Ijcp web march 2016

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Volume 26, Number 10

March 2016, Pages 901–1000

Peer Reviewed Journal

yy American Family Physician yy Cardiology yy Community Medicine yy Drugs yy Internal Medicine yy Obstetrics and Gynecology yy Pediatrics

an i c i ys ians

yy Medilaw

Phly Physic y l mi ami

yy Conference Update

Fademy of F n ica Aca

yy Around the Globe

er merican m A eA

yy Inspirational Story

ingurnal of th t a or d Jo

yy Lighter Reading

rp-reviewe o c In eer AP

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IJCP Group of Publications Dr Chopra Prof. of Medicine & Faculty Dean Harvard Medical School Group Consultant Editor Dr Deepak Chopra Chief Editorial Advisor

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

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

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

Volume 26, Number 10, March 2016 FROM THE DESK OF THE GROUP EDITOR-IN-CHIEF

905 New Hands-only CPR Guidelines

KK Aggarwal

AMERICAN FAMILY PHYSICIAN

906 Potassium Disorders: Hypokalemia and Hyperkalemia

Anthony J. Viera, Noah Wouk

916 Practice Guidelines 918 Photo Quiz CARDIOLOGY

920 Gender Differences in Prognosis of Systolic Heart Failure in Patients Undergoing Bypass Surgery

PS Gandhi, RK Goyal, AR Jain, SB Mallya, VM Gupta, DS Shah, BR Trivedi, NA Shastri, CB Mehta, KA Jain, NS Bhavsar, UJ Shah

COMMUNITY MEDICINE

927 Prevalence of Inducible Clindamycin Resistance among Staphylococci in an Urban Tertiary Care Hospital of Jalandhar, Punjab

Sheevani, Jaspal Kaur, Kailash Chand, Gomty Mahajan, Shashi Chopra

DRUGS

933 Recommendation Patterns by Various Practitioners in the Treatment of Colicky Abdominal Pain in India

Mukesh Gabhane, Lisa Braganza, Srirupa Das, Vishal Vaidya

938 Diclofenac: Dose and Formulation Based Protocol in Pain Management

HR Jhunjhunwala, Rajiva Gupta, MS Ghosh, Vikas Agashe, GPV Subbaiah, GVS Moorthy, AK Jain, JC Chowdhury, Vikas Gupta, Venkatramana Nagire, Amit Thavkar, Apurva Gawai

INTERNAL MEDICINE

947 Amebiasis Mimics Malignancy in the Transverse Colon and Transpires in Liver Abscess

BV Nagabhushana Rao, BVS Raman, Sailesh Modi, M Umamaheswara Rao

954 Clinical Pearls: Iron-deficiency Anemia

Bharat J Parmar, Jwal Doctor

957 Clinico-hematological Profile of Kala-azar in Nonendemic Area: A Case Series

Praveen Kumar, Kalpana Chandra

OBSTETRICS AND GYNECOLOGY

961 A Study to Evaluate Safety and Efficacy of Postpartum Intrauterine Contraceptive Device Insertion

Mamta Rani, Parneet Kaur, Khushpreet Kaur, Gurdip Kaur, Satinder Pal Kaur

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

965 Complete Hydatidiform Mole Coexisting with a Live Fetus in Twin Pregnancy: A Case Report

Avishek Bhadra, Pallab Kumar Mistri, Bandana Biswas, Shilpa Kumari, Sudip Mukherjee

PEDIATRICS

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

968 Constriction Band Syndrome

Copyright 2016 IJCP Publications Ltd. All rights reserved.

Sudivya Sharma, Pradnya Sawant

970 An Approach to Diagnosis of Skeletal Dysplasias in Children

The copyright for all the editorial material contained in this journal, in the form of layout, content including images and design, is held by IJCP Publications Ltd. No part of this publication may be published in any form whatsoever without the prior written permission of the publisher.

Manab Narayan Baruah

MEDILAW

977 Issues Involving Medical Negligence

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.

KK Aggarwal

CONFERENCE UPDATE

980 53rd Annual Conference of Indian Academy of Pediatrics (PEDICON 2016) 983 46th Annual Conference of the Indian Society of Nephrology (ISNCON 2015) 986 56th Annual Conference of Indian Society of Gastroenterology (ISGCON 2015) AROUND THE GLOBE

991 News and Views INSPIRATIONAL STORY

994 Only One Move LIGHTER READING

995 Lighter Side of Medicine

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

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FROM THE DESK OF THE GROUP EDITOR-IN-CHIEF

Prof. Dr KK Aggarwal

Group Editor-in-Chief IJCP Group, eMedinewS and eMediNexus

New Hands-only CPR Guidelines ÂÂ

Bystanders should initiate compression-only CPR 10.

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Chest compression should be done at the rate of 100-120 per minute (updated from “at least” 100 per minute).

ÂÂ

Compression depth should be 2-2.5 inches (upper limit added) but no more than 6 cm.

ÂÂ

Compression time should be maximized.

ÂÂ

After each compression allow the chest to recoil completely and minimize interruptions in compressions.

ÂÂ

Feedback devices may be used to optimize compression rate and depth.

ÂÂ

The bystander who is trained and able should assess the collapsed victim rapidly to determine if the victim is unresponsive and not breathing normally and then immediately alert the emergency services.

ÂÂ

The victim who is unresponsive and not breathing normally is in cardiac arrest and requires CPR.

ÂÂ

The emergency medical dispatcher plays an important role in the early diagnosis of cardiac arrest, the provision of dispatcher-assisted CPR (also known as telephone CPR), and the location and dispatch of an automated external defibrillation (AED).

ÂÂ

Social media may be used to summon rescuers to perform CPR.

ÂÂ

Bystanders and emergency medical dispatchers should be suspicious of cardiac arrest in any patient presenting with seizures and should carefully assess whether the victim is breathing normally.

ÂÂ

CPR providers should perform chest compressions for all victims in cardiac arrest.

ÂÂ

CPR providers trained and able to perform rescue breaths should combine chest compressions and rescue breaths.

ÂÂ

High-quality CPR remains essential to improving outcomes.

ÂÂ

When providing rescue breaths/ventilations spend approximately 1 second inflating the chest with sufficient volume to ensure the chest rises visibly. The ratio of chest compressions to ventilations remains 30:2.

ÂÂ

Do not interrupt chest compressions for more than 10 seconds to provide ventilations.

ÂÂ

Defibrillation within 3-5 minutes of collapse can produce survival rates as high as 50-70%. Early defibrillation can be achieved through CPR providers using public access and on-site AEDs. Public access AED programs should be actively implemented in public places that have a high-density of citizens.

ÂÂ

The adult CPR sequence can be used safely in children who are unresponsive and not breathing normally.

Chest compression depths in children should be at least one-third of the depth of the chest (for infants that is 4 cm, for children 5 cm).

ÂÂ

A foreign body causing severe airway obstruction is a medical emergency and requires prompt treatment with back blows and, if that fails to relieve the obstruction, abdominal thrusts. If the victim becomes unresponsive CPR should be started immediately whilst help is summoned.

Indian Journal of Clinical Practice, Vol. 26, No. 10, March 2016

905

AMERICAN FAMILY PHYSICIAN

Potassium Disorders: Hypokalemia and Hyperkalemia ANTHONY J. VIERA, NOAH WOUK

ABSTRACT Hypokalemia and hyperkalemia are common electrolyte disorders caused by changes in potassium intake, altered excretion, or transcellular shifts. Diuretic use and gastrointestinal losses are common causes of hypokalemia, whereas kidney disease, hyperglycemia, and medication use are common causes of hyperkalemia. When severe, potassium disorders can lead to life-threatening cardiac conduction disturbances and neuromuscular dysfunction. Therefore, a first priority is determining the need for urgent treatment through a combination of history, physical examination, laboratory, and electrocardiography findings. Indications for urgent treatment include severe or symptomatic hypo­kalemia or hyperkalemia; abrupt changes in potassium levels; electrocardiography changes; or the presence of certain comorbid conditions. Hypokalemia is treated with oral or intravenous potassium. To prevent cardiac conduction dis­turbances, intravenous calcium is administered to patients with hyperkalemic electrocardiography changes. Insulin, usually with concomitant glucose, and albuterol are preferred to lower serum potassium levels in the acute setting; sodium polystyrene sulfonate is reserved for subacute treatment. For both disorders, it is important to consider poten­tial causes of transcellular shifts because patients are at increased risk of rebound potassium disturbances.

Keywords: Hypokalemia, hyperkalemia, cardiac conduction disturbances, neuromuscular dysfunction, oral or intravenous potassium, intravenous calcium

P

otassium disorders are common. Hypokalemia (serum potassium level less than 3.6 mEq per L [3.6 mmol per L]) occurs in up to 21% of hospitalized patients and 2% to 3% of outpatients.1-3 Hyperkalemia (serum potas­ sium level more than 5 mEq per L [5 mmol per L] in adults, more than 5.5 mEq per L [5.5 mmol per L] in children, and more than 6 mEq per L [6 mmol per L] in neonates) occurs in up to 10% of hospitalized patients and approximately 1% of outpatients.4,5 The body’s plasma potassium concentration is closely regulated by a variety of mechanisms.

CAUSES OF HYPOKALEMIA Hypokalemia results from abnormal losses, transcellular shifts, or insufficient intake (Table 1).6-8 Abnormal losses are most com­ mon.9 Because the kidney can significantly lower potassium excretion in response to decreased intake, insufficient intake is rarely the sole cause of hypokalemia, but it often contrib­utes to hypokalemia in hospitalized patients.9

Renal Losses Diuretic use is a common cause of renally mediated hypokalemia.10 When given in the same dosage, chlorthalidone is more likely to induce hypokalemia than hydrochlorothia­zide, which is more often implicated because of its widespread use.11,12 Diureticinduced hypokalemia is dose-dependent and tends to be mild (3 to 3.5 mEq per L [3 to 3.5 mmol per L]), although it can be more severe when accompanied by other causes (e.g., gastroin­testinal [GI] losses).13

GI Losses GI losses are another common cause of hypokalemia, particularly among hospital­ized patients.9 The mechanism by which upper GI losses induce hypokalemia is indi­rect and stems from the kidney’s response to the associated alkalosis. As a portion of daily potassium is excreted in the colon, lower GI losses in the form of persistent diarrhea can also result in hypokalemia and may be accompanied by hyperchloremic acidosis.6 EVALUATION AND MANAGEMENT OF HYPOKALEMIA

ANTHONY J. VIERA, MD, MPH, is an associate professor in the Depart­ment of Family Medicine at the University of North Carolina at Chapel Hill School of Medicine.

NOAH WOUK, MD, is a resident in the Department of Family Medicine at the University of North Carolina at Chapel Hill School of Medicine.

Source: Adapted from Am Fam Physician. 2015;92(6):487-495.

906

Indian Journal of Clinical Practice, Vol. 26, No. 10, March 2016

General Principles Hypokalemia is often asymptomatic. Evalu­ation begins with a search for warning signs or symptoms warranting

AMERICAN FAMILY PHYSICIAN Table 1. Causes of Hypokalemia Abnormal losses Medications Diuretics Laxatives and enemas Corticosteroids Gastrointestinal losses Renal losses Osmotic diuresis Mineralocorticoid excess Types I and II renal tubular acidosis

Transcellular shifts (continued) Alkalosis Refeeding syndrome Increased beta2 adrenergic stimulation Delirium tremens Head injury Myocardial ischemia Thyrotoxicosis Familial hypokalemic periodic

Polydipsia

paralysis

Intrinsic renal transport defects

Inadequate intake

Hypothermia

Hypomagnesemia

Anorexia

Dialysis/plasmapheresis

Dementia

Transcellular shifts

Starvation

Medications

Total parenteral nutrition

Insulin overdose

Pseudohypokalemia

Beta2 sympathomimetics

Delayed sample analysis

Decongestants Xanthines

Amphotericin B

Significant leukocytosis (> 75,000 cells per mm3 [75.0 × 109 per L])

Verapamil intoxication Chloroquine intoxication Barium intoxication Cesium intoxication Note: Listed in approximate order of frequency.

Information from references 6 through 8.

urgent treatment (Figure 1).7,14 These include weakness or pal­pitations, changes on electrocardiography (ECG), severe hypokalemia (less than 2.5 mEq per L [2.5 mmol per L]), rapid-onset hypokalemia, or underlying heart disease or cirrhosis.7,15 Most cases of hypokalemiainduced rhythm disturbances occur in individuals with underlying heart disease.10 Early identification of transcellular shifts is important because management may differ. Identification and treatment of concurrent hypomagnesemia are also important because magnesium depletion impedes potassium repletion and can exacerbate hypokalemia-induced rhythm disturbances.16,17

History and Physical Examination A focused history includes evaluation for possible GI losses, review of medications, and assessment

for underlying cardiac comorbidities. A history of paralysis, hyper­thyroidism, or use of insulin or beta agonists suggests possible transcellular shifts leading to redistributive hypokalemia. The physical examination should focus on identifying cardiac arrhythmias and neurologic mani­festations, which range from generalized weakness to ascending paralysis.

Laboratory Analysis and ECG The diagnosis should be confirmed with a repeat serum potassium measurement. Other laboratory tests include serum glucose and magnesium levels, urine electrolyte and creatinine levels, and acid-base balance. The most accurate method for evaluating urinary potassium excre­tion is a 24-hour timed urine potassium collection; nor­mal kidneys excrete no more than 15 to 30 mEq per L (15 to 30 mmol per L) of potassium per day in response to hypokalemia. A more practical approach is calculation of the urine potassium-to-creatinine ratio from a spot urine specimen; a ratio greater than 1.5 mEq per mmol (13 mEq per g) is indicative of renal potassium wasting.18 If no cause is identified with the initial workup, assessment of thyroid and adrenal function should be considered.

Typically, the first ECG manifestation of hypokale­mia is decreased T-wave amplitude. Further progression can lead to ST-interval depression, T-wave inversions, PR-interval prolongation, and U waves. Arrhythmias associated with hypokalemia include sinus bradycar­ dia, ventricular tachycardia or fibrillation, and torsade de pointes.19 Although the risk of ECG changes and arrhythmias increases as serum potassium concentra­ tion decreases, these findings are not reliable because some patients with severe hypokalemia do not have ECG changes.20 TREATMENT OF HYPOKALEMIA The immediate goal of treatment is the prevention of potentially life-threatening cardiac conduction disturbances and neuromuscular dysfunction by raising serum potassium to a safe level. Further replenishment can pro­ceed more slowly, and attention can turn to the diagnosis and management of the underlying disorder.15 Patients with a history of congestive heart failure or myocardial infarction should maintain a serum potassium concen­tration of at least 4 mEq per L (4 mmol per L), based on expert opinion.15 Careful monitoring during treatment is essential because supplemental potassium is a common cause of hyperkalemia in hospitalized patients.21 The risk of

Indian Journal of Clinical Practice, Vol. 26, No. 10, March 2016

907

AMERICAN FAMILY PHYSICIAN Evaluation of Hypokalemia Potassium < 3.6 mEq per L (3.6 mmol per L) Check magnesium and replace if low Yes

Warning signs present?* No

Yes

Pseudohypokalemia?

Urgent therapy No further action

No Evidence of decreased intake or transcellular shifts?

Yes

No Urine potassiumto-creatinine ratio

≤ 1.5 mEq per mmol (13 mEq per g)

Treat according to etiology of transcellular shifts

> 1.5 mEq per mmol Renal losses

Extrarenal losses (e.g., gastrointestinal, inadequate intake, discontinued diuretic, transcellular shifts)

Elevated blood pressure or hypervolemia?

No Check acid-base status

Acidosis (e.g., types I and II renal tubular acidosis)

Variable (e.g., hypomagnesemia)

Yes

Evaluate for conditions associated with mineralocorticoid excess (e.g., primary and secondary hyperaldosteronism, renal artery stenosis, Cushing syndrome, congenital adrenal hyperplasia)

Alkalosis (e.g., emesis, diuretic use, Bartter and Gitelman syndromes†)

*Symptoms of hypokalemia, changes on electrocardiography, severe hypokalemia (less than 2.5 mEq per L [2.5 mmol per L]), rapid-onset hypokalemia, or underlying heart disease or cirrhosis. †Autosomal

recessive disorders of renal tubular transport.

Figure 1. Suggested algorithm for the evaluation of hypokalemia.

Information from references 7 and 14.

rebound hyperkalemia is higher when treating redis­ tributive hypokalemia. Because serum potassium concentration drops approximately 0.3 mEq per L (0.3 mmol per L) for every 100-mEq (100-mmol) reduction in total body potassium, the approximate potassium deficit can be estimated in patients with abnormal losses and decreased intake. For example, a decline in serum potassium from 3.8 to 2.9 mEq per L (3.8 to 2.9 mmol per L) roughly corresponds to a 300-mEq (300-mmol) reduc­tion in total body potassium.

Additional potassium will be required if losses are ongoing. Concomitant hypomag­ nesemia should be treated concurrently.

For hypokalemia associated with diuretic use, stopping the diuretic or reducing its dosage may be effective.15 Another strategy, if otherwise indicated to treat a comor­bid condition, is use of an angiotensin-converting enzyme (ACE) inhibitor, angiotensin receptor blocker (ARB), beta blocker, or potassium-sparing diuretic

908

Indian Journal of Clinical Practice, Vol. 26, No. 10, March 2016

because each of these drugs is associated with an elevation in serum potassium.

It is appropriate to increase dietary potassium in patients with low-normal and mild hypokalemia, particularly in those with a history of hypertension or heart disease.15 The effectiveness of increased dietary potassium is limited, however, because most of the potassium contained in foods is coupled with phosphate, whereas most cases of hypokalemia involve chloride depletion and respond best to supplemen­tal potassium chloride.6,15 Because use of intravenous potassium increases the risk of hyperkalemia and can cause pain and phlebitis, intravenous potassium should be reserved for patients with severe hypokalemia, hypokalemic ECG changes, or physical signs or symp­toms of hypokalemia, or for those unable to tolerate the oral form. Rapid correction is possible with oral potassium; the fastest results are

AMERICAN FAMILY PHYSICIAN likely best achieved by combin­ing oral (e.g., 20 to 40 mmol) and intrave­nous administration.22

Table 2. Causes of Hyperkalemia

When intravenous potassium is used, standard administration is 20 to 40 mmol of potassium in 1 L of normal saline. Correction typically should not exceed 20 mmol per hour, although higher rates using central venous catheters have been successful in emergency situations.22 Con­tinuous cardiac monitoring is indicated if the rate exceeds 10 mmol per hour. In chil­dren, dosing is 0.5 to 1.0 mmol per L per kg over one hour (maximum of 40 mmol).23 Potassium should not be given in dextrose-containing solutions because dextrose-stimulated insulin secretion can exacerbate hypokalemia.

Impaired excretion

Transcellular shifts

Acute kidney injury/chronic kidney disease

Insulin deficiency/resistance

Medications

Hypertonicity

Nonurgent hypokalemia is treated with 40 to 100 mmol of oral potassium per day over days to weeks. For the pre­vention of hypokalemia in patients with persistent losses, as with ongoing diuretic therapy or hyper­ aldosteronism, 20 mmol per day is usually sufficient.15 CAUSES OF HYPERKALEMIA Hyperkalemia is caused by excess potassium intake, impaired potassium excretion, or transcellular shifts (Table 2).8,24 The etiology of hyperkalemia is often multifactorial, with impaired renal function, medication use, and hyperglycemia as the most common contributors.25 Because healthy individuals can adapt to excess potassium consumption by increasing excretion, increased potas­sium intake is rarely the sole cause of hyper­kalemia, and underlying renal dysfunction is common.24

Impaired Potassium Excretion Renally mediated hyperkalemia results from derangement of one or more of the following processes: rate of flow in the distal nephron, aldosterone secretion and its effects, and functioning potassium secretory pathways. Hyperkalemia secondary to decreased distal delivery of sodium and water occurs with congestive heart failure, cirrhosis, acute kid­ney injury, and advanced chronic kidney disease. Conditions that cause hypoaldoste­ronism, such as adrenal insufficiency and hyporeninemic hypoaldosteronism (a com­mon complication of diabetic nephropathy and tubulointerstitial diseases), can lead to hyperkalemia.

Transcellular Shifts Various mechanisms promote the exit of potassium from cells or impede its entrance, thereby raising the plasma potassium concentration (redistributive

Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers

Acidosis Hyperglycemia Mannitol Medications

Nonsteroidal antiinflammatory drugs

Beta blockers

Potassium-sparing diuretics

Somatostatin

Trimethoprim Heparin Lithium Calcineurin inhibitors Decreased distal renal flow

Digoxin toxicity Succinylcholine Cell breakdown/leakage Hyperkalemic periodic paralysis Increased intake

Acute kidney injury/chronic kidney disease

Potassium supplementation

Congestive heart failure

Foods high in potassium*

Cirrhosis Hypoaldosteronism

Red blood cell transfusion Potassium-containing salt substitutes

Hyporeninemic hypoaldosteronism

Protein calorie supplements

Adrenal insufficiency

Certain forms of pica

Adrenocorticotropic hormone deficiency Primary hyporeninemia Primary renal tubular defects Sickle cell disease Systemic lupus erythematosus Obstructive uropathy Hereditary tubular defects Amyloidosis

Penicillin G potassium Pseudohyperkalemia Hemolysis Tourniquet use Fist clenching Blood sample cooling Intravenous fluids with potassium Cell hyperplasia Significant leukocytosis (> 75,000 cells per mm3 [75.0 × 109 per L]) Erythrocytosis Thrombocytosis Familial pseudohyperkalemia

Note: Listed in approximate order of frequency. *Dietary-induced hyperkalemia usually involves concurrent renal insufficiency.

Information from references 8 and 24.

hyper­kalemia). Increased plasma osmolality, such as with uncontrolled diabetes mellitus, establishes a concentra­ tion gradient wherein potassium follows

Indian Journal of Clinical Practice, Vol. 26, No. 10, March 2016

909

AMERICAN FAMILY PHYSICIAN water out of cells. Relative insulin deficiency or insulin resistance, which also occurs in persons with diabetes, prevents potassium from entering cells. In response to acidosis, extracellular hydrogen is exchanged for intracellular potassium, although the net result is highly variable and depends in part on the type of acidosis; metabolic acidosis produces the greatest effect.26 Because 98% of total body potassium is intracellular, any process that increases cell turnover, such as rhabdomyolysis, tumor lysis syndrome, or red blood cell transfusions, can result in hyperkalemia.

Medication-induced Hyperkalemia Medication use is a common cause of hyperkalemia, particularly in patients with baseline renal dysfunction or hypoaldosteronism.27 Medicationinduced hyperkalemia is most often a result of the medication interfering with potassium excretion. Also, the administration of potassium to treat or prevent hypokalemia can inadver­tently cause hyperkalemia.19 ACE inhibitors contributed to one-half of all cases of drug-induced hyperkalemia in one sample, and approxi­mately 10% of outpatients who start an ACE inhibitor or an ARB will develop hyperkalemia within one year.23,28 The incidence of hyperkalemia associated with use of potassium-sparing diuretics has risen since adding spi­ronolactone to standard therapy was shown to reduce morbidity and mortality in patients with congestive heart failure.29 Dual treatment with an ACE inhibitor and an ARB increases the risk of harmful adverse effects, including hyperkalemia, and should be avoided.11 Other commonly used medications known to cause hyperkalemia include trimethoprim, heparin, beta blockers, digoxin, and nonsteroidal anti-inflammatory drugs.3 EVALUATION AND MANAGEMENT OF HYPERKALEMIA

General Principles As with hypokalemia, the immediate danger of hyperkalemia is its effect on cardiac conduction and muscle strength, and initial efforts should focus on determining the need for urgent intervention (Figure 2).14,30 The absence of symptoms does not exclude severe hyperkalemia, because hyperkalemia is often asymptomatic. Because of their increased risk of developing hyperkalemia, patients with underlying renal dysfunction merit special attention.22

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Indian Journal of Clinical Practice, Vol. 26, No. 10, March 2016

Evaluation of Hyperkalemia Potassium > 5 mEq per L (5 mmol per L) Yes

Warning signs present?* No Pseudohyperkalemia?

Urgent therapy (Figure 3)

Yes

No further action

No Evidence of increased intake or transcellular shifts?

Yes

No Urine sodium > 25 mEq per L (25 mmol per L)?

Treat according to etiology of transcellular shifts Yes

No Decreased distal renal flow (e.g., acute kidney injury/chronic kidney disease, congestive heart failure, cirrhosis)

Low serum aldosterone?

Yes

No Medication use, pseudohypoaldosteronism, amyloidosis, systemic lupus erythematosus, sickle cell disease, primary renal tubular defects

Low serum renin?

Yes

No Primary adrenal insufficiency Medication use (e.g., angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, heparin)

Hyperglycemia, primary renal tubular defects, medication use (e.g., nonsteroidal antiinflammatory drugs, beta blockers)

*Symptoms of hyperkalemia, changes on electrocardiography, severe hyperkalemia (greater than 6.5 mEq per L [6.5 mmol per L]), rapid-onset hyperkalemia, or underlying heart disease, cirrhosis, or kidney disease.

Figure 2. Suggested algorithm for the evaluation of hyperkalemia.

Information from references 14 and 30.

History and Physical Examination Severe hyperkalemia (more than 6.5 mEq per L [6.5 mmol per L]) can cause muscle weakness, ascending paralysis, heart palpitations, and paresthesias. Chronic kidney dis­ease, diabetes, heart failure, and liver disease all increase the risk of hyperkalemia. Clinicians should review patients’ medications to identify those known to cause hyperkalemia, and ask patients about the use of salt sub­stitutes that contain potassium.

The physical examina­tion should include assessment of blood pressure and intravascular volume status to identify potential causes of kidney hypoperfusion, which can lead to hyperkale­mia. Neurologic signs

AMERICAN FAMILY PHYSICIAN of hypokalemia include general­ized weakness and decreased deep tendon reflexes.11

kidney disease, heart disease, or cirrhosis who have a new case of hyperkalemia. Find­ings on ECG are neither sensitive nor spe­cific for hyperkalemia. Therefore, although ECG changes should trigger urgent treatment, treatment decisions should not be based solely on the presence or absence of ECG changes.32

Laboratory Analysis and ECG Repeat measurement of serum potassium can help identify pseudohyperkalemia, which is common and typi­cally results from potassium moving out of cells during or after sample collection.31 Other laboratory studies include measurement of serum blood urea nitrogen and creatinine, measure­ment of urine electrolytes and creatinine, and assessment of acid-base status. Fur­ther evaluation may include measurement of serum glucose to evaluate for hyperglycemia, and measurement of serum renin, aldosterone, and cortisol to further inves­tigate kidney and adrenal function.

Peaked T waves are the prototypical, and generally the earliest, ECG sign of hyperkalemia. Other ECG changes include P-wave flattening, PR-interval prolongation, widening of the QRS complex, and sine waves.19 Hyperkalemia-induced arrhythmias include sinus bradycardia, sinus arrest, ventricular tachycardia, ventricular fibrillation, and asystole.19 TREATMENT OF HYPERKALEMIA

ECG should be considered if the potas­sium level is greater than 6 mEq per L; if there are symptoms of hyperkalemia; if there is suspicion of rapid-onset hyperka­lemia; or among patients with underlying

General Principles The goals of acute treatment are to pre­vent potentially life-threatening cardiac conduction and neuromuscular

Management of Hyperkalemia Potassium > 5 mEq per L (5 mmol per L) Potassium 5 to 5.9 mEq per L (5 to 5.9 mmol per L) and no risk factors?*

Yes

No

Evaluate potential causes (Figure 2) Consider dietary modification Consider medication adjustments

Potassium > 6 mEq per L (6 mmol per L) or risk factors?*

Consider sodium polystyrene sulfonate†

ECG changes present?

