue of Critical Pathways in Cardiology. If the clinical assessment and ECG are benign, such patients might be able to be discharged directly from the emergency department without stress testing for outpatient follow-up. The median chest pain duration was 180 minutes among the 10 patients who died and only 40 minutes for the others. Among patients with acute MI, longer chest pain duration was not associated with higher 30-day mortality, but it was associated with a higher initial level of cardiac troponin-I.

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CRITICAL CARE

Chickenpox Pneumonia with ARDS in a 46-year-old Immunocompetent Male KAMAL KUMAR*, SHIVANJALI KUMARâ&#x20AC;

ABSTRACT Chickenpox pneumonia with acute respiratory distress syndrome (ARDS) is an extremely rare presentation in adults in the absence of comorbidities and immunosuppression. We report one such case of a 46-year-old male with fulminant chickenpox having bilateral pneumonia and respiratory distress in the absence of predisposing factors and comorbidities. Patient recovered due to early diagnosis and prompt institution of treatment.

Keywords: Varicella pneumonia, chickenpox pneumonia, viral pneumonia

hickenpox pneumonia, a severe complication of varicella, has a 25-fold greater incidence in adults compared to children. Its incidence varies between 0.32-1.36 cases per 1,00,000 person years.1 Varicella pneumonia has a mortality rate ranging from 10% to 33% that may rise to almost 50% in patients with respiratory failure on mechanical ventilation.2 CASE REPORT A 46-year-old male was admitted with history of fever for 1 week, eruptions all over body for 2 days and cough with severe breathlessness for 1 day. He had no past history of chickenpox. There was history of recent chickenpox infection in his 6-year-old daughter who had contracted it from a schoolmate. He was a nonsmoker and had no history of chronic lung disease.

acute respiratory distress syndrome (ARDS) (Fig. 2). Laboratory investigations revealed leukocytosis (15,700/mm3 of blood), mild thrombocytopenia and mildly elevated serum transaminases. A diagnosis of chickenpox pneumonitis was made on the basis of history of close contact, clinical features including rash and chest X-ray. The patient was put on bilateral positive airway pressure (PAP) (inspiratory PAP [IPAP]: 18 cm H2O; expiratory PAP [EPAP] 6 cm H2O). He was managed with intravenous acyclovir (10 mg/kg every 8 hours), intravenous antibiotics (piperacillin-tazobactam and levofloxacin) to cover

On examination, the patient had a pleomorphic maculopapular rash all over his body (Fig. 1). He was tachypneic, had wide-spread crepitations over both lung fields and demonstrated progressive hypoxemia. Chest X-ray revealed diffuse scattered and confluent nodular opacities in both lung fields with prominence of bronchovascular markings and perihilar haze suggestive of chickenpox pneumonia with

*Senior Consultant â&#x20AC; Consultant Heartline Hospital and Cardiac Cath. Lab., Allahabad, Uttar Pradesh Address for correspondence Dr Kamal Kumar E-mail: drkamalkumar@rediffmail.com

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Figure 1. Generalized pleomorphic maculopapular rash.

CRITICAL CARE DISCUSSION Pneumonitis is a life-threatening complication of chickenpox infection among adults. However, it has rarely been reported in adult patients suffering from chickenpox who are not immunosuppressed or who do not have any other comorbidity like history of chronic smoking, pregnancy in females or chronic lung disease.1 Severity of rash signifies enhanced viremia and this may indicate chances of developing pneumonia. Also, exposure to an index case may mean a high infecting dose and more risk of pneumonitis. Our patient developed extensive chickenpox pneumonia with adult respiratory distress syndrome despite having no evidence of immunosuppression or other comorbidity.

Figure 2. Chest X-ray on admission.

Pneumonia usually develops 1-6 days after development of rash and may be associated with cough, dyspnea, chest tightness, pleuritic chest pain or hemoptysis. Lung involvement seems to be through bloodstream and not through the respiratory tree.3 Clinical trials have shown a clear benefit with the use of acyclovir.4 Steroids may be used as adjunctive therapy especially in life-threatening pneumonias.5 Early intervention drastically improves recovery and outcome.2 CONCLUSION Varicella pneumonia, though very rare, is a severe, lifethreatening complication with a high-risk of respiratory failure and requirement of mechanical ventilation. It is seldom seen in the absence of co-existent immunosuppression. Early recognition of symptoms and diagnosis with prompt therapy may significantly reduce the morbidity and mortality. REFERENCES

Figure 3. Chest X-ray at the time of discharge.

1. Mohsen AH, McKendrick M. Varicella pneumonia in adults. Eur Respir J 2003;21:886-91.

secondary infection and intravenous hydrocortisone. Extensive work-up did not reveal any evidence of immunosuppression. He had no history of intake of immunosuppressants, was nondiabetic, enzymelinked immunosorbent assay (ELISA) for human immunodeficiency virus (HIV) 1 and 2 was negative and immunoglobulin levels were normal. The patient showed signs of dramatic improvement within 48 hours of institution of therapy and was discharged from hospital by Day 8. Chest X-ray showed complete resolution of lesions (Fig. 3). He remained well on follow-up.

2. Alanezi M. Varicella pneumonia in adults: 13 yearsâ&#x20AC;&#x2122; experience with review of literature. Ann Thorac Med 2007;2(4):163-5. 3. Weigle K, Groce C. Varicella pneumonitis: immunodiagnosis with a monoclonal antibody. J Pediatr 1984;105:(2)265-8. 4. El-Daher N, Magnussen R, Betts RF. Varicella pneumonitis: clinical presentation and experience with acyclovir treatment in immunocompetent adults. Int J Infect Dis 1998;2(3):147-51. 5. Mer M, Richards GA. Corticosteroids in life-threatening varicella pneumonia. Chest 1998;114(2):426-31.

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DERMATOLOGY

A Randomized Open Label Comparative Clinical Study of Synbiotic as an Add-on Therapy to Standard Treatment with Standard Treatment Alone in the Management of Patients with Eczema T MEENAKSHI, R NANDINI*

ABSTRACT Introduction: Eczema refers to a chronic, inflammatory skin disorder that is marked by pruritic red rashes. Currently, there is no complete cure for eczema. An array of treatment modalities are used, which are predominantly symptom-based and have their own limitations. Thus, there is an unmet need for newer and more effective alternatives. One such approach is represented by the use of pre/probiotics in eczema. Objectives: To assess the efficacy and tolerability of synbiotic as add-on therapy to standard treatment in the management of eczema in comparison with standard treatment alone. The primary endpoint of the study was to assess the reduction in eczema severity index, while the reduction in serum IgE levels were assessed as secondary endpoint of the study. Methods: Adult patients diagnosed with eczema attending the outpatient Dermatology Department of Madras Medical College and Rajiv Gandhi Government General Hospital were recruited between June 2012 and July 2013. The study duration comprised of 8 weeks of treatment period and 4 weeks of follow-up. Sixty eligible subjects (30 patients in each group) were included in the study. The primary and secondary endpoints of the study were to assess the reductions in eczema severity index and serum IgE levels, respectively. Results: When the two groups were compared at the end of 8 weeks, there was a significant reduction in eczema severity index in both the groups following treatment. At the end of 8 weeks, a statistically significant decrease in serum IgE levels was noted in the study group (p < 0.0001) in comparison with the control group (0.527) without any adverse events. Conclusion: It can be concluded from the study results that addition of synbiotics to the standard therapy for eczema reduced the serum IgE levels significantly than standard treatment alone and is more effective in symptomatic improvement and exacerbation reduction. No significant adverse effects reported with the addition of synbiotics and thus synbiotics can be a safe therapeutic option for eczema patients as an add-on therapy.

Keywords: Eczema, synbiotic, eczema severity index, serum IgE levels

czema refers to a chronic, inflammatory skin disorder that is marked by pruritic red rashes. Eczema and dermatitis are the terms often used synonymously. Eczema is often, but not always, associated with atopy. It may be associated with atopic diseases like asthma, allergic rhinitis and positive family history of allergy. Factors commonly playing a causative role in eczema include genetic and environmental influences like house mites, pollution and microorganisms.1 Eczema presents as an acute or chronic disease where acute eczema is often associated

*Director and Professor Institute of Pharmacology Madras Medical College, Chennai

with erythema, vesicles and oozing, while chronic eczema is characterized by scaling, lichenification or altered pigmentation. The condition is most commonly seen in flexures, on the face and neck; however, any part of the body may be affected. The severe itching and scratching due to chronic eczema may cause sleep disturbances and significantly impact the patientâ&#x20AC;&#x2122;s quality-of-life.2 Eczema signifies the most common skin disorder encountered in children and may account for 5-20% of childhood diseases. The prevalence of eczema differs in different parts of the world, ranging from 20% in Northern Europe and the United States, to about 5% in the South-Eastern Mediterranean.3 The prevalence in India is about 2.4-9%.4 A rising trend in eczema has been observed in India also in last four decades. Currently, there is no complete cure for eczema.

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DERMATOLOGY An array of treatment modalities are used, which are predominantly symptom-based. The treatment options include emollients, topical steroids, tar, tacrolimus, etc. However, these treatments require application for long time and are also associated with side effects. There is, thus, an unmet need for a newer and more effective, alternative; one such approach is represented by the use of pre/probiotics in eczema. Probiotics are the live microorganisms that, when administered in adequate amounts, have beneficial effects for the host’s health. The Nobel Prize Winner, Eli Metchinikoff, had pointed that the dependence of intestinal microorganisms on food enables the modification of flora in human body and allows for the replacement of harmful microbes by beneficial ones.5 An ideal probiotic should be nonpathogenic, nontoxic and resistant to acidic pH and bile salts. By supplying nutrition, Prebiotics help the growth of good bacteria. The term ‘synbiotic’ refers to a synergistic combination of probiotics and prebiotics that has the potential to improve survival and implantation of beneficial live microbes in the host gastrointestinal tract. The composition of intestinal microflora varies in patients with eczema and may pave way for the development of acute eczema. A decreased percentage of Bifidobacteria species in the intestines of patients with eczema is the most consistent finding. This finding has contributed to the hypothesis that the altered intestinal microflora may cause or aggravate eczema.5 Several clinical trials have evaluated the potential of synbiotics in the treatment of eczema,6 yet their role still needs clarification. Additionally, potential data in Indian population is lacking. RATIONALE FOR USING SYNBIOTICS IN ECZEMA There is sufficient amount of evidence to suggest a role of deficient commensal microorganisms in the development of allergic disorders.7 The mechanism of action of synbiotics involve preservation of the intestinal barrier function, stimulation of production of IgA antibodies and regulation of host immune response via alteration of cytokine production. Probiotics have been shown to diminish Th2 cytokine production by stimulating Th1 cytokine production, for instance interleukin (IL)-12, IL-10 and interferon (IFN)-g. Th1 cytokines are stimulated by antigen presenting cells or by stimulating the production of IL-10 or transforming growth factor (TGF)-β by regulatory T cells. Atopic diseases, like eczema, may be prevented or treated by altering the microflora and this can well be achieved by using synbiotics.7

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OBJECTIVES The present study assessed the efficacy and tolerability of synbiotic as an add-on therapy to standard treatment in the management of eczema in comparison with standard treatment alone. The primary endpoint of the study was to assess the reduction in eczema severity index, while the reduction in serum immunoglobulin E (IgE) levels were assessed as secondary endpoint of the study. METHODS This was a randomized, open label, prospective, comparative study. Adult patients diagnosed with eczema attending the outpatient Dermatology Department of Madras Medical College and Rajiv Gandhi Government General Hospital were recruited between June 2012 and July 2013. The study duration comprised of 8 weeks of treatment period and 4 weeks of follow-up. Sixty subjects who fulfilled the following eligibility criteria (30 patients in control group and 30 patients in study group) were included in the study:

Inclusion Criteria ÂÂ Patients of either gender aged – 20-50 years. ÂÂ Patients diagnosed with eczema within 3 months. ÂÂ Patients willing to give written informed consent. ÂÂ Patients ready to follow all study procedures. Exclusion Criteria ÂÂ Patients with other dermatologic illness. ÂÂ History of hypersensitivity to any component of study medication. ÂÂ Individuals with significant systemic illness. ÂÂ Individuals who had been involved in an investigational drug/study device within 30 days prior to screening. ÂÂ Pregnant or lactating women and women of childbearing potential who are not willing to follow required contraceptive measures. The study was carried out after approval from Institutional Ethics Committee. Written informed consent was obtained from all the subjects recruited in the study. Subjects fulfilling the inclusion and exclusion criteria were recruited in the study and were randomized to receive either standard therapy alone or study drug in association with standard therapy. The control group comprised of 30 patients who received standard therapy, i.e., liquid paraffin applied after bath, 0.1% betamethasone ointment

DERMATOLOGY twice-daily application and chlorpheniramine maleate 8 mg once at night for 8 weeks. The study group also had 30 patients who were given standard therapy and a synbiotic capsule thrice-daily for 8-week period. Each 0.5 g capsule of the synbiotic contained: Streptococcus faecalis T-110 - 30 million, Clostridium butyricum TOA - 2 million, Bacillus mesentericus TOA - 1 million and Lactobacillus sporogenes - 50 million. Patients were subjected to hematological evaluation hemoglobin, total leukocyte count (TLC), differential leukocyte count (DLC), blood sugar, blood urea, serum creatinine; liver function tests - serum glutamicoxaloacetic transaminase (SGOT), serum glutamicpyruvic transaminase (SGPT) and serum IgE at baseline and at the end of 8 weeks. Eczema severity index8 assessed for redness, papulation, scratching and lichenification as none (0), mild (1), moderate (2) and severe (3). Routine follow-ups were done every 2 weeks for a period of 4 weeks. The obtained data was subjected to statistical analysis. Age distribution was analyzed using analysis of variance (ANOVA) and sex distribution was assessed by Chi-square test. Biochemical studies were conducted at baseline and at the end of 8 weeks. The differences within groups before and after treatment, in eczema severity index and serum IgE were assessed using Studentâ&#x20AC;&#x2122;s paired t-test. P value <0.05 was considered to be statistically significant. One way ANOVA was used to analyze the differences between groups. The study methodology is summarized in Figure 1.

was noted in both the study group and control group. However, the decrease in serum IgE levels was significantly more in study group (p < 0.0001) when compared to control group (0.527). Tables 1-3 and Figures 2-4 summarize the study results with respect to redness, papulation, scratching, lichenification scores and eczema severity index and serum IgE levels.

Screened - 124 Excluded - 56 Eligible but not willing - 8 Enrolled - 60

Randomization

Control group (n = 30)

Test group (n = 30)

Treatment period - 8 weeks

60 Patients completed the study

Statistical analysis

Figure 1. Study flow chart.

Control group Day 0

Study group Day 0

Control group end of 8 weeks

Study group end of 8 weeks

2.5

RESULTS The mean age of the patients in the control group was 46 years while in the study group, the mean age was 45 years. In both the groups, 67% patients were males. When the two groups were compared at the end of 8 weeks, there was a significant reduction in eczema severity index in both the groups following treatment; however, the study group showed more reduction in comparison with control group, though the difference was not statistically significant. At the end of 8 weeks, a statistically significant decrease in serum IgE levels

2 1.5 1 0.5 0 Redness score

Papulation score

Scratching score

Lichenification score

Figure 2. Redness, papulation, scratching, lichenification scores in study and control groups.

Table 1. Redness, Papulation, Scratching, Lichenification Scores in Study and Control Groups Group

Period

Redness score

Papulation score

Scratching score

Lichenification score

Control group

Day 0 End of 8 weeks

1.10 0.32

0.65 0.46

2.24 1.31

0.93 0.77

Study group

Day 0 End of 8 weeks

1.0 0.10

0.68 0.27

2.37 1.0

0.86 0.72

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DERMATOLOGY

Day 0

End of 8 weeks

Day 0 714.259

712.55 700

Serum IgE (mg/dL)

Eczema severity index

800

End of 8 weeks

4 3 2 1

600 500

489.882

400 300 210.612 200 100 0

0 Control group

Figure 3. Eczema severity index in study and control groups.

Table 2. Eczema Severity Index in Study and Control Groups

Figure 4. Serum IgE levels in study and control groups.

Table 3. Serum IgE Levels in Study and Control Groups

Eczema severity index Group

Study group

Control group

Study group

Serum IgE levels

Day 0

End of 8 weeks

Mean score

P value

Group

Control group

4.87

2.83

<0.0001

Control group

Study group

5.17

2.13

<0.0001

Study group

P value

0.443

0.713

Day 0

End of 8 weeks

Mean (mg/dL)

712.55

489.882

0.005

714.259

210.612

<0.0001

0.527

<0.0001

P value

Table 4. Laboratory Investigations Parameter

Control group

Study group

Day 0

At the end of 8 weeks

P value

Day 0

At the end of 8 weeks

P value

Total count

(cells/mm3)

11,557

11,465

0.79

12,043

11,876

0.87

Eosinophils

(cells/mm3)

0.32

0.41

Hemoglobin (g/dL)

0.55

11.5

0.71

SGOT (IU/mL)

0.33

0.45

SGPT (IU/mL)

0.68

0.78

Bilirubin (mg/dL)

1.1

0.97

1.1

0.92

Blood sugar (mg/dL)

105

110

0.9

106

109

0.21

Serum urea (mg/dL)

0.65

0.79

Serum creatinine (mg/dL)

0.52

0.95

The differences in hematological and biochemical parameters were not statistically significant in both the groups. The results of laboratory parameters are summarized in Table 4. Adverse events were mild, of which drowsiness was most commonly noted, followed by nausea, gastritis, loose stools and acneiform eruptions. No serious adverse events were observed in

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both the groups. The adverse events are summarized in Table 5. DISCUSSION Eczema represents a multifactorial inflammatory skin disorder defined by pruritic skin lesions. Deficiency in the innate as well as adaptive immune system,

DERMATOLOGY Table 5. Adverse Events Control group

Study group

Nausea

Loose stools

Acneiform eruptions

Drowsiness

Gastritis

as influenced by genetic predisposition, leads to skin barrier dysfunction with hyperreactivity to environmental stimuli and susceptibility to skin infections, thus affecting the course and severity of eczema. Eczema commonly presents as redness, papulation and itching, leading to scratching and lichenification. Elevated serum IgE is a common feature of eczema. The condition is often associated with relapses and exacerbations. Treatment of eczema is aimed at symptomatic improvement and includes topical corticosteroid therapy, oral antihistamines and moisturizers.2 Synbiotics, added to standard treatment, aims to modulate intestinal microflora and inflammatory markers. It balances the immune system and improves the treatment outcome and prevents exacerbations in patients with eczema.5 The current study recruited 30 patients in the control group who received standard therapy and 30 patients in the study group to receive synbiotic as an add-on to standard therapy as per prior randomization schedule. Both groups received treatment for 8 weeks. Patients were assessed clinically at an interval of every 15 days and laboratory investigations were done at baseline and at the end of treatment period. Males were more when compared to females in both the groups; the sex distribution was similar to a study conducted by Dhar et al that also exhibited a higher incidence of eczema in males.9

Figure 5. Shows the manifestation of eczema in a patient belonging to control group at Day 0.

Figure 6. Shows the resolution of signs of eczema at the end of 8 weeks (Control group).

The current study revealed a significant reduction in eczema severity index in both the groups following treatment; however, the study group showed more reduction in comparison with control group, though the difference was not statistically significant (Figs. 5-8). The greater reduction in eczema symptoms, on addition of synbiotics may be attributed to its ability to decrease allergen-induced production of inflammatory mediators. Similar reduction in eczema severity index has been seen in several studies.7,10,11 Additionally, in our study, a statistically significant reduction in IgE levels was evident in both the groups at the end of treatment period; the reduction in IgE levels was more statistically significant in the study

Figure 7. Shows the manifestation of eczema in a patient belonging to study group at Day 0.

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DERMATOLOGY REFERENCES 1. Johansson SG, Bieber T, Dahl R, Friedmann PS, Lanier BQ, Lockey RF, et al. Revised nomenclature for allergy for global use: Report of the Nomenclature Review Committee of the World Allergy Organization, October 2003. J Allergy Clin Immunol 2004;113(5):832-6. 2. Burns T, Breathnach S, Cox N, Griffiths C (Eds.). Rook’s Textbook of Dermatology. Vol. 1, 8th edition, WileyBlackwell: USA 2008:p.24. 3. Hoare C, Li Wan Po A, Williams H. Systematic review of treatments for atopic eczema. Health Technol Assess 2000;4(37):1-191.

Figure 8. Shows the resolution of signs of eczema at the end of 8 weeks (Study group).

group. Thus, adding synbiotics to standard treatment leads to better reduction in serum IgE levels in eczema patients. This reduction is a result of modulation of immune response by synbiotics. Similar results have been demonstrated by Abrahamsson et al and Sistek.12,13 Synbiotics did not have any significant effect on hematological and biological parameters as well as no significant adverse effect on liver and renal functions were seen. A meta-analysis by Boyle et al exhibited similar results with respect to hematological and biochemical laboratory parameters.14 Also, there is no significant variation in the occurrence of adverse effects in both the groups, thus pointing that the addition of synbiotics does not increase the incidence of adverse effects. Studies by Weston et al and Passeron et al also revealed that adding synbiotics to standard therapy does not increase the incidence of adverse effects. CONCLUSION It can be concluded from the study results that addition of synbiotics to the standard therapy for eczema reduced the serum IgE levels significantly than standard treatment alone and is more effective in symptomatic improvement as well. There were no significant adverse effects reported with the addition of synbiotics and thus synbiotics can be a safe therapeutic option for eczema patients as an add-on therapy.

Acknowledgment The authors thank Tablets (India) Ltd. for providing the study medication (BIFILAC).

Conflict of Interest No conflict of interest.

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4. Kanwar AJ, De D. Epidemiology and clinical features of atopic dermatitis in India. Indian J Dermatol 2011;56(5):471-5. 5. Weston S, Halbert A, Richmond P, Prescott SL. Effects of probiotics on atopic dermatitis: a randomised controlled trial. Arch Dis Child 2005;90(9):892-7. 6. Matricardi PM, Bjorksten B, Bonini S, Bousquet J, Djukanovic R, Dreborg S, et al; EAACI Task Force 7. Microbial products in allergy prevention and therapy. Allergy 2003;58(6):461-71. 7. Viljanen M, Savilahti E, Haahtela T, Juntunen-Backman K, Korpela R, Poussa T, et al. Probiotics in the treatment of atopic eczema/dermatitis syndrome in infants: a doubleblind placebo-controlled trial. Allergy 2005;60(4):494-500. 8. Hanifin JM, Thurston M, Omoto M, Cherill R, Tofte SJ, Graeber M. The eczema area and severity index (EASI): assessment of reliability in atopic dermatitis. EASI Evaluator Group. Exp Dermatol 2001;10(1):11-8. 9. Dhar S, Kanwar AJ. Epidemiology and clinical pattern of atopic dermatitis in a North Indian pediatric population. Pediatr Dermatol 1998;15(5):347-51. 10. Cross ML, Stevenson LM, Gill HS. Anti-allergy properties of fermented foods: an important immunoregulatory mechanism of lactic acid bacteria? Int Immunopharmacol 2001;1(5):891-901. 11. Passeron T, Lacour JP, Fontas E, Ortonne JP. Prebiotics and synbiotics: two promising approaches for the treatment of atopic dermatitis in children above 2 years. Allergy 2006;61(4):431-7. 12. Sistek D, Kelly R, Wickens K, Stanley T, Fitzharris P, Crane J. Is the effect of probiotics on atopic dermatitis confined to food sensitized children? Clin Exp Allergy 2006;36(5):629-33. 13. Abrahamsson TR, Jakobsson T, Böttcher MF, Fredrikson M, Jenmalm MC, Björkstén B, et al. Probiotics in prevention of IgE-associated eczema: a double-blind, randomized, placebo-controlled trial. J Allergy Clin Immunol 2007;119(5):1174-80. 14. Boyle RJ, Robins-Browne RM, Tang ML. Probiotic use in clinical practice: what are the risks? Am J Clin Nutr 2006;83(6):1256-64; quiz 1446-7.

DERMATOLOGY

Erythroderma: Epidemiology, Clinical Profile and Clinicopathological Correlation in 47 Patients US AGARWAL*, ANSHUL MAHESHWARI†, SUNIL KOTHIWALA‡, KARUNA GUPTA#, ARPITA JINDAL#

ABSTRACT Background: Erythroderma or generalized exfoliative dermatitis, is a disease characterized by erythema and scaling of greater than 90% of the body’s surface. There is paucity of Indian studies over the etiology, clinical profile and its histopathological correlation. Aims and objectives: To assess the demographic profile, clinical features and histopathological correlation in erythroderma patients. Material and methods: We registered all patients of erythroderma consecutively from January 2013 to December 2013. After a thorough history and clinical examination, a provisional clinical diagnosis was made. We performed biopsy from two representative sites of patient and it was sent for histopathological examination. The slides were examined by two pathologists and one dermatologist without any relevant clinical information. The clinical diagnosis was matched with the blinded microscopical diagnosis. Results: The mean age of onset was 54.1 years with a male-to-female ratio of 3.3:1. The most common causes were airborne contact dermatitis (53.2%) followed by psoriasis (21.2%), drug-induced erythroderma (12.7%), chronic actinic dermatitis (2.1%), atopic dermatitis (2.1%), endogenous dermatitis (2.1%), mycosis fungoides (2.1%), lichenoid dermatitis (2.1%) and idiopathic (2.1%). Histopathology was able to provide diagnosis in 32 (68%) patients. Out of these 32 patients, microscopical diagnosis was in accordance with clinical diagnosis in 28 patients. Conclusion: Most of the clinical features of erythroderma are overlapping. Specific and diagnostic features of disease are seen only in a few patients. Repeated evaluations, close follow-up and skin biopsy are recommended for a better clinical diagnosis and patient care.

Keywords: Erythroderma, generalized exfoliative dermatitis, erythema, biopsy, histopathological examination

rythroderma or exfoliative dermatitis is an inflammatory disorder in which erythema and scaling occur in a generalized distribution involving more than 90% of the body surface.1 Because most patients are elderly and skin involvement is widespread, the disease implies an important risk to the life of the patient.2 Hasan and Jansen estimated the annual incidence of erythroderma to be 1-2/1,00,000 patients.3 This disorder may represent a variety of cutaneous and systemic diseases, and therefore a thorough work-up is essential, which includes detailed history of triggering factors like drugs, occupation, sunlight exposure, pre-

*Professor and Head †Junior Resident ‡Senior Resident Dept. of Dermatology Venereology and Leprology #Associate Professor Dept. of Pathology SMS Medical College, Jaipur, Rajasthan Address of correspondence Dr US Agarwal Professor and Head Dept. of Dermatology, Venereology and Leprology SMS Medical College, Jaipur, Rajasthan

existing dermatoses, infections, malignancies, etc. It should be followed by a meticulous clinical examination for specific diagnostic clues to rule out its etiology. Histopathology can help in identifying the cause of erythroderma in up to 50% of cases, particularly by multiple skin biopsies.4 Indian studies showed a higher prevalence of erythroderma than other studies. Sehgal and Srivastava recorded the incidence of erythroderma from the Indian subcontinent as 35/1,00,000 dermatologic outpatients. But, there are conflicting views over role of histopathology as some studies were unrewarding.5 This study was performed to find out the causes of erythroderma in north-west part of India, to find out the epidemiological, clinical profile of these patients and histopathological correlation. MATERIAL AND METHODS The study was performed during January 2013 to December 2013. In this tenure, all cases of erythroderma attending skin outpatient department were included in the study. A thorough history which included duration, progression of disease, occupation, seasonal variation,

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DERMATOLOGY precipitating factors, site of onset, other existing skin disease and other comorbidities like hypertension, atopy, etc. was taken from patient. It was followed by a thorough general physical and dermatological examination. Laboratory investigations such as complete hemogram, blood glucose, blood urea, serum creatinine, liver function tests, serum electrolytes and chest radiograph were performed. Abdominal ultrasound, peripheral smear, fine needle aspiration cytology (FNAC) of lymph nodes, CT scan, etc. were done only if required. Four millimeter punch biopsy was performed in all patients from two representative sites. The slides were seen independently by two pathologist and dermatologist without relevant clinical information. Slides were examined by them independently for any specific diagnosis. The microscopical diagnosis was then correlated with clinical diagnosis. RESULTS

Table 1. Occupational Profile of Patients Occupation

No. of males

No. of females

Farmer

Laborer

Student

Housemaker

Carpenter

Sarpanch

Service

Army officer

Nonspecific Accordance Discordant with clinical diagnosis 8% 32%

Age of patients ranged from 14 to 86 years with median of 58 years and mean age of onset of 54.1 ± 17.8 years. Majority of patients belonged to age group of 51-60 years (Fig. 1). Male predominance was seen with male-to-female ratio of 3.3:1. The total duration of erythroderma in patients ranged from 10 days to 20 years with median of 2 years and mean of 4.1 ± 5.2 years. Exacerbation of disease ranged from 7 to 120 days with a mean of 43.3 ± 25.3 days. Majority of male patients were farmers (55.5%) followed by laborers (22.2%) and students (6.3%). Majority of female patients were housemakers (72.7%). Most common aggravating factor was seasonal exacerbation seen in about 26 patients (55.3%) with summer exacerbation in 17 patients (36.1%). Seasons had no effects on disease in 21 patients (44.7%). History of atopy was present in 11 (23.4%) patients. Other

60%

Figure 2. Clinical and histopathological diagnosis.

Airborne contact dermatitis

Lichenoid dermatitis

Psoriasis

Atopic dermatitis

Drug rash

Endogenous

Mycosis fungoides

Idiopathic

Chronic actinic dermatitis 2% 2% 2% 2% 2% 2% 13% 53% 22%

No. of patients

Figure 3. Etiology of erythroderma.

10 8

8 6

6 4

2 0

2 1 0

0-10 11-20 21-30 31-40 41-50 51-60 61-70 71-80 81-90 >90 Years

Figure 1. Age-wise distribution of patients.

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Indian Journal of Clinical Practice, Vol. 25, No. 9, February 2015

aggravating factors were sunlight and dust which were seen in 11 (23.4%) patients each. Drugs were responsible in 4 (8.5%) patients. History of pre-existing skin disease was present in 30 patients (63.8%). Other comorbidities like hypertension were present in 17 patients (36.1%), diabetes in 4 patients (8.5%) and tuberculosis in 4 patients (8.5%). In 17 patients of hypertension,

DERMATOLOGY Table 2. Clinical Profile of Patients Symptom/disease

Airborne contact dermatitis (n = 25)

Psoriasis (n = 10)

Drug-induced (n = 6)

Mycosis fungoides (n = 1)

Other (n = 5)

Pruritus

Fever

Loss of appetite

Weight loss

Edema

Lymphadenopathy

Nail changes

Palmoplantar keratoderma

1 ND

Hypertension

1ND

6 ND Diabetes

ND: Newly diagnosed case.

Table 3. Clinicopathological Correlation Clinical diagnosis

Histopathological diagnosis

Airborne contact dermatitis (n= 25)

Dermatitis (n = 10)

Clinicopathological correlation 40%

Psoriasis (n = 3) Nonspecific (n = 12) Psoriasis (n = 10)

70%

Psoriasis (n = 7) Dermatitis (n = 1) Nonspecific (n = 2)

Drug-induced (n = 6)

100%

Chronic actinic dermatitis (n = 1)

Dermatitis (n = 1)

100%

Endogenous dermatitis (n = 1)

Dermatitis (n = 1)

100%

Atopic dermatitis (n = 1)

Dermatitis (n = 1)

100%

Mycosis fungoides (n = 1)

100%

Lichenoid dermatitis (n = 1)

100%

Idiopathic (n = 1)

Nonspecific (n = 1)

nine were already on antihypertensive medicine but 8 patients were diagnosed with hypertension for the first time. The site of onset of erythroderma was scalp and face in 20 patients (42.6%), extremities in 18 patients (38.3%), and trunk and abdomen in 8 patients (17.0%). Most common clinical finding was pruritus (100%) followed by lymphadenopathy (70.2%), edema (57.4%), nail changes (55.3%), fever (38.2%), palmoplantar keratoderma (21.2%), weight loss (14.9%) and loss of appetite (10.6%) (Table 2). Severe pruritus causing disturbance in sleep was present in 29 (61.7%) patients. Inguinal lymphadenopathy was present in

33 (70.2%) patients and axillary lymphadenopathy in one patient. Most common nail change was Beauâ&#x20AC;&#x2122;s line followed by shiny nails, yellowish discoloration of nails, subungual hyperkeratosis, pitting and onycholysis. In 3 (6.3%) patients, 20 nail dystrophy was present. Pitting edema of the distal extremities was present in 21 (44.7%) patients. Generalized edema of pitting type was present in 4 (8.5%) patients. Histopathology was able to provide specific histopathological diagnosis e.g., psoriasis, dermatitis in 32 (68%) of patients. Out of these 32 patients, clinical correlation occurred in 28 (87%) patients. Overall in 28 (60%) patients,

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DERMATOLOGY Table 4. Histopathological Findings Psoriasis (n = 10) Hyperkeratosis Parakeratosis Munro microabscess Granular layer absent Acanthosis Suprapapillary thinning Dilated blood vessel Perivascular lymphocytic infiltrate Infiltrate having neutrophils

7 10 7 8 7 6 6 9 3

(70%) (100%) (70%) (80%) (70%) (60%) (60%) (90%) (30%)

5 4 3 5 4 3 5 3

(83%) (67%) (50%) (83%) (67%) (50%) (83%) (50%)

Drug-induced (n = 6) Hyperkeratosis Parakeratosis Necrotic keratinocyte Basal cell vacuolization Melanin incontinence Lichenoid infiltrate Perivascular lymhocytic infiltrate Eosinophils in infiltrate Dermatitis (n = 29)

25 (86%) 25 (86%) 24 (83%) 11 (70%) 27 (38%) 8 (26%)

Hyperkeratosis Parakeratosis Acanthosis Spongiosis Perivascular lymphocytic infiltrate Eosinophils in infiltrate

Table 5. Comparison of Different Etiology of Erythroderma in Various Studies Pal et al10

Rym et al11

Bandyaopadhyay et al9

Sudho et al12

Chaudhary et al13

Hulmani et al8

Our study

Psoriasis

37.8

51.25

33.33

21.2

Eczema

12.2

7.5

57.4*

Ichthyosis

7.8

1.33

Pityriasis rubra pilaris

2.2

5.25

1.33

3.33

Scabies

2.2

1.25

3.33

Pemphigus foliaceus

5.6

6.25

5.33

Lichen planus

1.25

Atopic dermatitis

13.33

6.66

6.6

2.1

Other dermatoses

6.6

3.75

2.1

Drug reaction

5.5

11.25

16.6

12.1

Malignancy

5.5

8.75

2.67

6.66

3.3

2.1

Idiopathic

14.6

7.5

21.33

16.6

2.1

Study causes

*Airborne contact dermatitis patients are included in this group.

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DERMATOLOGY clinical diagnosis matched with histopathological diagnosis. Nonspecific biopsy was seen in 15 (32%) of patients. Histopathology was most accurate in diagnosing drug reaction (100%), followed by mycosis fungoides (100%) and psoriasis (70%) (Fig. 2). The specific findings of biopsies are depicted in Table 4. The most common causes were airborne contact dermatitis (53.2%) followed by psoriasis (21.2%), drug-induced erythroderma (12.7%), chronic actinic dermatitis (2.1%), atopic dermatitis (2.1%), endogenous dermatitis (2.1%), mycosis fungoides (2.1%), lichenoid dermatitis (2.1%) and idiopathic (2.1%) (Fig. 3). DISCUSSION The approach to patients with erythroderma depends on their previous dermatologic background. Patients with pre-existing dermatoses are easy to diagnose. Otherwise, erythroderma remains a diagnostic challenge, especially in those patients without history of dermatologic diseases and who deny having recently taken any medications.6 In our study, age of patients ranged from 14 to 86 years with mean age of onset of 54.1 ± 17.8 years. This is in accordance with various previous studies.3,6,7 In this series, men outnumbered women in a ratio of 3.3:1. Similar findings were seen in other studies.1,5 In a recent study by Hulmani et al, male-to-female ratio was quite high of 14:1.8 As men are commonly involved than women in outdoor activities, male-to-female ratio is quite high in this study. Most common aggravating factor was seasonal variation seen in 26 patients. Summer exacerbation was seen in 17 patients. Dust and sunlight aggravated the condition in 11 patients each. This is in contrast to another study where winter season was aggravating factors seen in 30% patients.8 In our study, most common cause of erythroderma was airborne contact dermatitis compared to Hulmani et al where most common etiology was psoriasis.8 This might be the cause of winter exacerbation in their study. Most of the clinical findings were in accordance with other studies. Lymphadenopathy was seen in 70% of our patients and was quite high. Some studies showed it in between 19-33%.6,9 Others showed it to be around 55%.8,10 Nail changes were seen in 55% of patients. Nail changes were Beau’s lines, shining in the nails, subungual hyperkeratosis, pitting, yellowish discoloration and onychodystrophy. Similar findings were present in other studies.8,10 Histopathology was successful in determining the specific cause of erythroderma in 32

(68%) of the patients. So, overall clinicopathological correlation occurred in 60% of patients. As in our study, relevant clinical information wasn’t provided to the pathologist but still they were able to match the clinical diagnosis in 28 (60%) of patients. The percentage might push up higher with relevant clinical information. In a study by Rym et al histopathological correlation was found in 74% of patients11; in Bandyaopadhyay et al there was correlation in 52% of cases.9 Most common histopathological finding in our study was perivascular lymphocytic infiltrate. The findings are comparable with slight differences from study by Walsh et al.4 Comparison of our etiologic diagnosis with the previous studies is compiled in Table 5. In our case series, most common clinical diagnosis was airborne contact dermatitis. It is quite different from other studies where it constituted a minority group. REFERENCES 1. Vasconcellos C, Domingues PP, Aoki V, et al. Erythroderma: analysis of 247 cases. Rev Saude Publica 1995;29:177-82. 2. Botella-Estrada R, Sanmartin O, Oliver V, et al. Erythroderma: a clinicopathological study of 56 cases. Ama Arch Derm Syphilol 1994;130:1503-7. 3. Hasan T, Jansen CT. Erythroderma: a follow-up of fifty cases. J Am Acad Dermatol 1983;8:836-40. 4. Walsh NM, Prokopetz R, Tron VA, et al. Histopathology in erythroderma: review of a series of cases by multiple observers. J Cutan Pathol 1994;21:419-23. 5. Sehgal VN, Srivastava G. exfoliative dermatitis: a prospective study of 80 patients. Dermatologica 1986;173:278-84. 6. Li J, Zheng JU. Erythroderma: a clinical and prognostic study. Dermatology 2012;225(2):154-62. 7. Sehgal VN, Srivastava G, Sardana K, et al. Erythroderma/ exfoliative dermatitis: a synopsis. Int J Dermatol 2004;43:39-47. 8. Hulmani M, Nandakishore B, Bhat MR, et al. Indian Dermatol Online J 2014;5(1):25-9. 9. Bandyaopadhyay D, Chowdhury S, Roy A. Seventy five cases of exfoliative dermatitis. Ind J Dermatol 1999;44:55-7. 10. Pal S, Haroon TS. Erythroderma: a clinico-etiologic study of 90 cases. Int J Dermatol 1998;37:104-7. 11. Rym BM, Mourad M, Bechir Z, et al. Erythroderma in adults: A report of 80 cases. Int J Dermatol 2005;44:731-5. 12. Sudho R, Hussain SB, Bellraj E, et al. Clinicopathological study of exfoliative dermatitis. Indian J Dermatol Venereol Leprol 2003;69:30-1. 13. Chaudhary A, Gupte PD. Erythroderma: a study of incidence and aetiopathogenesis. Indian J Dermatol Venereol Leprol 1997;63:38-9.

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ENDOCRINOLOGY

Primary Hyperparathyroidism with Chronic Pancreatitis: A Case Report ACHINTYA PAL*, AVIK CHAKRABORTY†, ARKADIP CHOUDHURY‡

ABSTRACT The association between primary hyperparathyroidism and chronic pancreatitis is rare. Also, the occurrence and mechanism of this association is not well-understood. Here we present a case of a 44-year-old male who presented with features of chronic pancreatitis and hypercalcemia subsequently to be diagnosed as a case of primary hyperparathyroidism due to parathyroid adenoma, chronic pancreatitis, nephrocalcinosis, secondary diabetes mellitus with metabolic myopathy.

Keywords: Primary hyperparathyroidism, chronic pancreatitis, nephrocalcinosis

rimary hyperparathyroidism is a disorder of calcium, phosphate and bone metabolism because of excessive parathyroid hormone secretion.1 Cause of hyperparathyroidism in majority of the cases are adenoma followed by hyperplasia or carcinoma, etc.1-3 The occurrence of primary hyperparathyroidism and chronic pancreatitis is not that common and the mechanism of association is not clearly defined.1,4 CASE REPORT A 44-year-old male teacher, nonalcoholic from rural Tripura was admitted with complaints of loose stools off and on, pain upper abdomen and significant weight loss over last 1 year. Stools were greasy, offensive, voluminous and more after fatty meals. Pain was located over upper abdomen of 6/10 intensity in a scale of 0-10, increased after fatty meal and radiated to back and relieved by stooping forward. He also noticed significant weight loss of 19.2 kg over last 1 year. No history of high-risk behavior. There was history of

*2nd Year Postgraduate Trainee †Associate Professor ‡1st Year Postgraduate Trainee Dept. of Medicine Tripura Medical College and Dr BRAM Teaching Hospital Hapania, Agartala, West Tripura Address for correspondence Dr Avik Chakraborty Dept. of Medicine TMC and Dr BRAM Teaching Hospital Hapania, Agartala, West Tripura E-mail: dravik1975@gmail.com

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passage of white chalky pieces in urine four times in last 6 months, which broke on pressure. There was also history of increased frequency and volume of urine with past history of non-Helicobacter pylori-induced peptic ulcer disease 3 years back. On examination, patient has low body mass index (BMI) (18.2 kg/m2), mild pallor, dehydration, generalized wasting, decreased tone with proximal muscle weakness of both the lower limbs (4-/5). Rest of the general physical examination including thyroids were within normal limits and per abdomen revealed mild epigastric tenderness. Provisional diagnosis of chronic pancreatitis with malnutrition and renal calculus disease was made. Investigation revealed high blood sugar (F-151/PP-425 mg/dL), high glycated hemoglobin (Hb) (8.9 g/dL) and serum calcium (13.5 mg/dL) with normal phosphorus (2.5 mg/dL) level. Urea (16.4 mg/dL), serum creatinine (1.4 mg/dL) and lightly raised serum amylase 100 u/L (20-96) and serum lipase (70 u/L) (3-43). X-ray KUB (kidney, ureter, bladder) (Fig. 1), USG whole abdomen and CT abdomen (Fig. 2) revealed multiple calculi in pancreas, nephrocalcinosis and bilateral ureteric calculi. On further investigation for hypercalcemia - serum parathyroid hormone was found remarkably high 257.50 pg/mL (14-72) with normal 24-hour urine calcium (140.80 mg/dL [100-300]), serum vitamin D3 (55 ng/mL [20-100]). X-ray of both hands showed periosteal bone resorption of middle phalanx of both middle and ring fingers (Fig. 3). Dual-energy X-ray absorptiometry (DEXA) scan (T-score-spine -2.9, HIP [B/L] -2.6) showed

ENDOCRINOLOGY

Figure 1. X-ray KUB.

Figure 3. X-ray of both hands.

20 minutes image

120 minutes image

Figure 4. Tc-99m sestamibi scan.

Figure 2. CECT abdomen.

osteoporosis and Tc-99m sestamibi scan showed delayed focal uptake in the region of right inferior pole of thyroid gland consistent with parathyroid adenoma (Fig. 4).

Evaluation for MEN-1 was negative. The case was finally diagnosed as primary hyperparathyroidism due to right lower parathyroid adenoma, chronic pancreatitis, nephrocalcinosis, secondary diabetes mellitus with metabolic myopathy. He underwent parathyroidectomy with normalization of parathyroid hormone level. Histopathological examination is suggestive of parathyroid adenoma.

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ENDOCRINOLOGY DISCUSSION

REFERENCES

Though rare, primary hyperparathyroidism is to be always suspected in patients who present with dominant symptoms and signs of hypercalcemia.5 Most common primary involvement is of kidneys and skeletal system.

1. John TP, Herald J. Disorder of parathyroid gland and calcium homeostasis. In: Harrison’s Principle of Internal Medicine. 18th edition, Longo DL, Kasper DL, Jamson JL, Fauci AS, Hauser SL, Loskalzo J (Eds.), McGraw-Hill: USA 2012:p.3096.

There is deposition of calcium in renal parenchyma and there are occurrence of recurrent nephrolithiasis.1,3 Demineralization of bone occurs and significant structural abnormality occurs in the form of osteitis fibrosa cystica.1,3 X-ray changes may include subperiosteal bone resorption in digits.1 Clinical and experimental data suggest chronic pancreatitis as a rare association with primary hyperparathyroidism.4 But, its effect and cause is not clearly understood so far. Treatment is mainly surgical. In many cases, if parathyroid tumors are resected, there occurs significant improvement.4,6 Medical management is also of some benefit if surgery is contraindicated.

2. Nicki RC, Brian RW, Stuart HR (Eds.). Davidson’s Principles and Practice of Medicine. 21st edition, Churchill Livingstone Elsevier 2011:p.766-7. 3. Jakovljević B, Grubor G, Jakovljević A, Gruboret P. Primary hyperparathyroidism - case report of a female patient with advanced disease. Acta Medica Medianae 2009;48(2):52-4. 4. Bai HX, Giefer M, Patel M, Orabi AI, Husain SZ. The association of primary hyperparathyroidism with pancreatitis. J Clin Gastroenterol 2012;46(8):656-61. 5. Turchi JJ, Flandreau RH, Forte AL, French GN, Ludwig GD. Hyperparathyroidism and pancreatitis. JAMA 1962;180:799-804. 6. Katoh H, Kojima T, Shimozawa E, Tanabe T. Chronic calcifying pancreatitis associated with primary hyperparathyroidism - report of a case and review of the literature. Jpn J Surg 1990;20(6):704-6.

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Type 1 Diabetic Women More Prone to Heart Disease A large meta-analysis has found that women with type 1 diabetes have more than twice the risk of dying from heart disease compared with men who have the condition. The study is published in The Lancet Diabetes & Endocrinology.

Worse Hot Flashes could Mean Lower Bone Density Women who have moderate-to-severe vasomotor symptoms (VMS) are at higher risk of hip fractures than women with less severe or no hot flashes and night sweats, suggest new findings published in the Journal of Clinical Endocrinology and Metabolism. Researchers stated that higher VMS severity may be associated with lower bone mineral density (BMD).

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Indian Journal of Clinical Practice, Vol. 25, No. 9, February 2015

ENDOCRIONOLOGY

Alternatives to Conventional Hormone Replacement Therapy for Postmenopausal Outcomes SIPPY AGARWAL*, SAURABH AGARWAL†, G AGARWAL‡, VIVEK NIRANJAN#, PK AGARWAL¶, RICHA GOYAL$

ABSTRACT Conventional hormone replacement therapy, though, may counteract the postmenopausal health outcomes, but because of its potential harmful effects, its prescription is not recommended. This article highlights briefly the alternatives available to conventional hormone replacement therapy.