Yes

No A

Administer insulin with glucose, with or without nebulized albuterol

Administer intravenous calcium in addition to A

Consider dialysis Serial ECG and continuous cardiac monitoring

Monitor serum potassium, glucose Potassium < 6 mEq per L? No Return to A

Yes Continue to monitor potassium Consider more continuous cardiac monitoring Evaluate potential causes (Figure 2) Consider dietary modifications Consider medication adjustments Consider sodium polystyrene sulfonate†

Note: See Table 3 for a summary of medication therapy for hyperkalemia. *Symptoms of hyperkalemia, rapid-onset hyperkalemia, or underlying heart disease, cirrhosis, or kidney disease. †Avoid in patients with or at risk of developing abnormal bowel function.

Figure 3. Suggested algorithm for the management of hyperkalemia.

(ECG = Electrocardiography.)

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AMERICAN FAMILY PHYSICIAN dis­turbances, shift potassium into cells, eliminate excess potassium, and resolve the underlying disturbance.

Patients with chronic hyperkalemia should be counseled to reduce dietary potassium. Although redistributive hyperkalemia is uncommon, a cautious approach is warranted because treatment may not involve attempts to eliminate potassium, and correction of the underlying problem can provoke rebound hypokalemia. Indications for prompt intervention are symptoms of hyperkalemia, changes on ECG, severe hyperkalemia (greater than 6.5 mEq per L), rapid-onset hyperkalemia, or underlying heart disease, cir­rhosis, or kidney disease.24,30,33-35 Potassium should be monitored often because patients are at risk of rede­ veloping hyperkalemia until the underlying disorder is corrected and excess potassium is eliminated.

Figure 3 is an algorithm for the management of hyperkalemia, and Table 322,30,36 summarizes medications used in the treat­ment of the condition.

Urgent Treatment Intravenous Calcium Intravenous calcium, which helps prevent lifethreatening conduction disturbances by stabilizing the cardiac muscle cell membrane, should be administered if ECG changes are present.24,25,35 Intravenous calcium has no effect on plasma potassium concentration. If after five minutes, follow-up ECG con­tinues to show signs of hyperkalemia, the dose should be repeated.37 Clinicians should be aware that intrave­nous calcium has a short duration, ranging from 30 to 60 minutes.

Insulin and Glucose The most reliable method for shifting potassium intracellularly is administration of glucose and insulin.

Typically, 10 units of insulin are administered, followed by 25 g of glucose to prevent hypoglycemia.37 Because hypoglycemia is a common adverse effect even with the provision of glucose, serum glucose levels should be monitored regularly. Patients with a serum glucose level of more than 250 mg per dL (13.9 mmol per L) typically do not require coadministra­tion of glucose.

Inhaled Beta Agonists Albuterol, a beta2 agonist, is an underutilized adjuvant for shifting potassium intracellularly.24,37 All forms of administration (i.e., inhaled, nebulized, and intravenous where available) are effective. It should be noted that the recommended dose of nebulized albuterol (10 to 20 mg) is four to eight times greater than the typical respiratory dose. There

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is an additive effect when albuterol is combined with insu­lin.38 Albuterol’s potassium-lowering effect is mitigated in some patients, particularly those with end-stage kid­ney disease; therefore, albuterol should not be used as monotherapy.30 Sodium Bicarbonate Although sodium bicarbonate is often used to treat hyperkalemia, the evidence to sup­port this use is equivocal, showing minimal to no ben­efit.39 Therefore, sodium bicarbonate should not be used as monotherapy. It may have a role as adjuvant therapy, particularly among patients with concurrent metabolic acidosis.24,39,40

Lowering Total Body Potassium Potassium can be removed via the GI tract or the kid­neys, or directly from the blood with dialysis.

Dialysis should be considered in patients with kidney failure or life-threatening hyperkalemia, or when other treatment strategies fail.23,37 Other modalities are not rapid enough for urgent treatment of hyperkalemia.39 Currently available cation exchange resins, typically sodium polystyrene sulfonate in the United States, are not beneficial for the acute treatment of hyperkalemia but may be effective in lowering total body potassium in the subacute setting.25,39 Because sodium polystyrene sulfonate can be constipating, many formulations include sorbitol for its laxative effects. However, case reports linking the concomitant use of sodium polystyrene sulfonate and sorbitol to GI injury prompted a U.S. Food and Drug Administration boxed warning.41,42 More recent reports implicate sodium poly­styrene sulfonate alone.43 Therefore, use of the drug with or without sorbitol should be avoided in patients with or at risk of abnormal bowel function, such as postopera­tive patients and those with constipation or inflamma­tory bowel disease.42 There is no evidence supporting the use of diuret­ics for the acute treatment of hyperkalemia. However, diuretics, particularly loop diuretics, may play a role in the treatment of some forms of chronic hyperkalemia, such as that caused by hyporeninemic Fludrocortisone is hypoaldosteron­ism.39,44 an option for hyperkalemia associated with mineralocorticoid deficiency, including hyporeninemic hypoaldosteronism.29 Strategies to prevent chronic hyperkalemia include instructing patients to eat a lowpotassium diet, discontinuing or adjusting medications, avoiding nonsteroidal anti-inflammatory drugs, and adding a diuretic if the patient has sufficient renal function.

AMERICAN FAMILY PHYSICIAN Table 3. Medications for the Treatment of Hyperkalemia Medication

Dosage

Onset

Duration

Approximate Mechanism potassium-lowering effect

Cautions

Calcium

Calcium chloride, 10 mL of 10% solution IV over 5 to 10 minutes, or calcium gluconate, 30 mL of 10% solution IV over 5 to 10 minutes

Immediate

30 to 60 minutes

—

Stabilizes cardiac muscle cell membrane; no effect on serum potassium or total body potassium

May potentiate digoxin toxicity; calcium chloride can cause phlebitis and tissue necrosis

Insulin

Regular insulin, 15 minutes 10 units IV followed immediately by 50 mL of 50% glucose (25 g) IV

≥ 2 hours

0.7 to 1 mEq per L (0.7 to 1 mmol per L)

Shifts potassium into cells; no effect on total body potassium

May cause hypoglycemia; glucose is unnecessary if serum glucose level is > 250 mg per dL (13.9 mmol per L); additive effect when combined with albuterol

Albuterol

10 to 20 mg nebulized

30 minutes

≥ 2 hours

0.5 to 1 mEq per L (0.5 to 1 mmol per L)

Shifts potassium into cells; no effect on total body potassium

Can cause tachycardia and thus should be used with caution in patients with underlying heart disease; potassiumlowering effect not reliable in all patients; additive effect when combined with insulin

2 to 24 hours

Variable

Variable

Binds potassium in exchange for sodium; lowers total body potassium

Association with gastrointestinal complications, particularly when combined with sorbitol; should be avoided in patients at risk of abnormal bowel function

Acute treatment

Subacute treatment Sodium polystyrene sulfonate

Oral: 15 g, 1 to 4 times daily Rectal: 30 to 50 g every 6 hours in a retention enema

IV = Intravenously.

Information from references 22, 30, and 36.

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AMERICAN FAMILY PHYSICIAN REFERENCES 1. Paice BJ, Paterson KR, Onyanga-Omara F, Donnelly T, Gray JM, Law­son DH. Record linkage study of hypokalaemia in hospitalized patients. Postgrad Med J. 1986;62(725):187-191.

2. Lippi G, Favaloro EJ, Montagnana M, Guidi GC. Prevalence of hypo­kalaemia: the experience of a large academic hospital. Intern Med J. 2010;40(4):315-316.

3. Liamis G, Rodenburg EM, Hofman A, Zietse R, Stricker BH, Hoorn EJ. Electrolyte disorders in community subjects: prevalence and risk factors. Am J Med. 2013;126(3):256-263.

4. Shemer J, Modan M, Ezra D, Cabili S. Incidence of hyperkalemia in hos­pitalized patients. Isr J Med Sci. 1983;19(7):659-661.

5. Paice B, Gray JM, McBride D, Donnelly T, Lawson DH. Hyperkalaemia in patients in hospital. Br Med J (Clin Res Ed). 1983;286(6372):1189-1192.

18. Kamel KS, Ethier JH, Richardson RM, Bear RA, Halperin ML. Urine elec­trolytes and osmolality: when and how to use them. Am J Nephrol. 1990;10(2):89-102.

19. Diercks DB, Shumaik GM, Harrigan RA, Brady WJ, Chan TC. Electro­ cardiographic manifestations: electrolyte abnormalities. J Emerg Med. 2004;27(2):153-160.

20. Weaver WF, Burchell HB. Serum potassium and the electrocardiogram in hypokalemia. Circulation.

1960;21:505-521.

21. Crop MJ, Hoorn EJ, Lindemans J, Zietse R. Hypokalaemia and subse­quent hyperkalaemia in hospitalized patients.

Nephrol Dial Transplant. 2007;22(12):3471-3477.

22. Kim GH, Han JS. Therapeutic approach to hypokalemia.

Nephron. 2002;92(suppl 1):28-32.

23. Ingram TC, Olsson JM. In brief: hypokalemia. Pediatr Rev. 2008; 29(9):e50-e51.

24. Evans KJ, Greenberg A. Hyperkalemia: a review.

J Intensive Care Med. 2005;20(5):272-290.

6. Gennari FJ. Hypokalemia. N Engl J Med. 1998;339(7): 451-458.

25. Fordjour KN, Walton T, Doran JJ. Management of hyperkalemia in hos­pitalized patients. Am J Med Sci. 2014;347(2):93-100.

7. Weiner ID, Wingo CS. Hypokalemia—consequences, causes, and cor­rection. J Am Soc Nephrol. 1997;8(7): 1179-1188.

26. Aronson PS, Giebisch G. Effects of pH on potassium: new explanations for old observations. J Am Soc Nephrol.

2011;22(11):1981-1989.

8. Gennari FJ. Disorders of potassium homeostasis.

Hypokalemia and hyperkalemia. Crit Care Clin.

2002;18(2):273-288.

9. Reid A, Jones G, Isles C. Hypokalaemia: common things occur com­monly - a retrospective survey. JRSM Short Rep. 2012;3(11):80.

10. Schulman M, Narins RG. Hypokalemia and cardiovascular disease. Am J Cardiol. 1990;65(10):4E-9E. 11. Greenberg A. Diuretic complications. Am J Med Sci. 2000;319(1):10-24.

12. Dhalla IA, Gomes T, Yao Z, et al. Chlorthalidone versus hydrochlorothia­zide for the treatment of hypertension in older adults: a population-based cohort study. Ann Intern Med. 2013;158(6):447-455.

13. Morgan DB, Davidson C. Hypokalaemia and diuretics: an analysis of publications. Br Med J. 1980;280(6218):905-908.

14. Mount DB, Zandi-Nejad K. Disorders of potassium balance. In: Taal MW, Chertow GM, Marsden PA, Brenner BM, Rector FC, eds. Brenner and Rector’s The Kidney.

Philadelphia, Pa.: Elsevier/Saunders; 2012.

15. Macdonald JE, Struthers AD. What is the optimal serum potassium level in cardiovascular patients? J Am Coll Cardiol. 2004;43(2):155-161.

16. Whang R, Whang DD, Ryan MP. Refractory potassium repletion. A conse­quence of magnesium deficiency. Arch Intern Med. 1992;152(1):40-45.

17. Millane TA, Ward DE, Camm AJ. Is hypomagnesemia arrhythmogenic? Clin Cardiol. 1992;15(2):103-108.

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27. Perazella MA. Drug-induced hyperkalemia: old culprits and new offend­ers. Am J Med. 2000;109(4):307-314.

28. Raebel MA. Hyperkalemia associated with use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. Car­diovasc Ther. 2012;30(3):e156-e166.

29. Gross P, Pistrosch F. Hyperkalaemia: again. Nephrol Dial Transplant. 2004;19(9):2163-2166.

30. Alfonzo A, Soar J, MacTier R, et al. Treatment of acute hyperka­laemia in adults. March 1, 2014. http://www. renal.org/guidelines/ joint-guidelines/treatment-ofacute-hyperkalaemia-in-adults#sthash. o9MgdJbw.dpbs.

Accessed September 1, 2014.

31. Smellie WS. Spurious 2007;334(7595):693-695.

hyperkalaemia.

BMJ.

32. Montague BT, Ouellette JR, Buller GK. Retrospective review of the frequency of ECG changes in hyperkalemia.

Clin J Am Soc Nephrol. 2008;3(2):324-330.

33. Maxwell AP, Linden K, O’Donnell S, Hamilton PK, McVeigh GE. Manage­ment of hyperkalaemia. J R Coll Physicians Edinb. 2013;43(3):246-251.

34. Charytan D, Goldfarb DS. Indications for hospitalization of patients with hyperkalemia. Arch Intern Med. 2000;160(11):1605-1611.

35. Soar J, Perkins GD, Abbas G, et al. European Resuscitation Council guidelines for resuscitation 2010 section 8.

Cardiac arrest in special cir­ cumstances: electrolyte abnormalities, poisoning, drowning, acciden­tal hypothermia, hyperthermia, asthma, anaphylaxis, cardiac surgery, trauma, pregnancy, electrocution. Resuscitation.

2010;81(10):1400-1433.

AMERICAN FAMILY PHYSICIAN 36. Lexicomp online. https://online.lexi.com/crlsql/servlet/ crlonline [sub­scription required]. Accessed September 23, 2014.

sodium polystyrene (Kayexalate) in sorbitol enemas: clinical and experimental support for the hypothesis.

Surgery. 1987;101(3):267-272.

37. Weisberg LS. Management of severe hyperkalemia. Crit Care Med. 2008;36(12):3246-3251.

42. U.S. Food and Drug Administration. MedWatch.

Kayexalate (sodium polystyrene sulfonate) powder.

January 2011. http://www.fda.gov/ Safety/MedWatch/ SafetyInformation/ucm186845.htm. Accessed Sep­tember 23, 2014.

38. Lens XM, Montoliu J, Cases A, Campistol JM, Revert L. Treatment of hyperkalaemia in renal failure: salbutamol v. insulin. Nephrol Dial Trans­plant. 1989;4(3):228-232.

39. Mahoney BA, Smith WA, Lo DS, Tsoi K, Tonelli M, Clase CM. Emer­gency interventions for hyperkalaemia.

Cochrane Database Syst Rev. 2005;(2):CD003235.

40. Allon M, Shanklin N. Effect of bicarbonate administration on plasma potassium in dialysis patients: interactions with insulin and albuterol. Am J Kidney Dis. 1996;28(4):508-514.

43. Harel Z, Harel S, Shah PS, Wald R, Perl J, Bell CM. Gastrointestinal adverse events with sodium polystyrene sulfonate (Kayexalate) use: a systematic review. Am J Med. 2013;126(3):264.e9-e24.

44. Sebastian A, Schambelan M, Sutton JM. Amelioration of hyper­chloremic acidosis with furosemide therapy in patients with chronic renal insufficiency and type 4 renal 41. Lillemoe KD, Romolo JL, Hamilton SR, Pennington LR, Burdick JF, Wil­liams GM. Intestinal necrosis due to tubular acidosis. Am J Nephrol. 1984;4(5):287-300.

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Practice Guidelines vaccine that can be administered without a needle and syringe.

ACIP RELEASES RECOMMENDATIONS FOR INFLUENZA VACCINATION, 2015-2016 The Centers for Disease Control and Preven­ tion’s Advisory Committee on Immuniza­tion Practices (ACIP) has released its yearly recommendations for routine influenza vac­cination in the 2015-2016 season.

Updates this year include the antigenic composition of seasonal influenza vaccines available in the United States; information on influenza vaccines expected to be available this season; updated information for determining the number of doses required for children six months to eight years of age; and recommendations for the use of live attenuated influ­enza vaccine (LAIV) when both LAIV and inactivated influenza vaccine are available, including the removal of 2014-2015 preferential recommendation for LAIV in healthy children two to eight years of age.

Routine annual influenza vaccination is recommended for all persons six months and older who do not have contraindications. Vaccination should ideally occur before the onset of influenza activity in the community.

Clinicians should offer vaccination by October, if possible, and continue through the influenza season.

Children six months to eight years of age who require two doses should receive their first dose as soon as possible after vaccine becomes available, and the second dose no earlier than four weeks later.

For the 2015-2016 influenza season, U.S.-licensed trivalent influenza vaccines will include hemagglutinin derived from an A/California/7/2009 (H1N1)-like virus, an A/Switzerland/9715293/2013 (H3N2)-like virus, and a B/Phuket/3073/2013-like (Yamagata lineage) virus.

Quadrivalent vac­cines will contain these viruses plus a B/Brisbane/60/2008-like (Victoria lineage) virus.

Influenza vaccines expected to be avail­able this season are listed in Table 1. New vaccines and updated vaccine indications include the following: ÂÂ

The trivalent inactivated influenza vac­cine Afluria has been approved for intra­muscular administration via a needle-free jet injector in persons 18 to 64 years of age. Afluria is the only inactivated influenza

Source: Adapted from Am Fam Physician. 2015;92(8):732-740.

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ÂÂ

The trivalent recombinant influenza vac­cine, Flublok, (for persons with egg allergy) is now indicated for all adults 18 years and older. It was previously approved only for persons 18 to 49 years of age.

ÂÂ

The quadrivalent intradermal inacti­vated influenza vaccine, Fluzone Intrader­mal, is now indicated for adults 18 to 64 years of age. This formulation is expected to replace the previously available trivalent intradermal inactivated vaccine.

Children six months to eight years of age require two doses of influenza vaccine dur­ing their first season of vaccination. Since the emergence of influenza A(H1N1)pdm09 (the 2009 H1N1 pandemic virus), recommendations for determining the number of doses needed have been based on whether a child previously received vaccine containing influ­enza A(H1N1) pdm09. Because this strain continues to circulate as the predominant H1N1 virus, and because of the inclusion of an A/California/7/2009(H1N1)-like virus in seasonal influenza vaccines available in the United States since the 2010-2011 season, separate consideration of receipt of vaccine doses containing this virus is no longer rec­ommended. Children six months to eight years of age who received at least two doses of trivalent or quadrivalent influenza vaccine before July 1, 2015, need only one dose this season. The two previous doses do not have to have been given during the same season or consecutive seasons.

LAIV and inactivated influenza vaccine have both been proven effective in children and adults. Although ACIP previously rec­ ommended that LAIV be given to healthy children two to eight years of age, recent evidence has shown that LAIV is no more effective than inactivated influenza vaccine. Therefore, LAIV is no longer recommended over inactivated vaccine; when both vac­cines are available in an age-appropriate formulation, either can be given.

Egg Allergy Severe allergic and anaphylactic reactions can occur in response to various components of influenza vaccine, but such reactions are rare.

All currently available influenza vac­cines except

AMERICAN FAMILY PHYSICIAN trivalent recombinant influenza vaccine and cell-culture–based inactivated influenza vaccine are prepared by propagation of virus in embryonated eggs.

For the 2015-2016 influenza season, ACIP recommends the following: ÂÂ

ÂÂ

Persons with a history of egg allergy who have experienced only hives after exposure to egg should receive inactivated influenza vaccine or trivalent recombinant influenza vaccine.

Recombinant vaccine can be used in adults 18 years and older who have no contraindications.

However, inactivated vaccine may also be used if it is administered by a clinician who is familiar with the poten­ tial manifestations of egg allergy and if the patient can be observed for signs of a reac­tion for at least 30 minutes after vaccination.

Persons with a history of symptoms such as angioedema, respiratory distress, light­headedness, or recurrent emesis after expo­sure to egg, or who required epinephrine or another emergency medical intervention, may receive recombinant influenza vaccine if they are at least 18 years of age and have no other contraindications. If recombinant vaccine is not available or the recipient is not within the indicated age range, inactivated influenza vaccine should be administered by a clinician experienced in the recognition and management of severe allergic reactions.

ÂÂ

Regardless of allergy history, all vac­cines should be administered in settings in which personnel and equipment for rapid recognition and treatment of anaphylaxis are available.

ÂÂ

Persons who can eat lightly cooked egg (e.g., scrambled egg) without reaction are unlikely to be allergic. Egg-allergic persons may tolerate egg in baked products (e.g., bread, cake). Tolerance to eggcontaining foods does not exclude the possibility of egg allergy. Egg allergy can be confirmed by a consistent medical history of adverse reac­tions to eggs and egg-containing foods, plus skin or blood testing for immunoglobulin E directed against egg proteins.

ÂÂ

In persons with no history of egg expo­sure who are suspected of being allergic on the basis of allergy testing, consultation with a clinician who has expertise in the man­agement of allergic conditions should be obtained before vaccination.

Alternatively, trivalent recombinant influenza vaccine can be administered if the patient is at least 18 years of age.

ÂÂ

A history of severe allergic reaction to influenza vaccine is a contraindication to future receipt of the vaccine, regardless of the component suspected of causing the reaction.

Note: For complete article visit: www.aafp.org/afp.

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AMERICAN FAMILY PHYSICIAN

Photo Quiz UNILATERAL SHOULDER WEAKNESS AND VISUAL DEFORMITY IN A YOUNG MILITARY RECRUIT A healthy 18-year-old man with no significant medical history presented with right shoul­der weakness and pain that had been present for one week. He had recently started a daily intensive physical fitness regimen similar to military boot camp. The week before his symp­toms began, he had a particularly grueling workout session that involved multiple repeti­tions of push-ups, inchworms, and bear crawls that the patient found difficult to complete.

He had weakness in his right arm and could not lift it over his head, and he had dull, achy pain in his right shoulder. He had no numbness or tingling. He noticed that his right shoulder blade was protruding com­pared with the left side.

The examination revealed an obvious deformity (Figure 1). He was unable to abduct his arm above 90 degrees with­ out assistance. He had full passive range of motion. Otherwise, his musculoskeletal and neurologic examination findings were normal, except for 4/5 strength in shoulder abduction.

Question Based on the patient’s history and physical examination findings, which one of the fol­lowing is the most likely diagnosis?

A. Amyotrophic lateral sclerosis.

B. Backpack palsy.

C. Hereditary neuropathy.

D. Monomelic amyotrophy.

E. Neuralgic amyotrophy.

Source: Adapted from Am Fam Physician. 2015;92(8):725-726.

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Figure 1.

Discussion The answer is C: hereditary neuropathy with liability to pressure palsies. This is a rare autosomal dominant neurop­athy characterized by recurrent mononeuropathies that are typically associated with compression or minor trauma. In this case, the patient had carried two large duffel bags over his shoulders and participated in intensive workouts prior to the symptoms. The patient had a total palsy of the right long thoracic nerve, which accounted for the significant scapular winging seen on examination.

Electromyography and nerve conduction studies also found slowed conduc­tion in multiple nerves bilaterally without an apparent clinical manifestation, which is common with this disorder.

This hereditary neuropathy is usually associated with a deletion in the gene encoding peripheral myelin protein 22, although the pathophysiology is not com­ pletely understood. Typical sites of focal nerve block are identified with nerve entrapment. However, mild slowing of nerve conduction velocities, prolonged dis­tal motor latencies, and reduced amplitudes in clini­cally unaffected nerves also occur. For most patients, the first mononeuropathy occurs before 40 years of age, and the typical pattern of abnormalities in nerve conduction studies is usually found in patients older than 15 years.1 Treatment focuses on avoiding repeated trauma to peripheral nerves, which may lead to addi­tional mononeuropathies.1

AMERICAN FAMILY PHYSICIAN Summary Table Condition

Characteristics

Amyotrophic lateral sclerosis

Upper and lower motor neuron dysfunction; combination of spasticity, decreased coordination, muscle weakness, atrophy, fasciculations, and decreased reflexes

Backpack palsy

Affects the shoulder girdle and elbow flexors, with sensory disturbances in the lateral shoulder and upper arm and in the radial forearm and hand; paresis, numbness, and paresthesias of the upper extremities after carrying a heavy backpack

Hereditary neuropathy with liability to pressure palsies

Mononeuropathy; localization in areas of frequent trauma or compression

Monomelic amyotrophy

Atrophy of a distal upper extremity, most often the hand or forearm, usually in the absence of sensory disturbances, tendon reflex abnormalities, and upper motor neuron signs

Neuralgic amyotrophy

Acute, severe pain in the shoulder or arm; pain is followed by muscle weakness, atrophy, and sensory loss; may be preceded by viral infection, immunization, or strenuous exercise, or in the perioperative or peripartum periods

Amyotrophic lateral sclerosis is characterized by both upper and lower motor neuron dysfunction. Clinical manifestations vary widely based on involvement of different motor neurons in the brain, brainstem, and spinal cord. One or more body regions may be affected by a combination of spasticity, decreased coordination, weakness, atrophy, fasciculations, and decreased reflexes. There is no pain or sensory disturbance.2 Backpack palsy is typically associated with activities that involve wearing a backpack, such as hiking,

moun­taineering, and military duty, and affects the shoulder girdle and elbow flexors, with sensory disturbances in the lateral shoulder and upper arm and in the radial forearm and hand. Symptoms commonly include pare­sis, numbness, and paresthesias of the upper extremities. The long thoracic nerve is most often affected.3 Monomelic amyotrophy typically presents in males in their late teens to early 20s. It has an insidious onset and leads to slow progression of unilateral weakness.

There is atrophy of a distal upper extremity, most often the hand or forearm. Sensory disturbances, tendon reflex abnormalities, and upper motor neuron signs are rare. Nerve conduction studies of clinically unaffected nerves may have abnormal results.4 Neuralgic amyotrophy presents as acute, severe pain in the shoulder or arm that lasts for days to weeks.

Weakness, atrophy, and sensory loss develop as the pain diminishes. Bilateral involvement of the brachial plexus occurs in 30% of patients, but clinical features are com­ monly asymmetric. Symptoms may be preceded by viral infections, immunizations, and strenuous exercise, or in the perioperative or peripartum period.5 REFERENCES 1. Farrar MA, Park SB, Krishnan AV, Kiernan MC, Lin CS. Axonal dysfunc­tion, dysmyelination, and conduction failure in hereditary neuropathy with liability to pressure palsies. Muscle Nerve. 2014;49(6):858-865.

2. Creemers H, et al. Prognostic factors for the course of functional status of patients with ALS. J Neurol.

2014;262(6):1407-1423.

3. Nylund T, et al. Recovery of brachial plexus lesions resulting from heavy backpack use. BMC Musculoskelet Disord. 2011;12:62.

4. Yoo SD, et al. Monomelic amyotrophy (hirayama disease) with upper motor neuron signs. Ann Rehabil Med. 2015;39(1):122-127.

5. Stutz CM. Neuralgic amyotrophy: Parsonage-Turner syndrome. J Hand Surg Am. 2010;35(10):2104-2106.

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CARDIOLOGY

Gender Differences in Prognosis of Systolic Heart Failure in Patients Undergoing Bypass Surgery PS GANDHI*, RK GOYAL*, AR JAIN†, SB MALLYA†, VM GUPTA†, DS SHAH†, BR TRIVEDI†, NA SHASTRI†, CB MEHTA†, KA JAIN†, NS BHAVSAR†, UJ SHAH*

ABSTRACT Epidemiological studies, although relatively sparse, have suggested sex-related differences in the incidence and the prognosis of systolic heart failure (HF). The present study was carried out to compare the gender-based differences in prevalence and prognosis of HF in Indian patients undergoing coronary artery bypass grafting (CABG). Patients presented with systolic HF were included. They were divided in to two groups- Group I included female patients and Group II included male patients. Out of total 293 patients having systolic dysfunction undergoing CABG, 265 were males and 28 were female patients. At the time of hospitalization, female patients were found to have more preserved left ventricular (LV) function as revealed from baseline LV ejection fraction (LVEF) which was significantly greater (p < 0.05) in females (32.58 ± 1.09%) as compared to males (27.92 ± 0.39%). Further, LV end diastolic and systolic diameters were significantly smaller in this group at the time of hospitalization for CABG. Ten weeks following CABG, the LV contractility was found to be increased significantly from baseline levels in both the groups. The improvement in LVEF was significantly greater in women (27.13 ± 4.03) as compared to men (22.25 ± 1.63).