Keywords: Hormonal replacement therapy, alternatives, postmenopausal

enopause, whether natural or induced surgically, has significant impact on women physically and emotionally. Deficiency of estrogen leads to climacteric symptoms, functional disabilities, sexual dysfunctions, osteoporosis, loss of muscle mass and muscle strength, etc. Thus, women in this age group should be educated about these symptoms and treated accordingly. Ideal postmenopausal hormonal therapy, which in itself is a medical and social challenge, should achieve several benefits, minimal side-effects and enhanced compliance with optimum cost. Conventional hormone replacement therapy, though once accepted as an ideal strategy for postmenopausal health outcomes, has been challenged by number of randomized trials. With the release of Women Health Initiative results, the use of such therapy has become increasingly difficult. Conventional therapy

*Lecturer

SN Medical College, Agra, Uttar Pradesh Dept. of Orthopedics MLB Medical College, Jhansi, Uttar Pradesh ‡SR Infertility Centre, Jaipur, Rajasthan #Junior Resident Dept. Orthopedics MLB Medical College, Jhansi, Uttar Pradesh ¶Consultant, Dept. of General Surgery $Consultant, Dept. of Obstetrics and Gynecology Haridwar, Uttarakhand Address for correspondence Dr Saurabh Agarwal Head, Dept. of Orthopedics MLB Medical College, Jhansi, Uttar Pradesh E-mail: drsorabh@rediffmail.com †Head,

may have side-effects such as risk of breast cancer, thromboembolism, stroke and coronary events, etc. This led to a search for alternatives to this therapy. ALTERNATIVES AVAILABLE Alternatives available are: ÂÂ

SERMs (Selective estrogen receptor modulators, e.g. Raloxifene)

ÂÂ

STEARs (Selective tissue regulators, e.g. Tibolone)

estrogenic

activity

SERMs SERMs bind with high affinity and specifically to estrogen receptors (ER) consisting of ER α and ER β. So, these can act as either ER agonists or antagonists depending on tissue type. Raloxifene as SERM has agonist effects on bone, serum lipids and arterial vasculature with estrogen antagonist effects on breast and uterus. Being an estrogen antagonist, it is not fit for climacteric symptoms.

STEARs Tibolone, a synthetic STEAR steroid hormone and its three metabolites have estrogenic, gestagenic and weak androgenic effect on different organs. After ingestion, Tibolone is converted to three metabolites. The 3α and 3β metabolites exert estrogenic effect with positive effect on climacteric symptoms, the skeleton, muscle strength and vagina, whereas the Δ4 isomer binds to progesterone and androgen receptors inhibiting endometrial stimulations and enhancing libido. The Δ4 isomer inhibits formation of active estrogens in breast. As compared to conventional hormonal replacement

Indian Journal of Clinical Practice, Vol. 25, No. 9, February 2015

847

ENDOCRIONOLOGY therapy, Tibolone has no cardiovascular side effects and no increased risk of breast cancer in women with no previous history. As compared with raloxifene, tibolone also reduces risk of nonvertebral fractures. Adverse effects of tibolone include weight gain, breast discomfort, vaginal discharge and infection, pelvic pain, endometrial bleeding. Though, this effect of Tibolone on breast cancer and thromboembolism events is not well-defined, but its pharmacological profile provides a safer alternative to conventional hormone replacement therapy. CONCLUSION Though, long-term studies are to be done on tibolone and raloxifene with their selective effects on postmenopausal outcomes and with minimal side effects, they may serve to be interesting alternatives to conventional hormone replacement therapy. But, still a search for ideal alternative to conventional classical hormonal replacement therapy for postmenopausal women has to go on.

5. Jacobsen DE, Samson MM, Schouw Y, Grobbee DE, Verhaar HJ. Efficacy of tibolone and raloxifene for the maintenance of skeletal muscle strength, bone mineral density, balance, body composition, cognitive function, mood/depression, anxiety and quality of life/well-being in late postmenopausal women ≥70 years: Study design of a randomized, double-blind, double-dummy, placebo-controlled, single-center trial. Trials 2008:p.745-62. 6. Jacobsen DE, Samson MM, Kezic S, Verhaar HJ. Postmenopausal HRT and tibolone in relation to muscle strength and body composition. Maturitas 2007;58(1):7-18. 7. Kloosterboer HJ, Ederveen AG. Pros and cons of existing treatment modalities in osteoporosis: a comparison between tibolone, SERMs and estrogen (±progestogen) treatments. J Steroid Biochem Mol Biol 2002;83(1-5):157-65. 8. Kung HC, Hoyert DL, Xu J, Murphy SL. Deaths: final data for 2005. Natl Vital Stat Rep 2008;56(10):1-120. 9. Langer RD, Landgren BM, Rymer J, Helmond FA; OPAL Investigators. Effects of tibolone and continuous combined conjugated equine estrogen/medroxyprogesterone acetate on the endometrium and vaginal bleeding: results of the OPAL study. Am J Obstet Gynecol 2006;195(5):1320-7.

SUGGESTED READING

10. Beral V; Million Women Study Collaborators. Breast cancer and hormone-replacement therapy in the Million Women Study. Lancet 2003;362(9382):419-27.

1. Archer DF, Hendrix S, Gallagher JC, Rymer J, Skouby S, Ferenczy A, et al. Endometrial effects of tibolone. J Clin Endocrinol Metab 2007;92(3):911-8.

11. Modelska K, Cummings S. Tibolone for postmenopausal women: systematic review of randomized trials. J Clin Endocrinol Metab 2002;87(1):16-23.

2. Cummings SR, Ettinger B, Delmas PD, Kenemans P, Stathopoulos V, Verweij P, et al; LIFT Trial Investigators. The effects of tibolone in older postmenopausal women. N Engl J Med 2008;359(7):697-708.

12. Mois M. Tibolone study in breast cancer patients to close ahead of schedule. Auckland, New Zealand; Drugs. com. Available at http://drugs.com/news/tibolone-studybreast-cancer-patients-close-al-red-schedule-6164.html. Accessed July 25, 2008.

3. El-Hajj Fuleihan G. Tibolone and the promise of ideal hormone-replacement therapy. N Engl J Med 2008;359(7):753-5. 4. Beral V, Bull D, Reeves G; Million Women Study Collaborators. Endometrial cancer and hormonereplacement therapy in the Million Women Study. Lancet 2005;365(9470):1543-51.

13. Swegle JM, Kelly MW. Tibolone: a unique version of hormone replacement therapy. Ann Pharmacother 2004;38(5):874-81. 14. von Holst T. Alternatives to hormone replacement therapy: raloxifene and tibolone. Z Arztl Fortbild Qualitatssich 2000;94(3):205-9.

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ENT

Bacteriology of Chronic Suppurative Otitis Media: A Preliminary Study at a Tertiary Hospital MIRZA ANEESA AFZAL BEG*, IRFAN IQBAL†, IMTIYAZ DERWEISH†

ABSTRACT Background: Chronic suppurative otitis media (CSOM) is a commonly encountered infection of the middle ear caused by bacteria, fungi and viruses. It is defined as infection of the middle ear that lasts >3 months and is accompanied by tympanic membrane perforation. Objectives: The aim of the study was to find the local pattern of different microorganisms involved in cases of CSOM. Material and methods: A total of 100 patients with CSOM attending the outpatient clinic were included in the study. Swabs were taken and cultured for aerobic bacteria. Results: The results of the bacteriological studies on the 100 cases showed that microbiological culture was yielded from 93 samples (93%). Based on results from present study, P. aeruginosa was the most prevalent organism followed by S. aureus. Conclusion: Knowledge of the pathogens responsible for CSOM should guide the treatment and management of the disease and reduce the intracranial and extracranial complications of CSOM.

Keywords: Bacteria, complications, discharge, suppurative, tympanic membrane

hronic suppurative otitis media (CSOM) is a commonly encountered infection of the middle ear caused by bacteria, fungi and viruses. CSOM is a perforated tympanic membrane with persistent drainage from the middle ear. It is defined as infection of the middle ear that lasts >3 months and is accompanied by tympanic membrane perforation.1

The disease is common in all age groups but prevalent mainly in children belonging to lower socioeconomic group. It is most commonly seen in developing and underdeveloped countries affecting 0.5-30% of any community. CSOM has profound impact on society in terms of hearing of patient.2 It causes conductive and sensorineural hearing loss and has adverse effect on child development.3

OBJECTIVES The aim of the study was to find the local pattern of different microorganisms involved in cases of CSOM. MATERIAL AND METHODS This prospective, randomized and longitudinal study was carried out at the Outpatient Dept. of Otorhinolaryngology and Head and Neck Surgery, SMHS Hospital, an associated Hospital of Government Medical College, Srinagar from January 2012 to January 2013. A total of 100 patients with unilateral or bilateral CSOM were enrolled after detailed clinical history regarding the age, duration of ear discharge and especially any antibiotic treatment received and from whom informed consent was obtained.

Most frequently isolated bacteria in CSOM are Pseudomonas aeruginosa, Staphylococcus aureus, Proteus spp., Escherichia coli and Klebsiella spp.4

Inclusion Criteria ÂÂ Patients presenting with chronic ear discharge for >6-12 weeks. ÂÂ Patients with perforated tympanic membrane.

*Postgraduate Scholar †Registrar Dept. of Otorhinolaryngology, Head and Neck Surgery SMHS Hospital, Srinagar, Jammu and Kashmir Address for correspondence Dr Irfan Iqbal E-mail: irfaniqbal0809@yahoo.com

Exclusion Criteria ÂÂ Patients with cholesteatoma formation on clinical examination. ÂÂ Patients with intracranial or extracranial complications of CSOM (petrositis, facial paralysis, meningitis, abscess). ÂÂ Patients without any written informed consent.

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ENT Methodology

Table 3. Mixed Growth (n = 22)

Sterile cotton swabs were used to collect the samples. The pus swabs were cultured on Blood and MacConkeys agar and incubated aerobically at 37째C for 24-48 hours. All organisms isolated were identified according to standard microbiological methods. This study was limited to identification of aerobic bacterial isolates from the samples submitted for culture. No studies were done for anaerobes, viruses or fungi.

Type of organism

Total isolates

Percentage (%)

P. aeruginosa

27.27

S. aureus

22.72

E. coli

13.63

Proteus spp.

13.63

Klebsiella spp.

4.54

S. epidermidis

9.09

Streptococcus spp.

9.09

RESULTS There were a total of 100 patients in the study. The age range was 5-65 years with mean age of 36 years and most of the patients were of age group of <12 years. There were a total of 57 females and 43 males with ratio of 1.33:1. The results of the bacteriological studies on the 100 cases showed that microbiological culture was yielded from 93 samples (93%), 71 (71%) had a single organism isolated from the middle ear discharge, while the remaining 22 (22%) had two or more organisms isolated. There were seven (7%) samples who had a sterile culture with no organism isolated (Table 1), which can be attributed to anaerobes, fungi or viruses as our study was limited to identification of aerobic bacterial isolates only. In monobacterial infections Pseudomonas species 24 (33.80%) was the commonest microbial organism to Table 1. Type of Growth (n = 100) Total isolates

Percentage (%)

Pure growth

Mixed growth

No growth

Table 2. Pure Growth (n = 71) Type of organism

Total isolates

Percentage (%)

P. aeruginosa

33.80

S. aureus

29.57

E. coli

12.67

Proteus spp.

9.85

Klebsiella spp.

7.04

S. epidermidis

4.22

Streptococcus spp.

2.81

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Indian Journal of Clinical Practice, Vol. 25, No. 9, February 2015

cause ear discharge followed by S. aureus 21 (29.57%) and E. coli 9 (12.67%) (Table 2). In samples that yielded multiorganisms, Pseudomonas species were isolated in six (27.27%) samples followed by S. aureus in five (22.72%) samples (Table 3). DISCUSSION Chronic suppurative otitis media (CSOM) is the most common ear disease which is encountered in our daily clinical practice. Untreated cases of CSOM can result in a broad range of complications. Such complications range from persistent otorrhea, mastoiditis, labyrinthitis, facial nerve paralysis to more serious intracranial abscesses or thrombosis.5 Identification of microbiological organisms is important for prescribing appropriate treatment as a wide range of organisms are isolated in CSOM. Monobacterial isolation was observed in 71% cases, while Ayyagari et al6 found monobacterial isolation in 50.5% cases and Rao et al7 in 68.52% cases. Based on results from the present study, P. aeruginosa was the most prevalent organism followed by S. aureus. These findings correlate with earlier studies.8-10 Thus, the most common aerobic organisms of CSOM were P. aeruginosa, S. aureus, E. coli, Proteus species and Klebsiella as also reported in several studies.11,12 CSOM still ranks among the most important causes of preventable hearing loss. The main cause of CSOM is failure of treatment of acute otitis media. Morbidity from this disease remains significant in our country despite frequent use of systemic antibiotics to treat the illness and its complications. Thus, it has been recommended that culture studies be done before instituting topical, oral or intravenous antibiotics. Knowledge of the species of current pathogens is important for determining the appropriate antibiotics for patients with CSOM.

ENT CONCLUSION The study suggests that the common etiological agents for CSOM were P. aeruginosa followed by S. aureus. It is very much needed that the doctors should have knowledge about the pattern of causative agents as it gives them clue regarding the use of appropriate antibiotics and thus reduce the intracranial and extracranial complications of CSOM. REFERENCES 1. Goycoolea MV, Hueb MM, Ruah C. Otitis media: the pathogenesis approach. Definitions and terminology. Otolaryngol Clin North Am 1991;24(4):757-61. 2. Dugdale AE. Management of chronic suppurative otitis media. Med J Aust 2004;180(2):91; author reply 92-3. 3. El-Sayed Y. Bone conduction impairment in uncomplicated chronic suppurative otitis media. Am J Otolaryngol 1998;19(3):149-53. 4. Couzos S, Lea T, Mueller R, Murray R, Culbong M. Effectiveness of ototopical antibiotics for chronic suppurative otitis media in Aboriginal children: a community-based, multicentre, double-blind randomised controlled trial. Med J Aust 2003;179(4): 185-90.

5. Loy AH, Tan AL, Lu PK. Microbiology of chronic suppurative otitis media in Singapore. Singapore Med J 2002;43(6):296-9. 6. Ayyagari A, Paancho IVK, Pandhi SC, Goswami A. Chronic suppurative otitis media. Indian J Med Res 1991;73:860-4. 7. Rao BN, Reddy MS. Chronic suppurative otitis media - a prospective study. Indian J Otolaryngol Head Neck Surg 1994;46(2):72-7. 8. Shyamala R, Reddy PS. The study of bacteriological agents of chronic suppurative otitis media - aerobic culture and evaluation. J Microbiol Biotech Res 2012;2(1):152-62 . 9. Maji PK, Chatterjee TK, Chatterjee S, Chakrabarty J, Mukhopadhyay BB. The investigation of bacteriology of chronic suppurative otitis media in patients attending a tertiary care hospital with special emphasis on seasonal variation. Indian J Otolaryngol Head Neck Surg 2007;59(2):128-31. 10. Yeo SG, Park DC, Hong SM, Cha CI, Kim MG. Bacteriology of chronic suppurative otitis media - a multicenter study. Acta Otolaryngol 2007;127(10):1062-7. 11. Attallah MS. Microbiology of chronic suppurative otitis media with cholesteatoma. Saudi Med J 2000;21(10):924-7. 12. Smith JA, Danner CJ. Complications of chronic otitis media and cholesteatoma. Otolaryngol Clin North Am 2006;39(6):1237-55.

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FDA Clears OTC Flonase Nasal Spray for Allergy Relief The US Food and Drug Administration (FDA) has approved over-the-counter (OTC) fluticasone propionate 50 mg nasal spray (Flonase Allergy Relief, GlaxoSmithKline) for treatment of hay fever or upper respiratory allergies, the company announced. Flonase Allergy Relief is the first and only OTC nasal spray indicated for relief of all nasal and eye-related allergy symptoms including runny nose, sneezing, itchy nose, nasal congestion and itchy and watery eyes, according to a company news release.

Current Rules to Determine Strep Throat in Children not Accurate A new study indicates that current clinical prediction rules used by physicians to determine whether children have ‘strep throat’ caused by Group A streptococcal infection may not be accurate. The study is published in CMAJ (Canadian Medical Association Journal). Group A streptococcus bacteria cause about 30-40% of sore throats (pharyngitis) in children; the remaining cases are usually viral. Antibiotics are used to treat bacterial infections, but because there is overlap between symptoms of bacterial and viral pharyngitis, most clinical guidelines recommend microbiologic testing with a rapid antigen detection test or a throat culture.

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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

INTERNAL MEDICINE

Risk Factors Associated with Trimethoprimsulfamethoxazole and Ciprofloxacin Resistance Among Escherichia coli Strains Isolated from Communityacquired Urinary Tract Infection POTTATHIL SHINU*, RAJESH BAREJA†, VARSHA A SINGH‡, MONIKA BANSAL#, MANOJ GOYAL§, RUHI BUNGER‡, BEENA JAD£, AVNEET SINGH SETIA¥

ABSTRACT Urinary tract infections (UTIs) are common infections affecting all age groups particularly adults. The present study was carried out to determine the risk factors for trimethoprim-sulfamethoxazole (TMP-SMX) and ciprofloxacin-resistant Escherichia coli (E. coli) isolates obtained from community-acquired UTI. For the study, a total of 595 patients aged between 15 and 70 years with community-acquired UTI were prospectively recruited; 492 (82.69%) of these samples were sterile. Of the 93 Gram-negative isolates included in this study, 56 and 37 isolates were obtained from uncomplicated and complicated UTI, respectively. Since, all the male patients were categorized in the complicated UTI group, all 56 noncomplicated cases were female patients and 61 (84.72%) of the complicated cases were female patients. The median age was 55 (SD 15.7) and 49 (SD 16) for the uncomplicated and the complicated UTI patients, respectively. Approximately 30.36% and 86.49% of uncomplicated and complicated UTI patients were from a rural area. E. coli was the causative agent in 83.93% and 67.57% in the uncomplicated and complicated UTI, respectively (p < 0.0174). Nitrofurantoin and fosfomycin were found to have resistance rates of 3.57% and 1.18%, respectively for uncomplicated UTI strains. ESBL were detected in 3.6% and 5.66% of the E. coli strains isolated from uncomplicated and complicated UTIs, respectively. In summary, TMP/SMX may not be appropriate for the empirical treatment of communityacquired UTI due to its widespread resistance. However, ciprofloxacin may be used warily for both uncomplicated and complicated UTI because of emerging resistance.

Keywords: Ciprofloxacin resistance, trimethoprim-sulfamathoxazole resistance, community-acquired UTI

or lower tract.2 Further, urine culture continues to be the authoritative method to diagnose infection in this population and Escherichia coli (E. coli) continues to be the predominant etiology of UTI.1,3

*Assistant Professor Dept. of Microbiology, MMIMSR, MM University, Mullana, Ambala, Haryana †Dept. of Microbiology, SRMSIMSR, Bareilly, Uttar Pradesh ‡Dept. of Microbiology #Dept. of Physiology $Dept. of Pharmacology MMIMSR, MM University, Mullana, Ambala, Haryana £Dept. of Microbiology, GMC, Jammu ¥Dept. of Medicine, MMIMSR, MM University, Mullana, Ambala, Haryana Address for correspondence Dr Pottathil Shinu, Assistant Professor, Dept. of Microbiology MMIMSR, MM University, Mullana, Ambala -133 207, Haryana E-mail: shinup1983@gmail.com

UTI may be community-acquired or hospital-acquired.4 In case of community-acquired UTI, trimethoprimsulfamethoxazole (TMP-SMX), ciprofloxacin, cephalosporins, semi-synthetic penicillins with or without inhibitors, nitrofurantoin and fosfomycin are the most commonly used antibacterial drugs in the treatment.5 However, due to the increasing frequency of drug-resistant strains of uropathogens, the effectiveness of commonly used standard antibiotic regimens are decreasing.3 Infectious Diseases Society of America (IDSA) recommends, TMP/SMX to treat UTI in settings with low prevalence of drug-resistant strains (<10-20%). However, fluoroquinolones are indicated if the TMP/SMX resistance rate is higher than 20%.2 In the last two decades, the fluoroquinolones have been

rinary tract infections (UTIs) are common infections affecting all age groups particularly elderly populations.1 The treatment modalities of UTI depends on various factors such as age of the patient, sex, underlying disease, infecting agent and the site of involvement of the urinary tract such as upper

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Indian Journal of Clinical Practice, Vol. 25, No. 9, February 2015

INTERNAL MEDICINE used for community-acquired UTIs and an association between the increase in quinolone prescriptions and an increase in bacterial resistance has been reported from various countries.6-8 Therefore, therapeutic alternatives in the setting of high resistance against both TMP/SMX and quinolones need to be studied. The current study was designed to determine the various risk factors associated with TMP/SMX and ciprofloxacin resistance of uropathogenic E. coli strains isolated from patients suspected to be having community acquired UTI. MATERIAL AND METHODS

Study Setting and Duration This prospective observational study was conducted in the Dept. of Microbiology, MMIMSR, Mullana (Ambala) tertiary care hospital (750 bedded), over a period of March 2014 to October 2014. This study was approved by the MMIMSR, Mullana Ethical Committees and informed consent was obtained from the patients.

Study Population Patients aged between 15 and 70 years with communityacquired UTI were prospectively recruited for the study. Male patients, who had more than three episodes of UTI in the last year, those with upper UTI, pregnant patients, patients with urinary tract abnormalities, patients with a urinary catheter, those who had a urological operation and those who had urolithiasis were interpreted as having complicated UTI. However, patients with history of hospital stay in the last month were the excluded. A pre-tested questionnaire was collected from all the patents regarding the demographic characteristics such as age, sex, address, symptoms (like dysuria, urgency, pollakiuria), criteria indicating the presence of complicated UTI, history of hospital stay within the last month and antibiotic usage within the last year.

Specimen Collection and Processing Clean-catch midstream urine samples was collected from each patients and inoculated on cysteine lactose electrolyte deficient media (CLED) using 4 mm calibrated loop specifically; a semi-quantitative technique was used.9 Pyuria was detected if 5-10 leukocytes in the centrifuged (at 2,000 rpm for 5 mins) urine. Culture plates were incubated for 18-24 hours at 37°C.

Identification of Bacterial Isolates and Antibiotic Sensitivity Testing After incubation, the growth was identified by colony characteristics and standard biochemical tests.9 Antimicrobial susceptibility testing was performed by the Kirby-Bauer disc diffusion method as per the Clinical and Laboratory Standards Institute (CLSI) recommendations with few modifications;10 antimicrobial susceptibility testing was performed by a disc diffusion method using two panels of antibiotics; one tested against strains from uncomplicated UTI, the other tested against strains from complicated UTI. The antibiotics tested against both groups were ampicillin, amoxicillin-clavulanic acid, cefazolin, cefuroxime, ceftriaxone, cefixime, aztreonam, gentamicin, ciprofloxacin, ofloxacin, nalidixic acid, TMP-SMX and sulfisoxazole. In cases of uncomplicated UTI cefadroxil, nitrofurantoin and fosfomycin were tested. However, in complicated UTI; piperacillin, piperacillin/tazobactam, ticarcillin/clavulanate, cefepime, cefoperazone, ceftazidime and amikacin were tested. All the Gram-negative bacteria isolated from these clinical samples were tested for extended-spectrum beta-lactamase (ESBL) production using four disks (concentration in μg) ceftazidime (30), ceftazidime/ clavulanic acid (30/10), cefotaxime (30) and cefotaxime/ clavulanic acid (30/10) and interpreted as per CLSI guidelines.10

Quality Control Every new batch of culture media was incubated at 37°C overnight to ensure the sterility quality was assured by testing E. coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853 in every batch. However, a nonESBL-producing organism E. coli ATCC 25922 and an ESBL-producing organism Klebsiella pneumoniae ATCC 700603 was used, while testing ESBL screening and phenotypic confirmatory tests.

Statistical Analysis Data were analyzed using Microsoft Excel (Version 2007) and Graph Pad Prism Statistical Software (online version). Comparisons for categorical variables were done using Fisher’s exact test. Significance was set at p < 0.05 using two-sided comparisons. RESULTS A total of 595 urine samples from outpatients aged between 18 and 70 years were submitted to the microbiology laboratory MMIMSR, Mullana during

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INTERNAL MEDICINE the study period (March 2014 to October 2014); 492 (82.69%) of these samples were sterile. Patients who had UTI symptoms and >105 Gram-negative bacterial

growth in the urine were included in this study. Of the 93 Gram-negative isolates included in this study, 56 were isolated from uncomplicated UTI and 37

Table 1. Distribution of Gram-negative Isolates Obtained from Community-acquired UTI Organisms E. coli

Uncomplicated (n = 56)

Complicated (n = 37)

P value

47 (83.93%)

25 (67.57%)

0.0174

Klebsiella spp.

4 (7.14%)

5 (13.51%)

0.475

Proteus spp.

3 (5.36%)

2 (5.41%)

1.00

Entrobacter spp.