Similarly, there was a significantly greater reduction in LV end diastolic as well as systolic diameters in female patients as compared to male patients. The alternation in New York Heart Association class was found to be improved in both the classes with respect to their baseline levels. Further, this improvement was significantly greater in women as compared to men. In conclusion, among patients with systolic HF undergoing CABG, women seem to have less systolic dysfunction as compared to men. Women also seem to have better prognosis in terms of improvement in LV contractility, reversal of LV remodeling and improvement in functional status following CABG as compared to men.

Keywords: Systolic heart failure, CABG, gender-based differences, prognosis

E

pidemiological studies have suggested sexrelated differences in the incidence and the prognosis of heart failure (HF).1,2 The populationbased Framingham Heart Study found that after the onset of symptomatic HF, the prognosis of women was significantly better than men.1,3 Epidemiological studies have observed important differences in survival between men and women with HF.1,3-6 Both the Framingham Study1 and National Health and Nutrition Examination Survey6 revealed lower mortality for women compared with men after the initial diagnosis

*Dept. of Pharmacology LM College of Pharmacy, Ahmedabad, Gujarat †The Heart Care Clinic, Ahmedbad, Gujarat Address for correspondence

Dr Purvi S Gandhi Dept. of Pharmacology LM College of Pharmacy Navrangpura, Ahmedabad - 380 009, Gujarat E-mail: p_s_gandhi@yahoo.com

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of HF. The Framingham Study1 revealed increased survival at 1, 2, 5 and 10 years in women as compared to that of men. The improved survival in women is more striking when viewed in the context that women were older at diagnosis. The improved survival in women remained after controlling for age and etiology. The Flolan International Randomized Survival Trial (FIRST) and subgroup analysis also demonstrated that women with advanced HF experience better survival than men including patients with a nonischemic etiology of HF.4 An interesting study based on incidences of HF hospitalizations and survival in California was carried out on the patterns according to race/ethnicity.7 The study analysis showed that the relative rates of hospitalization for heart failure in women on the basis of race/ethnicity is highest with African American women (1.7 times that of white) but is lowest with Asians (0.8 times). Same is the case with male gender too. However, data on the relative rates of Indian men and women with moderate to severe systolic HF are scanty. Therefore, we carried out the retrospective

CARDIOLOGY study to compare the gender-based differences in prevalence and prognosis of systolic HF in Indian patients of western region undergoing coronary artery bypass grafting (CABG).

METHODS

Study Design It was a retrospective study. The study was carried out at Sterling Hospital, Ahmedabad. The Institutional Review Board and the management were informed about the conduct of the study and collection of the data.

Patient Selection Patients presented with ischemic systolic HF [i.e. left ventricular ejection fraction (LVEF) ≤35% as diagnosed by two-dimensional (2D) echocardiography] and undergoing CABG were included. Patients of age above 70 years, previous or recent history of second or third degree atrioventricular block, renal failure (serum creatinine >2.6 mg%), hepatic dysfunction (SGPT >45 IU/L), cerebrovascular events, previous history of revascularization or valve replacement surgery were excluded from the study.

Groups of Patients: They were divided into two groups. Group I included male patients and Group II included female patients.

Assessment of Patients: Biographic, clinical as well as biochemical parameter evaluation carried out at the time of hospitalization for CABG was collected. Their functional status as per New York Heart Association (NYHA) class for HF and 2D echocardiogram and color Doppler measurements recorded at the time of hospitalization and following CABG were also collected.

2D Echocardiography and Color Doppler Assessment Parameters under consideration included LVEF, left ventricular (LV) end diastolic diameter (LVEDd), LV end systolic diameter (LVEDs) and mitral regurgitation (MR)-grade. 2D echocardiography and color Doppler assessment was performed using CarisPlus (Esaote, USA) machine by expert cardiologist. Recommendations of the American Society of Echocardiography were followed by the cardiologist for measurement of various parameters.8 The images were obtained from a patient lying on the left side in a supine position with the body elevated at about 30°. LVEF was assessed using

standard parasternal and apical views. The LVEDd and LVEDs were measured using four-chamber and twochamber views with apical approach at the level of papillary muscle. Severity of MR was found out using color Doppler assessment.

Biographic Characteristic Assessment Patients’ biographic characteristics, viz. age, height, body weight and associated risk factors such as habit of smoking, tobacco chewing or alcoholism and family history of ischemic heart disease (IHD) were recorded at the time of hospitalization for CABG.

Clinical Assessment Clinical assessment was done in presence of physician.

Patients’ hemodynamic parameters, i.e. pulse rate, systolic and diastolic blood pressure were measured in patient’s seating position with elbow at the level of heart.

They were evaluated for the coronary artery disease (CAD) characteristic using coronary angiography pattern carried out preoperatively. Functional status was determined as per NYHA class for HF.9 This system assigns patients to 1 of 4 functional classes depending on the degree of effort needed to elicit symptoms.10

Data Analysis The results were analysed by finding mean ± standard error of mean (SEM) for continuous variables and percentage of number (n) of patients for discrete variables. Chi-square test was used to find significant difference of discrete variables between two groups. For continuous variables under consideration, the results were analysed by applying Student’s “t” test to find the change in characteristics from baseline levels and to find the significant difference between two groups.

Difference, from baseline in the same group or between two groups, was considered statistically significant if the probability value (P) was found to be less than 0.05 (p < 0.05).

RESULTS Out of 293 patients, 265 were males and 28 were female patients. The biographic characteristics were similar in female and male groups. However, smoking and alcoholism—the disease worsening habits were found in men but not in women (Table 1).

Biochemical parameters and angiographic characteristics did not differ significantly between two groups (Tables 2 and 3). The hemodynamic status of the two group at the time of hospitalization and following CABG is shown in Table 4. Medicines used, in both

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CARDIOLOGY Table 1. Biographic Characteristics at the Time of Hospitalization

Table 3. Coronary Angiographic Characteristics of Patients

Parameter

Group I (Male)

Group II (Female)

Coronary Angiography

Number (%)

265 (90.44%)

28 (9.55%)

Age (years)

59.22 ± 0.57

60.38 ± 1.40

Body weight (kg)

66.56 ± 0.63

59.58 ± 2.00

Dyspnea

129 (48.67%)

18 (64.28%)

Fatigue

5 (1.88%)

2 (7.14%)

160 (60.37%)

19 (67.85%)

Symptoms

Chest pain

Smoking

60 (22.64%)*

0 (0%)

Tobacco

57 (21.5%)

1 (3.57%)

10 (3.77%)

0 (0%)

Diabetes mellitus

105 (39.62%)

14 (50%)

Hypertension

97 (36.60%)

15 (53.57%)

Family history of IHD

34 (12.83%)

7 (25%)

Past history of MI

139 (52.45%)

11 (39.28%)

Alcohol

Values are presented as mean ± SEM or no. (%) of patients; *Statistically significant as compared to female group (p < 0.05); IHD = Ischemic heart disease; MI = Myocardial infarction.

Table 2. Biochemical Parameters at Baseline Level Biochemical parameter

Group I (Male)

Group II (Female)

Blood sugar (mg%)

160.17 ± 4.09

186.85 ± 8.74

Serum urea (mg%)

33.69 ± 1.07

28.46 ± 2.18

Serum creatinine (mg%)

1.23 ± 0.03

1.12 ± 0.08

SGPT (IU/L)

30.41 ± 0.80

26.05 ± 1.86

Serum K+ (mEq/L)

4.87 ± 0.55

4.34 ± 0.09

136.57 ± 0.33

135.47 ± 0.52

Serum

Na+ (mEq/L)

Values are presented as mean ± SEM; SGPT = Serum glutamate pyruvate transaminase; K+ = Potassium; Na+ = Sodium.

groups following CABG is shown in Table 5. At the time of hospitalization for CABG, women presented with significantly preserved LV function than men in terms of LV contractility as evidenced by significantly greater (p < 0.05) LVEF at baseline level and significantly less dilated LVs (Table 6). MR-grade was also found

922

3 (1.13%)

1 (3.57%)

DVD

47 (17.73%)

5 (17.85%)

TVD

215 (81.13%)

22 (78.57%)

LMCA ≥50% stenosis

45 (16.98%)

6 (21.42%)

106 (40.0%)

8 (28.57%)

34 (12.83%)

0 (0%)

103 (38.86%)

5 (17.85%)

LAD stenosis LCx 100% RCA 100%

Habits

Indian Journal of Clinical Practice, Vol. 26, No. 10, March 2016

Group II (Female)

SVD

100%

Risk factors

Group I (Male)

Values are presented as no. (%) of patients; SVD = Single vessel disease; DVD = Double vessel disease; TVD = Triple vessel disease; LMCA = Left main coronary artery; LAD = Left anterior descending artery; LCx = Left circumflex artery; RCA = Right coronary artery.

Table 4. Hemodynamic Status at the Time of Hospitalization and Following CABG Parameters

Group I (Male)

Group II (Female)

Baseline

82.08 ± 1.00

83.89 ± 2.03

Post CABG

79.90 ± 1.57

81.85 ± 1.13

Baseline

124.33 ± 1.13

124.68 ± 3.40

Post CABG

122.42 ± 1.61

120.38 ± 2.68

Baseline

79.92 ± 0.62

78.36 ± 1.63

Post CABG

81.48 ± 1.70

80.43 ± 1.37

HR (beats/min)

SBP (mmHg)

DBP (mmHg)

Values are presented as mean ± SEM; HR = Heart rate; SBP = Systolic blood pressure; DBP = Diastolic blood pressure.

Table 5. Medicines Affecting Heart Function Used in Both the Groups Following CABG Medication

Group I (Male)

Group II (Female)

Digoxin

152 (57.36%)

13 (46.43%)

Diuretics

195 (73.58%)

18 (64.29%)

β-adrenoceptor blocker

130 (49.06%)

16 (57.14%)

Angiotensin-converting enzyme inhibitor

265 (100%)

28 (100%)

Values are presented as no. (%) of patients.

CARDIOLOGY Table 6. Gender Difference in 2D Echocardiography and Color Doppler Characteristics and NYHA Class for HF at Baseline and Following CABG Parameters 2D Echocardiography and color Doppler LVEF (%)

Group I (Male)

Group II (Female)

% change from baseline

% change from baseline

Baseline

27.92 ± 0.39

Post CABG

33.37 ± 0.51*

32.58 ± 1.09† 22.25 ± 1.63

40.7 ± 1.1†,*

27.13 ± 4.03†

LVEDd (mm) Baseline

54.7 ± 0.43

Post CABG

54.11 ± 0.46

50.93 ± 1.12† 1.55 ± 0.90

45.93 ± 0.98†,*

9.32 ± 1.84†

LVEDs (mm) Baseline

42.53 ± 0.49

Post CABG

41.46 ± 0.48

37.13 ± 1.52† 1.14 ± 1.03

34.14 ± 0.87†,*

4.22 ± 4.71†

MR-grade Baseline

0.66 ± 0.04

Post CABG

0.50 ± 0.03*

1.2 ± 0.11† 24.63 ± 3.05

0.7 ± 0.09*

30.0 ± 7.96

NYHA class for HF Baseline

3.0 ± 0.05

Post CABG

2.08 ± 0.03*

3.09 ± 0.17 20.04 ± 2.76

2.02 ± 0.18*

36.46 ± 5.64†

†Significantly

45 40 35 30 25 20 15 10 5 0

†* *

†

60

Baseline Post CABG †

†

50 LVEDd (mm)

LVEF (%)

different from male group (p < 0.05); *Significantly different from baseline (p < 0.05); CABG = Coronary artery bypass grafting; LVEF = Left ventricular ejection fraction; LVEDd = Left ventricular end-diastolic diameter; LVEDs = Left ventricular endsystolic diameter; MR = Mitral valve regurgitation; NYHA = New York Heart Association; HF = Heart failure.

†*

40 30 20

†

10 0 Male

Female

Male Female (% change) (% change)

Figure 1. Gender difference in LVEF at the time of hospitalization and after 10 weeks of CABG. †Significantly

different from male group (p < 0.05); *Significantly different from baseline (p < 0.05); LVEF = Left ventricular ejection fraction.

to be significantly greater at baseline in women when compared with that found in men. 2D echocardiography and color Doppler evaluation following 10 weeks of CABG showed that CABG produced a significant (p < 0.05) increase in LVEF in both the groups. Further,

Baseline Post CABG

Male

Female

Male Female (% change) (% change)

Figure 2. Gender difference in LV diastolic diameter at the time of hospitalization and after 10 weeks of CABG. †Significantly

different from male group (p < 0.05); *Significantly different from baseline (p < 0.05); LVEDd = Left ventricular enddiastolic diameter.

the improvement in LVEF was significantly greater in female patients as compared to male patients (Fig. 1). LVEDd and LVEDs were found to be significantly decreased after 10 weeks of CABG in females but not in males (Figs. 2 and 3). MR-grade was also found to be significantly improved from respective baseline in

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923

LVEDs (mm)

CARDIOLOGY

50 45 40 35 30 25 20 15 5 0 -5

†

Baseline Post CABG †*

DISCUSSION †

Male

Female

Male Female (% change) (% change)

Figure 3. Gender difference in LV systolic diameter at the time of hospitalization and after 10 weeks of CABG. †Significantly

different from male group (p < 0.05); *Significantly different from baseline (p < 0.05); LVEDs = Left ventricular endsystolic diameter.

Baseline Post CABG

40 35 MR-grade

30 25 20 15 10 5 0

* Male

† * Female

Male Female (% change) (% change)

Figure 4. Gender difference in MR-grade at the time of hospitalization and after 10 weeks of CABG. †Significantly

different from male group (p < 0.05); *Significantly different from baseline (p < 0.05); MR = Mitral regurgitation.

NYHA class for HF

Baseline Post CABG 45 40 35 25 20 15 10 5 0

†

* Male

* Female

Male Female (% change) (% change)

Figure 5. Gender difference in functional status at the time of hospitalization and after 10 weeks of CABG. †Significantly

different from male group (p < 0.05); *Significantly different from baseline (p < 0.05); NYHA = New York Heart Association; HF = Heart failure.

924

both the groups following CABG (Fig. 4). NYHA class for HF was significantly decreased from baseline levels in both the groups. Further, the improvement in NYHA class was found to be significantly greater in females as compared to that in male patients (Fig. 5).

Indian Journal of Clinical Practice, Vol. 26, No. 10, March 2016

Gender is an independent risk factor associated with differential presentation and outcomes of treatment in patients with HF. In our study, Indian female patients of western region with systolic HF were found to be less in number to have systolic dysfunction as compared to men. Ours is the first study carried out to find out gender differences in the prognosis of systolic HF in patients undergoing CABG. Earlier reports have shown that men are at higher risk of developing systolic HF than women.11,12 Furthermore, it is reported that over the past 50 years (i.e. from 1950 to 1999), the incidence of LV dysfunction has declined among women but not among men.13 In our study, we found that male patients were significantly greater in number for having habit of smoking. Although a direct correlation between smoking and development as well as prognosis of systolic dysfunction is not reported, it is listed as a one of the hazards for the development of systolic HF.7,9 Coexistence of other diseases such as hypertension (HT), diabetes mellitus (DM) and positive family history of IHD were found to be more in women making them more prone to LV systolic dysfunction.

It is reported that the presence of DM and HT raises the risk of developing LV dysfunction rather than just being primary comorbid conditions.14 DM has negative effect on prognosis of LV dysfunction.

Diabetic women with HF have shown poorer prognosis than diabetic men. DM eliminates the female coronary protection probably by reducing beneficial effects of estrogen.15 No report is available on relation between presence of family history of IHD and development of systolic dysfunction and HF. However, Schildkraut et al16 reported that the relation between presence of family history of IHD and development of CAD is stronger for women as compared to men. In the present study, women were found to be symptomatic with marginal worse functional status at the time of hospitalization for CABG. These findings are consistent to earlier reports of Vaccarino et al14 and Riedinger et al17 which suggested that female patients with HF are more symptomatic with worse capacity of physical activity as compared to males.

CARDIOLOGY Earlier studies have shown greater occurrence of myocardial infarction (MI) as underlying cause of LV systolic dysfunction in men as compared to women patients.18-19 Furthermore, ischemia and/or hibernation may lead to myocyte apoptosis which results in the progression of LV dysfunction without a clear ischemic event.20-22 However, myocyte death by apoptosis, necrosis or both following ischemia and LV remodeling is reduced in women.23,24 In our study, female patients presented with relatively more preserved LV function as LVEF was significantly greater and LV diameters (systolic as well as diastolic) were significantly smaller in the female group as compared to male group. Vaccarino et al14 also suggested that women presented with HF have more preserved LV systolic function than men. In our study, the improvement in LVEF was greater in female patients as compared to that found in males after 10 weeks of CABG. A controversy prevails with regard to survival rate on the basis of gender difference in patients undergoing CABG.25 The original Framingham data showed that the prognosis of women with HF was better than that of men.26 Kurlansky et al27 also reported favorable results in 327 women in terms of hospital mortality, low postoperative morbidity, excellent functional improvement and enhanced longterm of survival following CABG. Bypass Angioplasty Revascularization Investigation (BARI) trial has also shown that female sex is an independent predictor of improved 5-year survival after controlling multiple risk factors.28 In our study, CABG produced significant reversal of diastolic as well systolic indices of LV remodeling in female group as there was a significant reduction in diastolic and systolic diameters in female group but not in male patients. At the time of hospitalization for CABG, MR was found to be significantly worse in women as compared to men in our study. However, the reduction in MR from baseline following CABG was statistically significant in female group as well as in male group. This may be secondary to significant cardiac function improvement including that in LV size and shape in females.29 Improvement in functional capacity produced following CABG was also significantly greater in women than that found in men. Thus, overall postoperative improvement was significantly greater in Indian women than men.

Though no report is available on gender difference in improvement of the above-mentioned parameters following CABG, it is well-accepted that CABG in

general improves overall health status of patients with ischemic LV systolic dysfunction and HF.9,30 CONCLUSION In conclusion, out results suggest that among patients with systolic HF undergoing CABG, women seem to have less systolic dysfunction as compared to men.

Women also seem to have better prognosis in terms of improvement in LV contractility, reversal of LV remodeling and improvement in functional status following CABG as compared to men.

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1993;88(1):107-15.

2. Simon T, Mary-Krause M, Funck-Brentano C, Jaillon P. Sex differences in the prognosis of congestive heart failure: results from the Cardiac Insufficiency Bisoprolol Study (CIBIS II). Circulation. 2001;103(3):375-80.

3. McKee PA, Castelli WP, McNamara PM, Kannel WB. The natural history of congestive heart failure: the Framingham study. N Engl J Med. 1971;285(26):1441-6.

4. Adams KF Jr, Sueta CA, Gheorghiade M, Oâ&#x20AC;&#x2122;Connor CM, Schwartz TA, Koch GG, et al. Gender differences in survival in advanced heart failure: insights from the FIRST study. Circulation. 1999;99(14):1816-21.

5. Adams K, Dunlap S, Sueta C, Clarke SW, Patterson JH, Blauwet MB, et al. Relation between gender, etiology and survival in patients with symptomatic heart failure.

J Am Coll Cardiol. 1996;28(7):1781-8.

6. Schocken, DD, Arrieta MI, Leaverton PE, Ross EA. Prevalence in mortality rate of congestive heart failure in the United States. J Am Coll Cardiol. 1992;20(2):301-6.

7. Alexander M, Grumbach K, Remy L, Rowell R, Massie BM. Congestive heart failure hospitalizations and survival in California: patterns according to race/ethnicity.

Am Heart J. 1999;137(5):919-27.

8. Schiller NB, Shah PM, Crawford M, DeMaria A, Devereux R, Feigenbaum H, et al. Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. J Am Soc Echo. 1989;2(5):358-67.

9. Hunt SA, Abraham WT, Mancini DM, Chin MH, Michl K, Feldman AM, et al. American College of Cardiology/ American Heart Association 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult. Circulation. 2005;112(12):e154-235.

10. Brown L. Diseases of the Heart and Blood Vessels: Nomenclature and Criteria for Diagnosis, 6th Edition.

Boston: Mass; 1964. p. 114.

11. Diller PM, Smucker DR, David B, Graham RJ. Congestive heart failure due to diastolic or systolic dysfunction.

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CARDIOLOGY Frequency and patient characteristics in an ambulatory setting. Arch Fam Med. 1999;8(5):414-20.

12. Halm MA, Penque S. Heart failure in women. Prog Cardiovasc Nurs. 2000;15(4):121-33.

13. Levy D, Kenchaiah S, Larson MG, Benjamin EJ, Kupka MJ, Ho KKL, et al. Long-term trends in the incidence of and survival with heart failure. N Engl J Med. 2002;347(18):1397-402.

14. Vaccarino V, Chen Y-T, Wang Y, Radford MJ, Krumholz HM. Sex differences in the clinical care and outcomes of congestive heart failure in the elderly. Am Heart J. 1999;138(5):835-42.

15. Merz BNB, Juhnson BD, Bittner V, Hodgson TK, Berga SL, Braunstein GD, et al. Diabetes and estrogen deficiency in premenopausal women: the NHLBI-sponsored WISE study. Circulation. 2002;106(II):508.

16. Schildkraut JM, Myers RH, Cupples LA, Kiely DK, Kannel WB. Coronary risk associated with age and sex of parental heart disease in the Framingham study. Am J Cardiol.

1989;64(10):555-9.

17. Riedinger MS, Dracup KA, Brecht ML, Padilla G, Sarna L, Ganz PA. Quality of life in patients with heart failure: do gender differences exist? Heart Lung. 2001;30(2): 105-16.

18. Kannel WB. Epidemiological aspects of heart failure.

Cardiol Clin. 1989;7(1):1-9.

19. Kimmelstiel C, Goldberg RJ. Congestive heart failure in women: focus on heart failure due to coronary artery disease and diabetes. Cardiology. 1990;77(Suppl 2):71-9.

20. Colucci WS. Apoptosis in the heart. N Engl J Med. 1996;335(16):1224-6.

21. Chen C, Ma L, Linfert DR, Lie T, Fallon JT, Gillam LD, et al. Myocardial cell death and apoptosis in hibernating myocardium. J Am Coll Cardiol. 1997;30(5):1407-12.

Outcomes Nationwide in Heart Failure. Consensus recommendations for the management of chronic heart failure. Am J Cardiol. 1999;83(2A):1A-38A. 23. Olivetti G, Giordano G, Corradi D, Melissari M, Lagrasta C, Gambert SR, Anversa P. Gender differences and aging: effects in the human heart. J Am Coll Cardiol.

1995;26(2A):1068-79.

24. Adams K, Dunlap S, Sueta C, Clarke SW, Patterson JH, Blauwet MB, et al. Relation between gender, etiology and survival in patients with symptomatic heart failure. J Am Coll Cardiol. 1996;28(7):1781-8.

25. Vaccarino V, Lin ZQ, Kasl SV, Mattera JA, Roumanis SA, Abramson JL, et al. Gender differences in recovery after coronary artery bypass surgery. J Am Coll Cardiol.

2003;41(2):307-14.

26. Kannel W, Sorlie P, McNamara P. Prognosis after initial myocardial infarction: the Framingham study.

Am J Cardiol. 1979;44(1):53-9.

27. Kurlansky PA, Dorman MJ, Galbut DL, Moreno NL, Traad EA, Carrillo RG, et al. Bilateral internal mammary artery grafting in women: a 21-year experience. Ann Thorac Surg. 1996;62(1):63-9.

28. Jacobs AK, Kelsey SF, Brooks MM, Faxon DP, Chaitman BR, Bittner V, et al. Better outcome for women compared with men undergoing coronary revascularization: a report from the bypass angioplasty revascularization investigation (BARI). Circulation. 1998;98(13):1279-85.

29. Kono T, Sabbah HN, Rosman H, Alam M, Jafri S, Goldstein S. Left ventricular shape is the primary determinant of functional mitral regurgitation in heart failure. J Am Coll Cardiol. 1992;20(7):1594-8.

30. Elefteriades JA, Tolis G, Levi E, Mills LK, Zaret BL. Coronary artery bypass grafting in severe left ventricular dysfunction: excellent survival with improved ejection fraction and functional state. J Am Coll Cardiol.

22. Packer M, Cohn JN. On behalf of the Steering Committee and Membership of the Advisory Council to Improve 1993;22(5):1411-7.

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Indian Journal of Clinical Practice, Vol. 26, No. 10, March 2016

COMMUNITY MEDICINE

Prevalence of Inducible Clindamycin Resistance among Staphylococci in an Urban Tertiary Care Hospital of Jalandhar, Punjab SHEEVANI*, JASPAL KAUR†, KAILASH CHAND*, GOMTY MAHAJAN†, SHASHI CHOPRA*

ABSTRACT Introduction: Clindamycin (CL) is a lincosamide antibiotic used in staphylococcal infections. It is highly bacteriostatic against Staphylococcus aureus. Clinical failure of clindamycin therapy has been reported due to multiple mechanisms that include resistance to macrolide, lincosamide and streptogramin antibiotics. In vitro routine tests for CL susceptibility may fail to detect inducible clindamycin resistance, thus necessitating the need to detect such resistance by a simple D-test on routine basis.

Material and methods: The present study was a prospective study which was undertaken with an aim and objective to know the prevalence rate of inducible CL resistance in the Staphylococcus species. Method used for the detection of inducible CL resistance was D-test as recommended by CLSI guidelines. Results: Out of 237 isolates of staphylococci, 194 were found to be S. aureus. Of these 194 strains, 106 were methicillin-resistant S. aureus (MRSA) and 88 were sensitive to it. Amongst MRSA strains only 15 (18.75%) were found to be positive for inducible CL resistance, while overall prevalence rate was 17.98% (16/89).

Discussion and conclusion: The inducible resistance can be easily missed by routine in vitro susceptibility tests, when the ER and the CL disks are placed in nonadjacent positions, which may result in clinical failure. Implementation of the D-test for iMLSB detection on a routine basis in the hospital laboratory should be practiced.

Keywords: Clindamycin, staphylococcal infections, bacteriostatic, inducible clindamycin resistance, D-test

M

ultidrug-resistant pathogens are increasing at a great pace, limiting the therapeutic options.

Methicillin-resistant Staphylococcus aureus (MRSA) is one such pathogen that is cross-resistant to all beta lactams, including penicillins and cephalosporins.

It is a frequently isolated pathogen from hospital- and community-acquired infections worldwide. Increasing frequency of MRSA infections and changing patterns in antimicrobial resistance have led to renewed interest in the use of macrolide lincosamide-streptogramin B (MLSB) antibiotics to treat such infections.1 The MLSB antibiotics are similar in their modes of action, but structurally these are unrelated. They inhibit protein synthesis by binding to the 23S rRNA.2,3 Clindamycin (CL), an antimicrobial belonging to the MLSB family,

is frequently used for treatment of infections caused

by S. aureus. However, the widespread use of the MLSB family of antimicrobials has led to the emergence of resistance.4 The common mechanism of resistance is mediated by erm genes that encode enzymes conferring inducible (iMLSB) or constitutive (cMLSB) resistance to MLSB agents by reducing binding by these agents to the bacterial ribosome.5-7 In this study, we have attempted to determine the prevalence of iMLSB type of resistance to CL among S. aureus isolates in our hospital. No previous data regarding the prevalence rate of iMLSB is available from either this Institution or this part of the state. This study was therefore undertaken to close this gap in our knowledge.

MATERIAL AND METHODS

*Professor †Associate Professor Dept. of Microbiology Punjab Institute of Medical Sciences, Jalandhar, Punjab Address for correspondence

Dr Sheevani 144, Gurjeet Nagar, Garha Road, Jalandhar - 144 022, Punjab E-mail: drsheevani@yahoo.com

A total of 237 nonduplicate, consecutive clinical isolates of Staphylococcus species were obtained from pus/ wound swab, respiratory tract, high vaginal swab, urine and body fluids derived from both outdoor and indoor patients of our hospital over a time period of 6 months (January 2013 to June 2013).

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927

COMMUNITY MEDICINE All the Staphylococcal species were identified by conventional microbiological methods including colony morphology, Gram stain, catalase, slide coagulase and tube coagulase test. Antibiotic susceptibility testing was performed by Kirby-Bauer disk diffusion method. Antibiotic disks used were ampicillin (10 μg), amoxiclav (20/10 μg), cephalexin (30 μg), cefadroxil (30 μg), cefuroxime (30 μg), ceftriaxone (30 μg), cephotaxime (30 μg), cefoxitin (30 μg) cefoperazonesulbactam (75/30 μg), cefepime (30 μg), ciprofloxacin (5 μg),) doxycycline (30 μg), erythromycin (ER) (15 μg), azithromycin, linezolid (30 μg), netilmicin (30 μg), piperacillin-tazobactam (100/10 μg) and vancomycin (30 μg) and teicoplanin (30 μg).

Methicillin resistance was detected by cefoxitin disk diffusion test as per Clinical and Laboratory Standards Institute (CLSI) guidelines.8 All the isolates were subjected to cefoxitin disk diffusion test using a 30 µg disk. A 0.5 McFarland standard suspension of the isolate was lawn cultured on Mueller-Hinton agar (MHA) plate. Plates were incubated at 37oC for 24 hours and zone of inhibition diameters measured.

An inhibition zone diameter of <19 mm was taken as cefoxitin-resistant and >19 mm was considered as cefoxitin-sensitive.

Disk approximation testing (D-test) was performed for each isolate according to CLSI method.8 A 0.5 McFarland suspension was prepared in normal saline for each isolate and inoculated on MHA plate. CL-2 μg and ER-15 μg disks were placed 15 mm apart edge-toedge manually. Plates were incubated at 37°C for 24 hours and zone diameters were recorded.

Forty-seven (58.75%) of MRSA isolates showed ERresistant and CL-susceptible zone diameters with no blunting of the zones (MS phenotype). Eighteen (22.50%) isolates showed ER and CL resistance (cMLSB phenotype) (Table 2). No hazy D (HD) zone or D+ Table 1. Comparative Percentage Antibiotic Susceptibility Pattern of MRSA and MSSA Antibiotic

MRSA (%) (n = 106)⃰

MSSA (%) (n = 88)

Cephalexin

3.77 (4)

76.93

Cefoxitin

0 (0)

100

Cefadroxil

23.58 (25)

73.07

Cefuroxime

32.08 (34)

84.62

Ceftriaxone

28.30 (30)

61.54

Amoxicillin + Clavulanic acid

35.85 (38)

96.16

Tigecycline

28

69.23

Amikacin

56

100

Ciprofloxacin

44

65.38

Ofloxacin

56

80.78

Vancomycin

100

100

Linezolid

100

100

Azithromycin

72

92.30

Erythromycin

24.53

89.77

Clindamycin†

68.78

98.86

Teicoplanin

100

100

Nitrofurantoin‡

90

100

*Total number in the parenthesis. †True

sensitivity percentage.

‡Antibiotic

tested only in urinary isolates.

RESULTS Out of 237 isolates, 194 (81.86%) were found to be S. aureus (coagulase-positive), while 43 (18.14%) were coagulase-negative staphylococci (CoNS). Of 194 S. aureus, 106 (54.64%) were cefoxitin-resistant i.e., MRSA and 88 (45.36%) were cefoxitin- or methicillinsensitive S. aureus (MSSA). Antimicrobial susceptibility pattern showed that MSSA isolates were relatively more susceptible to most of the groups of antimicrobial agents when compared to MRSA strains (Table 1).

Out of 106 MRSA strains, 80 (75.47%) were found to be resistant to ER in contrast to only 9 (9/88; 10.23%) of MSSA isolates. Eighty-nine (45.88%) clinical isolates of S. aureus, which showed ER resistance were tested for inducible resistance by double disk approximation test.

Out of 89 ER-resistant strains 16 (17.98%) were iMLSB phenotypes (18.75% MRSA, 11.11% MSSA [1/9]) (Fig. 1).

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Figure 1. D-test positive strain.

COMMUNITY MEDICINE Table 2. Phenotypic Characterization of ER-resistant Staphylococcal Isolates Isolates (Number)

ER-R;CL-S MS phenotype Percentage in parentheses

ER-R; CL-S D-test positive iMLSB

ER-R; CL-R cMLSB

MRSA (80)

47 (58.75)

15 (18.75)

18 (22.50)

MSSA (9)

8 (88.89)

1 (11.11)

-

MRCoNS (2)

-

1 (50)

1 (50)

MSCoNS (12)

8 (66.67)

-

4 (33.33)

phenotype was observed. Out of 43 CoNS, only two (4.65%) were methicillin-resistant CoNS (MRCoNS), while remaining were methicillin-sensitive. Resistance to ER was observed in 14 isolates, out of these 14 strains only one (7.14%) showed D-zone phenotype. D-zone phenotype was MRCoNS. Eight isolates showed MS phenotype with no blunting of the zones, while five strains were resistant to both EL and CL. DISCUSSION Our study aimed at finding the incidence of inducible CL resistance in staphylococcal isolates. CL, a lincosamide, has long been an option for treating staphylococcal skin, soft tissue and bone infections because of its proven efficacy, low cost, the availability of its oral and parenteral forms, tolerability, excellent tissue penetration, its good accumulation in abscesses and because no renal dosing adjustments are required.

It also directly inhibits the staphylococcal toxin production and is a useful alternative for patients who are allergic to penicillin.9 Its good oral absorption makes it an important option in the therapy of the outpatients or as a follow-up after an intravenous (IV) therapy (de-escalation). This reduces the burden of prolonged hospitalization as well as the risks associated with it.10 It is effective against both the methicillin-resistant and the methicillin-sensitive staphylococcal infections.6 The increased frequency of the staphylococcal infections, along with the changing drug-susceptibility patterns, have led to a renewed interest in the CL usage, but the possibility of an inducible resistance to CL remains a major concern and this could limit the use of this drug.11,12 In vitro and in vivo susceptibility of S. aureus to CL may vary especially when the strain is resistant to ER. This may be due to the presence of iMLSB. This kind of resistance can be missed out by conventional susceptibility testing methods unless specifically looked for using disk approximation D-test, which is easy to perform though it can also be detected using molecular methods. To report the CL susceptibility accurately, the staphylococci which are isolated from the clinical specimens should first

be subjected to the D-test, to exclude the isolates with an induced CL resistance (iMLSB); as such isolates, when treated with CL, can undergo a rapid in vitro conversion to a constitutive resistance (cMLSB) and this may result in the CL treatment failure. Many cases of CL therapy failures due to the iMLSB phenotype, have been reported in the past.13-16 Overall prevalence rate of 16.51% (S. aureus and CoNS) of inducible CL resistance with 18.75% in MRSA and 11.11% in MSSA was observed in our study. Our findings are in coherence with the findings of other authors with the prevalence rate of 19.4%, 20%, 24.82% and 27% of iMLSB in MRSA strains in four different studies conducted in different parts of the country.

Prevalence rate of iMLSB in MSSA strains in above mentioned studies was 6.3%, 1.6%, 1.66% and 6.2%, respectively, while it was 11.1% in our study.12,17-19 Higher prevalence of iMLSB 35.33%, 38.46%, 72% and 74% in MRSA strains has been quoted in other studies by various authors, respectively.20-23 Vast variation in the prevalence rates of iMLSB is a known fact. It varies with geographical area, environmental conditions and even from hospital to hospital. Extensive variability in the prevalence of ER-induced CL resistance further emphasize on the significance of knowledge of local prevalence rate of iMLSB. This study determined the prevalence of the inducible resistance among staphylococci from the upcoming medical institute and hospital and this is first study in this region. Since, our hospital is an upcoming medical institute and as molecular laboratory facilities were unavailable, so, the molecular diagnosis of these isolates was not possible. Also, the molecular markers for the erm genes are costly and inconvenient for everyday use. Patients coming to our hospital belong to rural as well as urban background and majority of them are below poverty line and hence are not able to bear the heavy expenditures.

In the Indian context, with the high burden of the staphylococcal infections, where the health-associated expenditures are borne by the patients, D-test is simple economical and reliable test, which can be easily

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COMMUNITY MEDICINE inculcated in the routine antimicrobial susceptibility testing. It helps to guide empiric therapy.

CONCLUSION The inducible resistance can be easily missed by routine in vitro susceptibility tests, when the ER and the CL disks are placed in nonadjacent positions, which may result into clinical failure. Implementation of the D-test for iMLSB detection on a routine basis in the hospital laboratory should be practiced. Consequently, early detection helps in the use of CL only in infections caused by truly CL-susceptible staphylococci and thus helps to avoid treatment failures. It is very important that the clinical microbiologists and the infectious disease experts keep a close watch on the developing patterns of drug resistance, which will help in guiding the therapy effectively.

10. Ruebner R, Keren R, Coffin S, Chu J, Horn D, Zaoutis TE. Complications of central venous catheters used for the treatment of acute hematogenous osteomyelitis.

Pediatrics. 2006;117(4):1210-5.

11. Frank AL, Marcinak JF, Mangat PD, Tjhio JT, Kelkar S, Schreckenberger PC, et al. Clindamycin treatment of methicillin-resistant Staphylococcus aureus infections in children. Pediatr Infect Dis J. 2002;21(6):530-4.

12. Jadhav SV, Gandham NR, Sharma M, Kaur M, Misra RN, Matnani GB, et al. Prevalence of inducible clindamycin resistance among community- and hospital-associated Staphylococcus aureus isolates in a tertiary care hospital in India. Biomed Res. 2011;22(4):465-9.

13. Lewis JS 2nd, Jorgensen JH. Inducible clindamycin resistance in Staphylococci: should clinicians and microbiologists be concerned? Clin Infect Dis. 2005;40(2):280-5.

REFERENCES

14. Levin TP, Suh B, Axelrod P, Truant AL, Fekete T. Potential clindamycin resistance in clindamycin-susceptible, erythromycin-resistant Staphylococcus aureus: report of a clinical failure. Antimicrob Agents Chemother.

2005;49(3):1222-4.

1. Saiman L, O’Keefe M, Graham PL 3rd, Wu F, Saïd-Salim B, Kreiswirth B, et al. Hospital transmission of communityacquired methicillin-resistant Staphylococcus aureus among postpartum women. Clin Infect Dis. 2003;37(10):1313-9.

15. Drinkovic D, Fuller ER, Shore KP, Holland DJ, EllisPegler R. Clindamycin treatment of Staphylococcus aureus expressing inducible clindamycin resistance. J Antimicrob Chemother. 2001;48(2):315-6

2. Mallick SK, Basak S, Bose S. Inducible clindamycin resistance in Staphylococcus aureus: A therapeutic challenge. J Clin Diagn Res. 2009;3(3):1513-8.

3. Lim HS, Lee H, Roh KH, Yum JH, Yong D, Lee K, et al.

Prevalence of inducible clindamycin resistance in staphylococcal isolates at a Korean tertiary care hospital.

Yonsei Med J. 2006;47(4):480-4.

4. Lowy FD. Antimicrobial resistance: the example of Staphylococcus aureus. J Clin Invest. 2003;111(9):1265-73.

5. Fiebelkorn KR, Crawford SA, McElmeel ML, Jorgensen JH. Practical disk diffusion method for detection of inducible clindamycin resistance in Staphylococcus aureus and coagulase-negative staphylococci. J Clin Microbiol.

2003;41(10):4740-4.

6. Angel MR, Balaji V, Prakash J, Brahmadathan KN, Mathews MS. Prevalence of inducible clindamycin resistance in gram positive organisms in a tertiary care centre. Indian J Med Microbiol. 2008;26(3):262-4.

7. Schreckenberger PC, Ilendo E, Ristow KL. Incidence of constitutive and inducible clindamycin resistance in Staphylococcus aureus and coagulase-negative staphylococci in a community and a tertiary care hospital.

J Clin Microbiol. 2004;42(6):2777-9.

8. Clinical Laboratory Standards Institute (CLSI).

“Performance standards for antimicrobial susceptibility testing.” In Proceedings of the 22nd International Supplement (M100-S22). National Committee for Clinical Laboratory Standards: Wayne PA, USA; 2012.

9. Kasten MJ. Clindamycin, metronidazole, and chloramphenicol. Mayo Clin Proc. 1999;74(8):825-33.

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16. Siberry GK, Tekle T, Carroll K, Dick J. Failure of clindamycin treatment of methicillin-resistant Staphylococcus aureus expressing inducible clindamycin resistance in vitro. Clin Infect Dis. 2003;37(9):1257-60.

17. Juyal D, Shamanth AS, Pal S, Sharma MK, Prakash R, Sharma N. The prevalence of inducible clindamycin resistance among staphylococci in a tertiary care hospital: A study from the Garhwal Hills of Uttarakhand, India.

J Clin Diagn Res. 2013;7(1):61-5.

18. Prabhu K, Rao S, Rao V. Inducible clindamycin resistance in Staphylococcus aureus isolated from clinical samples.

J Lab Physicians. 2011;3(1):25-7.

19. Deotale V, Mendiratta DK, Raut U, Narang P. Inducible clindamycin resistance in Staphylococcus aureus isolated from clinical samples. Indian J Med Microbiol.

2010;28(2):124-6.

20. Upadhya A, Biradar S. The prevalence of inducible clindamycin resistance in Staphylococcus aureus in a tertiary care hospital in north-east Karnataka, India.

Health Sciences: An International Journal. 2011;1(3):21-4.

21. Ciraj AM, Vinod P, Sreejith G, Rajani K. Inducible clindamycin resistance among clinical isolates of Staphylococci. Indian J Pathol Microbiol. 2009;52(1):49-51.

22. Gupta V, Datta P, Rani H, Chander J. Inducible clindamycin resistance in Staphylococcus aureus: a study from North India. J Postgrad Med. 2009;55(3):176-9.

23. Ajantha GS, Kulkarni RD, Shetty J, Shubhada C, Jain P. Phenotypic detection of inducible clindamycin resistance among Staphylococcus aureus isolates by using the lower limit of recommended inter-disk distance. Indian J Pathol Microbiol. 2008;51(3):376-8.

2016

DRUGS

Recommendation Patterns by Various Practitioners in the Treatment of Colicky Abdominal Pain in India MUKESH GABHANE, LISA BRAGANZA, SRIRUPA DAS, VISHAL VAIDYA

ABSTRACT Background: The aim of the survey was to determine the current trends of treatments recommended by physicians for abdominal colicky pain. Material and methods: This cross-sectional, observational survey was conducted across 21 sites of India where 200 registered physicians with at least 2-3 years of clinical practice and willing to participate in the survey were interviewed in their clinic or hospital from April to June 2015. They were asked to fill 20 questions in survey form regarding treatment of colicky abdominal pain. The interview took approximately 15-20 minutes. Results: Approximately 50% (99/200) of the physician recommended camylofin plus paracetamol as their first choice of treatment, of which 67.7% (67/99) recommended it for moderate, 18.2 (18/99) for mild and 14.1% (14.1/99) for severe colicky abdominal pain. Camylofin plus paracetamol was also the most recommended combination categorized by severity, site of origin, duration of pain, patientâ&#x20AC;&#x2122;s age and medical history.

Fifty-four percent of the patients achieved pain relief after treatment with camylofin and paracetamol, 55% after treatment with dicyclomine/hyoscine/any other antispasmodic, and 48% after treatment with NSAIDs/opioids/paracetamol/COX-2 inhibitors/ any other analgesic. Conclusion: Camylofin plus paracetamol is the most commonly used and preferred antispasmodic combination for the management of colicky abdominal pain by the practitioners.

Keywords: Camylofin, colicky abdominal pain, physician survey

A

bdominal pain is a common presentation in general practice and is often due to spasm of intra-abdominal visceral organs.1,2 Abdominal colicky pain is a severe and localized spasmodic pain that sharply increases, peaks and dissipates over time.

It is a self-limited condition and is typically caused by inflammation and enlargement of the visceral organs, and is triggered by sudden involuntary contractions proximal to a partial or complete obstruction. The initial assessment of abdominal colicky pain is based on the location of pain; however, its diagnosis is based on the associated symptoms.1

Various types of the abdominal colicky pain include, renal/ureteric colicky pain, commonly caused by the passage of urinary tract calculi; biliary colicky pain, caused by blockage of common bile duct or cystic duct by a gallstone; intestinal colicky pain, caused by

Abbott Healthcare Pvt. Ltd. Address for correspondence

Dr Mukesh Gabhane Abbott Healthcare Pvt. Ltd. 1st Floor, D-Mart Building, Mulund - Goregaon Link Road Mulund (West), Mumbai - 400 080, Maharashtra E-mail: Mukesh.gabhane@abbott.com

abnormal functioning of intestines and infantile colicky pain characterized by episodes of uncontrollable crying in an otherwise healthy and well-fed infant, younger than 3 months of age.3,4 Previous literature reported that up to 25% of adults have abdominal colicky pain at some time of their life.5 The prevalence of abdominal pain varies from 16% to 22% in older population (â&#x2030;Ľ60 years).6 Approximately 10-25% of infants have colic pain during the first few months of life, with 90% of cases occurring in the first few months.7,8 Renal colicky pain has an annual incidence of approximately 16/10,000 people and a lifetime incidence of 2-5% with a re-occurrence rate of about 50%.9 Antispasmodics relieve spasmodic pain either by direct relaxation of smooth muscle or by blocking cholinergic action or calcium channels.10 Antispasmodics like dicyclomine, hyoscine, camylofin and papaverine are commonly used in biliary colicky pain, colicky intestinal pain and renal colicky pain for the relief of smooth muscle spasm.2,9 However, the choice of analgesia for managing acute colicky pain is changing, with increasing use of nonsteroidal anti-inflammatory drugs (NSAIDs). NSAIDs have been shown synergistic effect when given along with spasmolytics.9,11 They have been shown to achieve greater reduction in pain scores than opioids and have a longer duration of

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DRUGS action, which reduces need for additional analgesia in the short-term. Opioid analgesics are prescribed in addition to, or as an alternative, to NSAIDs in patients at risk of NSAID-induced adverse effects. However, opioids are reported to have higher rates of nausea, vomiting and dizziness.12 The scenario of treatment modalities of colicky pain in India is unclear with hardly any published studies in this area. There are very few published studies assessing the safety and efficacy of NSAID-spasmolytic combinations in colicky pain, and the superiority of one combination over another.9 The treatment of colicky abdominal pain depends on its severity, site of origin, duration, patient’s age and medical history.1 Generally, physicians recommend adjunct or add-on medications along with antispasmodics for the treatment of colicky abdominal pain. Hence, the present survey was designed to determine the current trends of treatments recommended by physicians for abdominal colicky pain with a focus on assessing effectiveness and safety of camylofin plus paracetamol and other antispasmodics/ analgesics.

MATERIAL AND METHODS

Setting and Physicians In this cross-sectional observational survey, 200 registered physicians across 21 cities of India with at least 2-3 years of clinical practice and willing to participate in the survey were interviewed in their clinic or hospital from April to June 2015. The interviewed physicians included consulting physicians (who were working in hospital/private clinics), general practitioners and gastroenterologists. They were asked 20 questions (survey form) regarding treatment of colicky pain, drug selection as per patient attributes and effectiveness/ safety of fixed dose combination of camylofin and paracetamol versus other antispasmodics/analgesics in the treatment of colicky abdominal pain. The interview took approximately 15-20 minutes. After completion of an interview, the data from the survey form was entered into the paper case report forms and was sent across to Max Neeman’s Data Management Team where the data entry was validated and analyzed. The study did not require an Institutional Ethics Committee approval as it did not involve direct participation of any patient.

Endpoints The primary endpoints of the survey were to evaluate the percentage of physicians recommending camylofin plus paracetamol and other medications and percentage

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Indian Journal of Clinical Practice, Vol. 26, No. 10, March 2016

of physicians preferring different treatments by site of origin, duration of colicky abdominal pain, patient’s age and medical history. The secondary endpoints of the survey were to evaluate the adjunct or add-on medication(s) recommended along with antispasmodics; percentage of patients treated with camylofin plus paracetamol and experiencing pain relief as compared to those treated with other antispasmodics/ analgesics; average time of pain relief in patients treated with camylofin plus paracetamol as compared to those treated with other antispasmodics/analgesics; percentage of patients requiring adjunct or add-on treatment along with camylofin plus paracetamol as per physician’s opinion and adverse drug reactions (ADRs) reported due to camylofin plus paracetamol versus other antispasmodics/analgesics.

Data Analysis Due to noninterventional nature of the survey, no formal sample size was calculated. All the enrolled physicians constituted the analysis population. Descriptive statistics was used to analyze the study endpoints where the continuous variables were presented as mean ± standard deviation, and the categorical variables as frequency and number of patients. ADRs were coded using Medical Dictionary for Regulatory Activities version 18.0.

RESULTS

Study Demographics The mean age of physicians was 45 ± 11 years. Ninetyone percent (182/200) of the physicians were males. As regards their qualifications, 68% (136/200) were MD, 22.5% (45/200) were MBBS, 6% (12/200) were DM, 3% (6/200) were DNB and 0.5 (1/200) was a MS. The higher proportions of physicians were consulting physicians (67.5%; 135/200) and worked in hospitals (48.5%; 97/200) or private clinics (46%; 92/200). Depending upon the origin of colicky abdominal pain, patients were categorized to have renal/ureteric colic, biliary colic, intestinal colic, infantile colic and dysmenorrhea. As per severity of the colicky pain, patients were categorized to have mild, moderate or severe abdominal colic pain.

Primary Endpoints Camylofin plus paracetamol and dicyclomine plus NSAIDs was preferred by 49.5% (99/200) and 24.5% (49/200) of the physicians, respectively for the treatment of colicky abdominal pain (Fig. 1). Of 99 physicians recommending camylofin plus paracetamol for colicky abdominal pain, 67 (67.7%) recommended

DRUGS it for moderate cases, 18 (18.2%) for mild and 14 (14.1%) for severe cases (Fig. 2). On an average, physicians recommended camylofin plus paracetamol to 34 patients, dicyclomine plus NSAIDs to 22 patients, drotaverine to 19 patients, hyoscine to 15 patients and any other antispasmodic to 1 patient per month (Fig. 3).

Secondary Endpoints Eighty-six percent (172/200) of the physicians recommended adjunct or add-on medications along with antispasmodics for the treatment of colicky 80 Percentage of physicians

Camylofin plus paracetamol was recommended as the most common combination for the treatment of abdominal colicky pain categorized by type of pain (renal/ureteric colicky pain, biliary colicky pain, intestinal colicky pain, dysmenorrhea and infantile colicky pain), duration of pain (lasting for 1-3 days, 3-6 days and >6 days) and by patient’s age group (infants, children, adults, geriatrics) (Fig. 4). Based on the patient’s specific medical history, drotaverine, camylofin plus paracetamol and camylofin alone was recommended by 31 (15.5%), 28 (14%) and 27 (13.5%) physicians, respectively for the treatment of colicky abdominal pain.

Hyoscine

Any other antispasmodic

30 18.2

20

Mild

34

35 30 25

22

20

15

15 10

80

70.3

tis An pa y sm oth od er ic

e

e

cin

in

os

er

Hy

av ot

an

Dr

Di

cy NS clom AI in Ds e +

1

C Pa am ra ylo ce fin ta + m ol

Figure 1. Summary of recommendation of various antispasmodics by physicians.

Percentage of physicians

19

5

49.5%

18.5%

Figure 3. Number of patients per physician prescribed with different antispasmodics over a course of month.

Camylofin + Paracetamol 66.7

63.3

60 40

Severe

40

0

50

Moderate

Figure 2. Percentage of physicians prescribing camylofin with paracetamol based on choice in severity of colicky abdominal pain.

1%

70

14.1

Severity of colicky abdominal pain

6.5%

24.5%

50 40

0

Number of patients

Drotaverine

67.7

60

10

Dicyclomine + NSAIDs

Camylofin + Paracetamol

70

55.1 43

40.4 28.8

30

47.7

55.2

31.4

27.6

38.6

20 10 0

Renal/ ureteric

Biliary

Intestinal Dysmenorrhea Infantile

Site of origin

1-3 days

3-6 days

>6 days

Duration of pain

Children

Adults

Geriatric

Infantile

Age group

Figure 4. Percentage of physicians prescribing camylofin with paracetamol based on site of origin, duration of pain and patient’s age group.

Indian Journal of Clinical Practice, Vol. 26, No. 10, March 2016

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DRUGS

As per physicians, 54% of the patients achieved pain relief after treatment with camylofin and paracetamol, 55% after treatment with dicyclomine/hyoscine/any other antispasmodic, and 48% after treatment with NSAIDs/opioids/paracetamol/cyclooxygenase-2 (COX-2) inhibitors/any other analgesic. On an average, after 65 ± 82 min of taking camylofin plus paracetamol, the patient had pain relief; the average time taken for onset of pain relief after treatment with camylofin plus paracetamol was comparable to treatment with dicyclomine/hyoscine/any other antispasmodic (65 ± 70 min) and NSAIDs/opioids/paracetamol/COX-2 inhibitors/any other analgesic (68 ± 80 min) (Fig. 5).

As regards the ADRs, 28.5% (57/200) were reported for camylofin plus paracetamol as compared to 79.5% (159/200) for dicylomine/hyoscine/any other antispasmodic, and 85.5% (171/200) ADRs for NSAIDs/ opioids/paracetamol/COX-2 inhibitors/any other analgesic (Fig. 6). As per physicians, dry mouth was the most common ADR in patients prescribed with camylofin and paracetamol (31.6%; 18/57) and dicyclomine/hyoscine/any other antispasmodic (37.1%; 59/159) followed by nausea in patients prescribed with camylofin and paracetamol (29.8%; 17/57) and dicyclomine/hyoscine/any other antispasmodic (19.5%; 31/159), respectively.

80

Time (minutes)

70

64.6

65

68

60 50 40 30 20 10 0

Camylofin and paracetamol

Dicyclomine/ NSAIDs/Opioids/ Hyoscine/any other Paracetamol/COX-2 antispasmodic inhibitors/any other analgesic

Figure 5. Average time for relief in pain intensity in patients treated with different drugs.

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Indian Journal of Clinical Practice, Vol. 26, No. 10, March 2016

100 Percentage of physicians

abdominal pain. 59.9% (103/172) of the physicians recommended opioids, 58.7% (101/172) recommended NSAIDs and 28.5% (49/172) recommended paracetamol along with antispasmodics. 57.5% (115/200) of the physicians felt need for supportive therapy as an add-on treatment to camylofin plus paracetamol. Less than 15% physicians felt need for nonpharmacological treatment (11.5%; 23/200 physicians) and nerve blocks through local and regional analgesia (4%; 8/200) as an add-on treatment to camylofin plus paracetamol.

79.5

80

85.5

60 40

28.5

20 0

Camylofin + Paracetamol

Dicyclomine/ NSAIDs/Opioids/ Hyoscine/any other Paracetamol/COX-2 antispasmodic inhibitors/any other analgesic

Figure 6. Percentage of physicians reporting ADRs with different drugs.

DISCUSSION Colicky abdominal pain is the rhythmic pain resulting from intermittent spasms, which is most frequently encountered in routine clinical practice due to its common occurrence and numerous etiologies. The colic pain could be because of the spasm or obstruction of intestinal, biliary or uterine smooth muscles and it could be acute, subacute or chronic in nature.13 Amongst various types of spasmodic pain, patients with colicky abdominal pain more often seek medical attention.

Physicians are usually the first to evaluate and treat this condition. This is the first survey carried out in India to obtain data on recommendations and practice patterns of physicians toward colicky abdominal pain.