1 (1.79%)

1 (2.7%)

1.00

Citrobacter spp.

1 (1.79%)

1 (2.7%)

1.00

Morganella spp.

2 (5.41%)

Pseudomonas spp.

1 (2.7%)

Table 2. Antibiotic Resistance Pattern of E. coli Isolates Obtained from Community-acquired UTI Antimicrobial agent Gentamycin

Uncomplicated UTI (n = 56)

Complicated UTI (n = 37)

P value

6 (10.71%)

24 (16.22%)

0.0075

Amikacn*

0 (0)

3 (8.11%)

Ampicillin

9 (16.07%)

24 (62.16%)

0.0465

Amoxicillin-clavulanic acid

6 (10.71%)

23 (35.14%)

0.0037

Cefazoiln

3 (5.36%)

22 (32.43%)

0.0001

Cephalothin

2 (3.57%)

24 (35.14%)

0.0001

7 (8.93%)

26 (78.37%)

0.0594

51 (16.07%)

21 (62.16%)

0.0002

Cefuroxime

9 (8.92%)

18 (49.46%)

0.0005

Carbenicillin Cinoxacin Ceftriaxone

5 (14.28%)

26 (64.86%)

0.0123

Cefixime

8 (14.2%)

14 (70.27%)

0.0001

Aztreonam

4 (7.14%)

25 (56.76)

0.0038

Cefadroxil†

10 (17.85%)

Piperacillin*

19 (51.35%)

Piperacillin-tazobactam*

5 (13.51%)

Ticarcillin clavulanate*

8 (21.62%)

Cefepime*

7 (18.92%)

Cefoperazone*

13 (35.14%)

3 (8.1%)

8 (14.29%)

24 (64.86%)

0.0238

Ceftazidime* Trimethoprim/sulfamethoxazole Sulfisoxazole

2 (3.57%)

24 (35.14%)

0.0001

Ciprofloxacin

5 (8.93%)

13 (64.86%)

0.0001

Lomefloxacin

6 (10.71%)

24 (59.45%)

0.0001

Norfloxacin

7 (12.5%)

22 (62.56%)

0.0001

Ofloxacin

7 (12.5%)

25 (67.56%)

0.0337

Gatifloxacin

7 (12.5%)

23 (62.16%)

Fosfomycin†

1 (1.79%)

2 (3.57)

Nitrofurantoin†

*Tested only for complicated UTI; †Tested only for uncomplicated UTI.

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INTERNAL MEDICINE Table 3. Risk Factors for Ciprofloxacin Resistance Among E. coli Strains Isolated Total number of E. coli isolates (n = 72) (both complicated and uncomplicated)

Ciprofloxacin resistance among the strains isolated (n = 22)

P value

15-30

3 (4.17%)

1 (4.55%)

1.0000

31-45

30 (41.67%)

5 (22.73%)

0.1345

46 and above

39 (54.16%)

13 (59.09%)

0.0038

Rural

64 (88.89%)

8 (36.36%)

0.0102

Urban

8 (11.19%)

2 (9.09%)

0.0001

Risk factors

Age

Residential status

Gender Male

11 (15.27%)

2 (9.09%)

0.0001

Female

61 (84.72%)

9 (40.91%)

0.0165

Urolithiasis

6 (8.3%)

1 (4.54%)

0.0001

Renal diseases

4 (5.5%)

1 (4.54%)

0.0001 0.0003

Complicated UTI

8 (11.11%)

2 (9.09%)

Pregnancy

1 (1.38%)

Other surgical procedures performed in the urinary tract

7 (9.72%)

2 (9.09%)

0.0003

Catheterization of urinary tract

ESBL production antibiotic history Intake of ciprofloxacin at least once in the last year Intake of ciprofloxacin more than once in the last year Intake of antibiotic other than ciprofloxacin

were isolated from complicated UTI. As male patients were categorized in the complicated UTI group, all 56 uncomplicated cases were female patients and 61 (84.72%) of the complicated cases were female patients. The median age was 55 (SD 15.7) for the uncomplicated UTI patients and 49 (SD 16) for the complicated UTI patients. Seventeen (30.36%) of 56 uncomplicated UTI patients and 32 (86.49%) of 37 complicated UTI patients were from a rural area. E. coli was the causative agent in 83.93% of the uncomplicated UTIs and 67.57% in complicated UTI (p < 0.0174) (Table 1). Table 2 shows antibiotic resistance pattern of E. coli isolates obtained from community-acquired UTI. Nitrofurantoin and fosfomycin had the resistance rates 3.57% and 1.18%, respectively for uncomplicated UTI strains. ESBL were detected in 3.6% and 5.66% of the E. coli strains isolated from uncomplicated UTI and complicated UTI, respectively. Table 3 depicts risk factors for ciprofloxacin resistance among E. coli strains isolated. On analysis of the data for risk factors for ciprofloxacin

7 (9.72%)

3 (13.63%)

0.0001

12 (16.67%)

5 (22.72%)

0.0001

6 (8.33%)

3 (13.64.5%)

0.0001

14 (19.44%)

8 (36.36%)

0.135

resistance among E. coli strains (Table 3), age over 46 (p < 0.0038), isolates from a rural area (p < 0.0102), complicated UTI (p < 0.0001), ESBL production (p < 0.001) and ciprofloxacin use were found to be significantly associated with ciprofloxacin resistance among E. coli strains. Receiving ciprofloxacin more than once in the last year was significantly associated with ciprofloxacin resistance (p < 0.0001), whereas other antibiotic regimens were not (p > 0.135). Table 4 demonstrates risk factors for TMP/SMX resistance among E. coli strains isolated. On univariate analysis, the risk factors for TMP/SMX resistance among E. coli strains (Table 4), age over 46 (p < 0.0475), isolates from a rural area (p < 0.002), complicated UTI (p < 0.0003), ESBL production (p < 0.10) and TMP/ SMX use were found to be significantly associated with TMP/SMX resistance among E. coli strains. Receiving TMP/SMX more than once in the last year was significantly associated with TMP/SMX resistance (p < 0.0212), whereas other antibiotic regimens were not (p > 0.1369).

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INTERNAL MEDICINE Table 4. Risk Factors for Trimethoprim/Sulfamethoxazole Resistance Among E. coli Strains Isolated Total number of E. coli isolates (n = 72) (both complicated and uncomplicated)

Trimethoprim/ sulfamethoxazole resistance among the strains isolated (n = 29)

P value

15-30

3 (4.17%)

1 (3.45%)

0.0416

31-45

30 (41.67%)

8 (27.59%)

0.0097

46 and above

39 (54.16%)

19 (65.52%)

0.0475

Rural

64 (88.89%)

22 (75.86%)

0.002

Urban

8 (11.19%)

3 (10.34%)

0.0016

Male

11 (15.27%)

5 (17.24%)

0.0001

Female

61 (84.72%)

16 (55.17%)

0.4311

Urolithiasis

6 (8.3%)

2 (6.89%)

0.0003

Renal diseases

4 (5.5%)

2 (6.89%)

0.0001 0.0003

Risk factors

Age

Residential status

Gender

Complicated UTI

8 (11.11%)

3 (10.34%)

Pregnancy

1 (1.38%)

Other surgical procedures performed in the urinary tract

7 (9.72%)

3 (10.34%)

0.0003

ESBL production antibiotic history

7 (9.72%)

7 (72.41%)

0.1070

Intake of trimethoprim/sulfamethoxazole at least once in the last year

13 (18.05%)

12 (41.38%)

0.0212

Intake of trimethoprim/sulfamethoxazole more than once in the last year

14 (11.11%)

13 (44.83%)

0.0012

Intake of antibiotic other than trimethoprim/ sulfamethoxazole

16 (22.22%)

6 (20.68%)

0.1369

Catheterization of urinary tract

DISCUSSION Empirical antibiotic treatments are indicated in conditions where the community-acquired UTIs are diagnosed. However, the increasing incidence of antibiotic resistant bacterial infections makes empirical treatments more intricate.11 Therefore, it is essential to understand the local antibiotic susceptibility patterns for the prescription of the appropriate antibiotics. The current study was designed to establish the antibiotic susceptibility patterns of E. coli strains isolated from community-acquired UTIs and to describe the risk factors imparting to the resistance. The current study explores that the E. coli continues to be the most frequent pathogen in both community-acquired uncomplicated (83.93%) and complicated UTI (67.57%). This higher frequency of E. coli UTI could be attributed to the ability of these strains to ascend up from the perianal area (in female patients) into the urinary tract

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due to its close proximity. Further, the percentage of distribution of E. coli obtained in the current study was consistent with previous reports as well.12 In general, the antimicrobial resistance rates of E. coli strains isolated from complicated UTI are higher than the uncomplicated UTI E. coli strains.5,13 In the current study, Table 2 demonstrates the persistence of higher antimicrobial resistance among E. coli strains isolated from community-acquired complicated UTI. This higher resistance among the E. coli strains (isolated from complicated UTI) may be due to the transfer of drug-resistant genes (either plasmid or chromosomallymediated) from the drug-resistant bugs prevailing in the community. Further, the distribution of antimicrobial resistant strains were in accordance with the earlier studies as well.5,13 In community-acquired UTI, the TMP/SMX and ciprofloxacin are recommended for treatment.6 IDSA

INTERNAL MEDICINE also recommends the use of TMP/SMX as a drug choice for uncomplicated UTI. However, in the current study 37.93% of the uncomplicated strains and 62.07% of the complicated strains were resistant to TMP/SMX. This higher TMP/SMX rates were also reported from earlier studies as well.8,14 However, the exact causes of high TMP/SMX resistance were not explored. But investigators suggest that this higher resistance could be due to the irrational prescription and extensive usage of TMP/SMX in the community.11,15 IDSA recommends, TMP/SMX to treat UTI in settings with low prevalence of drug-resistant strains (<10-20%).2 Further, TMP/SMX may also be used for the empirical treatment of UTIs in the age group of 20-64 years of female patients and in the age group 0-6 years of male patients, wherein the resistance rates were low.15 However, fluoroquinolones are indicated when the TMP/SMX resistance rate is higher than 20%.2 In the current study, the resistance to ciprofloxacin is of great concern because fluoroquinolones are used as rational empirical agents for the treatment of both uncomplicated and complicated UTI in areas where resistance to TMP/SMX is over 20%.7,16 In the current study, ciprofloxacin resistance was found to be 36.36% in complicated UTI and 63.64% in uncomplicated UTI and this data was comparable with previous reports as well.12 This higher resistance rate could be due to the irrational and extensive use of ciprofloxacin since it is considered as drug of choice in UTI where the TMP/ SMX resistance is common. Further, the univariate analysis indicated that age over 46, ciprofloxacin use and complicated UTI were independent risk factors contributing to ciprofloxacin resistance (Table 3). The association between ciprofloxacin use and the emergence of resistance has been reported previously also.7,13,14,17,18 Similarly, complicated UTI (including male gender), urinary tract abnormalities, urinary catheterization and older age were found to be associated with high ciprofloxacin resistance rates in previous studies. This outcome was consistent with the current study as well.13,17,18 Further, it is evident from the Tables 3 and 4 that the frequency of ESBL production was more common among ciprofloxacin-resistant uropathogenic E. coli isolates (p < 0.001) as reported by Tolun et al.19 Generally, community-acquired UTI is treated using TMP/SMX and ciprofloxacin or higher generation betalactam group of antibiotics. However, nitrofurantoin and fosfomycin may also be used as reasonable alternatives for the treatment of uncomplicated UTI.12 In the current study, nitrofurantoin and fosfomycin

resistance was found to be 3.57% and 1.79%, respectively, indicating the potential to treat uncomplicated UTI. Further, nitrofurantoin is recommended for treating uncomplicated cystitis since its resistance to E. coli has been reported to be very low even after 50 years of use.16 Similarly, the use of fosfomycin is also limited to the treatment of uncomplicated cystitis with the advantage of single dose.20 However, due to the low level resistance of nitrofurantoin and fosfomycin among E. coli isolates obtained from uncomplicated UTI, suggests that these antimicrobial agents may be investigated for treating complicated UTI as well. In a nutshell, TMP/SMX may not be appropriate for the empirical treatment of community-acquired UTI, due to its widespread resistance. However, ciprofloxacin may be used warily for both uncomplicated and complicated UTI because of emerging resistance. Further, the study recommends the practice of routine urine culture and antibiotic susceptibility in the current study set up. The study also implies the use of nitrofurantoin and fosfomycin as alternatives for the treatment of uncomplicated UTI. However, the use of nitrofurantoin and fosfomycin should also be investigated for its clinical efficacy to use in the treatment of complicated UTI. REFERENCES 1. Martín-Gutiérrez G, Porras-González A, Martín-Pérez C, Lepe JA, Aznar J. Evaluation and optimization of the Sysmex UF1000i system for the screening of urinary tract infection in primary health care elderly patients. Enferm Infecc Microbiol Clin 2014 Oct 18. pii: S0213005X(14)00292-4. 2. Warren JW, Abrutyn E, Hebel JR, Johnson JR, Schaeffer AJ, Stamm WE. Guidelines for antimicrobial treatment of uncomplicated acute bacterial cystitis and acute pyelonephritis in women. Infectious Diseases Society of America (IDSA). Clin Infect Dis 1999;29(4):745-58. 3. Karlowsky JA, Jones ME, Thornsberry C, Critchley I, Kelly LJ, Sahm DF. Prevalence of antimicrobial resistance among urinary tract pathogens isolated from female outpatients across the US in 1999. Int J Antimicrob Agents 2001;18(2):121-7. 4. Venkat Ramanan P, Sharma S, Krishna V. Changing profile of pediatric community-acquired UTI in a hospital in South India. J Trop Pediatr 2014;60(6):483. 5. Hryniewicz K, Szczypa K, Sulikowska A, Jankowski K, Betlejewska K, Hryniewicz W. Antibiotic susceptibility of bacterial strains isolated from urinary tract infections in Poland. J Antimicrob Chemother 2001;47(6):773-80. 6. Zervos MJ, Hershberger E, Nicolau DP, Ritchie DJ, Blackner LK, Coyle EA, et al. Relationship between fluoroquinolone use and changes in susceptibility to fluoroquinolones of

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INTERNAL MEDICINE selected pathogens in 10 United States teaching hospitals, 1991-2000. Clin Infect Dis 2003;37(12):1643-8.

acquired urinary tract infections in relation to demographic and clinical data. Clin Microbiol Infect 2005;11(3):199-203.

7. Goettsch W, van Pelt W, Nagelkerke N, Hendrix MG, Buiting AG, Petit PL, et al. Increasing resistance to fluoroquinolones in Escherichia coli from urinary tract infections in the Netherlands. J Antimicrob Chemother 2000;46(2):223-8.

14. Kahlmeter G; ECO.SENS. An international survey of the antimicrobial susceptibility of pathogens from uncomplicated urinary tract infections: the ECO. SENS Project. J Antimicrob Chemother 2003;51(1):69-76.

8. Karlowsky JA, Kelly LJ, Thornsberry C, Jones ME, Sahm DF. Trends in antimicrobial resistance among urinary tract infection isolates of Escherichia coli from female outpatients in the United States. Antimicrob Agents Chemother 2002;46(8):2540-5. 9. Baron EJ, Finegold SM (Eds.). Overview of conventional methods for bacterial identification (Chap. 13), In: Bailey and Scott’s Diagnostic Microbiology. Mosby Publishers: St. Louis 1994:p.167. 10. Clinical and Laboratory Standards Institute. Performance standards for antimicrobial disk tests. Approved Standards, 9th edition. CLSI Document M2-A9, Vol. 26 No 1. Wayne PA 2006. 11. Steinke DT, Seaton RA, Phillips G, MacDonald TM, Davey PG. Prior trimethoprim use and trimethoprim-resistant urinary tract infection: a nested case-control study with multivariate analysis for other risk factors. J Antimicrob Chemother 2001;47(6):781-7. 12. Arslan H, Azap OK, Ergönül O, Timurkaynak F; Urinary Tract Infection Study Group. Risk factors for ciprofloxacin resistance among Escherichia coli strains isolated from community-acquired urinary tract infections in Turkey. J Antimicrob Chemother 2005;56(5):914-8. 13. Alós JI, Serrano MG, Gómez-Garcés JL, Perianes J. Antibiotic resistance of Escherichia coli from community-

15. Uzunovic-Kamberovic S. Antibiotic resistance of coliform organisms from community-acquired urinary tract infections in Zenica-Doboj Canton, Bosnia and Herzegovina. J Antimicrob Chemother 2006;58(2): 344-8. 16. Hooton TM. Fluoroquinolones and resistance in the treatment of uncomplicated urinary tract infection. Int J Antimicrob Agents 2003;22 Suppl 2:65-72. 17. Ena J, Amador C, Martinez C, Ortiz de la Tabla V. Risk factors for acquisition of urinary tract infections caused by ciprofloxacin resistant Escherichia coli. J Urol 1995;153(1):117-20. 18. Howard AJ, Magee JT, Fitzgerald KA, Dunstan FD; Welsh Antibiotic Study Group. Factors associated with antibiotic resistance in coliform organisms from community urinary tract infection in Wales. J Antimicrob Chemother 2001;47(3):305-13. 19. Tolun V, Küçükbasmaci O, Törümküney-Akbulut D, Catal C, Anğ-Küçüker M, Anğ O. Relationship between ciprofloxacin resistance and extended-spectrum betalactamase production in Escherichia coli and Klebsiella pneumoniae strains. Clin Microbiol Infect 2004;10(1): 72-5. 20. Schito GC. Why fosfomycin trometamol as first line therapy for uncomplicated UTI? Int J Antimicrob Agents 2003;22 Suppl 2:79-83.

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ACIP Releases its Recommended Adult Immunization Schedule for 2015 All adults aged 65 and over should now have the 13-valent pneumococcal conjugate vaccine (PCV13) in addition to the 23-valent pneumococcal polysaccharide vaccine (PPSV23) to protect against pneumococcal infection, according to the 2015 Advisory Committee on Immunization Practices (ACIP) Recommended Immunization Schedule for adults being published in Annals of Internal Medicine. Despite extensive and targeted recommendations for use of the PCV13 and PPSV23, pneumococcal infection continues to be a major cause of morbidity, including bacteremia, meningitis and pneumonia, among older adults. Expanding use of PCV13 to all adults along with use of PPSV23 should serve as added protection against pneumococcal infection. This is the only major change from the 2014 schedule. The complete schedule, including footnote changes, is being simultaneously published in Annals of Internal Medicine and on the Centers for Disease Control and Prevention (CDC) web site at www.cdc.gov/vaccines.

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Indian Journal of Clinical Practice, Vol. 25, No. 9, February 2015

OBSTETRICS AND GYNECOLOGY

To Compare Maternal Outcome in Registered (Booked) and Unregistered (Unbooked) Cases of Placenta Previa: A Prospective Study at a Tertiary Care Center of Northern India SHAVETA JAIN, PUSHPA DAHIYA, NITIN JAIN, ROOPA MALIK

ABSTRACT Background: Antepartum hemorrhage (APH) is a grave obstetrical emergency. It is a leading cause of maternal death. Very few studies have compared the demographic profile of women having APH; most of the studies dealt with maternal and perinatal outcome. Objectives: Aim of the present study was to compare the maternal outcome in registered (booked) and unregistered (unbooked) cases of placenta previa. Material and methods: It is a prospective study carried out over a period of 1 year on 100 women admitted in 2011-12 with the diagnosis of APH at Pt. BD Sharma Medical College, Rohtak, Haryana, India, a tertiary care center. Patients of placenta previa were divided into registered and unregistered cases and the maternal complications were recorded. Results and conclusion: Registered patients with placenta previa have better hemoglobin profile at time of delivery, need less blood transfusion and both third stage complications as well as delayed complications in mother was less in booked patient. In conclusion, registered patient of placenta previa have better outcome than unregistered.

Keywords: Antepartum hemorrhage, placenta previa, registered, expectant treatment

aginal bleeding at any stage of pregnancy constitutes a significant concern to the patient and her doctor. Antepartum hemorrhage (APH) is still a grave obstetric emergency contributing to a significant amount of maternal and perinatal morbidity and mortality in India.1

Hemorrhage is one of the leading causes of maternal mortality and morbidity. According to the Center for Disease Control and Prevention (CDC), hemorrhage was a direct cause of maternal death in about 30% of cases.2 In this study, we compared patients of placenta previa who were registered and admitted in hospital and given expectant management with patients of placenta, previa coming in emergency with APH.

Dept. of Obstetrics and Gynecology Pt. BD Sharma, PGIMS, University of Health Sciences, Rohtak, Haryana Address for correspondence Dr Nitin Jain House No. 629, Sector 14 Rohtak - 124 001, Haryana E-mail: logindrnitin@gmail.com

MATERIAL AND METHODS Patients who came after single episode of bleeding per vaginum after 28 weeks of gestation and diagnosed placenta previa on ultrasonography were admitted in hospital and kept on expectant management were taken as registered and rest of patients of APH who came in emergency were taken unregistered. Patients were managed according to her registered or unregistered status in placenta previa. During our study period (2011-12), there were 4,100 deliveries. Number of cases with APH were noted and the incidence of APH was calculated (Table 1). A general physical examination was carried out, vitals were recorded. Degree of anemia and signs of pregnancy- induced hypertension were noted. Indication of expectant treatment for registered patients of placenta previa: ÂÂ

Duration of pregnancy ≤37 weeks

ÂÂ

No active bleeding and patient hemodynamically stable

ÂÂ

No evidence of fetal distress.

Expectant treatment was given with the aim to allow the pregnancy to continue to achieve maximum fetal

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OBSTETRICS AND GYNECOLOGY Table 1. Incidence of Antepartum Hemorrhage Type of APH

Number of cases

Percentage (%)

Incidence

Placenta previa

1.31

Abruptio placentae

0.82

Unclassified hemorrhage

0.29

Total

100

2.43

Table 2. Number of Registered and Unregistered Cases of Placenta Previa Type of cases

maturity up to 37 weeks. It consisted of good diet, bed rest, sedation, steroids to induce lung maturation, periodic inspection of vulval pads and auscultation of fetal heart rate and supplementary blood transfusion and hematinics. Indication of active interference in patient of placenta previa (registered/unregistered): ÂÂ

Severe and continuous bleeding likely to cause hemodynamic changes

ÂÂ

Fetal maturity ≥37 weeks

ÂÂ

Patients in labor

ÂÂ

Baby was dead or known to be congenitally malformed.

Abruptio placentae patients were managed according to grade of abruption. If it was of revealed type and patient was in labor then artificial rupture of membranes ± oxytocin was done. If it was of concealed type, artificial rupture of membrane ± oxytocin done; if no response was there or fetal distress was noted, cesarean section was done.

Number of cases

Percentage (%)

Registered

51.8

Unregistered

48.2

Total

100

Table 3. Incidence According to Degree of Placenta Previa Degree

Number of cases

Percentage (%)

7.4

18.5

Posterior

Third-degree

18.5

Fourth-degree

40.7

Total

100

First-degree Second-degree

Table 4. Hemoglobin Status of Placenta Previa Cases at Time of Delivery Hemoglobin (gm%)

Registered*

Unregistered*

No.

(%)

No.

(%)

15.3

4-6

10.7

61.5

6-8

15.3

8-10

7.6

>10 gm

21.4

Total

RESULT

*P < 0.001 (unpaired t-test).

Out of 54 cases of placenta previa, 28 patients (51.8%) were registered and rest were unregistered (48.2%) (Table 2). Out of 54 cases of placenta previa, major degree placenta previa was detected in 74.2% of patients. First-degree of placenta previa was seen in four cases (7.4%) and second-degree anterior was seen in 10 cases (18.5%) (Table 3).

expectant management. While 92.4% of unregistered cases received blood transfusion. There was increase of absolute number of blood transfusion given to unregistered patients, but it was not statistically significant (p > 0.01) (Table 5).

Out of 26 unregistered cases of placenta previa, four patients had hemoglobin <4 gm%, while none of registered cases had hemoglobin level <4 gm%. Hemoglobin level was >10 gm% in six registered patients, while none of unregistered patients had hemoglobin level >10 gm%. This was statistically highly significant (p < 0.001) (Table 4). Approximately 78.6% registered cases of placenta previa received blood transfusion during their

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Indian Journal of Clinical Practice, Vol. 25, No. 9, February 2015

In the registered cases, three had atonic postpartum hemorrhage (PPH), one had placenta accreta. In unregistered cases, six had atonic PPH, two had scar dehiscence, one had placenta accreta. More number of complications in unregistered cases than registered, was statistically significant also (p < 0.02) (Table 6). Approximately 92.3% of unregistered patients had postpartum anemia, while only 42.8% of registered patients had postpartum anemia; 7.1% of registered cases had febrile morbidity, 3.5% puerperal sepsis and

OBSTETRICS AND GYNECOLOGY Table 5. Number of Blood Units Used in Registered and Unregistered Cases of Placenta Previa Cases

None

One unit

Two units

More than 2 units

No.

Registered*

51.8

21.4

10.7

42.8

Unregistered*

48.2

7.6

15.3

46.1

30.7

*P > 0.01 (unpaired t-test).

Table 6. Incidence of Third Stage Complications in Registered/Unregistered Cases of Placenta Previa Complications

Registered* cases

Unregistered* cases

No.

Atonic PPH*

10.7

Hemorrhagic shock*

11.5

Scar dehiscence

7.6

Retained placenta

7.6

Placenta accreta

3.5

3.8

Bilateral uterine artery ligation

11.5

Bilateral internal illiac artery ligation

7.6

B-lynch sutures

3.8

Hysterectomy

3.5

3.8

*P <0.02, Fisherâ&#x20AC;&#x2122;s Exact test

Table 7. Incidence of Delayed Complications in Registered/Unregistered Cases of Placenta Previa Complications

Febrile morbidity

Registered cases

Unregistered cases

No.

7.1

15.3

Table 8. Analysis of Mode of Treatment Given to the Patients and the Perinatal Outcome in Antepartum Hemorrhage Mode of treatment

Placenta previa registered

Placenta previa unregistered

No.

Conservative followed by LSCS

44.4

Puerperal sepsis

3.5

11.5

Stitch sepsis

11.5

Urinary tract infection

3.5

15.3

Conservative followed by vaginal delivery

11.1

Postpartum anemia

42.8

92.3

Immediate LSCS

40.7

Immediate vaginal delivery

7.4

3.5% urinary tract infection; 15.3% of unregistered cases had febrile morbidity, 11.5% had puerperal sepsis, 11.5% stitch sepsis and 15.3% urinary tract infection (Table 7). Approximately 40.7% patients of placenta previa had immediate lower-segment cesarean section (LSCS). 44.4% patients of placenta previa were kept on conservative management and later LSCS was done after expectant management (Table 8). DISCUSSION Antepartum hemorrhage is an important cause of maternal and perinatal morbidity and mortality. In our study, 61.5% of unregistered patients had hemoglobin

Total

between 4-6 gm% while only 11% of registered patients had hemoglobin between 4-6 gm% (Table 4). Hemoglobin level was >10 mg% in six registered patient, while none of unregistered patients had hemoglobin level >10 gm% (p < 0.001). This is due to expectant management of registered patients which included blood transfusion, oral and injectable iron therapy, bed rest and proper care. Results of our study is consistent with the study conducted by Cotton et al.3 In our study, 78.6% registered cases

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OBSTETRICS AND GYNECOLOGY of placenta previa received blood transfusion (Table 5) during their expectant management, while 92.4% of unregistered cases received blood transfusion. As unregistered cases came in emergency with massive hemorrhage and low hemoglobin level, they were given more blood transfusion than registered cases. But, this was not statistically significant (p > 0.05) as registered patients were also given blood transfusion after each episode of bleeding during their hospital stay. In the present study, patients of placenta previa who delivered vaginally (11.1%) after conservative management show comparable perinatal mortaility (16.6%) to those patient delivered by cesarean section (18.2%) (Table 8). All these cases are of low-lying and marginal placenta previa. Similarly, Chervenak et al suggested that routine cesarean section is not necessary for all cases of partial placenta previa.4 MaCafee and Johnson also suggested similarly that vaginal delivery is appropriate in selected cases of placenta previa.5

by ultrasound, inpatient and expectant management, repeated blood transfusion and liberal use of cesarean section. Cotton et al in their study identified 170 cases of documented placenta previa. Sixty-six percent (112) of patients were managed expectantly and 34.1% (58) were delivered immediately. The perinatal mortality in expectant group was 7.1%, while it was 24.1% in the immediately delivered group.3 Silver et al in their study described the outcome of 95, expectantly managed cases of placenta previa who were diagnosed after 21 weeks gestation. Patients at risk for preterm delivery because of hemorrhage or preterm labor received aggressive care, including multiple transfusions, volume expansion and tocolytic therapy, and amniotic fluid surfactant determinations to achieve the goal of delivery at 37 weeks gestation, with fetal lung maturation. In their study, perinatal mortality was 4.3% only, when 75% of patients were on expectant management.12

In the present study, out of 54 cases of placenta previa nine (16.6%) had atonic PPH, three (5.5%) had hemorrhagic shock, two (3.7%) had scar dehiscence and two (3.7%) had retained placenta, two (3.7%) had placenta accreta. Emergency hysterectomy was done in two patients (3.7%), one for placenta accreta and another for atonic PPH (Table 6).

CONCLUSION

Crane et al also reported similar complications of placenta previa like PPH (20%), hemorrhagic shock (7%), scar dehiscence (5%) and placenta accreta (5%) in their study. Our study showed more number of maternal complications in unregistered causes than registered (p < 0.02).6

Registered cases has better outcome in terms of maternal mortality, morbidity and perinatal morbidity than unregistered cases of placenta previa. This was statistically significant. Wider acceptance of expectant line of management, meticulous attention to correction of anemia, the use of present day aids like, ultrasonography to decide about the time of interventions and the more liberal use of cesarean section in well-equipped hospitals with availability of blood transfusion services, will help to lower the maternal morbidity and mortality.

Surgical management of PPH was done in five cases. In three cases, bilateral uterine artery ligation was done and another two cases required bilateral internal iliac artery ligation to control PPH. In one patient, additional B-lynch sutures were applied to control PPH (Table 7). The use of bilateral uterine artery ligation, bilateral internal iliac artery ligation and B-lynch sutures to control PPH are also reported in various studies.7-9 In our study, most of the complications of placenta previa occurred in unregistered cases of placenta previa. The incidence of maternal mortality was 2% in APH in our study, which was consistent with study of Motwani et al who reported similar incidence.10 Six percent maternal mortaility was seen in abruptio placentae. It is similar to the published literature.11 No maternal mortality was observed in cases of placenta previa and unclassified hemorrhage. No mortality in patients of placenta previa in our series was due to early diagnosis

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Analyzing the incidence of APH, we observed that it is still a significant obstetric problem in our setup. Though maternal mortality has reduced with modern management of APH, perinatal mortality still remains high.

REFERENCES 1. Arora R, Devi U, Majumdar K. Perinatal morbidity and mortality in antepartum haemorrhage. J Obstet Gynaecol India 2001;51(3):102-4. 2. Cunningham FG, Gant NF, Leveno KJ, Gistrap III LC, Hauth JC, Wenstrom KD. Obstetrical hemorrhage: Williams Obstetrics. 21st edition, McGraw-Hill: New York 2001:p.619-69. 3. Cotton DB, Read JA, Paul RH, Quilligan EJ. The conservative aggressive management of placenta previa. Am J Obstet Gynecol 1980;137(6):687-95. 4. Chervenak FA, Lee Y, Hendler MA, Monoson RF, Berkowitz RL. Role of attempted vaginal delivery in

OBSTETRICS AND GYNECOLOGY the management of placenta previa. Obstet Gynecol 1984;64(6):798-801. 5. MaCafee CHG, Johnson R. Placenta previa: A study of 174 cases. J Obstet Gynaecol Br Emp 1945;52(4):313-24. 6. Crane JM, Van den Hof MC, Dodds L, Armson BA, Liston R. Maternal complications with placenta previa. Am J Perinatol 2000;17(2):101-5. 7. B-Lynch C, Coker A, Lawal AH, Abu J, Cowen MJ. The B-Lynch surgical technique for the control of massive postpartum haemorrhage: an alternative to hysterectomy? Five cases reported. Br J Obstet Gynaecol 1997;104(3):372-5. 8. O’Leary JA. Uterine artery ligation in the control of postcesarean hemorrhage. J Reprod Med 1995;40(3): 189-93.

9. Clark SL, Phelan JP, Yeh SY, Bruce SR, Paul RH. Hypogastric artery ligation for obstetric hemorrhage. Obstet Gynecol 1985;66(3):353-6. 10. Motwani MN, Sheth J, Narvekar NM, Purandene MC, Hansotia MD. Maternal mortality resulting from antepartum hemorrhage - review of 20 years. J Obstet Gynecol India 1989;39:364-6. 11. Dutt DC. Antepartum haemorrhage. In: Textbook of Obstetrics. 6th edition, Konar H (Ed.), New Central Book Agency: Calcutta 2004:p.243-61. 12. Silver R, Depp R, Sabbagha RE, Dooley SL, Socol ML, Tamura RK. Placenta previa: aggressive expectant management. Am J Obstet Gynecol 1984;150(1): 15-22.

■■■■

Fetal Death Risk Climbs with First Signs of Pre-eclampsia Pregnancies diagnosed with pre-eclampsia in the preterm period have a very high relative risk for fetal death, according to findings of a population-based cohort study published online February 4 and in the March issue of Obstetrics & Gynecology. “Although the pathologic origins of pre-eclampsia likely occur during placentation, the clinical signs and symptoms typically do not emerge until after 20 weeks of gestation,” write Quaker E. Harmon, MD, PhD, from the Epidemiology Branch and Biostatistics Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, and colleagues. “The most relevant estimate of fetal risk in the presence of preterm pre-eclampsia would be one that considers the timing of pre-eclampsia diagnosis - a diagnosis that often occurs well before the time of delivery.

Pregnancy: Hypertensive Emergency Recommendations Updated Updated best practice recommendations for the emergency treatment of acute-onset, severe hypertension during pregnancy and the postpartum period include the addition of nifedipine as a first-line therapy. In an updated opinion published in the February issue of Obstetrics & Gynecology, the American College of Obstetricians and Gynecologists Committee on Obstetric Practice reports that studies of the oral dihydropyridine calcium channel blocker reduced women’s blood pressure more quickly than either intravenous labetalol or hydralazine, which are the current first-line treatments, and produced a significant increase in urine output.

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Laparoscopic Resection of Large Cornual Pregnancy HASINA BANU*, JU WEN HUI†, LI HUI†

ABSTRACT Cornual pregnancy is a pregnancy that implants in the intrauterine portion of fallopian tube. It is rarest and is one of the most dangerous type of all tubal pregnancies. It posses significant diagnostic and therapeutic challenge and carries a greater maternal mortality than other tubal pregnancies. Management depends upon the time at diagnosis. Early cornual gestation can be managed medically while advanced cornual gestation needs surgery that may range from conservative to radical depending upon clinical presentation. Traditionally, it was treated with laparotomy (hysterectomy or cornual resection), but today, it can be managed with recent laparoscopic approach. This report describes the laparoscopic resection of large cornual pregnancy using temporary tourniquet suture without diluted vasopressin injection for maintaining hemostasis. In conclusion, with the appropriate patients, setup and in the presence of well-skilled laparoscopic surgeons, laparoscopic management for large cornual pregnancies can be done with this method.

Keywords: Cornual pregnancy, interstitial pregnancy, ectopic pregnancy, laparoscopy, cornual resection

ornual pregnancy is a pregnancy that implants in the intrauterine portion of the fallopian tube. It is a rarest and dangerous type of all tubal ectopic pregnancy, accounting for 2-4% of all tubal pregnancies.1 The surrounding myometrial tissue allows progression of the pregnancy into the second trimester, but rupture at an advanced gestational age, usually 14-16 weeks, can result in catastrophic hemorrhage with a mortality rate up to 2%. This mortality is mainly due to the difficulty in diagnosis as well as the speed of hemorrhage after rupture.2 The risk factors are similar to other ectopic pregnancies. The diagnosis are usually made by transvaginal sonography (TVS) and b-human chorionic gonadotropin (b-hCG), but in suspected case or failure to diagnose by TVS, laparoscopy is considered gold standard for diagnosing it. An early cornual gestation can be managed medically while advanced cornual gestation needs surgery that may range from conservative to radical depending upon

*2nd

Year Resident

†Professor

Dept. of Obstetric and Gynecology Jingzhou Central Hospital Affiliated to Yangtze University, Medical College Jingzhou Hubei Province, China Address for correspondence Dr Hasina Banu 2nd Year Resident Dept. of Obstetric and Gynecology Jingzhou Central Hospital Affiliated to Yangtze University, Jingzhou - 434 020, Hubei Province, China

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clinical presentation. Traditionally, it was treated by laparotomy either cornual resection or hysterectomy. But, recent advances in laparoscopic techniques and the increased sophistication of surgical instruments have offered new operative methods and techniques for managing cornual pregnancy. Currently, the laparoscopy is perceived as a minimally invasive surgical technique. Since, it provides a panoramic and magnified view of the pelvic organs and allows surgery at the time of diagnosis, laparoscopy has become the preferred method for management of cornual pregnancy. The following case report demonstrates a successful laparoscopic technique for managing large cornual pregnancy. CASE PRESENTATION A 21-year-old lady with history of per vaginal bleeding since 12 days was referred from a local hospital to our Gynecology Department on 23rd January 2014. She had a history of amenorrhea for 57 days. Her last menstrual period was 27th November 2013. She was Gravida 2 Para 1 with a living child who had been delivered by cesarean section in April 2013. Her menstruation cycle was irregular following delivery. Her vitals were: Pulse rate 76 bpm, blood pressure (BP) 110/70 mmHg and respiratory rate 20/min. On examination, she did not present with pallor. Per abdomen examination was soft, but tender at left iliac fossa on palpation. Per speculum examination revealed brownish discharge with a healthy cervix and vagina

OBSTETRICS AND GYNECOLOGY with closed os. Bimanual examination revealed an anteverted normal size uterus with a mass on left side about 4 × 5 cm, which was soft and tender. Cervical motion tenderness was absent and bilateral fornix were clear. On investigation, hemoglobin was 100 g/ dL. Urine for hCG was positive. Her serum b-hCG level and serum progesterone levels were 2,668 mIU/ mL, 1.89 ng/mL, respectively. TVS revealed normalsized uterus with empty uterine cavity. The uterine contour was regular, but the contrast of myometrium was not equally distributed and endometrial thickness was 1 cm. There was hypoechoic mass between the left ovary and the left uterine cornua, measuring 2.2 × 2.6 cm with hyperechoic mass in center, about 0.5 × 0.4 cm. The thickness of mass wall was 1 cm. The boundary between the left uterine cornua and the left ovary was not clear suspecting left cornual pregnancy. Both ovaries were normal. Presence of freefluid in Pouch of Douglas was negative. The patient and patient party was counseled regarding the findings and the decision to proceed with laparoscopic management. The patient was taken to

Figure 3. Left cornual pregnancy placing temporary tourniquet suture using (1-0 vicryl) around the ectopic mass.

the operation theater and placed in dorsal lithotomy position. Following pneumoperitoneum with carbon dioxide insufflators 12 mm/L, the laparoscope was introduced in abdominal cavity and immediately about 5 cm ectopic mass was seen in the left uterine cornua. Both fallopian tubes and ovaries were normal. There was cesarean section scar at lower-segment of uterus, but no adhesions or any collection in Pouch of Douglas. After confirmed diagnosis, a second 10 mm port was then placed in the left mid quadrant and two 5 mm ports in the left and right lower quadrant were placed under direct visualization and transillumination to avoid any damage to the vessels. A temporary circumferential tourniquet suture was made using 1-0 vicryl around the protruding mass with a 1 cm safety margin through anterior fundus and posterior surface of the uterus over fallopian tube and round ligament for maintaining hemostasis. The tourniquet suture was kept superficial as possible to prevent endometrial injury and entrapment of the collateral circulation. After placement, the two ends of the suture were tightened, and a knot was tied for maintaining tension to produce a tourniquet effect (Fig. 3).

Figures 1 and 2. Transvaginal ultrasound before operation.

The cornual mass was excised with the help of bipolar forceps and scissor. The inferior edge of the mass was coagulated with bipolar forceps and was cut with

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OBSTETRICS AND GYNECOLOGY scissors from the lateral aspect of the uterus into the uterine cavity thus removing about one-fourth of the uterine fundus, finishing on the superior medial edge of the mass with out any difficulty and the excision area was coagulated with bipolar forcep. The temporary tourniquet suture was removed at the end and further hemostasis was maintained by using bipolar forceps. The incision was left open to allow healing by secondary intention of wound healing. The specimen was removed through the 10 mm ports. At the end of procedure peritoneal washing was done with normal saline. Injection methotrexate 20 mg was given locally and nonadhesive gel was applied at the incision site for prevention of adhesions. A drain of 5 mm was kept on the right lower quadrant and the skin incision was closed. The specimen was sent for histopathological examination (HPE). The estimated blood loss was about 80 mL. The patient recovered without any complication and was discharged on 6th postoperative day. The pathology confirmed chorionic villi consistent with ectopic pregnancy (left cornual pregnancy). Serum b-hCG concentration decreased from 2,668 mIU/mL at the time of the operation to 68 mIU/mL on 4th postoperative day. FOLLOW-UP The patient came for follow-up at 4-month postoperative without any complaint. But, she confirmed her desire for further pregnancy. Per abdominal, per speculum and per vaginal examination were done, and everything was found normal. Ultrasonography of the pelvic cavity was also advised which was normal with good sign of healing. We strongly recommended her for long interpregnancy interval and elective cesarean section as the best delivery option for future pregnancies. As with any surgery on uterus, there is chances of uterine rupture in further pregnancy, but the chances of rupture decreases if prolonged interpregnancy interval is considered, allowing time for scar to reach its maximal tensile strength before ending the mechanical stress and strain of a subsequent pregnancy.3 DISCUSSION It is the rarest and the most dangerous type of all tubal ectopic pregnancies, accounting for 2-4% of all tubal pregnancies.1 The cornual pregnancy posses a significant diagnostic and therapeutic challenge and carries a greater maternal mortality than other tubal ectopic pregnancies, due to late rupture and enormous

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blood supply from uterine artery and ovarian artery. Several effective treatment options for treatment of cornual pregnancy have been described, but the most appropriate technique remains controversial. Managing a cornual ectopic pregnancy depends upon whether the ectopic pregnancy has ruptured, the stability of the patient, the gestational size at diagnosis and the patientâ&#x20AC;&#x2122;s desire for future fertility.4,5 A ruptured cornual pregnancy is a surgical emergency that requires surgical intervention with either laparoscopy or laparotomy, depending on the patientâ&#x20AC;&#x2122;s condition and available surgical assets.4,6 If the diagnosis is made early or before rupture, conservative treatment options such as locally or systemic methotrexate or transcervical resection or cornuostomy, etc. are possible. In this case report, the patient had a large ectopic gestation which was not suitable for medical management, but was hemodynamically stable, thus a candidate for laparoscopic surgery. Although some authors7 have reported expectant management of selected ectopic gestation, we do not believe that this approach of management should be used for cornual pregnancies, which are prone to catastrophic hemorrhage. However, severe hemorrhage may also occur during the surgical procedure. Therefore, a laparoscopic approach should only be attempted, if the surgeon is well-skilled in laparoscopic techniques, and also has the ability to convert the operation quickly to laparotomy. When these conditions are met, laparoscopy provides several advantages over laparotomy such as fewer postoperative pain and analgesic requirement, shorter hospital stay, faster return to normal activity, cosmetic scar and cost-effective.8 If possible, therefore, laparoscopy is preferred approach and in this case we have demonstrated the feasibility of laparoscopy to manage a large cornual pregnancy. The choice between laparoscopic cornostomy and cornual resection may be difficult sometimes as in our case. Some authors agree that the size of cornual pregnancy to decide the type of procedure to be adopted. Cornuostomy is recommended in cornual pregnancy (<3.5 cm), whereas cornual resection for mass (>4 cm);9 so, we chose laparoscopic cornual resection inspite of patients wish for a further pregnancy and that some authors have reported that after cornual resection fertility is decreased. Fernandez et al10 reported tubal patency after cornuostomy to be as high as 90% and Choi et al,11 also found laparoscopic cornuotomy to have advantage to preserve the cornu in cornual pregnancy, because cornuostomy is believed to cause less anatomical damage to the fallopian tube in comparison

OBSTETRICS AND GYNECOLOGY to cornual resection, but the patient in this case report did not fit under the criteria for cornuostomy. The cornual resection offers more certainty in the complete elimination of trophoblastic tissue, and less risk of subsequent ectopic pregnancy on the same side. The size of gestational mass was big; so, we gave injection methotrexate 20 mg locally for prophylaxis of persistent trophoblastic tissue. However, we do not have enough information to definite the optimal technique; many authors use vasopressin for hemostasis and some authors have attempted to optimize hemostasis through end loop of ectopic mass at cornua plus injection vasopressin prior to incision and found it to be safe, effective and bloodless. We agree, by doing this hemostasis can be maintained, but hemostasis can be also maintained by just placing temporary tourniquet suture tightly at the base of cornua without injecting vasopressin as we did in our case and cardiovascular risk of vasopressin can be avoided. However, it needs further study for its safety and applications. The main concern about laparoscopic surgery for cornual pregnancy is the risk of rupture in future pregnancy. As it is a novel method of treatment, there is insufficient data to demonstrate its safety for future pregnancy. Cases of cornual ruptures have been reported.12 Good surgical technique and minimal use of diathermy to reduce adjacent tissue damage is bound to reduce this risk. Retrospective review of 52 cases of laparoscopic surgical treatment of cornual pregnancy has provided some promising results.13 For women who wish to have another pregnancy, sonohysterography has been recommended to look for myometrial thinning.14 Careful monitoring of all subsequent pregnancies is essential and cesarean delivery is highly recommended for prevention of uterine rupture. As with any surgery on uterus, there is chances of uterine rupture in further pregnancy, but the chances of rupture decreases if interpregnancy interval is prolonged allowing time for scar to reach its maximal tensile strength so that it can endure the mechanical stress and strain of a subsequent pregnancy.3 Finally, we believe that hemostasis, as well as future pregnancy outcome is optimized with our procedure, others disagree and used a suture for closure of the cornual defects. CONCLUSIONS In conclusion, with the appropriate patients, appropriate setup and in the presence of well-skilled laparoscopic surgeons, laparoscopic management for large cornual pregnancies can be undertaken with this procedure

and cardiovascular risk of injection vasopressin can be avoided, but we needs further studies for its safety and applications. Laparoscopic surgery is safe and feasible for managing cornual pregnancy but, the subsequent pregnancy should be carefully monitored with regular ultrasound throughout the pregnancy for prevention of uterine rupture. REFERENCES 1. Lau S, Tulandi T. Conservative medical and surgical management of interstitial ectopic pregnancy. Fertil Steril 1999;72(2):207-15. 2. Tulandi T, Al-Jaroudi D. Interstitial pregnancy: results generated from the Society of Reproductive Surgeons Registry. Obstet Gynecol 2004;103(1):47-50. 3. Nahum G, Pham K Q. Uterine rupture in pregnancy. Emedicine. Available at: http://www.emedicine.com/ med/topic 3746htm 4. Moawad NS, Mahajan ST, Moniz MH, Taylor SE, Hurd WW. Current diagnosis and treatment of interstitial pregnancy. Am J Obstet Gynecol 2010;202(1):15-29. 5. Rizk B, Holliday CP, Abuzeid M. Challenges in the diagnosis and management of interstitial and cornual ectopic pregnancies. Middle East Fertil Soc J 2013;18:235-40. 6. Fylstra DL. Ectopic pregnancy not within the (distal) fallopian tube: etiology, diagnosis, and treatment. Am J Obstet Gynecol 2012;206(4):289-99. 7. Maymon R, Shulman A. Controversies and problems in the current management of tubal pregnancy. Hum Reprod Update 1996;2(6):541-51. 8. Baumann R, Magos AL, Turnbull A. Prospective comparison of videopelviscopy with laparotomy for ectopic pregnancy. Br J Obstet Gynaecol 1991;98(8):765-71. 9. Tulandi T, Vilos G, Gomel V. Laparoscopic treatment of interstitial pregnancy. Obstet Gynecol 1995;85(3): 465-7. 10. Fernandez H, Lelaidier C, Thouvenez V, Frydman R. The use of a pretherapeutic, predictive score to determine inclusion criteria for the non-surgical treatment of ectopic pregnancy. Hum Reprod 1991;6(7):995-8. 11. Choi YS, Eun DS, Oh YS, Park JN. Cornual patency and integrity following laparoscopic cornuotomy for interstitial pregnancy. Open J Obstet Gynecol 2012;2: 127-30. 12. Weissman A, Fishman A. Uterine rupture following conservative surgery for interstitial pregnancy. Eur J Obstet Gynecol Reprod Biol 1992;44(3):237-9. 13. Ng S, Hamontri S, Chua I, Chern B, Siow A. Laparoscopic management of 53 cases of cornual ectopic pregnancy. Fertil Steril 2009;92(2):448-52. 14. Maruthini D, Sharma V. A case of live birth after uterine reconstruction for recurrent cornual ectopic pregnancy following IVF treatment. Case Rep Obstet Gynecol 2013;2013:625261.