The survey participants included consulting physicians, general practitioners and gastroenterologists who are known to treat patients with abdominal colicky pain in daily practice. Patients with colicky abdominal pain are treated by all surveyed participants. The majority of physicians considered colicky pain as a common and underestimated health problem in India. From physician treated subjects over a course of month, the incidence of intestinal colic pain was higher followed by renal/ureteric colic pain, biliary colic pain, infantile colic pain and dysmenorrhea.

Antispasmodics are routinely used in the management of spasmodic conditions like abdominal cramping pain, renal colic, acute abdominal spasm, spasm of biliary system or genitourinary tract, irritable bowel syndrome, dysmenorrhea, pain in paraumbilical region, peptic ulcer, gastric pain and labor pain. In the present survey, camylofin plus paracetamol was the most preferred antispasmodic combination for the management of colicky abdominal pain categorized by site of origin,

DRUGS duration of pain, patient’s age and medical history.

Our observations were in concordance to the results of other surveys where physicians were reluctant to administer antispasmodics like mefenamic acid plus dicyclomine, drotaverine and hyoscine butylbromide to patients with spasmodic conditions by practicing safe and adequate prescriptions.14-18 In another crosssectional survey, Gabhane and Braganza evaluated the preferential trend for antispasmodics among Indian healthcare professionals and reported that camylofin plus paracetamol has been recalled by about 9 out of 10 healthcare practitioners for the treatment of spasmodic pain.19 The results of the present survey will be useful for physicians to understand the overall prescription pattern of antispasmodic agents and decide a strategy for selecting an antispasmodic agent in conditions like colicky abdominal pain.

CONCLUSION Camylofin plus paracetamol is the most commonly used and preferred antispasmodic combination for the management of colicky abdominal pain by the practitioners.

Acknowledgments The authors wish to thank all the participating physicians, site management organization and the medical writing agency (Max-Neeman International) for their efforts.

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8. Roberts DM, Ostapchuk M, O’Brien JG. Infantile colic. Am Fam Physician. 2004;70(4):735-40.

9. Porwal A, Mahajan AD, Oswal DS, Erram SS, Sheth DN, Balamurugan S, et al. Efficacy and tolerability of fixed-dose combination of dexketoprofen and dicyclomine injection in acute renal colic. Pain Res Treat. 2012;2012:295926.

10. Annaházi A, Róka R, Rosztóczy A, Wittmann T. Role of antispasmodics in the treatment of irritable bowel syndrome. World J Gastroenterol. 2014;20(20):6031-43.

11. Best Practice Advocacy Centre New Zealand (BPAC NZ). Managing patients with renal colic in primary care: Know when to hold them. 2014. Available at: http://www.bpac.org.nz/BPJ/2014/April/colic.aspx.

12. Golzari SE, Soleimanpour H, Rahmani F, Zamani Mehr N, Safari S, Heshmat Y, et al. Therapeutic approaches for renal colic in the emergency department: a review article.

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15. Tytgat GN. Hyoscine butylbromide: a review of its use in the treatment of abdominal cramping and pain. Drugs.

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16. Dash A, Maiti R, Akantappa Bandakkanavar TK, Arora P. Intramuscular drotaverine and diclofenac in acute renal colic: a comparative study of analgesic efficacy and safety.

Pain Med. 2012;13(3):466-71.

17. Lacy BE, Wang F, Bhowal S, Schaefer E; study group. Ondemand hyoscine butylbromide for the treatment of selfreported functional cramping abdominal pain. Scand J Gastroenterol. 2013;48(8):926-35.

18. Sugumar R, Krishnaiah V, Channaveera GS, Mruthyunjaya S. Comparison of the pattern, efficacy, and tolerability of self-medicated drugs in primary dysmenorrhea: a questionnaire based survey. Indian J Pharmacol.

2013;45(2):180-3.

19. Gabhane M, Braganza L. Preference trends for antispasmodics among Indian healthcare professionals: results of a cross sectional survey. Indian Practitioner.

6. Sandler RS, Stewart WF, Liberman JN, Ricci JA, Zorich NL. Abdominal pain, bloating, and diarrhea in the United 2015;68(5):32-7.

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DRUGS

Diclofenac: Dose and Formulation Based Protocol in Pain Management HR JHUNJHUNWALA, RAJIVA GUPTA, MS GHOSH, VIKAS AGASHE, GPV SUBBAIAH, GVS MOORTHY, AK JAIN, JC CHOWDHURY, VIKAS GUPTA, VENKATRAMANA NAGIRE, AMIT THAVKAR, APURVA GAWAI

ABSTRACT Many patients with osteoarthritis (OA) also commonly experience multiple comorbidities, such as cardiovascular, gastrointestinal and endocrine disorders. Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used in the world due to their demonstrated efficacy in reducing pain and inflammation. Pain control with NSAIDs is an effective option and diclofenac, a nonselective NSAID, is considered as the gold standard for inflammatory arthritic conditions being both effective and inexpensive.

Diclofenac has been used in more than 1 billion patients globally. NSAID like diclofenac is also one of the most commonly used drug for OA in India.

Keywords: Nonsteroidal anti-inflammatory drugs, pain, inflammation, diclofenac, osteoarthritis

O

steoarthritis (OA) is a chronic, painful, degenerative joint condition that most commonly affects the hips, knees and hands and often requires long-term treatment to manage acute symptoms and prevent long-term complications. These complications include the destruction of particular cartilage and subchondral bone, bone remodeling, atrophy of periarticular muscles, capsular stretching and synovitis in weight-bearing joints. Additional health-related problems associated with OA include emotional stress, fatigue and impaired sleep, all of which may significantly diminish the quality of a patientâ&#x20AC;&#x2122;s life.

doctor-diagnosed arthritis, those in the age group 45-64 years, 30.3% report doctor-diagnosed arthritis, and of those age 65 or older, 49.7% report doctordiagnosed arthritis. Twenty-six percent of women and 19.1% men report doctor-diagnosed arthritis.1

RHEUMATIC DISEASES: THE SIZE OF THE PROBLEM

RHEUMATOID ARTHRITIS IN INDIA

It has long been known that arthritis is one of the biggest causes of disability affecting people of all ages, in particular older people. In 2010-2012, 49.7% of adults, 65 years or older, reported an arthritis diagnosis.1 The most common form of arthritis is osteoarthritis. Other common rheumatic conditions include gout, fibromyalgia and rheumatoid arthritis.

Of persons in the age group 18-44 years, 7.3% report

Dr HR Jhunjhunwala Bombay Hospital and Research Centre Post Graduate Institute of Medical Sciences E-mail: drhrj2@gmail.com

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Indian Journal of Clinical Practice, Vol. 26, No. 10, March 2016

Approximately 1 in 3 people with arthritis (31%) in between the ages of 18 and 64 report arthritis-attributable work limitation.2 People with doctor-diagnosed arthritis have significantly worse health-related quality-of-life than those without arthritis. Adults with arthritis report 2-4 times as many unhealthy days in the past month than those without arthritis.3

Rheumatoid arthritis (RA) is a very common disease in India affecting elderly ladies. The Indian prevalence rate (0.9%) almost equals the world prevalence rate.4 The variation in the level of sex hormones of women (estrogen and progesterone, which regulate the inflammatory process) is the main cause of the development of RA among them.5 CLINICAL GUIDELINES FOR OSTEOARTHRITIS MANAGEMENT Currently available US guidelines for OA management include those developed by the American Academy of Orthopedic Surgeons (AAOS), the American College of Rheumatology (ACR), the American Geriatrics Society (AGS), the American Pain Society (APS) and the

DRUGS Osteoarthritis Research Society International (OARSI).

In Europe, the European League Against Rheumatism (EULAR) and the United Kingdomâ&#x20AC;&#x2122;s National Institute for Health and Clinical Excellence (NICE) have developed OA management guidelines. All the guidelines irrespective of the formulation recommend nonsteroidal anti-inflammatory drugs (NSAIDs) as the first-line of treatment for OA management.6 CONSENSUS ON USE OF NSAIDs NSAIDs are among the most commonly used medications for musculoskeletal conditions because of their known effectiveness as anti-inflammatory and analgesic agents.7 A recent study in The Journal of Pain found that NSAIDs were the most preferred and prescribed drugs for chronic pain.7 In 2012, 98 million prescriptions were filled for NSAIDs, and approximately 23 million people in the United States used over-thecounter (OTC) NSAIDs regularly.8,9 Diclofenac is the most popularly used NSAID throughout the world.10,11 NSAIDs have anti-inflammatory, analgesic and antipyretic properties.12 They are indicated for the treatment of mild-to-moderate pain in various acute and chronic inflammatory conditions. Their efficacy has been established in numerous acute and chronic pain conditions including OA, RA, low back pain, neck pain, headache, dysmenorrhea and gout. NSAIDs are generally preferred over opioids because of their established effectiveness and limited potential for abuse. NSAIDs comprise traditional NSAIDs and cyclooxygenease-2 (COX-2) inhibitors (or coxibs). All NSAIDs inhibit the production of prostaglandins by inhibiting the activity of PGG/H synthase, also known as cyclooxygenase (COX).13 COX exists in 2 isoforms (COX-1 and COX-2), which differ in tissue expression and regulation. The therapeutic effects of NSAIDs are attributed to inhibition of COX-2 in inflammatory sites. Specificity to the COX isoform is a key factor that influences both efficacy and safety.

NSAIDs are available both OTC and by prescription and in oral and topical formulations. In 2007, a topical diclofenac patch was approved for the treatment of pain. Diclofenac is the first and only NSAID approved for topical use.14 Currently, 3 topical formulations, all salts of diclofenac, are available for use in pain: 1.3% diclofenac epolamine transdermal patch, 1% diclofenac sodium gel and diclofenac sodium 1.5% topical solution.15-17 The transdermal patch is approved for acute musculoskeletal injury (minor sprains, strains and contusions), and the solution and gel are approved for the treatment of OA pain.

Topical NSAIDs were developed as an alternative to oral NSAIDs and may be beneficial for localized pain.18 A meta-analysis evaluating studies from 7,688 adults with chronic musculoskeletal pain found that topical NSAIDs provided adequate pain relief, equivalent to oral NSAIDs for hand and knee OA.19 Currently, there is a lack of sufficient evidence comparing oral and topical NSAIDs for other chronic pain conditions. Systemic absorption is lower with topical agents; thus, they are associated with fewer adverse events. The incidence of local adverse events, however, is increased with topical NSAIDs. In the past 5 years, various updated guidelines have included recommendations for the use of topical NSAIDs, particularly in patients considered at gastrointestinal or cardiovascular high risk.20,21 SAFETY CONCERNS In the May 2013 issue of The Lancet, the international consortium known as the Coxib and traditional NSAID Trialists (CNT) Collaboration released their findings from a meta-analysis of 639 clinical trials that included more than 3,50,000 NSAID users.22 The investigators assessed cardiovascular and gastrointestinal risks of certain NSAID regimens among various types of patients, particularly those considered to be high risk for vascular disease. Researchers of the CNT Collaboration explained that once baseline characteristics and risks are obtained, these adverse events can be predicted.

They urged clinicians to broaden their view on NSAIDs and include all potential concerns and benefits in their decision-making.

APPROPRIATE USE OF NSAIDs: BALANCING RISK VERSUS BENEFIT Professional organizations, including the AAOS, ACR, AGS, OARSI, NICE and EULAR, have updated their guidelines to include the proper use of oral and topical NSAIDs and strategies for prevention of side effects; however, the recommendations vary.23-26 For example, the ACR and AAOS support the use of topical or oral NSAIDs as an effective option for the initial management of knee or hand OA, along with other treatments such as acetaminophen and tramadol.

In the guidelines by NICE, oral NSAIDs and coxibs are only regarded as adjunctive treatments. Topical NSAIDs are recommended as first-line therapy. OARSI, on the other hand, suggests using topical NSAIDs as an adjunct or alternative to oral NSAIDs.23-26

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DRUGS PREVENTION OF NSAID-ASSOCIATED RISKS The appropriate use of NSAIDs involves tailoring treatment to the individual’s gastrointestinal and cardiovascular risk profile.

STRATEGIES TO REDUCE GASTROINTESTINAL RISK Two strategies were described in the ACG guidelines for preventing gastric mucosal damage in chronic NSAID users: ÂÂ

Coadministration of gastroprotective agents such as misoprostol or proton pump inhibitors (PPIs)

ÂÂ

Substituting a traditional NSAID with a coxib.27

BALANCING GASTROINTESTINAL AND CARDIOVASCULAR RISKS Strategies to balance both gastrointestinal and cardiovascular risks are summarized in Table 1.27

not required in the elderly or in those patients with renal or hepatic impairment. The drug has a relatively short elimination half-life, which limits the potential for drug accumulation. In numerous clinical trials, the efficacy of diclofenac is equivalent to that of the many newer and established NSAIDs with which it has been compared. As an analgesic, it has a fast onset and long duration of action. When administered intramuscularly it is at least comparable to, and frequently superior to, many narcotic and spasmolytic combinations in renal and biliary colic. Extensive clinical experience has been gained with diclofenac, clearly establishing its safety profile. It is well-tolerated compared with other NSAIDs and rarely produces gastrointestinal ulceration or other serious side effects. Thus, diclofenac can be considered as one of the few NSAIDs of ‘first choice’ in the treatment of acute and chronic painful and inflammatory conditions.30 APPROPRIATE USE OF DICLOFENAC: ORAL FORMULATION

BALANCING RENAL EFFECTS The dose and duration of NSAIDs are important predicators of renal risk.28 Short-term use of NSAIDs is generally safe in patients who are well-hydrated; who have good renal function and who do not have heart failure, diabetes or hypertension. Serum creatinine measurements should be done every 2 to 4 weeks, for several weeks, after initiation of therapy because renal insufficiency may occur early in the course of therapy.29

Diclofenac is available as 25 mg, 50 mg, 75 mg, 100 mg and 150 mg oral formulations (Fig. 1). As diclofenac is used in many indications, there is a need for identifying the correct strengths and formulations of diclofenac in these different indications.31

Mechanisms of Action of Diclofenac: Analgesic and Anti-inflammatory32 Established

ÂÂ

DICLOFENAC Diclofenac is advocated for use in painful and inflammatory rheumatic and certain nonrheumatic conditions. It is available in a number of administration forms which can be given orally, rectally or intramuscularly. Conveniently, dosage adjustments are

zz

Inhibition of COX-1 and COX-2 activity

zz

Inhibition of the synthesis of prostaglandin E2 and thromboxane A2

Putative

ÂÂ

zz

Inhibition of leukotriene synthesis

Table 1. Balancing Gastrointestinal and Cardiovascular Risks27 Gastrointestinal risk Low

Moderate 1-2 risk factors

High 2 risk factors

Cardiovascular risk Low (does not require aspirin)

Traditional NSAID alone

Traditional NSAID + gastroprotective agenta

Consider alternative non-NSAID therapy or Coxib + gastroprotective agenta

High (requires aspirin) aPPI

Naproxen + gastroprotective agent

Naproxen + gastroprotective agent

Alternative non-NSAID therapy

or misoprostol as gastroprotective agent. H. pylori is considered an independent risk factor and should be treated separately.

Coxib = Cyclooxygenease-2 (COX-2) inhibitor; NSAIDs = Nonsteroidal anti-inflammatory drugs; PPI = Proton pump inhibitor.

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Indian Journal of Clinical Practice, Vol. 26, No. 10, March 2016

DRUGS

25 mg

50 mg

75 mg SR

100 mg SR

150 mg SR

Not frequently used in India

Frequently used

Frequently used

Not frequently used

Availabe as OTC in USA and Europe

Enteric coated

Wax Matrix technology for sustained release

Bilayer technology for immediate and sustained release

Very few brands in India

Gelatin + Enteric coated Dispersible Potassium salt

Figure 1. Oral formulations of diclofenac. zz

Central effects: Increase plasma-endorphin levels and inhibition of N-methyl-D-aspartate pathway

ÂÂ

Emerging

ÂÂ

Reduction in plasma and synovial substance P and interleukin-6 levels.

DICLOFENAC SODIUM VS. DICLOFENAC POTASSIUM Diclofenac potassium is an immediate-release tablet formulated to dissolve under the acid conditions of the stomach.33 It has 3-fold shorter tmax than the entericcoated sodium salt. It has approximately 20 times faster onset of absorption. There is more rapid onset of analgesia seen with the immediate-release potassium formulation than with the enteric-coated sodium salt of diclofenac in dental pain.34

APPROPRIATE USE OF DICLOFENAC: INJECTABLE FORMULATION Effective postoperative pain control is an essential component of the care of the surgical patient. Inadequate pain control, apart from being inhumane, may result in increased morbidity or mortality. Evidence suggests that surgery suppresses the immune system and that this suppression is proportionate to the invasiveness of the surgery. Good analgesia can reduce this deleterious effect.

Data available indicate that afferent neural blockade with local anesthetics is the most effective analgesic technique. Next in order of effectiveness are highdose opioids, epidural opioids and clonidine, patient controlled opioid therapy and nonsteroidal antiinflammatory agents.35

Advantages of Diclofenac 3 mL Injection

RECOMMENDED DOSAGES

ÂÂ

Achieves peak plasma concentration in 20-30 minutes after IM injection.

Management of Osteoarthritis

ÂÂ

Fast drug liberation is suitable for acute analgesic treatment.

ÂÂ

Mean onset of analgesic action is 19 minutes.

ÂÂ

Analgesic action lasts for 6 to 8 hours.

ÂÂ

Acute OA: 100-150 mg/day for up to 4 weeks.

ÂÂ

Chronic OA: maintenance.

ÂÂ

75-100

mg/day

for

long-term

Acute flare ups triggered by inflammation: 150 mg/ day for 1-2 weeks.

Management of RA and Ankylosing Spondylosis

Advantages with 2 mL Diclofenac Formulations The advantages of 2 mL formulations of diclofenac when compared with the 3 mL formulations are summarized in Table 2.

ÂÂ

Start with 100-150 mg.

ÂÂ

Maintain with 75-100 mg.

Advantages with 1 mL Diclofenac Formulations

ÂÂ

For flare ups: 150 mg/day for 1-2 weeks.

ÂÂ

Significantly more patients achieved analgesia in less than 5 minutes.

ÂÂ

Less pain at the site of injection with the 1 mL formulation.

ÂÂ

Can be administered IV and IM in the gluteal as well as deltoid muscle.

Management of Low back pain ÂÂ

50 mg t.d.s. or 75 mg b.i.d. or 100 mg o.d. depending on severity of pain.

ÂÂ

150 mg for spinal OA and Cox arthrosis.

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941

DRUGS Table 2. Advantages with 2 mL Diclofenac Formulations Diclofenac 2 mL

Diclofenac 3 mL

Advantages

Solvent

HPbetaCD

Propylene glycol

Less irritant

Buffering

No

Yes

Ease of administration

Phlebitis

Less

More

Less side effects

IV

Rapid bolus over 1 min

Slow infusion 30 mins

Quick onset of action

IM

Yes

Yes

Less volume of injection

Onset

15 mins

15 mins

Comparable

Duration

6 hrs

6 hrs

Comparable

% patients with 30% pain relief

52

21

More efficacious

ÂÂ

More convenient in women.

ÂÂ

Intradeltoid injection is suitable for obese/ overweight patients with thick subcutaneous fat in the gluteal region. Reduces chances of failure.

ÂÂ

Faster absorption from the deltoid region than from the gluteal region.

ÂÂ

Absence of propylene glycol, which is a known irritant on parenteral administration in the formulation, could be advantageous in terms of improved tolerability.

APPROPRIATE USE OF DICLOFENAC: TOPICAL FORMULATION

Advantages of Topical Drug Delivery Systems36 ÂÂ Avoidance of first pass metabolism. ÂÂ Convenient and easy to apply. ÂÂ Avoidance of the risks and inconveniences of IV therapy and of varied conditions of absorption like pH changes, presence of enzymes, gastric emptying time. ÂÂ Ability to easily terminate the medications, when needed. ÂÂ Ability to deliver drug more selectively to a specific site. ÂÂ Avoidance of gastrointestinal side effects. ÂÂ Improve patient compliance. ÂÂ Provide suitability for self-medication, etc.

Advantages of Topical Diclofenac vs. Oral Diclofenac37 ÂÂ Diclofenac is predominantly prescribed in oral form. ÂÂ Topical formulations of diclofenac are thought to be as efficacious as oral formulations without the risk of systemic side effects.

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Indian Journal of Clinical Practice, Vol. 26, No. 10, March 2016

ÂÂ

There is also the added benefit of adherence with medication and patient preference for topical rather than oral drugs.

Barriers to Penetration of Topical NSAIDs ÂÂ There are a number of factors that influence skin absorption of drugs. ÂÂ The greatest challenge for dermal penetration is stratum corneum (SC), the uppermost layer of the skin, which is the rate limiting step for epidermal drug transport.38 Mechanism of Diclofenac TPM Gel Formulation ÂÂ Tocopheryl phosphate mixture (TPM) = Tocopheryl phosphate (TP) + di-tocopheryl phosphate (T2P). ÂÂ They are phosphorylated forms of vitamin E (α-tocopherol). ÂÂ 1 g of diclofenac TPM 1% gel corresponds to 10 mg diclofenac sodium. ÂÂ Drug is embedded in a multilayered nanovesicle 100-130 nm. ÂÂ Diclofenac entrapped in high concentrations between the layers. ÂÂ Allows passage of diclofenac through the skin. ÂÂ Less skin irritation. ÂÂ Dual mechanism of action.

Role of Diclofenac Suppository in Pain Management Diclofenac can also be administered in the suppository form. Different trials with the use of diclofenac suppositories in management of pain are summarized in Table 3.39-41 DICLOFENAC PATCH ÂÂ

Fabrication of transdermal patch requires lots of attention regarding the amount of components used for it.42

DRUGS Table 3. Role of Diclofenac Suppository in Pain Management39-41 Author

Methods

Duration and No. of patients

Indication

Result

Conclusion

Vosoughin et al.

IV ketamine compared with diclofenac suppository

80 patients

Gynecologic laparoscopy

Pain scores and morphine requirements were lower in the rectal diclofenac suppository group at the 1st, 3rd and 6th postoperative hours

Diclofenac 100 mg suppositories were more effective in suppressing acute pain than 0.15 mg/kg IV ketamine

Ebrahim et al.

Diclofenac suppository vs. IV pethidine

180 patients

Postoperative pain

Nine (15%), 10 (16.65%) and 24 (40%) of patients in diclofenac, pethidine and control groups reported pain Pruritus was repetitive in the pethidine group

A single dose of sodium diclofenac suppository can provide satisfactory analgesia immediately after surgery and decrease shivering

Diclofenac sodium was a more effective analgesic than indomethacin suppositories for right mediolateral episiotomy pain

Diclofenac sodium suppositories are the preferred choice because they were more effective

Altungul et al.

Diclofenac sodium suppository vs. indomethacin suppository

70 patients

Mediolateral episiotomy

ÂÂ

Because of varied nature of polymer and plasticizer, transdermal patches have different properties and different drug release.42

ÂÂ

Injection pain was observed in the IM diclofenac group, but for both groups no skin reactions were observed at the application sites of the drugs.

ÂÂ

Transdermal patches offer added advantages such as maintenance of constant and prolonged drug level, reduced frequency of dosing, selfadministration and easy termination of medication leading to patient compliance.42

Diclofenac transdermal patch provided pain relief for postoperative laparoscopic surgery as effectively as IM diclofenac.43 PROTOCOL DEVELOPMENT

Diclofenac Patch vs. IM Diclofenac

Oral Diclofenac

Post laparoscopic surgery, pain management can reduce the discharge and recovery time. Thus conventional NSAIDs and opioids have been used for this purpose. Patients were randomized to receive IM diclofenac 75 mg (n = 30) 15 minutes before anesthesia or transdermal diclofenac (n = 30) 3 hours before laparoscopic surgery. Transdermal or IM diclofenac were reapplied 12 hours later. All patients were administered tramadol intravenously before surgery. Postoperative pain management was maintained with tramadol using a patient-controlled analgesia device. Postoperative visual analog pain scores (VAS, 0-10 cm) and adverse reactions were recorded over a 24-hour period.

ÂÂ

ÂÂ

In both groups, VAS scores were higher in the first 4 hours.

ÂÂ

The postoperative tramadol consumption, and rescue analgesic needs of the patients between both groups were not statistically significant.

Laryngitis/Pharyngitis.

IM Diclofenac ÂÂ Rheumatoid arthritis. ÂÂ Ankylosing spondylitis. ÂÂ Osteoarthritis. ÂÂ Acute attacks of gout. ÂÂ Post-traumatic and postoperative inflammation and swelling. ÂÂ

pain,

Severe migraine attacks.

IV Diclofenac ÂÂ

Treatment or prevention of postoperative pain.

Topical Diclofenac ÂÂ Post-traumatic inflammation of the tendons, ligaments, muscles and joints. ÂÂ Localized forms of soft-tissue rheumatism. ÂÂ

Osteoarthrosis.

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DRUGS Table 4. Recommendations for Topicals18,44 Guideline

Treatment recommendation

American Academy of Orthopedic Surgeons (2008)

Knee OA: Patients with symptomatic knee OA and increased risk for GI adverse events (age 60 years or older, comorbid medical conditions, history of peptic ulcer disease or GI bleeding and/or concomitant use of corticosteroids or anticoagulants) should receive one of the following analgesics for pain yy Acetaminophen (≤400 mg/day) yy Topical NSAIDs yy Nonselective oral NSAIDs plus gastroprotective agent yy COX-2 inhibitors

National Institute for Health and Clinical Excellence (2008)

Hand or knee OA: Acetaminophen or topical NSAIDs should be considered as first-line pharmacologic therapy after nonpharmacologic therapy. Acetaminophen or topical NSAIDs should be considered ahead of oral NSAIDs, COX-2 inhibitors or opioids as first-line pharmacologic therapies

American College of Rheumatology (2012)

Hand OA: First-line pharmacologic therapy for hand OA should included one or more of the following yy Topical NSAIDs, including trolamine salicylate yy Oral NSAIDs, including COX-2 inhibitors yy Topical capsaicin yy Tramadol Knee OA: First-line pharmacologic therapy for knee OA should include one of the following yy Acetaminophen yy Topical NSAIDs yy Oral NSAIDs yy Tramadol yy Intra-articular corticosteroid injections Patients aged 75 years or older with hand or knee OA should receive topical rather than oral NSAIDs

Table 5. Indications for Use of Different Oral Formulations 50 mg

75 mg SR

100 mg SR

150 mg SR

B.i.d./t.d.s.

O.d./b.i.d.

O.d.

Acute flare up of arthritis

Acute musculoskeletal injuries

Low back pain Postoperative pain

Dysmenorrhea

Maintenance OA

Initiation and Maintenance OA RAAS and LBP

Spinal OA (back pain)

Migraine

Cox arthrosis

Low back pain Dental pain

Recommendations for Topicals

ÂÂ

Short-term use of NSAIDs is generally safe in patients who are well-hydrated, have good renal function and do not have associated heart failure, diabetes or hypertension.

ÂÂ

Diclofenac when used at high doses of 150 mg/day for ≥4 weeks, marginally increases the risk of gastrointestinal complications, which is comparable to coxibs.

ÂÂ

However, the gastrointestinal complications associated with diclofenac is considerably less when compared to other NSAIDs, e.g., naproxen and ibuprofen.

The recommendations for use of topical NSAIDs are summarized in Table 4.18,44 The indications of the use of different oral formulations of diclofenac are summarized in Table 5.

DISCUSSION ÂÂ

944

Pain management with NSAIDs should consider the associated gastrointestinal, cardiovascular and renal risks.

Indian Journal of Clinical Practice, Vol. 26, No. 10, March 2016

DRUGS ÂÂ

Diclofenac is effective for pain management in OA with an anti-inflammatory and analgesic action.

ÂÂ

It is well-tolerated appropriately.

ÂÂ

Topical formulations of diclofenac are thought to be as efficacious as oral formulations without the risk of systemic side effects.

and

safe

when

used

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36. Ramsay MA. Acute postoperative pain management. Proc (Bayl Univ Med Cent). 2000;13(3):244-7.