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OBSTETRICS AND GYNECOLOGY

Three Different Presentations of Ectopic Pregnancy in the Same Patient MADHUPRIYA, KUNDAVI SHANKAR, LAKSHMI SHANMUGASUNDARAM, THANKAM R VARMA

ABSTRACT We present a case report of ectopic pregnancy in a patient on the residual stump of the salpingectomized tube. In the case scenario presented below, there were three different kinds of presentation of ectopic pregnancy in the same patient-left tubal, ectopic pregnancy implanted in scar site and repeat ectopic in the tubal stump of previously salpingectomised tube.

Keywords: Ectopic pregnancy, scar implantation pregnancy, tubal pregnancy, tubal stump pregnancy, salpingectomy, methotrexate

psilateral ectopic pregnancy following salpingectomy (total or partial) is rare with <12 cases reported in the literature in the last 10 years.1 Takeda et al2 reported that the incidence of tubal stump pregnancy was 1.16% of all ectopic pregnancies. Ko et al3 reported an incidence of six tubal stump pregnancies among 1,466 ectopic pregnancies amounting to 0.4%. The ectopic pregnancy on the residual tubal stump after salpingectomy has been sporadically reported.2,4-10 The true incidence of pregnancy in scar has not been determined because so few cases have been reported in the literature; there are only 18 published cases in the English medical literature between 1978 and 2001.11 CASE REPORT A 27-year-old lady came to us in 2008 for secondary subfertility evaluation. She was married for about 5 years with regular cycles. She had two previous spontaneous conceptions. First pregnancy ended in missed miscarriage at 8 weeks; cytogenetic analysis of the evacuated products of conception showed karyotype of 69 XXY (Triploidy). Karyotyping of both partners were done and were found to be normal.

Institute of Reproductive Medicine, Madras Medical Mission Mogappair, Chennai, Tamil Nadu Address for correspondence Dr Madhupriya C/o: Institute of Reproductive Medicine Madras Medical Mission Mogappair, Chennai, Tamil Nadu E-mail: kalakanda_amp@yahoo.co.in

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Second pregnancy was a left ampullary ruptured ectopic pregnancy. Laparoscopic left salpingectomy was done. In the interval period, antiphospholipid antibodies were assessed and found to be normal; semen analysis done was normal. She conceived for the third time with clomipheneinduced cycle with timed intercourse. It was a viable singleton pregnancy evidenced by fetal cardiac activity on ultrasound at 6 weeks gestation. But, the pregnancy ended in missed miscarriage at 8+ weeks. Fetal karyotyping of the evacuated products of conception was reported to be normal. She then conceived spontaneously in 2009; was under cover of low-dose aspirin and low-molecular-weight heparin throughout the pregnancy. She had gestational diabetes mellitus (GDM) and was taking insulin; she developed fetal intrauterine growth restriction (IUGR) in the third trimester. She delivered at term by lowersegment cesarean section (LSCS). Her 5th pregnancy was a spontaneous conception. Scan done at 6 weeks and 6 days showed a sac located in the lower endometrial cavity. She was counseled about the finding and followed up conservatively. Scan done at 8 weeks gestation (transabdominal sonography [TAS] + transvaginal sonography [TVS]) showed a gestational sac with large yolk sac in endometrial cavity only about 5 mm from the uterine serosa. Re-check TAS done revealed the sac in the lower, anterior uterine serosa suggestive of scar implantation ectopic pregnancy. Sac was located 13 mm above the cervix with no abnormal vasculature in the lower anterior abdominal wall.

OBSTETRICS AND GYNECOLOGY

Figure 1. Left tubal stump - ectopic pregnancy.

The diagnosis of ectopic pregnancy implanted in the previously done LSCS scar site was made. She was managed medically with injection methotrexate 75 mg and followed up with b-human chorionic gonadotropin (b-hCG) titers, until it decreased to baseline. The uterine cavity re-checked after her first periods showed no sac at the scar implantation site. Her 6th pregnancy in 2014 was a spontaneous conception. She had slowly doubling b-hCG levels. Scan (TAS + TVS) was suggestive of left adnexal pregnancy at 5+ weeks gestation. In view of previously salpingectomized status of the patient, re-evaluation of the finding by a repeat ultrasound was done. The ultrasound findings confirmed the ectopic tubal pregnancy in the stump of previously salpingectomized left tube. She was initially managed medically with methotrexate injection. An emergency, laparoscopic excision of the left tubal stump was done in view of suspected ectopic pregnancy rupture with signs of hemoperitoneum. Histopathological report confirmed the ruptured left tubal stump with ectopic pregnancy within. DISCUSSION

Figure 2. Tubal stump with pregnancy in situ.

Figure 3. Scar implantation pregnancy - in previous LSCS scar.

Reviewing the literature, the incidence of ectopic pregnancies in tubal stump and ectopic pregnancies in the scar implantation sites have been quoted to be very low. Implantation of a pregnancy within a cesarean fibrous tissue scar is considered to be the rarest form of ectopic pregnancy and a lifeâ&#x20AC;?threatening condition.11 This is because of the very high-risk for uterine rupture and all the maternal complications related to it.12-14 Of the many theories for explaining its occurrence, the most reasonable one seems to be that the blastocyst enters into the myometrium through a microscopic dehiscent tract. This may be created throughout a trauma of a previous cesarean section or any other uterine surgery15 or even following manual removal of the placenta.11 Another mechanism for intramural implantation is in vitro fertilization (IVF) and embryo transfer, even in the absence of any previous uterine surgery.16 The true incidence of pregnancy in scar has not been determined because so few cases have been reported in the literature; there are only 18 published cases in the English medical literature between 1978 and 2001.11 Between 2002 and mid-2003; however, 25 additional cases were reported 18 of which took place in a single center.14 This may reflect both the increasing number of cesarean sections being performed and the more widespread use of the TVS that allows earlier detection of such pregnancies. This apparent

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OBSTETRICS AND GYNECOLOGY increase is likely multifactorial, related to increasing numbers of cesarean deliveries, increased use of TVS and a heightened awareness of this diagnosis.14,17,18 The diagnosis of cesarean scar pregnancy is made primarily using TVS with a reported sensitivity of 84.6%.18 The major differential diagnoses to consider are spontaneous abortion in progress or cervical ectopic pregnancy.14,18 Several imaging criteria have been proposed to improve diagnostic accuracy. These include an empty uterine cavity and endocervical canal, location of the gestational sac peripherally within the anterior portion of the lower uterine segment, deficient or absent myometrium between the gestational sac and the bladder12,19 and complete encasement of the gestational sac by myometrium and/or fibrous scar tissue.17 Peritrophoblastic flow should be detected at the site of implantation at the scar.14,17 The rarity of this entity results in a lack of consensus on optimal management. Reported strategies include expectant management, systemic methotrexate therapy, local injection of methotrexate or other embryocides, gestational sac aspiration, dilatation and curettage, surgical laparotomy/hysterotomy, hysteroscopy, laparoscopy and uterine artery embolization.18,20 The most difficult question in clinical practice is whether termination of a desired live first trimester scar pregnancy is justified based on current clinical experience. To answer this question, we need to be reasonably confident that there are significant risks to a mother’s health, if pregnancy is allowed to continue. We need to provide evidence showing that treatment in early pregnancy is safe and effective, that this treatment will preserve woman’s fertility and that the risk of recurrence of scar implantation is low. Recommendations of the recent enquiry into maternal deaths in the UK have strengthened the arguments in favor of early intervention. The enquiry has identified abnormally adherent placenta following previous cesarean section as one of the leading causes of maternal morbidity and mortality and has advised clinicians to make every effort to identify an abnormally adherent placenta as soon as possible in order to minimize maternal risks.21 Recent studies have shown that surgical treatment of scar ectopics in the first trimester can be accomplished safely and effectively with a relatively little blood loss.22 There is also emerging evidence that women’s fertility is not compromised by the treatment of scar pregnancy, that the subsequent pregnancy outcomes are not adversely affected by the scar implantation and the risk of recurrence is very low.23

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The available evidence suggests that the first trimester surgical evacuation of nonviable scar pregnancy is relatively simple and safe. In view of the low-risk of recurrence, it is difficult at present to justify the use of any surgical procedures, either minimally invasive or open, to repair defective cesarean section scars. Research has speculated that the mechanism for tubal stump pregnancy involves normal fertilization of an oocyte after ovulation from one ovary. The fertilized oocyte in the ipsilateral tube later is carried to the contralateral remnant tube by the intrauterine fluids. This speculation is supported by the ectopic pregnancy cases involving contralateral to unilateral intrafallopian gamete transfer.24 Ectopic pregnancy in the stump of the ligated tube can be explained either by the trapped fertilized ovum or by the tuboperitoneal fistula formation theory.25-27 In both the instances, fertilized ovum would have been entrapped in the stump because of the narrow isthmic portion of the tube. When the diagnosis of repeat ectopic pregnancy in the stump of the previously salpingectomized patient is considered, the differential diagnosis of cornual pregnancy is ruled out when preoperatively: ÂÂ

There was no evidence of an abnormal uterine horn

ÂÂ

Presence of round ligament on the medial aspect of the gravid swelling

ÂÂ

Presence of a narrow part separating the mass from the uterus

ÂÂ

It was sufficient to just apply an artery forceps between the gravid swelling and the uterus

ÂÂ

There was no need to cut into the uterine cornu to remove the stump.6

REFERENCES 1. Fischer S, Keirse MJ. When salpingectomy is not salpingectomy—ipsilateral recurrence of tubal pregnancy. Obstet Gynecol Int 2009;2009:524864. 2. Takeda A, Manabe S, Mitsui T, Nakamura H. Spontaneous ectopic pregnancy occurring in the isthmic portion of the remnant tube after ipsilateral adnexectomy: report of two cases. J Obstet Gynaecol Res 2006;32(2):190-4. 3. Ko PC, Liang CC, Lo TS, Huang HY. Six cases of tubal stump pregnancy: complication of assisted reproductive technology? Fertil Steril 2011;95(7):2432.e1-4. 4. Corti A, Rolandi L. Ectopic pregnancy in the site of prior adnexectomy. Osp Maggiore 1964;59:413-22. 5. Benzi G, Mazza L. Recurrence of ectopic pregnancy in a residual tubal stump after prior adnexectomy for extra-uterine pregnancy. Minerva Ginecol 1967;19(4): 171-8.

OBSTETRICS AND GYNECOLOGY 6. Krzaniak S. Ectopic gestation in a tubal stump. Postgrad Med J 1968;44(508):191-2. 7. Bernardini L, Valenzano M, Foglia G. Spontaneous interstitial pregnancy on a tubal stump after unilateral adenectomy followed by transvaginal colour Doppler Ultrasound. Hum Reprod 1998;13(6):1723-6. 8. Milingos DS, Black M, Bain C. Three surgically managed ipsilateral spontaneous ectopic pregnancies. Obstet Gynecol 2008;112(2 Pt 2):458-9. 9. Faleyimu BL, Igberase GO, Momoh MO. Ipsilateral ectopic pregnancy occurring in the stump of a previous ectopic site: a case report. Cases J 2008;1(1):343. 10. Sturlese E, Retto G, Palmara V, De Dominici R, Lo Re C, Santoro G. Ectopic pregnancy in tubal remnant stump after ipsilateral adnexectomy for cystic teratoma. Arch Gynecol Obstet 2009;280(6):1015-7. 11. Fylstra DL, Pound-Chang T, Miller MG, Cooper A, Miller KM. Ectopic pregnancy within a cesarean delivery scar: a case report. Am J Obstet Gynecol 2002;187(2):302-4.

17. Seow KM, Huang LW, Lin YH, Lin MY, Tsai YL, Hwang JL. Cesarean scar pregnancy: issues in management. Ultrasound Obstet Gynecol 2004;23(3):247-53. 18. Rotas MA, Haberman S, Levgur M. Cesarean scar ectopic pregnancies: etiology, diagnosis, and management. Obstet Gynecol 2006;107(6):1373-81. 19. Vial Y, Petignat P, Hohlfeld P. Pregnancy in a cesarean scar. Ultrasound Obstet Gynecol 2000;16(6):592-3. 20. Maymon R, Halperin R, Mendlovic S, Schneider D, Herman A. Ectopic pregnancies in a caesarean scar: review of the medical approach to an iatrogenic complication. Hum Reprod Update 2004;10(6):515-23. 21. Confidential Enquiry into Maternal and Child Health. Saving Mothers’ Lives: Reviewing Maternal Deaths to Make Motherhood Safer 2003-2005. The Seventh Report of the Confidential Enquiries into Maternal Deaths in the United Kingdom. CEMACH: London 2007:p78.

12. Fylstra DL. Ectopic pregnancy within a cesarean scar: a review. Obstet Gynecol Surv 2002;57(8):537-43.

22. Jurkovic D, Ben-Nagi J, Ofilli-Yebovi D, Sawyer E, Helmy S, Yazbek J. Efficacy of Shirodkar cervical suture in securing hemostasis following surgical evacuation of cesarean scar ectopic pregnancy. Ultrasound Obstet Gynecol 2007;30(1):95-100.

13. Herman A, Weinraub Z, Avrech O, Maymon R, Ron-El R, Bukovsky Y. Follow up and outcome of isthmic pregnancy located in a previous caesarean section scar. Br J Obstet Gynaecol 1995;102(10):839-41.

23. Ben Nagi J, Helmy S, Ofili-Yebovi D, Yazbek J, Sawyer E, Jurkovic D. Reproductive outcomes of women with a previous history of caesarean scar ectopic pregnancies. Hum Reprod 2007;22(7):2012-5.

14. Jurkovic D, Hillaby K, Woelfer B, Lawrence A, Salim R, Elson CJ. First-trimester diagnosis and management of pregnancies implanted into the lower uterine segment cesarean section scar. Ultrasound Obstet Gynecol 2003;21(3):220-7.

24. Keeping D, Harrison K, Sherrin D. Ectopic pregnancy contralateral to unilateral GIFT. Aust N Z J Obstet Gynaecol 1993;33(1):95-6.

15. Cheng PJ, Chueh HY, Soong YK. Sonographic diagnosis of a uterine defect in a pregnancy at 6 weeks’ gestation with a history of curettage. Ultrasound Obstet Gynecol 2003;21(5):501-3.

26. McCausland A. High rate of ectopic pregnancy following laparoscopic tubal coagulation failures. Incidence and etiology. Am J Obstet Gynecol 1980;136(1):97-101.

16. Hamilton CJ, Legarth J, Jaroudi KA. Intramural pregnancy after in vitro fertilization and embryo transfer. Fertil Steril 1992;57(1):215-7.

25. Tindal VR (Ed.). Jeffcoate’s Principles of Gynecology. 5th edition, Butterworths: London 1987:p.214.

27. McCausland AM. Recanalization and fistulization of the fallopian tubes are thought to be the causes of pregnancies following female sterilization. Am J Obstet Gynecol 1981;139(1):114-5.

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New Guidance Recommends HPV DNA Test for Primary Screening Primary screening for human papilloma virus (HPV) using a DNA test can be considered as an alternative to current US cytology-based cervical cancer screening strategies, according to new interim guidance from multiple societies published online January 7 in Gynecologic Oncology. "HPV screening is highly sensitive, but specificity depends on subsequent evaluation strategies and screening frequencies," write Warner K. Huh, MD, from the University of Alabama at Birmingham, and colleagues. "[US Food and Drug Administration] approval does not include specific recommendations for applying HPV screening in the US."

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ORTHOPEDICS

Atypical Periosteal Osteoid Osteoma: A Case Report SS SURESH*, V RANIâ&#x20AC;

ABSTRACT Osteoid osteoma is a benign osteoblastic tumor usually seen in adolescent and young males. In the pediatric age group, since the history may be difficult to elicit, there are often problems in early diagnosis. The author reports an unusual presentation of osteoid osteoma in a 10-year-old girl, which could not be diagnosed by conventional X-rays and CT scan.

Keywords: Osteoid osteoma, osteoblastic tumor, lower extremity

steoid osteoma first described by Jaffe in 1935, is a benign osteoblastic tumor, mostly seen in adolescent and young males.1

The lesions being more common in the lower extremity, children present with painful limping.1 Conventional radiographs are effective in diagnosis, the radiological picture is of a central radiolucent area (nidus) surrounded by an area of cortical thickening. The imaging modality of choice is computed tomography (CT) scan which is considered far superior for osteoid osteoma to an magnetic resonance imaging (MRI) in diagnosis.1,2 Tumor presents in its classic form only in two-thirds of the patients.3 Subperiosteal location of the lesion can lead to difficulty in diagnosis. There are reports that osteoid osteomas arise in the subperiosteal region4 initially and later on become cortical or intramedullary. CASE REPORT A 10-year-old girl was seen in the orthopedic clinic with recurrent episodes of pain in left ankle of around five months duration. She was not having diurnal variation of her symptoms and her medical history was unremarkable. There was a small tender swelling over the posteromedial aspect of the left ankle between the posteromedial border of tibia and the tibialis posterior tendon.

*Dept. of Orthopedics â&#x20AC; Dept. of Anesthesia Ibri Regional Referral Hospital, Sultanate of Oman Address for correspondence Dr SS Suresh E-mail: dr.s.s.suresh@gmail.com

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Movements of the ankle joint were free. Her blood parameters were normal. Routine X-ray of the left ankle showed a ballooned out lesion over the posterior aspect of the left tibia close to the growth plate, with a thin outer shell (Fig. 1). There was no sclerosis around the lesion and no calcification could be seen inside. Ultrasound scan of the lesion did not reveal any gross abnormality. A CT scan was done which showed an elliptical hypodense area in the posterior distal tibia with only minimal sclerosis. There was no soft tissue component and periosteal reaction. The radiological diagnosis was fibrous cortical defect (Fig. 2). The patient was advised surgery as she was symptomatic. Through a posteromedial incision, the lesion was approached after retracting the tibialis posterior tendon and the neurovascular bundle. Ballooning of the distal posterior tibia was found, which was curetted. Punctuate bleeding tissue was removed with high speed burr. Histopathology report was consistent with osteoid osteoma. The patient was asymptomatic at 1 year follow-up.

Figure 1. X-ray of the left ankle showing periosteal lesion with thin outer shell (white arrow heads).

ORTHOPEDICS Nidus in cancellous bone may be difficult to visualize as there is less periosteal reaction and new bone formation. Subperiosteal lesion shows less periosteal bone formation than the cortical lesion.4 Authors found that subperiosteal osteoid osteoma like any tumor may erode into the cortex beneath.4

Figure 2. CT scan showing the same lesion as in the X-ray, with doubtful calcification inside (white arrow head).

DISCUSSION Clinical symptoms and radiological findings are enough to make the diagnosis of osteoid osteoma at presentation. The location of the osteoid osteoma may be intracortical, subperiosteal, endosteal or medullary. The lesion is most commonly located in the cortex of the long bones with dense reactive sclerosis. Presence of area of sclerosis around the lucent area, due to reactive bone formation, is typical of osteoid osteoma.2 The nidus, on maturity, may be radiodense due to mineralization. The nidus is better demonstrated in a CT scan than in an MRI.1,2 CT scanning with 2 mm cuts delineates the nidus properly. CT scan shows a nidus which is a well-defined area of low attenuation which is surrounded by an area of high attenuation of reactive sclerosis.1 Radiographic appearance may vary with location of the tumor.1 The tumor presents in its typical form only in twothirds of the patients3 as the initial radiographs may be misleading. The difficulties in diagnosis arise from the absence of reactive new bone formation in atypical sites, as in our case. Radiographs in nondiaphyseal osteoid osteomas may be misleading and the tumor may be missed in most of the cases. In a small series by Davidson et al, there was a delay of 6 months in making the diagnosis because of the atypical radiographic appearance.3 The delay in diagnosis can range from six months to 2 years. Most of the osteoid osteomas are cortical, which is associated with more marked reactive formation compared to medullary and subperiosteal osteoid osteomas.

Subperiosteal osteoid osteoma as reported by Shankman et al,4 is a rare tumor on the surface of the bone. There is scanty mineralization and less reactive sclerosis of the adjacent bone. Contrary to this, Kayser et al5 believe that most osteoid osteomas arise in the subperiosteal location and later appear as intracortical or intramedullary. The authors propose two mechanisms for this transition: continuous remodeling of the bone causing shift of the nidus, and differential remodeling and cortical drift of immature bone. The frequency of osteoid osteoma arising in the subperiosteal location is not that rare. Osteoid osteoma tends to regress over a period of time even without treatment. Salicylates can accelerate healing in osteoid osteoma and is a good diagnostic and therapeutic consideration.1 The standard treatment of osteoid osteoma is en bloc resection, though other modalities of treatment including radioablation have been practiced. Patients operated with high speed burr have less morbidity compared with en bloc resection.1 Subperiosteal osteoid osteomas produce atypical radiographic picture and the radiological features may be misleading. Subperiosteal osteoid osteoma is a rare lesion with atypical radiographic features. Our case was also not diagnosed as osteoid osteoma as the location of the tumor was atypical, and there was no reactive new bone formation. REFERENCES 1. Erol B, Pill SG, Meyer JS, et al. Limping in a 12-year-old boy. Clin Orthop Relat Res 2002;403:281-9. 2. Goswami P, Medhi N, Sarma PK, et al. Imaging features of osteoid osteoma in plain radiograph, CT and MR: A case report and review of literature. Ind J Radio Imag 2005; 15:481-4. 3. Davidson RS, Mahboui S, Heyman S, Drummond DS. Nondiaphyseal osteoid osteomas in the pediatric patient. Clin Orthop Relat Res 1989;(243):230-4. 4. Shankman S, Desai P, Beltran J. Subperiosteal osteoid osteoma: radiographic and pathologic manifestations. Skeletal Radiol 1997;26:457-62. 5. Kayser F, Resnick D, Haghighi P, et al. Evidence of the subperiosteal origin of osteoid osteoma in tubular bones: Analysis of CT and MR imaging. Am J Roentgenol 1998; 170:609-14.

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PEDIATRICS

A Randomized, Double-blind, Placebo-controlled Study of Synbiotics (BIFILAC®) in Children with Acute Diarrhea SABRINA HARRIS AYDEROSS*, CHIDAMBARANATHAN S†, RAMESH S‡

ABSTRACT Objectives: To evaluate the efficacy and tolerability of synbiotic as add-on therapy to standard treatment in the management of diarrhea in comparison with standard treatment and placebo. Methods: A total number of 104 children of both sexes in the age group of 6 months to 10 years, with acute diarrhea were randomized into two groups - Group A and Group B. While both the groups received standard treatment (ORS plus zinc), Group A received placebo and Group B received synbiotic (Bifilac dry syrup) for a period of 5 days. Results: Patients in the synbiotic group exhibited rapid improvement in terms of decrease in the frequency of diarrheal episodes per day i.e., within 36-48 hours, as compared to the control group. Mean duration of diarrhea was shorter in the synbiotic group (2.87 days) as compared to the control group (5.11 days). Average duration of hospitalization was shorter in the synbiotic group in comparison with the control group (2.28 days vs 3.84 days). Conclusion: Addition of synbiotic dry syrup (Bifilac dry syrup) to standard therapy led to rapid improvement in terms of decrease in the frequency of diarrheal episodes per day, decreased duration of diarrhea and shorter hospital stay, as compared to standard treatment alone. Therefore, it can be concluded from the study that addition of synbiotic dry syrup (Bifilac dry syrup) to standard therapy for the management of acute diarrhea in children is safe and effective.