27. Lanza FL, Chan FK, Quigley EM; Practice Parameters Committee of the American College of Gastroenterology.

Guidelines for prevention of NSAID-related ulcer complications. Am J Gastroenterol. 2009;104(3):728-38.

38. Nurse Prescribing 7.8 (2009): 346-350.

28. Stürmer T, Erb A, Keller F, Günther KP, Brenner H. Determinants of impaired renal function with use of nonsteroidal anti-inflammatory drugs: the importance of half-life and other medications. Am J Med. 2001;111(7):521-7.

29. Bennett WM, Henrich WL, Stoff JS. The renal effects of nonsteroidal anti-inflammatory drugs: summary and recommendations. Am J Kidney Dis. 1996;28(1 Suppl 1): S56-62.

30. Gambaro G, Perazella MA. Adverse renal effects of anti-inflammatory agents: evaluation of selective and nonselective cyclooxygenase inhibitors. J Intern Med. 2003;253(6):643-52.

31. Todd PA, Sorkin EM. Diclofenac sodium. A reappraisal of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy. Drugs. 1988;35(3):244-85.

32. Nurse Prescribing 2006 4:7, 290-3.

33. Jhunjhunwala HR, Naik AK. New dimension in pain management: diclofenac-colestyramine. Indian J Clin Pract. 2012;22(12):23-7.

37. Purushottam SS, Bhaskarrao GS, Bhanudas SR. Gelfield emulsion: A newborn formulation for topical delivery of hydrophobic drugs. World J Pharm Pharmaceut Sci. 2013;3(1):233-51.

39. Vosoughin M, Mohammadi S, Dabbagh A. ketamine compared with diclofenac in suppressing acute postoperative pain undergoing gynecologic laparoscopy.

2012;26(5):732-7.

Intravenous suppository in women J Anesth.

40. Ebrahim AJ, Mozaffar R, Nadia BH, Ali J. Early postoperative relief of pain and shivering using diclofenac suppository versus intravenous pethidine in spinal anesthesia. J Anaesthesiol Clin Pharmacol. 2014;30(2): 243-7.

41. Altungül AC, Sapmaz E, Kale A. Comparison of diclofenac sodium with indomethacin suppositories for mediolateral episiotomies. Clin Exp Obstet Gynecol. 2012;39(1):112-4.

42. Modi C. Effect of components (polymer, plasticizer and solvent) as a variable in fabrication of diclofenac transdermal patch. J Pharm Bioallied Sci. 2012;4 (Suppl 1):S57-9.

43. Karabayirli S, Demircioğlu RI, Muslu B, Usta B, Sert H, Gözdemir M. The comparative effects of transdermal and intramuscular diclofenac on post laparoscopic surgery pain. Surg Laparosc Endosc Percutan Tech. 2012;22(4): 374-8.

34. Hinz B, Chevts J, Renner B, Wuttke H, Rau T, Schmidt A, 44. Nair B, Taylor-Gjevre R. A review of topical diclofenac use et al. Bioavailability of diclofenac potassium at low doses. in musculoskeletal disease. Pharmaceuticals. 2010;3(6): Br J Clin Pharmacol. 2005;59(1):80-4.

1892-908.

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INTERNAL MEDICINE

Amebiasis Mimics Malignancy in the Transverse Colon and Transpires in Liver Abscess BV NAGABHUSHANA RAO*, BVS RAMAN†, SAILESH MODI‡, M UMAMAHESWARA RAO#

ABSTRACT Amebiasis is the problem of developing countries with inadequate sanitation. It may affect visitors from affluent nations if they stick around long enough. Presentation can be intestinal or extraintestinal. Amebiasis may present as pain abdomen, fever and weight loss without increased bowel movements. Ameboma, a rare complication of intestinal amebiasis may mimic malignancy or inflammatory bowel disease. We present a case of ameboma of transverse colon, an unusual site, which may increase suspicion of malignancy. Our patient developed liver abscess during illness, giving clues to the diagnosis. Metronidazole or tinidazole is the drug of choices; liver abscess may require drainage if it is large and where is impending rupture, it is located in the left lobe or there is delayed response to medical management. It is prudent to check for complete resolution of ameboma, not to leave behind a malignant lesion.

Keywords: Ameboma, transverse colon, mimics, malignancy, hepatic, abscess

A

mebiasis is caused by Entamoeba histolytica, a protozoan. Clinical manifestation can be either intestinal or extraintestinal. Over 50 million people are affected annually with a mortality of 1,00,000 people a year.1

Hepatic abscess is the most common extraintestinal problem, other organs that are affected less frequently are the lungs, heart and the brain. It is a disease of economically disadvantaged communities; in developed countries, it is commonly seen in immigrants or travelers.

Very rarely colonic infection may localize to form a mass of granulation tissue, an ameboma which may mimic colonic carcinoma in clinical presentation.

Metronidazole or tinidazole is the drug of choice for intestinal and extraintestinal amebiasis, paromomycin or diloxanide furoate need to be used in patients carrying intestinal cysts.

*Dept. of Medicine †Dept. of Surgery ‡Dept. of Neurology #Dept. of Radiology Queens NRI Hospital, Visakhapatnam, Andhra Pradesh Address for correspondence

Dr BV Nagabhushana Rao Dept. of Medicine Queens NRI Hospital, Visakhapatnam - 530 013, Andhra Pradesh E-mail: bhavanavnrao@gmail.com

CASE REPORT A 73-year gentleman was admitted to the hospital with symptoms of abdominal pain of 20 days duration. He was a diabetic on glimepiride 2 mg and metformin long-acting 500 mg daily.

His blood sugar was not under control and glycosylated hemoglobin (HbA1c) at the time of admission was 9%.

He is a frequent traveler and preferred to eat vegetable salads as he was a pure vegan. The pain was in periumbilical region and in right iliac fossa. Pain was not related food or radiating to other areas.

The patient was not nauseated and there were no loose motions or vomitings. He lost 6 kg weight in spite of normal appetite. There was no history of mucus or blood in the feces. The patient began to have fever 5 days prior to hospitalization, which was treated by family physician with intravenous ceftriaxone without much response. He underwent ultrasound examination of the abdomen, which revealed bowel wall thickening of ileocecal junction, which was suspicious of tuberculosis or inflammatory bowel disease.

Contrast-enhanced computed tomography (CECT) of the abdomen was performed for further evaluation of the intestinal lesions. It was found on computed tomography (CT) to be a focal eccentric mural thickening of cecum and transverse colon (Fig. 1). He underwent colonoscopy, the gastroenterologist felt that patient might be having tuberculosis or malignancy in

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INTERNAL MEDICINE

Figure 1. CECT of the abdomen, showing focal eccentric mural thickening of transverse colon.

Figure 3. CT scan of chest demonstrated 55 × 50 × 39 abscess in the left lobe of liver.

ameba were demonstrated in the aspirate. He was given tinidazole 2 g a day intravenously for 5 days and orally for another 10 days. His fever subsided in 3 days and intestinal lesions resolved in a month’s time on colonoscopy and CT scan.

DISCUSSION

Figure 2. Ulcerated nodular lesions in the transverse colon with skipped lesions by colonoscopic examination.

the view of ulcerated nodular lesions in ileocecal valve and transverse colon with skipped lesions (Fig. 2).

Multiple biopsies were taken and sent for histopathological examination. At that stage he was referred to our hospital. Histopathologist reported it to be focal active colitis with super added ulcers and acute inflammation. On CD3 IHC and CD20 IHC, they found it positive in a few lymphocytes. This indicated that it may be inflammatory bowel disease. As the patient was persistently pyrexial, we did CT chest to find out any evidence of pulmonary tuberculosis or mediastinal lymphadenopathy. To our surprise, we found that he had a 55 × 50 × 39 abscess in the left lobe of liver (Fig. 3).

Under CT guidance 100 mL anchovy sauce-colored pus was aspirated and on saline mounting multiple

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Intestinal and extraintestinal complications of amebiasis are more common in adult males and travelers within the community. Amebic hepatic abscess is more common in a diabetic.2 Ameba establishes hepatic infection through the portal circulation. Our patient was a poorly controlled diabetic and a frequent traveler too, exposing himself to amebic infection and its complications. Factors that predispose one to severe infections include genetic susceptibility, age, immune status, pregnancy, corticosteroid treatment, malignancy, malnutrition and alcoholism. Amebiasis commonly presents with dysentery, but may only present with abdominal pain and weight loss as in our patient.

Rarely, colonic infection may localize to form a mass of granulation tissue, an ameboma mimicking a colonic malignancy.3 It has been reported that sometimes, it may present as acute intestinal obstruction or intussusception. Our patient presented with pain abdomen, fever and weight loss. His ultrasound and CT scan abdomen displayed thickenings of cecum and transverse colon. On colonoscopy, nodular ulcerated skip lesions were found which were suspected to be malignant. Histopathological examination of a biopsy specimen taken at colonoscopy suggested that it might be inflammatory bowel disease. At times, it may be difficult to differentiate amebic colitis from

FOR PRODUCTIVE COUGH

FOR DRY, IRRITATING AND ALLERGIC COUGH

FOR NOCTURNAL COUGH

2015 2016

in Cough Management

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 inflammatory bowel disease clinically, endoscopically and histopathologically.4 In such situations, administration of steroids can be detrimental if the patient has an amebiasis instead of inflammatory bowel disease. We should be extravigilant when managing ulcerative intestinal lesions in endemic areas of amebiasis. As we were searching for any other cause of fever in this individual, we found an abscess in the liver which was not seen in the previous ultrasound and abdominal CT scan.

Anchovy sauce-colored pus was aspirated pointing towards amebic abscess rather than pyemic abscess.

We could also demonstrate amebic trophozoites confirming the diagnosis which is often difficult to do.

Colonic mass in the form of ameboma and liver abscess have been reported in the literature, confounding with colonic malignancy and hepatic metastasis leading to surgical procedures like colonic resection.5 But there are not many reports of transverse colonic ameboma with liver abscess.

Liver abscess may rupture into pleura, pericardium, lungs or peritoneum. Unless large in size or located in the left lobe of liver, it can an be managed with medical treatment without recourse to aspiration. In our patient, we demonstrated clearance of pathological lesions endoscopically. Complete resolution of ameboma should be observed by colonoscopic examination, otherwise we may miss a concomitant malignant lesions.

CONCLUSIONS Ameboma, a rare intestinal manifestation of amebic infection may present with pain abdomen alone without a history of dysentery and mimic malignancy or inflammatory bowel disease. Vigilance should be maintained as a liver abscess may develop during the course of illness rather at inception.

Acknowledgment We thank Dr Ramakoteswara Rao, Pathologists, Chaitanya Medical Centre for his expertise.

REFERENCES 1. Bercu TE, Petri WA, Behm JW. Amebic colitis: new insights into pathogenesis and treatment. Curr Gastroenterol Rep. 2007;9(5):429-33.

2. Jha AK, Das A, Chowdhury F, Biswas MR, Prasad SK, Chattopadhyay S. Clinicopathological study and management of liver abscess in a tertiary care center. J Nat Sci Biol Med. 2015;6(1):71-5.

3. Misra SP, Misra V, Dwivedi M. Ileocecal masses in patients with amebic liver abscess: etiology and management.

World J Gastroenterol. 2006;12(12):1933-6.

4. Tucker PC, Webster PD, Kilpatrick ZM. Amebic colitis mistaken for inflammatory bowel disease. Arch Intern Med. 1975;135(5):681-5.

5. Moorchung N, Singh V, Srinivas V, Jaiswal SS, Singh G. Caecal amebic colitis mimicking obstructing right sided colonic carcinoma with liver metastases: a rare case.

J Cancer Res Ther. 2014;10(2):440-2.

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Clinical Pearls: Iron-deficiency Anemia BHARAT J PARMAR*, JWAL DOCTOR†

ABSTRACT Iron deficiency is a very common nutritional disorder affecting at least one-third of world population. Iron-deficiency anemia (IDA) is the most common form of anemia in the world. The aim of this review article is to cover the global nature of the disease, iron homeostasis in normal and iron-deficient states, clinical findings, treatment and causes of iron-resistant iron deficiency. Iron is crucial to biologic functions, including respiration, energy production, DNA synthesis and cell proliferation. Although the prevalence of IDA has declined somewhat recently, iron deficiency continues to be the top-ranking cause of anemia worldwide.

Though anemia is common manifestation of iron deficiency, other effects of iron deficiency on various tissues, organs and systems are usually under recognized. Impaired brain development and cognitive, behavioral and psychomotor impairment are worrisome manifestation of iron deficiency. Studies have demonstrated that some of the changes occurring during period of brain growth spurt (<2 years age) may be irreversible. Association of iron deficiency with febrile convulsion, pica, breath holding spells, restless leg syndrome and thrombosis is increasingly being recognized. Impaired cell-mediated immunity and bactericidal function are generally noted in iron deficiency; however, the findings are inconsistent.

Keywords: Iron-deficiency anemia, cognition, breath holding spells, pica, febrile convulsion, thrombosis, restless leg syndrome, infections

I

ron deficiency affects at least a third of world’s population and is second only to hunger, as a major worldwide, nutritional problem.1 Iron-deficiency anemia (IDA) is a very well-known concept, but what is often not appreciated is the broad canvas of effects of iron deficiency on various tissues, organs and systems in human beings leading to the concept of “iron deficiency disease”.

deficiency not only breaks the machine, but also breaks the machinery”. This article reviews impaired brain development, cognitive, behavioral and psychomotor impairment, immune dysfunction and role of iron deficiency in febrile seizures, pica, breath holding spells, restless leg syndrome and thrombosis.2-4

Anemia is just one manifestation of iron deficiency, there are other forms of mild-to-moderate iron deficiency in which anemia is absent but tissue function is impaired.

In iron deficiency, not only tissue delivery of oxygen is compromised but proliferation, growth, differentiation, myelinogenesis, immune function, energy metabolism, absorption and biotransformation are also affected leading to abnormal growth and behavior, reduced cardiac performance and work efficiency, infection, etc., which ultimately leads to the concept that “iron

The human body has evolved to conserve iron in several ways, including the recycling of iron after the breakdown of red cells and the retention of iron in the absence of an excretion mechanism. The mechanism is controlled by hepcidin hormone, which maintains total-body iron within normal range, avoiding both iron deficiency and excess. Iron deficiency is associated with increased red cell porphyrin, which inhibits ferrochelatase enzyme, which further inhibits heme synthesis. This eventually leads to decreased hemoglobin synthesis and IDA ensues. Besides this, decreased activity of ribonucleotide reductase and pyruvate dehydrogenase enzyme has also been demonstrated in iron deficiency, which explain decreased DNA synthesis and impaired cellular oxidation, respectively. Iron is also require for normal oligodendrocyte function and myelination; synthesis of neurotransmitters (dopamine, norepinephrine and epinephrine) by tryptophan hydroxylase and tyrosine hydroxylase enzymes and for normal brain energy metabolism.5,6

*Associate Professor

Dept. of Pediatrics

BJ Medical College, Civil Hospital, Ahmedabad, Gujarat †Institute of Pharmacy, Nirma University, Ahmedabad, Gujarat Address for correspondence

Dr Bharat J Parmar Associate Professor Dept. of Pediatrics BJ Medical College, Civil Hospital, Ahmedabad - 380 004, Gujarat

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PATHOGENESIS

INTERNAL MEDICINE Erythropoiesis Fe

DMT1

+ EPO

Fe HIF-2α

Erythroblasts

Enterocyte

HIF-2α

ERFE? TMPRSS6

FPN

Kidney

Fe

Red cells BMP6

All organs

Fe

Fe

Fe

Hepcidin

Hepatocyte Fe Heart

Fe

Fe

Apotransferrin

Skeletal muscle

Fe FPN

Fe

Spleen macrophage

Figure 1. The iron cycle—mechanisms of adaptation to iron deficiency.

IRON AND BRAIN Behavioral and cognitive dysfunction are the most worrisome manifestation of iron deficiency. Recent research has revealed that anemia is late manifestation of iron deficiency, brain deficiency occurs even with normal level of hemoglobin, as iron is prioritized to red blood cells over all other organs including brain. The biological basis of the behavioral and cognitive development delays is abnormalities in neurotransmitter metabolism, decreased myelin formation and alterations in brain energy metabolism.5 IDA AND INFANTS <2 YEARS AGE In infants, adverse effects of iron deficiency on behavior are of special concern because the latter part of brain spurt coincides with the period in which IDA is most prevalent (6-24 months). Observational studies have suggested that iron-deficient children have lower IQ scores, decreased attentiveness and lower scores on tests of academic performance compare with nonanemic controls. These studies indicates that IDA in infancy, perhaps of particular severity and chronicity, has irreversible cognitive impairment.7 IDA IN CHILDREN >2 YEARS AGE Observational studies in children over 2 years have reported poorer cognition and school achievement in

iron-deficient children. Adolescent girls are particularly susceptible to iron deficiency because of poor dietary intake along with increased iron requirement related to rapid growth and menstrual blood loss and are at greater risk of cognitive impairment.8 PREVENTIVE TRIALS Two recent trials reported developmental and behavioral benefits from iron supplementation in infancy.

IDA AND PICA The word pica is derived from Latin root meaning magpie, a bird capable of eating a variety of things.

Lanzkowsky define pica as “a perversion of appetite with persistent and purposeful ingestion of unsuitable substances seemingly of no nutrient value”. Common pica includes geophagia (dirt or clay ingestion) trichophagia (hair ingestion), amylophagia (starch ingestion) and pagophagia (ice ingestion). Whether iron deficiency causes pica vice versa is subject to debate.

Exact pathophysiology of pica in association with iron deficiency state is unknown, but decreased activity of cytochrome oxidase in buccal mucosa has been reported, which might explain various forms of pica.

Besides this, a central mechanism due to deficiency of iron requiring enzymes in central nervous system has also been postulated.9

Indian Journal of Clinical Practice, Vol. 26, No. 10, March 2016

955

INTERNAL MEDICINE IDA AND BREATH HOLDING SPELLS

IDA AND RESTLESS LEG SYNDROME

The exact role of iron in breath holding spells is not known. However, abnormalities in catecholamine metabolism and various neurotransmitters may explain association of breath holding spells with IDA. The correction of spells with iron therapy may be related to the functional restoration of these neurotransmitters.10

Restless leg syndrome is characterized by repeated aphasic involuntary muscles contractions. It is mostly reported in adult patients and largely under reported from pediatric population. Although, most of the cases with restless leg syndrome are idiopathic or hereditary; decreased brain iron content and metabolism can lead to RLA. Iron deficiency state may precipitate restless leg syndrome in as much as 25-30% of people. Magnetic resonance imaging (MRI) studies have demonstrated decreased iron content in substantia nigra and red nucleus.13

IDA AND FEBRILE SEIZURES Febrile seizures are the most common type of seizures, occurring in 2-5% of all children. Kebrinsky et al studied the role of iron in febrile seizures and they reported significantly increased incidence of iron deficiency in nonseizures compared to seizure group.

They postulated that iron deficiency may raise the seizure threshold and protect against the development of febrile seizures. Exact etiology of febrile seizures is not clear; however, dependent metabolism of several neurotransmitters, enzyme activities and cerebral erythropoietin has been postulated as causative factor for seizures.7 IDA AND THROMBOSIS Over the last few years, association of iron deficiency and thrombotic complications is being increasingly recognized. This increased incidence of thrombotic complications in IDA has been linked to various factors. Increased level of erythropoietin in IDA has been incriminated to have a possible role in stimulating megakaryopoiesis, resulting in thrombocytosis.

Recently, Bilic and Bilic have reported that amino acid sequences homology of thrombopoietin and erythropoietin may explain the thrombocytosis in children with IDA. In addition to the increased thrombotic risk associated with high platelet count, other possible mechanism suggested is decreased antioxidant defense in IDA leading to increased oxidative stress, which in turn may result in a tendency toward platelet aggregation. Reduced deformability and increased viscosity of microcytic red blood cells in iron deficiency may be contributory by affecting blood flow patterns within the vessels.

Furthermore, anemic hypoxia secondary to iron deficiency could precipitate situations of increased metabolic stress (i.e., infection) particularly in vulnerable area of brain supplied by end arteries, such as the basal ganglia, thalamus and hypothalamus resulting in stroke.11,12

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IRON AND INFECTION Iron is required for normal immune function, cell differentiation and growth. Iron is also required for peroxide generating mechanism, cytokine production and myeloperoxidase function in neutrophils. Impaired cell-mediated immunity and bactericidal function are generally noted in iron-deficient children; however, the findings are inconsistent.14 CONCLUSION Being the most common nutritional disorder, it is imperative to recognize effects and long-term consequences of iron deficiency. Though anemia is common, iron deficiency state without anemia is largely under-recognized. Studies have reported lower cognitive scores even in children with iron deficiency without anemia.

Irreversible cognitive impairment has been reported in children who experienced iron deficiency during period of critical brain growth (<2 years of age). IDA is highly prevalent in India (reported 55.7-85.1% in different states in the National Family Health Survey [NFHS]-3) and there is a much larger population having iron deficiency without anemia; hence, it is critical to recognize the cognitive impairment and treat early.

REFERENCES 1. Zeng X, Wu T. Iron supplementation for iron deficiency anemia in children. Cochrane Database Syst Rev. 2007;(2):CD006465.

2. Panagiotou JP, Douros K. Clinicolaboratory findings and treatment of iron-deficiency anemia in childhood. Pediatr Hematol Oncol. 2004;21(6):521-34.

3. Saloojee H, Pettifor JM. Iron deficiency and impaired child development. BMJ. 2001;323(7326):1377-8.

4. Ghosh K. Non haematological effects of iron deficiency - a perspective. Indian J Med Sci. 2006;60(1):30-7.

Contâ&#x20AC;&#x2122;d on page 967...

INTERNAL MEDICINE

Clinico-hematological Profile of Kala-azar in Nonendemic Area: A Case Series PRAVEEN KUMAR*, KALPANA CHANDRAâ&#x20AC;

ABSTRACT The incidence of Kala-azar is highest in India among the world and is mostly confined in plains. High altitudes adversely affect the distribution of this protozoan as well as its vector, but recently few sporadic cases and even outbreak from nonendemic hilly areas roughly 2,000 ft above sea levels has been reported. We are reporting eight cases of Kala-azar hailing from Uttarakhand and Western Uttar Pradesh over a period of 3 years, who were admitted in SRMS-IMS, Bareilly. In our cases, patients were having fever, hepatomegaly with moderate-to-massive splenomegaly and pancytopenia. There was no travel history to any endemic area and were being treated on the lines of long list of its close differentials by the local doctors. This warns the treating physicians that every case presenting with pyrexia of unknown origin with pancytopenia and extreme emaciation with moderate-to-severe splenomegaly should be investigated for Kala-azar even in those patients who have not traveled in endemic areas.

Keywords: Kala-azar, pancytopenia, pyrexia of unknown origin

L

eishmaniasis is a vector-borne disease that is caused by obligate phlebotomine sand flies, which manifest diseases in two forms: The cutaneous (dry and wet) and the visceral (Kala-azar).

The annual estimate for the incidence and prevalence of Kala-azar worldwide is 0.5 million and 2.5 million, respectively. Of these, 90% of the confirmed cases occur in India, Nepal, Bangladesh and Sudan. In India, it is a serious problem in Bihar, West Bengal and Eastern Uttar Pradesh. Untreated cases of Kala-azar are associated with up to 90% mortality, which with treatment reduces to 15% and is 3.4% in specialized hospitals.1 Kala-azar is normally distributed in plains.

projects such as forest clearing, cultivation projects, large water resources schemes, colonization and resettlement programs exposing more people to leishmaniasis by bringing human being into areas of high-vector and resource concentration.3 Secondly, the laborers employed are mainly from Bihar, Jharkhand, Eastern Uttar Pradesh and Nepal where this disease is endemic.4

High altitude adversely affects the distribution of this protozoan as well its vector. Recently, there is significant increase in the number of cases of Kala-azar in highlands.2 This may be the result of developmental

CASES

*Associate Professor Dept. of Medicine Indira Gandhi Institute of Medical Sciences, Patna, Bihar â&#x20AC; Consultant Pathologist Dept. of Pathology Mahavir Cancer Sansthan, Patna, Bihar Address for correspondence

Dr Praveen Kumar Flat-501, Yamuna-1, Jalalpur City, Near BR Ambedkar Dental College Ramjaipal Road, Bailey Road, Danapur, Patna - 801 503, Bihar E-mail: praveenkmr_23@yahoo.co.in

All the eight cases, we will be discussing were clinically unsuspected, had no travel history to any endemic area and were being treated on the lines of long list of its close differentials by the local doctors.

Case 1 A 24-year-old male, resident of Western Uttar Pradesh admitted in Pulmonary Department with chief complaints of fever, cough, generalized weakness and weight loss for 5 months. Physical examination revealed palor, mild hepatomegaly and massive splenomegaly without any lymphadenopathy or free fluid in abdomen. Biochemical investigation revealed serum bilirubin total/direct (T/D) - 1.9/1.1 mg/dL, serum glutamic oxaloacetic transaminase/serum glutamic pyruvic transaminase (SGOT/SGPT) - 112/26 IU/L; total protein - 6.1 g/dL and albumin:globulin (A:G) ratio - 0.8.

Chest X-ray was normal. Bone marrow aspiration was

Indian Journal of Clinical Practice, Vol. 26, No. 10, March 2016

957

INTERNAL MEDICINE done, which revealed hypercellular marrow with heavy load of extracellular and intracellular amastigotes of Leishmania donovani. Recombinant kinesin 39 (rK39) was not done in this case. During the investigation period, the platelet count further diminished. Treatment for Kala-azar started, but the patient expired after 2 days.

Case 2 A 53-year-old male, resident of Champawat, Uttarakhand presented with history of fever, loss of appetite, vomiting and cough associated with hemoptysis for 3 months. On physical examination, patient had moderate splenomegaly without any hepatomegaly or lymphadenopathy.

Biochemical investigation revealed serum bilirubin T/D - 0.8/0.5 mg/dL, SGOT/SGPT - 34/12 IU/L, total protein - 7.5 g/dL and A:G ratio - 0.7. Chest X-ray was normal. Bone marrow aspiration cytology revealed normocellular marrow with 16% of reactive plasmacytosis. No hemoparasite was found. rK39 was positive. Patient was treated with amphotericin and improved completely.

Case 3 A 35-year-old female, resident of Naukuchiatal, Uttarakhand presented with fever with chills, headache, bodyache and cough for 2 months. On physical examination, mild hepatomegaly and moderate splenomegaly was found without lymphadenopathy.

Biochemical investigation revealed serum bilirubin T/D - 0.4/0.2 mg/dL, SGOT/SGPT - 91/48 IU/L, total protein - 7.3 g/dL, A:G ratio - 0.4. USG abdomen showed hepatosplenomegaly with cholelithiasis. Bone marrow aspiration cytology showed hypercellular marrow displaying erythroid hyperplasia with megaloblastoid changes and myeloid series showed features of dysmyelopoiesis. rK39 was positive. With treatment, patient recovered completely.

Case 4 A 11-year-old female of Mahendranagar, Nepal presented with abdominal distension with fever and weakness for 4 months. On physical examination, marked splenomegaly and mild hepatomegaly was found. Biochemical investigation revealed serum bilirubin T/D - 0.8/0.4 mg/dL, SGOT/SGPT - 60/45 IU/L, total protein - 7.8 g/dL, A:G ratio - 0.5. Bone marrow was done, which was hypercellular for age along with extracellular and intracellular amastigote form of L. donovani. rK39 was positive. With treatment, patient recovered completely.