Keywords: Synbiotic, diarrhea, ORS plus zinc, hospitalization, children

ccording to reports from the World Health Organization (WHO) and UNICEF, about two billion cases of diarrheal disease are seen worldwide every year, and among these 1.9 million children <5 years of age die from diarrhea each year, especially in developing countries.1 In India, diarrhea is among the top five causes of death among infants and under-five children and appears to be accountable for 14% deaths in this age group.2 Children in this age group suffer from an average of 2-3 episodes of diarrhea per year.2 In developing countries, enteric bacteria and parasites are more prevalent than viruses and peak during the summer months.1 The commonest causative organisms include diarrheagenic Escherichia coli, Campylobacter,

*Student †Assistant Professor ‡Professor and Head Dept. of Pediatrics Rajah Muthiah Medical College and Hospital (RMMCH) Annamalai University, Tamil Nadu

Shigella species, Vibrio cholera, Salmonella, rotavirus, human calciviruses, adenovirus and parasitic agents including Cryptosporidium parvum, Giardia intestinalis, Entamoeba histolytica and Cyclospora cayetanensis.1 Over the years, extensive availability and use of oral rehydration salts (ORS), improved attention to the benefits of breastfeeding, improved nutrition, better sanitation and hygiene, and increased coverage of immunization have contributed to a reduction in the mortality rate in developing countries.1 Diarrheal episodes can be segregated into three categories:1 ÂÂ

Acute diarrhea manifests as three or more abnormally loose or watery stools in the preceding 24 hours

ÂÂ

Dysentery presents as visible blood in stools

ÂÂ

Persistent diarrhea is characterized by an acutely starting diarrheal episode that lasts >14 days.

Management of children with diarrhea and its prevention involve an integrated approach with oral rehydration, supplementation with zinc, multivitamins and minerals, diet and probiotics.1 Probiotics have

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PEDIATRICS proven efficacy for the treatment of acute diarrhea in children and the effect depends on the strains and dose.3 The WHO defines probiotics as nonpathogenic living microorganisms having benefit for the host if given in enough amounts. Prebiotics include materials that improve the proliferation and development of probiotic microorganisms. Synbiotic refers to a preparation containing both pre- and probiotics.4

ÂÂ

Children with chronic/severe respiratory, CVS, CNS, GIT or endocrinal disorders.

ÂÂ

History of probiotic/synbiotic administration in the past 1 month.

METHODS

This study was conducted to evaluate the efficacy and tolerability of synbiotic (Bifilac dry syrup) as add-on therapy to standard treatment in the management of diarrhea in comparison with standard treatment and placebo.

All patients were segregated into two groups - Groups A and B, based on randomization by an independent statistician. Group A received placebo (methylcellulose dry syrup) and standard treatment, while Group B was randomized to receive synbiotic (Bifilac dry syrup) in addition to standard therapy. Standard treatment includes ORS and oral zinc supplementation (elemental zinc 20 mg/day). All patients received treatment for a period of 5 days.

Study Design

Each 5 mL of reconstituted Bifilac dry syrup contains:

An observational, randomized, double-blind, phase IV study was conducted among children with acute diarrhea visiting the Dept. of Pediatrics, Rajah Muthiah Medical College and Hospital (RMMCH), Annamalai Nagar, Tamil Nadu.

ÂÂ

Streptococcus faecalis T-110 - 30 million

ÂÂ

Clostridium butyricum TO-A - 2 million

ÂÂ

Bacillus mesentericus TO-A - 1 million

ÂÂ

Lactobacillus sporogenes - 50 million.

OBJECTIVES

The study was conducted after obtaining clearance from the Institutional Ethics Committee, Rajah Muthiah Medical College, Annamalai University and was carried out as per the International Conference on Harmonization-Good Clinical Practice (ICH-GCP) guidelines.

Study Population In total, 368 children were screened. Of these, 104 children with diarrhea, aged 6 months to 10 years, both male and female, were recruited in the study after obtaining consent from their parents or guardians. The inclusion as well as exclusion criteria were as follows: Inclusion Criteria ÂÂ

Children of either sex having acute diarrhea of any origin.

ÂÂ

Aged 6 months to 10 years.

ÂÂ

Diarrhea duration <3 days.

ÂÂ

Informed consent from parent/guardian of each participating child.

The efficacy variables included the following: ÂÂ

Number of episodes of diarrhea in a day (frequency)

ÂÂ

Mean duration of diarrhea in days

ÂÂ

Degree of dehydration

ÂÂ

Duration of hospitalization.

RESULTS

Exclusion Criteria ÂÂ

Severe malnourishment.

ÂÂ

Severe dehydration.

ÂÂ

Respiratory/systemic infection.

ÂÂ

Children with known probiotics/synbiotic.

878

Patients were assessed for a period of 1 week. At the first visit, after obtaining consent, patient details and medical history were recorded. All patients were subjected to a detailed clinical examination and the degree of dehydration was assessed. Laboratory investigations were also conducted at the first visit. Laboratory investigations included complete blood count, serum electrolytes, blood urea and serum creatinine. During the follow-up visit (visit 2), the child was assessed for decrease in symptoms and duration of diarrhea.

hypersensitivity

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for

Data obtained revealed that patients who received synbiotic fared better than those in the control group. Patients in the synbiotic group exhibited rapid improvement in terms of decrease in the frequency of diarrheal episodes per day i.e., within 36-48 hours, as compared to the control group (Fig. 1). Mean duration of diarrhea was shorter in the synbiotic group (2.87 days) as compared to the control group (5.11 days) (Fig. 2). The hydration status of patients in the synbiotic group was seen to normalize faster

PEDIATRICS Table 1. Efficacy Findings on Key Parameters Assessed Control group Synbiotic group (Group A) (Group B) 0.94

Mean duration of diarrhea (Days)

5.11

2.87

Average duration of hospitalization (Days)

3.84

2.28

Diarrhea episodes frequency (Mean value)

Frequency of diarrhea/ day (at the end of visit 3)

0.2

6.19 4.05

4 2 0.94 Visit 1

Visit 2

Visit 3

Frequency of diarrhea episodes per day in synbioitc group (Group B)

8 6 4 2

Visit 1

0.49

0.2

Visit 2

Visit 3

Visit 1: Screening and enrollment on Day 1; Visit 2: Day 2 of treatment; Visit 3: Day 5-7

Figure 1. Frequency of diarrhea in the control and synbiotic group.

6 Mean duration (Days)

5.11 5 4 2.87

3 2 1 0

Control group

Synbiotic group

Minimal weight loss was noted in the control group as compared to the synbiotic group over the study period of 1 week. In the group receiving placebo, three children had to be started on oral antibiotics due to persisting/ worsening diarrhea. On the contrary, only two children in the synbiotic group complained of constipation on Day 5 of taking the medication as a side-effect. DISCUSSION

5.31

2.28 2

Figure 3. Average duration of hospitalization in the control and synbiotic group.

3.84

Frequency of diarrhea episodes per day in control group (Group A)

4 Average duration of hospitalization (Days)

Parameters

Control group

Synbiotic group

Figure 2. Mean duration of diarrhea in the control and synbiotic and group.

compared to those in the control group as a rapid improvement in symptoms was evident within 24-48 hours. Average duration of hospitalization was shorter in the synbiotic group in comparison with the control group (2.28 days vs 3.84 days) (Fig. 3).

Diarrhea is a common illness in children below the age of 5 years, especially in the developing world. Of all child deaths from diarrhea, 78% are estimated to occur in the African and South-East Asian regions.1 Synbiotics have been shown to reduce the duration and severity of diarrhea.5 Our study revealed that the mean duration of diarrhea was shorter in the synbiotic (Bifilac) group (2.87 days) as compared to the placebo group (5.11 days). These results are in line with a study by Passariello et al5 that showed a significant reduction in the duration of diarrhea in the synbiotic group compared with placebo. Similar results were also evident in a study by Vandenplas and De Hert.6 Average duration of hospitalization was shorter in the synbiotic group (Bifilac) in comparison with the placebo group (2.28 days vs 3.84 days) in our study. Passariello et al5 also reported similar results in terms of reduction in hospitalization rate. CONCLUSION In our study, addition of synbiotic dry syrup (Bifilac dry syrup) to standard therapy led to rapid improvement in terms of decrease in the frequency of diarrheal episodes per day, decreased duration of diarrhea and shorter hospital stay, as compared to standard treatment alone. Therefore, it can be concluded from the study that addition of synbiotic dry syrup (Bifilac dry syrup) to

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PEDIATRICS standard therapy for the management of acute diarrhea in children is safe and effective.

Acknowledgment The author thank Tablets (India) Ltd. for providing the study medication (Bifilac Dry Syrup).

Conflict of Interest No conflict of interest. REFERENCES 1. World Gastroenterology Organisation Global Guidelines. Acute diarrhea in adults and children: a global perspective. 2012. 2. Shah D, Choudhury P, Gupta P, Mathew JL, Gera T, Gogia S, et al. Promoting appropriate management of diarrhea: a systematic review of literature for advocacy and action: UNICEF-PHFI series on newborn and child health, India. Indian Pediatr 2012;49(8):627-49.

3. Dinleyici EC, Dalgic N, Guven S, Ozen M, Kara A, Arica V, et al. The effect of a multispecies synbiotic mixture on the duration of diarrhea and length of hospital stay in children with acute diarrhea in Turkey: single blinded randomized study. Eur J Pediatr 2013;172(4): 459-64. 4. Jafari SA, Ahanchian H, Kiani MA, Khakshour A, Noorbakhsh Z, Zamani E, et al. Synbiotic for prevention of antibiotic-associated diarrhea in children: A randomized clinical trial. Int J Pediatr 2014;2(1):55-62. 5. Passariello A, Terrin G, Cecere G, Micillo M, De Marco G, Di Costanzo M, et al. Randomised clinical trial: efficacy of a new synbiotic formulation containing Lactobacillus paracasei B21060 plus arabinogalactan and xilooligosaccharides in children with acute diarrhoea. Aliment Pharmacol Ther 2012;35(7):782-8. 6. Vandenplas Y, De Hert SG; PROBIOTICAL-study group. Randomised clinical trial: the synbiotic food supplement Probiotical vs. placebo for acute gastroenteritis in children. Aliment Pharmacol Ther 2011;34(8):862-7.

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PEDIATRICS

Severe Anemia and Hypothyroidism SUPRABHA SHUKLA*, DILLIP KUMAR DAS†, JNANINDRA NATH BEHERA‡

ABSTRACT Thyroid hormone plays an important role in different metabolism in the body. Hematopoietic system is the primary one among the affected systems and anemia is the most important one. Anemia in hypothyroidism is usually of mild-to-moderate degree, but severe anemia is rarely reported. A 6-year-old child presented with poor appetite and examination showed severe anemia, short stature, X-ray of bilateral knee joints revealed epiphyseal dysgenesis in the lower end of femur and thyroid function showed decreased T3 and T4 with increased TSH levels. Other tests like Hb electrophoresis, G6PD, DCT, ANA, iron, vitamin B12 and folic acid level were normal. So, the diagnosis of acquired hypothyroidism with severe anemia was made. Though anemia is a known entity in hypothyroidism, but severe anemia with Hb 3 g/dL is rare.

Keywords: Severe anemia, epiphyseal dysgenesis, hypothyroidism, short stature

hyroid hormone is secreted from the thyroid gland. Frequency of hypothyroidism differs from one society to another. A prevalence of 2.5% has been reported throughout the world. However, the prevalence of subclinical hypothyroidism is approximately 4-8.5% and can reach up to 20% in women aged 60 years or older. Thyroid hormones play an important role in different metabolism in the body. There is a metabolic deceleration in hypothyroidism. All organ systems are affected and clinical features depend on the age of occurrence and the degree of hypothyroidism (deficiency or insufficiency). Hematopoietic system is the primary one among the affected systems and anemia is the most important one. Anemia is reported in 20-60% of the patients with hypothyroidism. Anemia in hypothyroidism is usually of mild-to-moderate degree, but severe anemia is rarely reported. Anemia can be normochromic normocytic, hypochromic microcytic and macrocytic. Anemia severity is associated with

*Senior Resident Dept. of Pediatrics SCB Medical College, Cuttack, Odisha †Assistant Professor Hi-Tech Medical College, Bhubaneswar, Odisha ‡Professor Dept. of Pediatrics, SCB Medical College, Cuttack, Odisha Address for correspondence Dr Suprabha Shukla C/o: Bijay Mohan Biswal, House No. - 14, Malha Sahi, Mangalabag, Cuttack, Odisha E-mail: suprabhashukla@gmail.com

the degree of hypothyroidism. Severe anemia, in a case of hypothyroidism is very rarely described in the available literature. We are presenting a child with severe anemia due to hypothyroidism. CASE REPORT A 6-year-old boy presented to our OPD with chief complaints of poor appetite. On examination, child had severe anemia, but no clubbing or jaundice. There was no past history of blood transfusion. Also, there was no family history of mental retardation or similar illness or multiple blood transfusions. Development was normal except mild delay in motor development. His height was less than third percentile (WHO chart), but weight was normal. Abdominal examination revealed no hepatosplenomegaly. Cardiovascular examination showed ejection systolic murmur in pulmonary area. On standing, child had varus deformity in both lower limbs (Fig. 1). Laboratory investigation showed hemoglobin (Hb) 3 g/dL with normal total leukocyte and platelet count. Peripheral smear showed microcytic hypochromic picture. X-ray of bilateral knee joints showed epiphyseal dysgenesis (Fig. 2). So, from the above findings, etiological work up for anemia was done. Iron, vitamin B12 and folic acid levels were normal. Vitamin D level and renal function tests were normal. Hb electrophoresis was normal. Thyroid function tests were done, which showed low tri-iodothyronine (T3) and thyroxine (T4) levels with increased thyroid-stimulating hormone (TSH) level (T3-, T4-, TSH-). Thyroid ultrasound showed

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PEDIATRICS DISCUSSION According to WHO, prevalence of anemia is 24.8% throughout the world and it is seen more frequently in underdeveloped countries. Most common cause of anemia is nutritional. Thyroid hormones (T3 and T4) also have a significant influence on erythropoiesis. Most commonly encountered anemia in hypothyroidism is normochromic normocytic anemia and cause of anemia is bone marrow depression due to thyroid hormone deficiency as well as lack of erythropoietin production arising from the reduction in need of oxygen due to decreased activity. Erythrocyte life cycle in hypothyroidism is normal, and there is hypoproliferative erythropoiesis. Thyroid hormones also increase 2-3 DPG (diphosphoglycerate) levels, which help in the transmission of oxygen into the tissues. Figure 1. Photograph taken at the time of discharge showing cubitus varus deformity of the legs.

Figure 2. X-ray of both knee joints showing epiphyseal dysgenesis of lower end of femur.

atrophic thyroid gland. Thyroid scan showed very minimal uptake of radioisotope in the thyroid tissue. Antinuclear antibodies (ANA) and direct Coomb’s test were negative. From the above clinical picture and laboratory investigations, diagnosis of acquired hypothyroidism with severe anemia was made. Child was transfused with 2 units (total 20 mL/kg) of packed red cell. Post-transfusion Hb was 6 g/dL. Child was started with thyroid hormone (50 µg/day). Though iron study was normal, child was also given iron and folic acid to meet the excess demand of increased erythropoiesis. After 2-month of follow-up, child’s Hb was 12 g/dL and thyroid function tests were normal. Appetite and physical activity had improved.

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Autoimmune thyroiditis can be seen with other autoimmune disorders. Pernicious anemia can accompany hypothyroidism as a constituent of polyglandular autoimmune syndrome. Failure of vitamin B12 absorption occurs in pernicious anemia due to intrinsic factor (IF) deficiency and gastric achlorhydria. This is one of the reasons of macrocytic anemia in hypothyroidism. Macrocytosis is found in 55% of the hypothyroid patients. Folic acid is another vitamin with impaired intestinal absorption causing macrocytic anemia in hypothyroidism. Iron deficiency anemia is related to menorrhagia occurring as a result of various hormonal imbalances and also malabsorption, which is seen in hypothyroidism. In the study, by R Carnel and colleagues, thyroid disorders and hypothyroidism were determined respectively in 24.1% and 11.7% of the patients with pernicious anemia. Insufficient intake, absorption change arising from deceleration in intestinal motility, intestinal wall edema and bacterial infiltration are blamed among other reasons causing vitamin B12 deficiency in hypothyroidism. Folic acid deficiency occurs as a result of intestinal malabsorption. Again hypothyroidism ruins folate mechanism by decreasing hepatic level of dihydrofolate reductase such as methylenetetrahydrofolate reductase. In hypothyroidism, malabsroption and iron deficiency anemia occurs as a result of various hormonal instability. In a study carried out by Cinemre and colleagues, they showed that the efficacy and absorption of oral iron treatment in women with subclinical hypothyroidism improved after levothyroxine replacement. This demonstrates that hypothyroidism should be assessed in patients with anemia.

PEDIATRICS Anemia is not always due to nutritional deficiency and we should always try to find the exact etiology whenever possible especially when there is certain other clinical finding apart from anemia. Hypothyroidism is an endocrine disorder that is frequently seen in the society. Anemia in hypothyroid patient occurs as a result of various causes. Determination of etiological reasons of anemia and their treatment is important. SUGGESTED READING 1. Wilson GR, Curry RW Jr. Subclinical thyroid disease. Am Fam Physician 2005;72(8):1517-24.

3. Das KC, Mukherjee M, Sarkar TK, Dash RJ, Rastogi GK. Erythropoiesis and erythropoietin in hypo- and hyperthyroidism. J Clin Endocrinol Metab 1975;40(2):211-20. 4. Lawrence E, Shapiro A, Surks I. Hypothyroidism. In: Principles and Practice of Endocrinology and Metabolism. 3rd edition, Kenneth LB, Lippincott Williams & Wilkins: Philadelphia 2001:p.445-51. 5. Cinemre H, Bilir C, Gokosmanoglu F, Bahcebasi T. Hematologic effects of levothyroxine in iron-deficient subclinical hypothyroid patients: a randomized, double-blind, controlled study. J Clin Endocrinol Metab 2009;94(1):151-6. 6. Jabbar A, Yawar A, Waseem S, Islam N, Ul Haque N, Zuberi L, et al. Vitamin B12 deficiency common in primary hypothyroidism. J Pak Med Assoc 2008;58(5):258-61.

2. Christ-Crain M, Meier C, Huber P, Zulewski H, Staub JJ, Müller B. Effect of restoration of euthyroidism on peripheral blood cells and erythropoietin in women 7. Benoist B, McLean E, Egli I, Cogswell M. Worldwide with subclinical hypothyroidism. Hormones (Athens) Prevalence of Anemia 1993-2005; Global Database on Anemia. WHO, Geneva 2008:p.1-2. 2003;2(4):237-42. ■■■■

Pediatrics Update Taper desmopressin rather than abrupt discontinuation In a multicenter trial involving patients diagnosed with nocturnal enuresis and responding to desmopressin, structured withdrawal of desmopressin (giving one-half the usual dose each day or by giving the usual dose every other day) for 2 weeks before discontinuation) reduced relapse rates as compared to abrupt withdrawal of the drug. Structured withdrawal was also an independent factor associated with lower initial effective dose and number of wet nights per week.1 Public smoking ban also benefits perinatal and child health A systematic review and meta-analysis of 11 quasi-experimental observational studies published between 2008-2013, involving more than 2.5 million births and 2,47,168 asthma exacerbations found that smoke-free legislation is associated with considerable decrease in preterm births and hospital admissions for asthma.2 Avoid helmets for infants with positional skull flattening A randomized controlled trial (HEADS, HElmet therapy Assessment in Deformed Skulls) which randomly assigned infants aged 5-6 months with moderate-to-severe skull deformation to helmet therapy vs observation found both to be comparable in terms of effectiveness. Because of high prevalence of side effects, and high costs associated with helmet therapy, the authors discourage the use of a helmet as a standard treatment for healthy infants with moderate to severe skull deformation.3 REFERENCES 1. Gökçe Mİ, Hajıyev P, Süer E, et al. Does structured withdrawal of desmopressin improve relapse rates in patients with monosymptomatic enuresis? J Urol 2014;192(2):530-4. 2. Been JV, Nurmatov UB, Cox B, et al. Effect of smoke-free legislation on perinatal and child health: a systematic review and meta-analysis. Lancet 2014;383(9928):1549-60. 3. van Wijk RM, van Vlimmeren LA, Groothuis-Oudshoorn CG, et al. Helmet therapy in infants with positional skull deformation: randomised controlled trial. BMJ 2014;348:g2741.

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EXPERT VIEW

Actions Necessary to Implement to Ensure Continuous Improvement... SUNIL KUMAR SAGGAR

We all know, Change is inevitable and it is bound to happen. If we do not drive continuous improvement in our processes, we may not even survive:

rowing competition, buyer beware, continuous advancement, shifting conditions require newer and renewed thinking to remain, sustain and to ensure continuous northwards movement. Implementing a continuous improvement program is one way an institution can harness change and create competitive advantage. As institutions launch continuous improvement programs, they should consider the following 5 elements leading to successful and sustainable efforts. ÂÂ

Align continuous improvement with strategic objectives: Continuous improvement (‘CI’) should not be considered a stand alone initiative or self-contained goal; it must align with strategic objectives. When launching a continuous improvement program, aim to make an impact quickly for credibility and momentum. Pick your battles and don’t try to tackle all objectives at once. Always use strategic objectives as the litmus test for deciding if something should be done and how it should be done.

ÂÂ

Don’t overdo process excellence at outset; this is an evolutionary process: Conduct a continuous improvement assessment to determine where your biggest opportunities are, but start small and gain some momentum. Resort to PDCA (Plan-DoCheck-Adjust) besides applying DMAIC. (DefineMeasure-Analyze-Improve-Control).

ÂÂ

Integrate continuous improvement into a culture of strategic execution: High performance cultures require a clear strategy. Clarify your vision, mission and values and set objectives throughout

Chief Executive Officer Jaipur Golden Hospital, Rohini, Delhi -110 085 E-mail: ceo@jghdelhi.net

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the organization. WORK on your culture, and communicate, communicate! It is important to remember that the organization is a very important consideration for continuous improvement as shown below. ÂÂ

Blend the best practices from the different methodologies: Focusing on one methodology for continuous improvement can limit progress, restraining the organization’s ability to realize its full continuous improvement potential. Use the best tool for the activity picking from Six Sigma, Lean, Kaizen and other techniques to delivers results!

ÂÂ

Focus on data, not emotions: No more “We have always done it that way.” Embrace the discipline of the process and the rigor of data-driven decisions. Emphasize measures and metrics. Hold people accountable. This will become your new culture. Remember that the company’s strategy and data are the only things used justify projects.

The first step to institute any change is to determine where you stand. And since continuous improvement goes hand-in-hand with a culture of strategic execution, it is suggested that be focused. Ensure that the change being planned has to conform to the VOC (Voice of Customer) and VOB (Voice of Business) and with the involvement of all the constituents of the process. Once planned the suggested way, these processes will pinpoint where you should start and provide a list of the highest ROI projects that deal with our strategic and operational gaps.

AROUND THE GLOBE

News and Views

at treating dry eye than sodium hyaluronate (HA) ophthalmic solution, according to results of a large, randomized clinical trial published online January 28 in the British Journal of Ophthalmology.

Lancet Diabetes & Endocrinology, researchers from the School of Public Health at The University of Queensland in Australia found that women with type 1 diabetes had a 37% higher excess risk of death from any cause compared with male type 1 diabetes patients. Female type 1 diabetes patients were also found to have nearly twice the risk of dying from cardiovascular disease than men, a 37% increased risk of stroke and a 44% increased risk of death from kidney disease.

ÂÂ Optimal use of modern contraceptives could

ÂÂ Researchers have determined that two mutations

ÂÂ Mobile

devices equipped with cameras can effectively enable patients to monitor atypical nevi and send images to their healthcare providers, according to an article published online January 28 in JAMA Dermatology.