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Indian Journal of Clinical Practice, Vol. 26, No. 10, March 2016

Case 5 A 30-year-old female, resident of Almorah came with complaints of intermittent fever for 25 days and abdominal pain for 10 days. Vomiting was present, which contained undigested particle. On physical examination, massive splenomegaly with hepatomegaly was present. Biochemical investigation revealed serum bilirubin - T/D 3.4/2 mg/dL, SGOT/SGPT - 393/78 IU/L, serum alkaline phosphatase (ALP) - 319 IU/L, total protein - 8.1 g/dL with A:G ratio of 0.2. C-reactive protein was done, which was 11.9 mg/dL (normal value - <0.6 g/dL). Bone marrow aspiration cytology showed normocellular marrow with reactive plasmacytosis of 16% and amastigote L. donovani bodies consistent with leishmaniasis. rK39 was positive. With treatment, patient recovered completely.

Case 6 A 27-year-old male, resident of Srinagar, Uttarakhand presented with fever off and on and swelling of lower limbs for 5 months, cough with sputum for 2 months, malena for 2 days and 2 episodes of hemoptysis. On physical examination; palor, icterus and edema was present. Cardiovascular system and respiratory system was within normal limits. Abdominal examination showed moderate splenomegaly with mild hepatomegaly. Biochemical investigations were serum bilirubin T/D - 2.3/ 1.4 mg/dL, SGOT/SGPT - 455/260 IU/L, total protein - 6.5 g/dL, A:G ratio - 0.3. Bone marrow cytology showed hemoparasite consistent with amastigote form of L. donovani bodies. rK39 was positive. With treatment, patient recovered completely.

Case 7 A 46-year-male, resident of Rudrapur, near Udham Singh Nagar presented with fever with chills, bodyache and weakness for 1 month. On physical examination, mild hepatomegaly and moderate splenomegaly was found.

Other relevant investigations were serum bilirubin T/D - 3.8/2.8 mg/dL, SGOT/SGPT - 150/34 IU/L, total protein - 6.8 g/dL, A:G ratio - 0.8. Bone marrow was done, which showed hypercellular marrow fragments with numerous L. donovani bodies within macrophages and lying extracellularly. With treatment patient recovered completely.

Case 8 A 21-year-old male, resident of Uttarakhand presented with fever for 2 months, loss of appetite for 1 month, mild jaundice for 15 days, pain abdomen for 15 days and edema of lower limb for 15 days. He was treated

INTERNAL MEDICINE outside with no improvement where his renal function and liver function tests were deranged. He was referred to our hospital for dialysis. On physical examination, he had hepatomegaly and moderate slpenomegaly.

His biochemical investigation revealed serum bilirubin - T/D-3.4/2.2 mg/dL, SGOT/SGPT - 1,780 IU/L/10, 39I U/L, serum urea - 146 g/dL and serum creatinine - 5 mg/dL. On bone marrow aspiration cytology, amastigote form of L. donovani bodies were present lying both extracellularly and intracellularly. rk39 was also positive. The treatment of Kala-azar was started and patient recovered fully.

In all the patients discussed above viral markers like human immunodeficiency virus (HIV) hepatitis B and anti-hepatitis C virus (HCV) were negative.

DISCUSSION Kala-azar is a tropical infectious disease of reticuloendothelial system caused by amastigote form of L. donovani. Sand fly is the vector, whereas man is the usual reservoir. Sand fly is infected by sucking blood of patients of Leishmaniasis where this protozoan proliferates as promastigote forms in the gut of sand fly and assumes amastigote form when transmitted to vertebrate host. They replicate in the macrophages of the mononuclear system and spreads to reticuloendothelial system causing marked hyperplasia of it. It affects all age groups with a peak in 5-9 years of age. Male is twice commonly affected than female.5 The incubation period is 2-6 months. The main clinical features of this disease are fever usually associated with chills and

rigors, fatigue, loss of appetite, weight loss, weakness, anemia and hepatosplenomegaly.5 It is diagnosed in endemic area by persistent fever of more than 2 weeks duration with splenomegaly and is confirmed by rapid diagnostic therapy (RDT) or a biopsy.5 Early diagnosis and treatment are essential for both the patient and for the community as untreated patients act as reservoir for parasite.

In our cases, patients were having fever, hepatomegaly with moderate-to-massive splenomegaly and pancytopenia. These features are there in Kala-azar and also in other febrile conditions such as malaria, enteric fever, tuberculosis, hepatitis. So, to diagnose Kala-azar in nonendemic area is always difficult and challenging.

All cases in my study were negative for malaria, typhoid, hepatitis B, HCV and HIV. Hematologically, Kala-azar patients are having pancytopenia which is having high specificity of about 98% but lacks sensitivity (16%).6 In our patients, there was marked leukopenia in majority of cases with lymphocytosis, anemia and thrombocytopenia (Table 1). These findings were consistent with the findings observed by Chandra et al where they found pancytopenia and thrombocytopenia in 96.2% of cases.2 Liver function was deranged in five cases with features of hepatitis. Few workers have reported mild-to-severe derangements of liver function which improved after treatment. The exact etiology of hepatic damage is unclear but may have an immunological basis. Kumar et al have also reported functional derangement of liver function in visceral leishmaniasis, whereas Mathur et al

Table 1. Hematological Profile of Patients Case No.

Hb (g/dL)

TLC (cumm)

DLC

Platelets (cumm)

ESR (mm/1st hour)

MP/Widal

Bone marrow

rK39

1

5.3

900

N46,L50,E0,M4

51,000

124

Negative

LD body present

Not done

2

6.1

9,700

N49,L48,E0,M3

90,000

72

Negative

Reactive lymphocytosis & plasmacytosis

Positive

3

6.1

1,100

N35,L62,E0,M3

63,000

73

Negative

Erythroid hyperplasia with megaloblastoid change

Positive

4

8.2

5,100

N31,L68,E0,M1

1,00,000

69

Negative

LD body present

Positive

5

7.9

600

N35,L63,E1,M1

22,000

69

Negative

LD Body present

Positive

6

5.11

2,400

N31,L66,E0,M03

20,000

52

Negative

LD body present

Positive

7

7.2

1,700

30,000

-

Negative

LD body present

Positive

8

6.9

2,100

88,000

65

Negative

LD body present

Positive

N59,L40,M01

Hb = Hemoglobin; TLC = Total leukocyte count; DLC = Differential leukocyte count; ESR = Erythrocyte sedimentation rate; LD = Leishmania donovani.

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INTERNAL MEDICINE found hepatitis in their case which was associated with hemophagocytic syndrome (HPS).7,8 One patient had deranged renal function and liver function and was managed by supportive care, hemodialysis and specific treatment for Kala-azar.

Renal abnormalities caused by Leishmania have been well-documented in experimental animal studies.

It is probably mediated by an immune complex.

Histopatholgically, it is characterized as proliferative glomerulonephritis and interstitial nephritis.9 Dutra et al conducted a study on renal involvement in 50 patients of visceral leishmaniasis. Proteinuria and/or microscopic hematuria or pyuria was observed in 51%.

There was a tubulointerstitial involvement in all seven patients who underwent kidney biopsy and, in five of them, a proliferative glomerulonephritis was also detected.10 Daher et al reviewed 57 patients with visceral leishmaniasis in 2008. Acute kidney injury (AKI) was observed in 15 patients (26.3%); 8 of these patients had AKI before amphotericin B administration.11 On bone marrow aspiration cytology, erythroid hyperplasia, plasmacytosis and dysmyelopoiesis were frequently observed findings in all the eight cases discussed above. Similar observations on bone marrow aspiration cytology were made by Chandra et al and concluded that these findings are helpful indicators of leishmaniasis.2 Direct visualization of amastigote forms of parasite is most specific but not very sensitive, ranging from 53% to 86%.6 On bone marrow aspiration cytology, we also could not appreciate L. donovani bodies in two cases on direct microscopy (Fig. 1). rK39 was done in all cases except one and was positive in all cases. This test is rapid, cheap and easy to perform

and gives reproducible result. Recently, this test has given excellent diagnostic performance on Indian and Nepalese patients.6 A meta-analysis that included 13 validation studies of rK39 ICT showed sensitivity and specificity estimates of 93.9% and 95.3%, respectively.12 rK39 is currently the best available diagnostic tool for visceral leishmaniasis.

CONCLUSION Kala-azar should be considered a possible diagnosis in patients with unexplained fever, pancytopenia, and extreme emaciation with moderate-to-severe splenomegaly even in nonendemic area without any significant travel history. This may save time and money as well as timely intervention may decreases numbers of death.

Acknowledgment I take this opportunity to extend my gratitude and sincere thanks to all those who helped me to complete this study. I am highly thankful to Dept. of Medicine, Pediatric, Pulmonology, Pathology and Biochemistry for providing me adequate facility, which helped me to carry out this study. I owe great sense of indebtedness to dean SRMS-IMS, Bhojipura, Bareilly for permitting me to carry out this study.

REFERENCES 1. Bora D. Epidemiology of visceral leishmaniasis in India.

Natl Med J India. 1999;12(2):62-8.

2. Chandra H, Chandra S, Kaushik RM. Visceral leishmaniasis with associated common, uncommon, and atypical morphological features on bone marrow aspirate cytology in non endemic region. J Trop Med. 2013;2013:861032.

3. Kumar A, Rawat V, Thapliyal N, Saxena SR. Kala-azarA case series from non endemic area, Uttarakhand. Ann Trop Med Public Health. 2013;6(3):355-7.

Extracellular LD body

5. Park K. Leishmaniasis. In: Park’s Textbook of Preventive and Social Medicine. 23rd Edition, India: M/s Banarasidas Bhanot Publishers; 2015. pp. 304-8.

Late normoblast

Extracellular LD body

Figure 1. Bone marrow smear (MGG, oil immersion) showing L. donovani body.

960

4. Raina S, Mahesh DM, Kaul R, Satindera KS, Gupta D, Sharma A, et al. A new focus of visceral leishmaniasis in the Himalayas, India. J Vector Borne Dis. 2009;46(4):303-6.

Indian Journal of Clinical Practice, Vol. 26, No. 10, March 2016

6. Chappuis F, Sundar S, Hailu A, Ghalib H, Rijal S, Peeling RW, et al. Visceral leishmaniasis: what are the needs for diagnosis, treatment and control? Nat Rev Microbiol.

2007;5(11):873-82.

7. el Hag IA, Hashim FA, el Toum IA, Homeida M, el Kalifa M, el Hassan AM. Liver morphology and function in visceral leishmaniasis (Kala-azar). J Clin Pathol.

1994;47(6):547-51.

Cont’d on page 976...

OBSTETRICS AND GYNECOLOGY

A Study to Evaluate Safety and Efficacy of Postpartum Intrauterine Contraceptive Device Insertion MAMTA RANI*, PARNEET KAUR†, KHUSHPREET KAUR‡, GURDIP KAUR#, SATINDER PAL KAUR¥

ABSTRACT Introduction: The postpartum period presents a critical window of opportunity to provide family planning counseling and methods to women who may not otherwise receive family planning services. Postpartum intrauterine contraceptive device (PPIUCD) insertion is one such method. Objective: To determine safety and efficacy of PPIUCD insertion in normal vaginal delivery and during cesarean section. Methods: This study was conducted in Dept. of Obstetrics and Gynecology, Government Medical College and Rajindra Hospital, Patiala from January 2012 to September 2013. The subjects were divided into two groups, Group I in which Copper-T 380 A insertion was done within 10 minutes of delivery of placenta and Group II in which insertion was done during cesarean section using PPIUCD forceps. Follow-up was done at 6 weeks, 3 months and 6 months.

Observations: Continuation rate was 89.79% in Group I and 96% in Group II at the end of 6-month follow-up period. Among both the groups, continuation rate was 92.9%. Expulsion rate was higher in Group I (4.08%) as compared to Group II, in which no expulsion occurred. Removal rate was 6.12% in Group I and 4% in Group II. None of the clients reported with perforation, infection or failure in our study. Conclusions: PPIUCD insertion is a safe, convenient, cost-effective, reversible and long-term birth spacing method. It can be used as an alternative to permanent sterilization. It should be part of every maternal/newborn/ reproductive health package.

Keywords: Copper-T 380 A, PPIUCD, postplacental, intracesarean

C

urrent population of India is 1.21 billion as per 2011 census. India contributes to about 20% of births worldwide.1 Approximately 61% of births in India occur at intervals that are shorter than recommended birth-to-birth interval of approximately 36 months.

Women in an unplanned pregnancy account for a significant number of inpatients in maternity hospitals.

Recent studies estimate that prevention of unplanned and unwanted pregnancies could help avert 20-35% of maternal deaths and as many as 20% of child deaths.2

POSTPARTUM PERIOD The postpartum period presents a critical window of opportunity to provide family planning counseling and

*Junior Resident †Professor ‡Professor and HOD #Associate Professor ¥Medical Officer Dept. of Obstetrics and Gynecology Government Medical College and Rajindra Hospital, Patiala, Punjab Address for correspondence

Dr Parneet Kaur House No. 52, Phulkian Enclave, Patiala - 147 001, Punjab E-mail: parneetkd@yahoo.co.in

methods to women who may not otherwise receive family planning services. Family planning methods can be used immediately following childbirth and will help prevent subsequent mistimed or unwanted pregnancies, especially since women’s fertility can return within weeks of delivery.

The time during pregnancy and immediately after delivery may be the only time for physician to connect with women who are poorly motivated to obtain routine healthcare, best described as crises-oriented.3 The World Health Organization’s recently revised guidelines on postpartum and newborn care include a provision for family planning counseling as a core component of postpartum care.2 Thus, postpartum period is potentially an ideal time to begin contraception as women are more strongly motivated to do so at this time, which also has the advantage of being convenient for both patients and healthcare providers.4 The following family planning methods can be used in postpartum period:2 ÂÂ

Postpartum intrauterine (PPIUCD) insertion

ÂÂ

Lactational amenorrhea

ÂÂ

Progestin only pills

contraceptive

Indian Journal of Clinical Practice, Vol. 26, No. 10, March 2016

device

961

OBSTETRICS AND GYNECOLOGY ÂÂ

Combined estrogen progestin pill

ÂÂ

Barrier methods like diaphragm/cervical cap

ÂÂ

Sterilization

ÂÂ

Emergency contraception in the form of pills or intrauterine contraceptive device (IUCD).

ÂÂ

condoms/spermicides,

Taking advantage of the immediate postpartum period for counseling on family planning and IUCD insertion, overcomes multiple barriers to service provision. The increased institutional deliveries are the opportunity to provide woman with easy access to immediate PPIUCD services.

Various type of PPIUCD insertions are:

Group II: Intracesarean - Copper-T 380 A was inserted immediately after delivery of placenta and before closure of uterine incision.

In all the clients, insertion was done using PPIUCD forceps. All the clients were interviewed in accordance with enclosed proforma. The counseling was done during antenatal period or early stages of labor or while preparing for scheduled cesarean section for PPIUCD insertion. Informed written consent was taken from all patients.

Inclusion Criteria ÂÂ

All the women whether undergoing vaginal delivery or cesarean section.

Those who don’t have any contraindications for IUCD insertion.

ÂÂ

Postplacental: Within 10 minutes after delivery of placenta

ÂÂ

ÂÂ

Intracesarean: During cesarean section, immediately after delivery of placenta and before closure of uterine incision

Exclusion Criteria

Immediate postpartum: With 48 hours after delivery.

ÂÂ

Chorioamnionitis.

ÂÂ

Membranes ruptured for greater than 18 hours prior to delivery.

ÂÂ

Unresolved PPH.

ÂÂ

PPIUCD offers several benefits which are as follows: ÂÂ

It is convenient, saves time and additional visit

ÂÂ

Safe, because it is certain that she is not pregnant at the time of insertion

ÂÂ

Women and family are highly motivated for a reliable birth spacing method

ÂÂ

Has no risk of uterine perforation because of thick uterine wall

ÂÂ

Reduced perception of initial side effects

ÂÂ

Reduced chance of heavy bleeding especially among lactational amenorrhea method (LAM) users

ÂÂ

It has no effect on amount or quality of breast milk

ÂÂ

The woman has an effective method for contraception before discharge from hospital.5

The main disadvantage of IUCD contraception is rate of expulsion and side effects, such as pain and bleeding, which may necessitate its early removal.

METHODS The present study was conducted in the Dept. of Obstetrics and Gynecology, Government Medical College and Rajindra Hospital, Patiala. One hundred women undergoing vaginal or cesarean delivery were included in the study. The cases were divided into two groups of 50 each. ÂÂ

962

Group I: Postplacental - Copper-T 380 A was inserted within 10 minutes of expulsion of placenta following vaginal delivery.

Indian Journal of Clinical Practice, Vol. 26, No. 10, March 2016

Regular follow-ups were carried out at: 6 weeks, 3 months and 6 months interval.

RESULTS The age of the study subjects ranged from 19 to 40 years. Mean age in Group I was 24.8 years and 24.9 years in Group II. Forty-four percent of the subjects in Group I and 54% in Group II were primiparas (Table 1). Only 13% subjects in both groups had history of previous contraception use. Very few subjects in study groups had history of previous IUCD use i.e., only 4% (Table 2). The most common complaint (Table 3) by subjects in study groups was request for removal.

Table 1. Demographic Profile Characteristics

Group I

Group II

Mean age (years)

24.8

24.9

Primiparas

44%

54%

Multiparas

56%

46%

Table 2. Previous Contraceptive Use Contraceptive history

Group I

Group II

Total

Previous contraception (any method)

9 (18%)

4 (8%)

13 (13%)

Previous IUCD use

3 (6%)

1 (2%)

4 (4%)

OBSTETRICS AND GYNECOLOGY In Group I, 8 (16.3%) and in Group II, 7 (14%) requested for IUCD removal. All these clients were reassured and counseled regarding benefits of PPIUCD. Complaint of pain was more in Group I i.e., 4 (8.16%) and in Group II, pain was experienced by 3 (6%) subjects. All these were counseled and were managed conservatively with mefenamic acid. Still one client in each group got the IUCD removed (Table 4).

Side effect in the form of disturbed bleeding pattern was almost same in both groupsâ&#x20AC;&#x2122; i.e., 3 subjects in each group. These subjects were given medication in form of tranexamic acid orally. But still in Group I, one client got IUCD removed. Complaint of missing strings was reported by 2 (4%) subjects in Group II. These subjects came with this complaint because they got their Copper-T checked from local practitioner who told them Copper-T was not in place and got worried.

Ultrasound was done to confirm Copper-T, which showed Copper-T in situ and they were reassured. In Group I, 5 (10.20%) and in Group II, 3 (6%) presented with complaint of irritation by threads of the device.

Table 3. Side Effects/Complaints of Clients at Followup Visits Side effect/ Complaint

Group I Post-placental (n = 49)

Group II Intracesarean (n = 50)

Total (n = 99)

Request for removal

8 (16.3%)

7 (14%)

15 (15.15%)

Bleeding

3 (6.12%)

3 (6%)

6 (6.06%)

Pain

4 (8.16%)

3 (6%)

7 (7.07%)

-

2 (4%)

2 (2.02%)

5 (10.20%)

3 (6%)

8 (8.08%)

Missing strings Any other (threads irritation)

(Lost in follow-up -1 in Group I).

Group I Group II Post-placental Intracesarean (n = 49) (n = 50)

Total (n = 99)

Pain

1 (2.04%)

1 (2%)

2 (2.02%)

Bleeding

1 (2.04%)

-

1 (1.01%)

Personal reasons

1 (2.04%)

1 (2%)

2 (2.02%)

Total

3 (6.12%)

2 (4%)

5 (5.05%)

(Lost in follow-up -1 in Group I).

Outcome

Group I Postplacental (n = 49)

Group II Intracesarean (n = 50)

Total (n = 99)

Expulsion

2 (4.08%)

-

2 (2.02%)

Removal

3 (6.12%)

2 (4%)

5 (5.05%)

Failure (pregnancy)

-

-

-

Infection

-

-

-

44 (89.79%)

48 (96%)

92 (92.92%)

Continuation

Threads were trimmed and counseling was done in these patients and also all their myths and misconceptions regarding Copper-T were allayed.

Two clients (one in each study group) insisted and got it removed because of personal reasons (one due to irritation by thread and another due to follow-up problem). During examination, missing strings were mostly noticed in Group II, which occurred in 30% subjects. Only 4.08% clients in Group I had missing strings. In both the groups, ultrasound examination was performed in all clients with missing strings and Copper-T in situ was confirmed in all of them.

We concluded that threads take time to descend in intracesarean PPIUCD cases.

Only 2 (2.02%) clients had expulsion in study groups.

Both expulsion occurred in study Group I. In Group I, 4.08% patients had expulsion, 6.12% got removed and rest (89.79%) were continuing the PPIUCD, whereas in Group II, none of patients had expulsion and 4% got Copper-T removed and 96% continued with use of PPIUCD at the end of study period. Continuation rate was 92.92% among all the subjects and majority of them were satisfied with their choice of contraceptive method. None of clients had failure, infection or perforation with the use of PPIUCD (Table 5).

DISCUSSION

Table 4. Showing Causes of Removal Causes of removal

Table 5. Outcome of PPIUCD

In developing countries and in particular in the rural or semi-urban areas, women with limited resources have difficulty in reaching to a family planning clinic or a Mother-Child Health-Family Planning Centre after child birth. This emphasizes the need and importance of providing family planning services in the postpartum period.7 India started repositioning postpartum family planning in February 2009. If we accept that pregnancy spacing of at least 24 months is recommended, that there is large unmet need for postpartum family planning, that

Indian Journal of Clinical Practice, Vol. 26, No. 10, March 2016

963

OBSTETRICS AND GYNECOLOGY there have been advances in understanding of IUCD and that there is new focus on skilled attendance at birth, giving us unique opportunity to provide woman with postpartum family planning then; PPIUCD is a potential answer to all these issues.

further visits and also clients can make clear decision regarding use of Copper-T in immediate postpartum period.

The present study was planned to evaluate the safety and efficacy of PPIUCD insertion. Our study showed follow-up of 100% at 6 weeks and 98.93% at 6 months.

In our study, lost in follow-up rate was 1%. The results of this study showed that expulsion rates in Group I were 4.08% which is in accordance with study of Gupta et al8 and total expulsion rate was 2.02%, which was comparable to Khatun,9 Lopez‐Farfan et al10 and Kittur et al.11 No expulsion occurred in intracesarean Group II, which is comparable to study of Letti Müller et al.12 This lower expulsion rate during cesarean insertion as compared to vaginal insertion may be due to direct placement of PPIUCD at the fundus during cesarean section. This wide variation in the expulsion rates in different studies could be due to the difference in the technique of insertion (hand or ring forceps or PPIUCD forceps), use of USG guidance for immediate insertion following vaginal delivery and skill and experience of practitioner.

1. Census 2011. Provisional Population Totals: Office of the Registrar General and Census Commissioner, India, Ministry of Home Affairs, 2011. Available at: www. censusindia.gov.

In Group I, complications/side effects rate in form of pain, bleeding and expulsion occurred in 9 (18.36%) and in Group II, 6 (12%) clients had complications/ side effects. Complications/side effects in terms of pain, bleeding and expulsion which occurred in our study is in comparison with Celen et al6 and Gupta et al.8 No case of perforation, failure was reported in the present study. None of the subject in our study had infection.

Gupta et al8 showed continuation rate of 87.33% which is in accordance with our study subjects of post-placental Group I over 6 months interval. Higher continuation rates (96%) were obtained for Group II in our study, which is comparable to Gupta et al8 with continuation rate 92.66% and Lopez‐Farfan et al10 with 90% continuation rate.

CONCLUSION PPIUCD insertion is a safe, convenient, cost-effective, reversible and long-term birth spacing method. It is an alternative to permanent sterilization, being longterm reversible method with comparable failure rate.

It should be part of a maternal/newborn/reproductive health package. This method may be particularly beneficial in our setting, where women do not come routinely for postnatal contraception counseling and usage. Ideally, the counseling for PPIUCD should be done during routine antenatal visits, so that myths and misconceptions regarding IUCD can be allayed during

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Indian Journal of Clinical Practice, Vol. 26, No. 10, March 2016

REFERENCES

2. The ACQUIRE Project. The postpartum intrauterine device: A training course for service providers. Participant Handbook. New York: Engender Health, Postpartum IUCD Overview. 2008; (Module 2, 10): 5-64. Available at: http://www.acquireproject.org/archive/files/10.0_training_ curricula_and_materials/10.2_resources/PPIUCD_PH_ complete_updated.pdf. Accessed on 25th Feb 2016.

3. Darnel L, Jones MD, David R, Helbert MD. Postpartum contraception. Clin Med. 1975;82:20-2.

4. Xu JX, Reusché C, Burdan A. Immediate postplacental insertion of the intrauterine device: a review of Chinese and the world’s experiences. Adv Contracept.

1994;10(1):71-82.

5. Postpartum IUCD Reference Manual. Postpartum Family Planning. Family Planning Division, Ministry of Health and Family Welfare, Government of India.

2010;1:1-4. Available at: http://www.jhpiego.org/files/ PPIUCDReference%20ManualFeb2011.pdf.

6. Çelen Ş, Sucak A, Yıldız Y, Danışman N. Immediate postplacental insertion of an intrauterine contraceptive device during cesarean section. Contraception.

2011;84(3):240-3.

7. Akkuzu G, Vural G, Eroglu K, Dilbaz B, Taskin L, Akin A. Reasons for continuation or discontinuation of IUD in postplacental/early postpartum periods and postpuerperal/interval periods: one-year follow-up.

Turkiye Klinikleri J Med Sci. 2009;29(2):353-60.

8. Gupta A, Varma A, Chauhan J. Evaluation of PPIUCD versus interval IUCD (380A) insertion in a teaching hospital of Western UP. Int J Reprod Contracept Obstet Gynecol. 2013;2(2):204-8.

9. Khatun HA. Post-partum IUCD - A new method in post-partum contraception. Int J Gynaecol Obstet.

2009;107(2):620.

10. Lopez‐Farfan JA, MacIel‐Martínez M, Velez‐Machorro IJ, Vazquez‐Estrada L. Application of Mirenaan during caesarean section (CS). Euro J Contracep Reprod Health Care. 2010;15 Suppl 1:165‐6.

11. Kittur S, Kabadi YM. Enhancing contraceptive usage by post-placental intrauterine contraceptive devices (PPIUCD) insertion with evaluation of safety, efficacy, and expulsion. Int J Reprod Contracept Obstet Gynecol.

2012;1(1):26-32.

12. Letti Müller AL, Lopes Ramos JG, Martins-Costa SH, Palma Dias RS, Valério EG, Hammes LS, et al. Transvaginal ultrasonographic assessment of the expulsion rate of intrauterine devices inserted in the immediate postpartum period: a pilot study. Contraception. 2005;72(3):192-5.

OBSTETRICS AND GYNECOLOGY

Complete Hydatidiform Mole Coexisting with a Live Fetus in Twin Pregnancy: A Case Report AVISHEK BHADRA*, PALLAB KUMAR MISTRI†, BANDANA BISWAS‡, SHILPA KUMARI#, SUDIP MUKHERJEE¥

ABSTRACT Twin pregnancy with one complete hydatidiform mole (CHM) and coexisting live fetus is a very rare condition. It is an obstetric problem, which may put mother into harmful complications of molar pregnancy. It is associated with advanced maternal

age and associated treatment for artificial reproductive techniques. The risk of persistent trophoblastic disease in live fetus with coexisting CHM in twin pregnancy is 19-50%. We present a case of a 33-year-old female in whom a CHM was coexisting with a live fetus in twin pregnancy. As the conservative management of such pregnancy was difficult due to risk of persistent trophoblastic disease and as she had completed her family, the couple opted for termination of the ongoing pregnancy.

Keywords: Complete hydatidiform mole, twin pregnancy

T

win pregnancy with one complete hydatidiform mole (CHM) and coexisting live fetus is a very rare condition. It is an obstetric problem, which may put mother into harmful complications of molar pregnancy. Most common causes for termination of pregnancy are antepartum hemorrhage, thyrotoxicosis, pre-eclampsia and risk of persistent gestational trophoblastic diseases.1,2 Incidence of such type of pregnancy is one in 20,000 to one in 1,00,000 cases.3 The incidence is associated with advanced maternal age and associated treatment for artificial reproductive techniques. In our case report, we are reporting such a case where it was associated with advanced maternal age only.