ÂÂ Diquafosol ophthalmic solution is more effective

avert an estimated 15 of 16.7 million unwanted pregnancies each year in 35 low- and middleincome countries, according to a demographic health survey by Saverio Bellizzi, MSc, from the World Health Organization (WHO), Western Pacific Regional Office, Manila, Philippines and coauthors and published online February 3 in Human Reproduction.

ÂÂ The WHO is still worried about the spread of MERS,

a respiratory disease that has infected and killed hundreds of people, overwhelmingly in Saudi Arabia. In an update issued after a meeting of its emergency committee on Middle East Respiratory Syndrome, the United Nations health agency said more must be done to track the virus, which is known to have infected at least 965 people, of whom some 357 have died.

ÂÂ Physicians may be able to predict which patients

with knee osteoarthritis (OA) will be subject to severe pain by determining whether meniscal lesions are contributing to neuropathic pain (NP) in the knee, according to an article published online December 14 in Arthritis Research & Therapy. Using magnetic resonance imaging (MRI) to make a diagnosis of NP could help physicians determine which patients may benefit from a treatment aimed at NP symptoms, rather than prescribing prolonged use of anti-inflammatory drugs or narcotic analgesics.

ÂÂ A large meta-analysis involving more than 2,00,000

participants has found that women with type 1 diabetes have more than twice the risk of dying from heart disease compared with men who have the condition. In the new study, published in The

on a single gene can interact in a way that lowers the carrier’s risk for a heart attack. The variants are found in a gene called DBH, which regulates an enzyme involved in the conversion of dopamine to norepinephrine - both of which are important chemical messengers and hormones. When considered alone, each variant had either an undetectable or minimal effect on the gene’s effect on disease risk. But their interaction substantially reduced expression of the DBH gene, creating conditions in the body that protect against a heart attack. The research is published in a recent issue of the journal Circulation Research.

ÂÂ ST-segment analysis (STAN) used as an adjunct to

conventional intrapartum monitoring of the fetal heart rate does not improve perinatal outcomes or reduce operative deliveries, at least in the United States, according to new research presented at the Society for Maternal-Fetal Medicine (SMFM) 2015 Annual Pregnancy Meeting.

ÂÂ Children under age 5 living in sub-Saharan Africa

were 54% less likely to develop malaria if they had been given a single large dose of vitamin A, new research led by the Johns Hopkins Bloomberg School of Public Health suggests. The researchers say their findings, published in the online journal eLife, indicate that vitamin A may protect children against the mosquito-borne malaria parasite, especially if administered under certain conditions, such as during the wet season, when malariainfected mosquitoes are most prevalent.

ÂÂ The following three simple steps can help you

sleep better:

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AROUND THE GLOBE Cut down on caffeine: Caffeine drinkers may find it harder to fall asleep than people who don’t drink caffeine. Once they drift off, their sleep is shorter and lighter. For some, a single cup of coffee in the morning means a sleepless night. That may be because caffeine blocks the effects of adenosine, a neurotransmitter thought to promote sleep. Caffeine can also interrupt sleep by increasing the need to urinate during the night. People who suffer from insomnia should avoid caffeine as much as possible, since its effects can endure for many hours. Because caffeine withdrawal can cause headaches, irritability and extreme fatigue, it may be easier to cut back gradually rather than go cold turkey. Those who can’t or don’t want to give up caffeine should avoid it after 2 pm, or noon if they are especially caffeine-sensitive. Stop smoking or chewing tobacco: Nicotine is a central nervous system stimulant that can cause insomnia. This potent drug makes it harder to fall asleep because it speeds your heart rate, raises blood pressure and stimulates fast brain wave activity that indicates wakefulness. In people addicted to nicotine, a few hours without it is enough to induce withdrawal symptoms; the craving can even wake a smoker at night. People who kick the habit fall asleep more quickly and wake less often during the night. Sleep disturbance and daytime fatigue may occur during the initial withdrawal from nicotine, but even during this period, many former users report improvements in sleep. If you continue to use tobacco, avoid smoking or chewing it for at least one to two hours before bedtime. Limit alcohol intake: Alcohol depresses the nervous system, so a nightcap may seem to help some people fall asleep. However, alcohol suppresses REM sleep, and the soporific effects disappear after a few hours. Drinkers have frequent awakenings and sometimes frightening dreams. Alcohol may be responsible for up to 10% of chronic insomnia cases. Also, alcohol can worsen snoring and other sleep breathing problems, sometimes to a dangerous extent. Even one drink can make a sleep-deprived person

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drowsy. In an automobile, the combination significantly increases a person’s chance of having an accident. You can also improve the amount and quality of your sleep by getting regular physical activity and creating and sticking to a regular sleep schedule and routine. ÂÂ More than 600 events in over 100 countries

marked the celebration of World Cancer Day, 4th February 2015. This year’s theme “Not Beyond Us” highlighted existing solutions across the continuum of cancer that are within our reach to help diminish the global disease burden.

ÂÂ Although procalcitonin testing can help detect

degrees of bacterial infection, including sepsis, compliance seems to be low and algorithms have had a negligible impact on the guidance of appropriate antibiotic therapy, suggests new research presented at the Society of Critical Care Medicine 44th Critical Care Congress.

ÂÂ A study comparing bariatric surgical procedures

for severe obesity suggests that biliopancreatic diversion with duodenal switch results in better weight loss and metabolic outcomes in comparison with Roux-en-Y gastric bypass, but it is also associated with more adverse events. The study is published online February 4 in JAMA Surgery.

ÂÂ Celiac disease may be at the root of some women’s

problems with infertility, suggests new research from India, published online in the Journal of Clinical Gastroenterology. Researchers say that women who do not have a ready explanation for their failure to conceive should be screened for celiac disease.

ÂÂ The findings from the Coronary Sinus Reducer

for Treatment of Refractory Angina (COSIRA) phase 2 trial have revealed that those who had the Reducer implanted into their coronary sinus had significantly reduced symptoms and improved quality-of-life 6 months later, compared with patients who underwent a sham procedure. The findings are published in the February 5 issue of the New England Journal of Medicine.

ÂÂ Patients with spondyloarthritis not exposed to

nonsteroidal anti-inflammatory drugs (NSAIDs) had a higher risk of congestive heart failure compared with patients on any NSAID, reported a new study published in Arthritis Care and Research. The increased risk was likely due to increased baseline comorbidities and physician choice, not to use NSAIDs in these patients.

AROUND THE GLOBE ÂÂ Paramedics may be first-line of treatment for

stroke: A study from NIH designed to test the benefits of early administration of magnesium sulfate suggests that stroke patients may not have to wait until they get to the hospital for treatment - paramedics may be able to start therapy as soon as stroke is suspected. Although the drug did not improve outcome in stroke patients, the study demonstrated the feasibility of early therapy in the ambulance. The results were published in the New England Journal of Medicine.

ÂÂ In December 2014, visitors to Disneyland and the

Disney California Adventure in Anaheim were exposed to measles, also known as rubeola. One of the most infectious diseases in humans, the airborne illness spread to 102 people across 14 states between January 1 and January 30, 2015. Once an ‘eliminated’ disease, measles is making a comeback due in part to declining vaccination rates. Health officials continue to recommend that children, unless immunocompromised, get vaccinated and that adults check with their doctor if they’re unsure about whether they are vaccinated for measles. Anne S MD director of the CDC’s National Center for Immunization and Respiratory Diseases, told reporters on a conference call that 84 people in 14 states have been diagnosed with measles so far in 2015 and, of them, 67 are linked to the Disneyland outbreak.

ÂÂ Clinicians

should treat allergic rhinitis with intranasal steroids when patients’ symptoms impair their quality-of-life, suggest clinical practice guidelines published February 2 in Otolaryngology– Head and Neck Surgery. The guidelines also suggest that clinicians should recommend second-generation oral antihistamines for patients complaining primarily of sneezing and itching.

ÂÂ For patients with severe trauma and major

bleeding, transfusion of plasma, platelets and red blood cells in a balanced 1:1:1 ratio seems superior to a 1:1:2 ratio for reducing death due to hemorrhage, reported a new trial sponsored by the U.S. Department of Defense and the National Institutes of Health. The report is published February 3 in JAMA.

ÂÂ The US Food and Drug Administration (FDA)

has granted accelerated approval to palbociclib, a new drug for the treatment of breast cancer with a novel mechanism of action. The drug is indicated for use with the aromatase inhibitor letrozole as

first-line treatment in postmenopausal women with metastatic breast cancer that is estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative. ÂÂ Antiviral

prophylaxis with valganciclovir in living kidney donors may reduce transmission of cytomegalovirus (CMV) and Epstein-Barr virus (EBV), suggests a pilot study published online in Transplantation.

ÂÂ Baseline and serial measures of high-sensitivity

cardiac troponin T (hs-TnT) predict incident atrial fibrillation independently of traditional risk factors, suggests a new analysis from the Cardiovascular Health Study (CHS), published online in Heart Rhythm.

ÂÂ A large study reports that one in nine patients

hospitalized with heart failure received not only diuretics in their first 2 days of hospitalization, but also IV fluids. Additionally, patients who received IV fluids were more likely to later be admitted to critical care, be intubated, have renal-replacement therapy, or die in the hospital. The study is published in the February 2015 issue of JACC: Heart Failure.

ÂÂ In children with comorbid conditions, invasive

pneumococcal disease causes higher morbidity and mortality, reported a surveillance study published online in Pediatrics.

ÂÂ Pregnancy outcomes for kidney recipients are

similar whether the transplant was done in childhood or adulthood, suggests a new study published online in JAMA Pediatrics.

ÂÂ Most

patients presenting to the emergency department (ED) with syncope or dizziness may not benefit from a computed tomography (CT) scan of the head unless they are older than 60 years, have a focal neurologic deficit or have a history of recent head trauma, researchers have found. Myles Mitsunaga, MD, resident at John A. Burns School of Medicine, University of Hawaii, Honolulu, and Hyo-Chun Yoon, MD, from the Department of Diagnostic Imaging, Kaiser Foundation Hospital, Honolulu, studied the clinical factors that potentially predict acutely abnormal head CT findings and hospital admission.

ÂÂ Curcumin, a constituent of the turmeric rhizome,

is a bright-yellow polyphenolic compound, chemically diferuloylmethane. Preliminary

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AROUND THE GLOBE research suggests that turmeric and curcumin have a variety of pharmacologic properties, including anti-inflammatory, antitumor and antimicrobial activities. Some research suggests that curcumin might have neuroprotective and antioxidant activity, which might be useful for treatment of seizures. Studies in several animal models have shown that curcumin can reduce seizures that have been induced chemically or electrically.

subtherapeutic dosage (19.0%) and nonadherence (17.2%). ÂÂ Ebola vaccine trial opens in Liberia: A large

approved the empagliflozin/linagliptin combination as adjunctive treatment to diet and exercise for adults with type 2 diabetes. The tablets contain 10 or 25 mg of empagliflozin and 5 mg of linagliptin.

clinical trial to assess the safety and efficacy of two experimental vaccines to prevent Ebola virus infection is now open to volunteers in Liberia. The trial is being led by a recently formed Liberia-U.S. clinical research partnership and is sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. The Partnership for Research on Ebola Vaccines in Liberia or PREVAIL, a Phase 2/3 study, is designed to enroll approximately 27,000 healthy men and women aged 18 years and older.

ÂÂ Even just a little jogging done at a very easy

ÂÂ A new study shows how lurking pools of dormant

ÂÂ The US Food and Drug Administration has

pace helps in increasing longevity, suggests a new analysis. However, too much running, done more frequently, for longer periods or at a greater intensity, was not associated with any additional mortality benefits compared with sedentary nonrunners. The report is published February 2 in the Journal of the American College of Cardiology.

HIV may hold the secret to curing the disease. Researchers, in their report published in the journal Cell, state that HIV cure possibly lies in targeting dormant virus reserves.

ÂÂ All adults aged 65 and above should now have

are at heightened risk for a number of long-term adverse cardiovascular, metabolic, psychological, oncologic and reproductive health consequences, reported a new study published online in the Journal of Clinical Endocrinology & Metabolism.

the 13-valent pneumococcal conjugate vaccine (PCV13) in addition to the 23-valent pneumococcal polysaccharide vaccine (PPSV23) to protect against pneumococcal infection, suggests the 2015 Advisory Committee on Immunization Practices (ACIP) Recommended Immunization Schedule for adults being published in Annals of Internal Medicine.

ÂÂ The more boxers and martial arts practitioners

ÂÂ An oral supplement containing arginine, zinc and

experience head trauma, the more likely they are to have lower brain volume, particularly caudate and thalamus volume, suggests a new study published online in the British Journal of Sports Medicine.

antioxidants seems to improve healing of mild-tosevere pressure ulcers in malnourished patients, suggests an article published in Annals of Internal Medicine.

ÂÂ Two-thirds of medication-related visits (MRVs) to

ÂÂ The US Food and Drug Administration (FDA) has

ÂÂ Women with polycystic ovary syndrome (PCOS)

the emergency room by pediatric patients were deemed preventable, and the most common reason for those MRVs was an adverse drug reaction in a prospective observational study. Peter Zed, BSc, PharmD, of the University of British Columbia in Vancouver, and colleagues, reported that 65% of pediatric ER visits were defined as preventable “if drug treatment or lack thereof was inconsistent with current best practice.” Medication-related visits were most frequently associated with adverse drug reactions (26.4%) followed by

approved a new formulation of hydrocodone with abuse-deterrent properties. The product will be formulated with BeadTek, a technology designed to provide abuse-deterrent properties without changing the release properties of hydrocodone.

ÂÂ A

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new report published in Mayo Clinic Proceedings advises people to replace processed foods containing high levels of added sugars and fructose with whole foods such as fruit and vegetables. Added fructose has been identified as major driver of type 2 diabetes ‘epidemic’.

MEDILAW

Drugs and Ethical Advertising KK AGGARWAL

What is the procedure of lodging a complaint with the ASCI?

a) the procurement of miscarriage in women or prevention of conception in women; or

Any individual or company can lodge a complaint with the following details:

b) the maintenance or improvement of the capacity of human beings for sexual pleasure; or

ÂÂ

Product/company about which there is a complaint

c) the correction of menstrual disorder in women; or

ÂÂ

TV channel and program in which the advertisement appeared or

ÂÂ

Newspaper, magazine, advertisement appeared

ÂÂ

Nature of complaint, i.e., whether the claim is false, misleading or the advertisement is found to be offensive, indecent and vulgar.

d) the diagnosis, cure, mitigation, treatment or prevention of any disease, disorder or condition specified in the Schedule, or any other disease, disorder or condition (by whatsoever name called) which may be specified in the rules made under this Act;

outdoor

where

the

When a complaint is received about an advertisement, the ASCI gives an opportunity to the advertiser to review the advertisement for its likely impact on the sensibilities of individual viewers of TV, or readers of press publications. The advertiser is given a notification of a complaint received at ASCI with the details as above and is asked to respond within a short time span. If the complaint is withheld by the ASCI, then it seeks assurance from the advertiser to withdraw or modify the advertisement. If the assurance is not received, then the concerned agency (in this case, the Medical Council of India) is advised that the advertisement contravenes the ASCI code.

What is the law on advertisement of treatment or cure? The Drugs and Magic Remedies (Objectionable Advertisements) Act, 1954 prohibits the advertisement of certain drugs for treatment of some diseases. 3. Prohibition of advertisement of certain drugs for treatment of certain diseases and disorders: Subject to the provisions of this Act, no person shall take any part in the publication of any advertisement referring to any drug in terms which suggest or are calculated to lead to the use of that drug for–

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

Provided that no such rule shall be made except– (i) In respect of any disease, disorder or condition which requires timely treatment in consultation with a registered medical practitioner or for which there are normally no accepted remedies, and (ii) After consultation with the Drugs Technical Advisory Board constituted under the Drugs and Cosmetics Act, 1940 (23 of 1940) and, if the Central Government considers necessary, with such other persons having special knowledge or practical experience in respect of Ayurvedic or Unani systems of medicines as that Government deems fit. 4. Prohibition of misleading advertisements relating to drugs: Subject to the provisions of this Act, no person shall take any part in the publication of any advertisement relating to a drug if the advertisement contains any matter which– a) directly or indirectly gives a false impression regarding the true character of the drug; or b) makes a false claim for the drug; or c) is otherwise false or misleading in any material particular. 5. Prohibition of advertisement of magic remedies for treatment of certain diseases and disorders: No person carrying on or purporting to carry on the profession of administering magic remedies shall take any part in the publication of any advertisement referring to any magic remedy which directly or indirectly claims to be efficacious for any of the purposes specified in Section 3.

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MEDILAW The Act has identified 54 diseases (see below) for which it prohibits any advertisement suggesting the use of any drug for diagnosis, cure, mitigation, treatment or prevention.

26. Heart diseases

Diseases and ailments (by whatever Name described) which a drug may not purport to prevent or cure or make claims to prevent or cure

29. Hysteria

1. Appendicitis 2. Arteriosclerosis 3.

Blindness

Blood poisoning

Bright’s disease

Cancer

Cataract

8. Deafness 9.

Diabetes

10. Diseases and disorders of the brain 11. Diseases and disorders of the optical system 12. Diseases and disorders of the uterus 13. Disorders of menstrual flow 14. Disorders of the nervous system 15. Disorders of prostatic gland 16. Dropsy 17. Epilepsy 18. Female diseases in general 19. Fevers (in general) 20. Fits 21. Form and structure of the female bust 22. Gallstones, kidney stones and bladder stones 23. Gangrene 24. Glaucoma 25. Goiter

27. High or low blood pressure 28. Hydrocele 30. Infantile paralysis 31. Insanity 32. Leprosy 33. Leukoderma 34. Lockjaw 35. Locomotor ataxia 36. Lupus 37. Nervous debility 38. Obesity 39. Paralysis 40. Plague 41. Pleurisy 42. Pneumonia 43. Rheumatism 44. Ruptures 45. Sexual impotence 46. Small pox 47. Stature of persons 48. Sterility in women 49. Trachoma 50. Tuberculosis 51. Tumors 52. Typhoid fever 53. Ulcers of the gastrointestinal tract 54. Venereal diseases, including syphilis, gonorrhea, soft chancre, venereal granuloma and lymphogranuloma

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INSPIRATIONAL STORY

Be a Good Friend One day, when I was a freshman in high school, I saw that a kid from my class was walking home from school. His name was Kyle. It looked like he was carrying all of his books. I thought to myself, “Why would anyone bring home all his books on a Friday? He must really be a nerd.” I had quite a weekend planned (parties and a football game with my friends tomorrow afternoon) so I shrugged my shoulders and went on. As I was walking, I saw a bunch of kids running toward him. They ran at him, knocking all his books out of his arms and tripping him so he landed in the dirt. His glasses went flying, and I saw them land in the grass about 10 feet from him. He looked up and I saw this terrible sadness in his eyes. My heart went out to him. So, I jogged over to him as he crawled around looking for his glasses, and I saw a tear in his eye. As I handed him his glasses, I said, “Those guys are jerks. They really should get lives.” He looked at me and said, “Hey thanks!” There was a big smile on his face. It was one of those smiles that showed real gratitude. I helped him to pick up his books, and asked him where he lived. As it turned out, he lived near me, so I asked him why I had never seen him before. He said he had gone to private school until now. I had never hung out with a private school kid before. We talked all the way home, and I carried some of his books. He turned out to be a pretty cool kid.

knew that we would always be friends, that the miles would never be a problem. He was going to be a doctor and I was going for business on a football scholarship. Kyle was valedictorian of our class. I teased him all the time about being a nerd. He had to prepare a speech for graduation. I was so glad it wasn’t me having to get up there and speak. Graduation day, I saw Kyle. He looked great. He was one of those guys who really found himself during high school. He filled out and actually looked good in glasses. He had more dates than I had and all the girls loved him. Boy, sometimes I was jealous! Today was one of those days. I could see that he was nervous about his speech. So, I smacked him on the back and said, “Hey, big guy, you’ll be great!” He looked at me with one of those looks (the really grateful one) and smiled. “Thanks!” he said. As he started his speech, he cleared his throat, and began: “Graduation is a time to thank those who helped you make it through those tough years. Your parents, your teachers, your siblings, may be a coach…but mostly your friends… I am here to tell all of you that being a friend to someone is the best gift you can give them. I am going to tell you a story.” I just looked at my friend with disbelief as he told the story of the first day we met. He had planned to kill himself over the weekend. He talked of how he had cleaned out his locker so his mom wouldn’t have to do it later and was carrying his stuff home.

I asked him if he wanted to play a little football with my friends, he said yes. We hung out all weekend and the more I got to know Kyle, the more I liked him, and my friends thought the same of him. Monday morning came and there was Kyle with the huge stack of books again. I stopped him and said, “Boy, you are gonna really build some serious muscles with this pile of books everyday!”

He looked hard at me and gave me a little smile. “Thankfully, I was saved. My friend saved me from doing the unspeakable.” I heard the gasp go through the crowd as this handsome, popular boy told us all about his weakest moment.

He just laughed and handed me half the books. Over the next 4 years, Kyle and I became best friends. When we were seniors we began to think about college. Kyle decided on Georgetown and I was going to Duke. I

Never underestimate the power of your actions. With one small gesture you can change a person’s life…for better or for worse. God puts us all in each other’s lives to impact one another in some way.

I saw his Mom and dad looking at me and smiling that same grateful smile. Not until that moment did I realize its depth.

■■■■

Indian Journal of Clinical Practice, Vol. 25, No. 9, February 2015

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LIGHTER READING

LAUGH-A-WHILE

Lighter Side of Medicine GET YOURSELF A TRAIN! Dear Dad, Berlin is wonderful, people are nice and I really like it here, but Dad, I am bit ashamed to arrive to my college with my Gold Mercedes, when all my Teachers travel by train. Your Son, Nasser. Sometime later Nasser gets reply to his e-mail from his Dad:

The boat guy said nothing. After a while the boat developed a fault and started sinking. The boatman then asked the tourist, “Do you know Swimology and Escapology from Crocodiology?” The tourist said, “No!” The boat guy replied, “Well, today you will Drownology and Crocodiology will eat you. I will not Helpology and you will Dieology because of your Badmouthology.”

20 million dollars transferred to your account, please stop embarrassing us, go and get yourself a train too. VISITING A BARBER A man enters a barber shop for a shave. While the barber is foaming him up, he mentions the problems he has getting a close shave around the cheeks. “I have just the thing,” says the barber taking a small wooden ball from a nearby drawer. “Just place this between your cheek and gum.” The client places the ball in his mouth and the barber proceeds with the closest shave the man has ever experienced.

QUOTES

Loving son,

“It does not matter how slowly you go as long as you do not stop.” –Confucius

“The best thing about dreams is that fleeting moment, when you are between asleep and awake, when you don’t know the difference between reality and fantasy, when for just that one moment you feel with your entire soul that the dream is reality, and it really happened.” –David Brinkley

Dr. Good and Dr. Bad SITUATION: A patient with Mediclaim policy hospitalization for dental treatment.

required

After a few strokes the client asks in garbled speech. “And what if I swallow it?” “No problem,” says the barber. “Just bring it back tomorrow like everyone else does.”

It will not be covered

It will be covered

NEVER BE RUDE TO ANYONE

The tourist then said, “What the hell do you know on the face of this Earth? You will die of illiteracy!”

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Indian Journal of Clinical Practice, Vol. 25, No. 9, February 2015

©IJCP Academy

An American tourist asked a boat guy in Zanzibar, “Do you know Biology, Psychology, Geography, Geology or Criminology?” The boat guy said, “No. I don’t know any of these.” LESSON: Clause 4.7 excludes dental treatment/surgery unless requiring hospitalization. KK Aggarwal

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.

Indian Journal of Clinical Practice, Vol. 25, No. 9, February 2015

895

Discussion –

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

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

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

Do not use clips/staples on photographs and artwork.

–

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

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

Books

5. Special requests _____________________________

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

Indian 1.____________Foreign 1.________________

Articles in Books

2.____________ 2.________________

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

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. –

896

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. 9, February 2015

6. Suggestions for reviewers (name and postal address)

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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