CASE REPORT A 33-year-old female, Asma Khatoon, gravida 4, para 3, with living issue 4 with a history of twin pregnancy in her 2nd pregnancy, presented to Gynecology and

*Assistant Professor †Associate Professor ‡Professor #Junior Resident ¥RMO cum Clinical Tutor Dept. of Obstetrics and Gynecology, Medical College, Kolkata, West Bengal Address for correspondence Prof. Dr Bandana Biswas 69, Chandi Ghosh Road, Regent Park, Kolkata - 700 040, West Bengal E-mail: bandana.biswas2010@gmail.com

Obstetrics outdoor of a tertiary care teaching hospital in eastern India on 10th August 2015, referred from a District Hospital, with a complaint of 4 months amenorrhea and occasional spotting for the last 2-3 months. She had a transabdominal ultrasound done from outside revealing a live pregnancy of 22 weeks gestation with a placenta in the posterior wall and upper segment of the uterus, along with a heterogeneous space-occupying lesion (SOL) with small cystic component, seen in lower part of anterior wall of the uterus, which was suggestive of a partial molar or pseudomolar pregnancy.

On examination, patient had pulse rate - 80/min, blood pressure (BP) - 110/80 mmHg, negative urine dipstick for protein, mild palor and no feature suggestive of thyrotoxicosis. Per abdomen, the uterine height was 32 weeks, not corresponding to the period of amenorrhea. She perceived fetal movements and fetal heart sound was audible with stethoscope. Patient was advised admission and counseled regarding her pregnancy and its probable outcome.

After admission, she underwent another ultrasound scan at the Radiology Department and one serum betahuman chorionic gonadotropin (β-hCG) quantification.

Ultrasound done on 11th August revealed a live fetus of 22 weeks and 1 day with fundoposterior placenta in one sac and one 9.4 × 6.4 cm heterogeneous multicystic SOL adhered to anterior wall of uterine cavity close to internal os, in another sac (Fig. 1). β-hCG done

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OBSTETRICS AND GYNECOLOGY

Figure 1. A well-defined gestational sac with fetus and separate molar tissue near internal os at 22weeks of gestation.

Figure 2. A normal looking premature baby with umbilical cord attached to a normal looking placenta and molar tissue separately.

on the same day was 2.5 lac IU/dL, which was quite high suggesting molar pregnancy. She experienced two episodes of vaginal bleeding after admission. All routine laboratory investigations were done; reports including liver function test (LFT), renal function test (RFT), blood sugar were within normal limits except Hb%, which was 8.08 g/dL.

confirmed the mass as CHM; placenta was normal and uterus showed features of invasion. Karyotyping of both placenta and molar tissue was 46, XX. Patient was discharged from hospital on Day 6 and asked to come for follow-up. During her follow-up period, β-hCG showed pattern of plateau for which she was prescribed single agent chemotherapy (methotrexate).

After first cycle of chemotherapy, there was marked fall in the β-hCG level and the value reached 78 IU/dL. She is still under follow-up for any necessary subsequent chemotherapy and until β-hCG becomes <5 IU/dL.

On 14th August, another ultrasound scan was performed with color Doppler, which showed a fetus and placenta in upper part enclosed within a sac, separate from a heterogeneous SOL having vascularity in it, located at lower part of the uterus. A diagnosis of twin pregnancy with single fetus and coexisting molar pregnancy was confirmed. Patient was kept under strict observation and counseling was done. As the conservative management of such pregnancy was difficult due to risk of persistent trophoblastic disease and as she had completed her family, the couple opted for termination of the ongoing pregnancy.

She was planned for termination by hysterotomy in the operation theater with 2 units of blood component in hand. On the day of operation, a fetus of 1,200 g was delivered along with normal looking placenta in one sac and a complete molar tissue in another sac (Fig. 2). During separation of molar tissue, it was found to be an invasive mole and there was severe hemorrhage. Decision of hysterectomy was taken and total hysterectomy was done. Baby was sent to Sick Neonatal Care Unit (SNCU) and placenta, uterus and molar tissue were sent for histopathology and karyotyping. Postoperatively, there was remarkable decrease in β-hCG level; it was 51,990 IU/dL on the 3rd postoperative day. Histopathological report

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DISCUSSION Twin pregnancy with a CHM and a single normal fetus is an extremely rare condition. So far, there have only been about 200 cases of twin pregnancy with CHM fully documented in literature; only 56 cases resulted in a live birth.4 There are two different pathologic entities, partial and CHM, with different mechanisms of origin based on cytogenetic analysis.5 Partial moles arise from dispermic fertilization of a haploid normal oocyte and produce a triploid set of chromosomes. A CHM contains a diploid set of 46 chromosomes, all of paternal origin and no traces of fetal parts can be identified. There has always been dilemma about continuation or termination of pregnancy. The risk of persistent trophoblastic disease is more in CHM. The risk of persistent trophoblastic disease in live fetus with coexisting CHM in twin pregnancy is 19-50%. The true incidence of this rare entity is difficult to establish, and some suggest that the modern increased incidence of iatrogenic multiple gestations will cause a higher incidence of CHM with

OBSTETRICS AND GYNECOLOGY fetus.1,6 In cases of partial hydatidiform mole, as the fetus is triploid, it is an indication for termination of pregnancy, while in case of CHM with live fetus continuation of pregnancy is frequently associated with severe maternal complications.1 It is important to differentiate between CHM with partial mole when fetus coexists because it has been reported that CHM has higher tendency of invasive mole and choriocarcinoma when compared with partial mole.7 Ultrasonography has made possible diagnosis of a hydatidiform mole and coexistent fetus.8 With regard to our case, there was extremely high concentration of β-hCG, which confirmed the ultrasonographic diagnosis of molar pregnancy and possibility of later developing trophoblastic disease.

REFERENCES 1. Matsui H, Sekiya S, Hando T, Wake N, Tomoda Y. Hydatidiform mole coexistent with a twin live fetus: a national collaborative study in Japan. Hum Reprod.

2000;15(3):608-11.

complete hydatidiform mole and coexisting fetus. Obstet Gynecol. 1994;83(1):35-42.

3. Cunningham ME, Walls WJ, Burke MF. Grey-scale ultrasonography in the diagnosis of hydatidiform mole with a coexistent fetus. Br J Obstet Gynaecol. 1977;84(1): 73-5.

4. Dolapcioglu K, Gungoren A, Hakverdi S, Hakverdi AU, Egilmez E. Twin pregnancy with a complete hydatidiform mole and co-existent live fetus: two case reports and review of the literature. Arch Gynecol Obstet. 2009;279(3):431-6.

5. Moini A, Riazi K. Molar pregnancy with a coexisting fetus progressing to a viable infant. Int J Gynaecol Obstet.

2003;82(1):63-4.

6. Sebire NJ, Foskett M, Paradinas FJ, Fisher RA, Francis RJ, Short D, et al. Outcome of twin pregnancies with complete hydatidiform mole and healthy co-twin. Lancet.

2002;359(9324):2165-6.

7. Callen PW. Ultrasound evaluation of gestational trophoblastic disease. In: Callen PW (Ed.). Ultrasonography of Obstetrics and Gynaecology. 2nd edition, Philadelphia, PA: WB Saunders; 1988. p. 416.

8. Montes-de-Oca-Valero F, Macara L, Shaker A. Twin pregnancy with a complete hydatidiform mole and co2. Steller MA, Genest DR, Bernstein MR, Lage JM, Goldstein existing fetus following in-vitro fertilization: case report.

DP, Berkowitz RS. Natural history of twin pregnancy with Hum Reprod. 1999;14(11):2905-7.

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...Cont’d from page 956

5. Beard J. Iron deficiency alters brain development and functioning. J Nutr. 2003;133(5 Suppl 1):1468S-1472S. 6. Lozoff B. Perinatal iron deficiency and the developing brain. Pediatr Res. 2000;48(2):137-9.

7. Berg AT. Febrile seizures and epilepsy: the contributions of epidemiology. Paediatr Perinat Epidemiol. 1992;6(2):145-52.

8. Grantham-McGregor S, Ani C. A review of studies on the effect of iron deficiency on cognitive development in children. J Nutr. 2001;131(2S-2):649S-666S; discussion 666S-668S.

11. Bilic E, Bilic E. Amino acid sequence homology of thrombopoietin and erythropoietin may explain thrombocytosis in children with iron deficiency anemia. J Pediatr Hematol Oncol. 2003;25(8): 675-6.

12. Tekin D, Yavuzer S, Tekin M, Akar N, Cin S. Possible effects of antioxidant status on increased platelet aggregation in childhood iron-deficiency anemia. Pediatr Int. 2001;43(1):74-7.

9. Lanzkowsky P. Investigation into the aetiology and treatment of pica. Arch Dis Child. 1959;34(174):140-8.

13. Trenkwalder C, Högl B, Winkelmann J. Recent advances in the diagnosis, genetics and treatment of restless legs syndrome. J Neurol. 2009;256(4):539-53.

10. Mocan H, Yildiran A, Orhan F, Erduran E. Breath holding spells in 91 children and response to treatment with iron.

Arch Dis Child. 1999;81(3):261-2.

14. Oppenheimer SJ. Iron and its relation to immunity and infectious disease. J Nutr. 2001;131(2S-2):616S-633S; discussion 633S-635S.

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PEDIATRICS

Constriction Band Syndrome SUDIVYA SHARMA*, PRADNYA SAWANT†

ABSTRACT Constriction band syndrome (CBS) or amniotic band syndrome is a group of congenital birth defects believed to be caused by entrapment of fetal parts (usually a limb or digits) in fibrous amniotic bands while in utero. The commonly accepted view is

the extrinsic theory, that CBS occurs when the inner membrane (amnion) ruptures without injury to the outer membrane (chorion). The chorionic side of the amnion emanates numerous mesoblastic fibrous strings, which entrap and catch the fetal parts. On the other hand, the intrinsic theory proposed by George Streeter, explains the ring constrictions as areas of defectively formed tissue due to defective germ plasma areas, and due to the closeness to the amnion caused its connection. CBS not only causes esthetic deformity in the affected limb, but may also cause vascular compromise, which can lead to lymphedema and/or amputation. Concerning the treatment of congenital CBS, the use of Z-plasty or W-plasty after the excision of the constriction band, in a one- or two-stage approach is recommended.

Keywords: Constriction band syndrome, mesoblastic fibrous strings, defective germ plasma areas, lymphedema, amputation

C

onstriction band syndrome (CBS) or amniotic band syndrome is a group of congenital birth defects believed to be caused by entrapment of fetal parts (usually a limb or digits) in fibrous amniotic bands while in utero. Other names include amniotic band syndrome, also known as “Adam Complex”, Streeter’s dysplasia, annular groove, ring constriction syndrome and pseudoainhum. It has an incidence of one in 1,200 to one in 15,000 live births and affects both sexes at a ratio of 1:1. There is a significant predilection for the upper extremities and an increased frequency in distal limbs, and longer digits are significantly more involved than shorter ones.1-6

THEORIES The commonly accepted view is the extrinsic theory, that CBS occurs when the inner membrane (amnion) ruptures without injury to the outer membrane

*Fellow Pediatric Anesthesia †Chief of Department Dept. of Pediatric Anesthesia BJ Wadia Hospital for Children, Mumbai, Maharashtra Address for correspondence

Dr Sudivya Sharma Flat No. 77, B-Wing, Mahavir Krupa Building TJ Road, Sewri (W), Mumbai - 400 015, Maharashtra E-mail: drsudivyasharma@gmail.com

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(chorion). The chorionic side of the amnion emanates numerous mesoblastic fibrous strings, which entrap and catch the fetal parts. This extrinsic theory was proposed by Richard Torpin, an obstetrician, in 1965.7 In some cases, complete “natural” amputation of a digit(s) or limb may occur before birth or the digit(s) or limbs may be necrotic (dead) and require surgical amputation following birth.

There is an intrinsic theory proposed by George Streeter, the director of embryology at Carnegie Institute, in 1930 which is called, “Streeter’s dysplasia”. He explained the ring constrictions as areas of defectively formed tissue due to defective germ plasma areas, and due to the closeness to the amnion caused its connection. This theory is supported by evidence of cases in which the infant affected is born with the amnion intact.8 PRESENTATION The variable clinical manifestations of congenital CBS can best be explained as the response of the growing, embryologically defined limb to intrauterine deformation or band-induced compression and ischemia. In the hand, digital amputations are most common in the index, middle and ring fingers (Figs. 1 and 2), whereas in the foot, amputations of the hallux are most often noted. Band indentations are often present at multiple levels. Proximal bands may be associated with neural compression.

PEDIATRICS MANAGEMENT

Figure 1. X-ray hand showing absence of distal digits.

CBS not only causes esthetic deformity in the affected limb, but may also cause vascular compromise, which can lead to lymphedema and/or amputation. The treatment of CBS is therefore aimed at improvement of function and improvement of cosmetic appearance.

Concerning the treatment of congenital CBS, most references recommend the use of Z-plasty or W-plasty after the excision of the constriction band, in a one- or two-stage approach.9 Very rarely if CBS is detected in utero, fetal surgery may be performed to save a limb or other deformity.

CONCLUSION

Figure 2. Hand of a child with CBS with mutilated digits.

There are several features that are relatively consistent: ÂÂ

Syndactyly

ÂÂ

Distal ring constrictions

ÂÂ

Deformity of the nails

ÂÂ

Stunted growth of the small bones in the digits

ÂÂ

Limb length discrepancy

ÂÂ

Distal lymphedema

ÂÂ

Congenital band indentations

ÂÂ

If a band wraps tightly around a limb, the limb can actually be completely amputated.

A strong relationship between CBS and clubfoot exists.

In 1961, Patterson used a classification that is still widely used today.4 The classifications are as follows: ÂÂ

Simple ring constrictions

ÂÂ

Ring constrictions accompanied by deformity of the distal part with or without lymphedema

ÂÂ

Ring constrictions accompanied by fusion of distal parts ranging from mild-to-severe acrosyndactyly

ÂÂ

Intrauterine amputations.

The future for those suffering from CBS is continually improving because of upcoming in utero surgical procedures. Regardless, what theory proves to be evident in causing CBS, it is extremely important to seek prenatal medical attention when pregnant. It is likely that genetic predisposing factors are involved, as can be inferred by the higher incidence of the syndrome in first-degree relatives of the affected individuals. No less important; however, appear to be acquired yearly factors, such as the use of drugs, tobacco, diabetes, known for their action on the vascular system or even iatrogenic factors like the sting from amniocentesis, which are an insult to the amniotic membranes.

REFERENCES 1. Foulkes GD, Reinker K. Congenital constriction band syndrome: a seventy-year experience. J Pediatr Orthop.

1994;14(2):242-8.

2. Al-Qattan MM. Classification of the pattern of intrauterine amputations of the upper limb in constriction ring syndrome. Ann Plast Surg. 2000;44(6):626-32.

3. Garza A, Cordero JF, Mulinare J. Epidemiology of the early amnion rupture spectrum of defects. Am J Dis Child.

1988;142(5):541-4.

4. Patterson TJ. Congenital ring-constrictions. Br J Plast Surg. 1961;14:1-31 5. Kino Y. Clinical and experimental studies of the congenital constriction band syndrome, with an emphasis on its etiology. J Bone Joint Surg Am. 1975;57(5):636-43.

6. Flatt AE. The Care of Congenital Hand Anomalies.

St Louis: CV Mosby Company; 1977.

7. Torpin R. Amniochorionic mesoblastic fibrous rings and amniotic bands: associated constricting fetal malformations or fetal death. Am J Obstet Gynecol. 1965;91:65-75.

8. Streeter GL. Focal deficiencies in fetal tissues and their relation to intrauterine amputations. Contrib Embryol Carnegie Inst. 1930;22:1-44.

9. Wiedrich TA. Congenital constriction band syndrome.

Hand Clin. 1998;14(1):29-38.

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PEDIATRICS

An Approach to Diagnosis of Skeletal Dysplasias in Children MANAB NARAYAN BARUAH

ABSTRACT Skeletal dysplasias are a heterogeneous group of disorders of bone and cartilage with a phenotypic spectrum that can vary from mild short stature to perinatal lethality. A detailed physical examination and radiological evaluation can help in identifying many of the dysplasias. Emerging molecular tests can establish the underlying genetic basis of hitherto unexplained dysplasias and help in assessment of carrier status as well as recurrence risk in subsequent pregnancies.

Keywords: Skeletal dysplasia, short stature, skeletal survey

T

he skeletal dysplasias are a heterogeneous inheritable group of disorders characterized by abnormalities of cartilage and bone development.

They have a wide phenotypic spectrum ranging from lethality in the perinatal period to only mild short stature. Although individual lesions are rare, collectively they constitute 1/5,000 of all births. The incidence of skeletal dysplasia at birth was 19.6/1,00,000 and lethal dysplasia 5.2/10,000 in a study from Southern India.

Progressive advances in molecular biology have changed our understanding of these heterogeneous disorders. In 1960, patients with short limbed dwarfism were classified either as achondroplasia (short-limbed dwarfism) or short trunked dwarfism (Morquio syndrome). As of now, the 2010 revision of the Nosology and Classification of Genetic Skeletal disorders identifies 456 human dysplasias placed into 40 groups on the basis of clinical, radiological and molecular criteria. Out of these, 316 were associated with mutations in one or more of 226 different genes.

In day-to-day practice, the exhaustive molecular classification may not be practical for most physicians.

Therefore, the diagnostic approach to skeletal dysplasia

Assistant Professor Dept. of Pediatrics Srimanta Sankaradeva University of Health Sciences, Assam Jorhat Medical College and Hospital, Jorhat, Assam Address for correspondence

Dr Manab Narayan Baruah Dept. of Pediatrics Jorhat Medical College and Hospital, Jail Road, Jorhat - 785 001, Assam E-mail: drmnbaruah@rediffmail.com

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is based on a judicious combination of history, clinical and radiological findings. Establishing a precise diagnosis for an individual lesion is difficult but important for the purpose of prediction of adult height, recurrence risk assessment, prenatal diagnosis in future pregnancies and specific clinical management.

Most lethal as well as many nonlethal dysplasias can be identified on a prenatal ultrasound examination. An attempt should be made to make a precise diagnosis during pregnancy, but it may not always be possible till termination of pregnancy or delivery. An experienced radiologist can usually make a prenatal distinction between those disorders compatible with life and those lethal prenatally or during early postnatal life. Patients with nonlethal skeletal dysplasia generally presents to the physician for evaluation of short stature.

HISTORY AND PHYSICAL EXAMINATION When presented with a child with a disproportionate short stature, a focussed history can give invaluable clues to the diagnosis.

Family History ÂÂ History (including spontaneous abortions), medical records, photographs, radiographs of affected individuals and family members. ÂÂ Parents, siblings and other relatives should be carefully examined for mild manifestations of the disorder due to variable clinical penetrance and expressivity. ÂÂ Family history should include a three generation pedigree with specific enquiry into unexplained fetal deaths, consanguinity, short stature, orthopedic

PEDIATRICS problems (early onset arthritis, kyphoscoliosis), previous surgery for congenital malformations. ÂÂ

Parental age and height should be noted.

Pregnancy and Birth History ÂÂ Maternal polyhydramnios is a significant associated event during pregnancy. ÂÂ Fetal hydrops is frequently observed. ÂÂ Decreased fetal movements may be noted in lethal types of dysplasias. ÂÂ Intrauterine death or immediate postpartum deaths suggest lethal dysplasias. ÂÂ Enquire about any abnormal findings on prenatal ultrasounds especially discrepancy between fetal size and gestational age. ÂÂ Prenatal ultrasound may reveal short long bones, small chest and associated anomalies like cardiac defects or cleft palate. ÂÂ Abnormalities of vision and hearing may be present in disorders of type 2 collagen e.g., spondyloepiphyseal dysplasia congenita. ÂÂ Maternal ingestion of drugs e.g., warfarin/phenytoin may cause stippled epiphysis (chondrodysplasia punctata).

Postnatal History ÂÂ Immediately after birth, respiratory distress may be present due a combination of airway anomalies (choanal atresia, laryngo/tracheo/bronchomalacia, micrognathia), small thoracic cavity and hypotonia. ÂÂ Age of onset of short stature-many nonlethal dysplasias present with short stature at birth e.g., achondroplasia; others like pseudoachondroplasia have normal length at birth with subsequent growth failure. ÂÂ Developmental history: Most have normal intellectual development.

Exceptions are achondroplasia with gross motor delay in the first 2 years of life. ÂÂ Learning disabilities are seen in hypochondroplasia and achondroplasia.

ÂÂ

Dysteosclerosis is associated with severe to profound mental retardation.

Physical Examination ÂÂ

Detailed physical examination of the patient, parents and other family members is imperative in diagnosis.

ÂÂ

As most dysplasias present with disproportionate short stature, basic anthropometry should include weight, length/height, head circumference, sitting height, upper segment lower segment ratio, arm span.

ÂÂ

If limbs are short, the diagnosis of short-limbed dysplasia is based on the most severely affected segment of long bone as enumerated in Table 1.

ÂÂ

Short trunk dysplasia includes Morquio syndrome, Kniest syndrome and spondyloepiphyseal dysplasia.

Important clinical features of various dysplasias are enumerated in Table 2.

Diagnostic Work-up ÂÂ Skeletal survey ÂÂ Biochemical ÂÂ Cartilage histology ÂÂ Molecular study Skeletal Survey A full genetic skeletal survey is not indicated in children with proportionate short stature. A left wrist and hand X-ray for determining bone age is sufficient for initial evaluation of these patients.

In children with disproportionate short stature a full skeletal survey is carried out. ÂÂ

Skull AP and lateral view

ÂÂ

Whole spine AP and lateral view

ÂÂ

Pelvis AP view

Table 1. Different Dysplasias Based on Limb Length Type

Key feature

Example

Rhizomelia

Shortening of proximal segments (e.g., humerus, femur)

Achondroplasia, hypochondroplasia, spondyloepiphyseal dysplasia, thanatophoric dysplasia, diastrophic dysplasia, atelosteogenesis

Mesomelia

Shortening of middle segments (e.g., radius, ulna, tibia, fibula)

Langer and Nievergel type of mesomelic dysplasia, Robinow syndrome, Reinhardt syndrome

Acromelia

Shortening of distal segments (e.g., metacarpals, phalanges)

Acrodysostosis, peripheral dysostosis

Micromelia

Shortening of extremities involving entire limb

Achondrogenesis

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PEDIATRICS Table 2. Important Clinical Features of Various Skeletal Dysplasias Site of involvement

Examples of dysplasias

Craniofacial yy Disproportionately large head

yy Achondroplasia, thanatophoric dysplasia

yy Cloverleaf skull

yy Thanatophoric dysplasia, Apert, Carpenter and Crouzon syndrome

yy Multiple Wormian bones

yy Cleidocranial dysplasia, osteogenesis imperfecta

yy Frontal bossing

yy Achondroplasia

yy Wide open sutures, delayed fontanelle closure

yy Cleidocranial dysostosis

yy Pierre Robin sequence

yy Campomelic dysplasia

Spine yy Foramen magnum stenosis (leading to cervicomedullary compression)

yy Achondroplasia

yy Odontoid hypoplasia (leading to atlanto-axial instability)

yy Spondyloepiphyseal dysplasia (SED)

yy Thoracolumbar kyphoscoliosis

yy Morquioâ&#x20AC;&#x2122;s syndrome

Eyes yy Congenital cataract

yy Chondrodysplasia punctata

yy Myopia

yy Kniest dysplasia, SED congenita

Oral cavity yy Bifid uvula, high-arched palate, cleft palate

yy Kniest dysplasia, SED congenita, diastrophic dysplasia, campomelic dysplasia

Ears yy Acute swelling of pinna (cauliflower ear)

yy Diastrophic dysplasia

yy Hearing loss

yy Achondroplasia, cleidocranial dysplasia, osteogenesis imperfecta

Extremities yy Hands and feet

Hitchhikers thumb Clubfoot

yy Diastrophic dysplasia yy Diastrophic dysplasia, Kniest dysplasia, osteogenesis imperfecta

yy Nails

Hypoplastic nails Short and broad nails

yy Chondroectodermal dysplasia yy McKusick metaphyseal dysplasia

yy Polydactyly

Preaxial Postaxial

yy Chondroectodermal dysplasia, short rib polydactyly syndrome yy Jeune syndrome

yy Long bone fracture

yy Osteogenesis imperfecta, hypophosphatasia, osteopetrosis

yy Joints - multiple joint dislocation

yy Larsen syndrome

Thorax/Ribs yy Long/Narrow thorax

yy Asphyxiating thoracic dystrophy, chondroectodermal dysplasia, metatrophic dysplasia

yy Pear-shaped chest

yy Thanatophoric dysplasia, short rib polydactyly syndromes, homozygous achondroplasia

Cardiovascular yy Atrial septal defect

yy Chondroectodermal dysplasia

yy Patent ductus arteriosus

yy Lethal short limbed skeletal dysplasia

yy Transposition of great vessels

yy Majewski syndrome

Genitals yy XY reversal

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yy Campomelic dysplasia

Indian Journal of Clinical Practice, Vol. 26, No. 10, March 2016

PEDIATRICS ÂÂ

Four extremities AP view with separate view of hands and feet

ÂÂ

Knee lateral view.

After obtaining the radiographs, a three step assessment is then used for making a specific diagnosis.

of segmental disproportion.

Step 2 (Assessment of Diaphyseal Ossification)

ÂÂ

Assessment of spine will identify presence of platyspondyly leading to short trunk disproportion.

Assessment of limb bones will identify presence

in

short-limbed

Epiphyseal/Metaphyseal/

ÂÂ

Epiphyseal dysplasia-characterized by small (delayed ossification) and/or irregularly ossified epiphysis.

ÂÂ

Metaphyseal dysplasia-characterized by widening, flaring or irregularity of metaphysis.

Step 1 (Assessment of Disproportion) ÂÂ

shortening

Table 3. Radiological Features of Different Dysplasias Achondroplasia group Thanatophoric dysplasia

yy Skull: Large skull, narrow base yy Spine: Flat, small vertebral bodies, rounded anterior ends yy Pelvis: Small flared iliac bones, narrow sciatic notch and dysplastic acetabulae yy Extremities: Generalized micromelia, telephone receiver femurs, round proximal femoral metaphysis with medial spike

Achondroplasia

yy Skull: Large, mid face hypoplasia, narrow foramen magnum, uncommonly hydrocephalus yy Spine: Short anteriorly rounded vertebral bodies, short pedicles with decreased interpeduncular distance in lumbar spine, posterior vertebral scalloping yy Pelvis: Elephant ear iliac wings (flared, superolaterally flattened ilia), hemispheric capital femoral epiphysis yy Extremities: Rhizo, meso, acromelia, proximal and distal fibular overgrowth yy Hands: Brachydactyly

Hypochondroplasia

yy Features similar to achondroplasia but of a milder degree

Metatropic dysplasia group Metatropic dysplasia

yy Thorax: Small, short ribs yy Spine: Dense wafer vertebral bodies (newborn), platyspondyly (child) yy Pelvis: Short squared iliac wings, flat acetabular roof, hunting axe-shaped proximal femurs yy Extremities: Trumpet-shaped metaphyses, dumb bell-shaped long bones

Short rib polydactyly group Short rib polydactyly dysplasia

yy Thorax: Small, short horizontal ribs yy Spine: Normal yy Pelvis: Small, dysplastic ilia yy Extremities: Micromelia, severe brachydactyly, polydactyl

Asphyxiating thoracic dystrophy (Jeune syndrome)

yy Thorax: Long, barrel-shaped; handlebar clavicles; short horizontal ribs yy Spine: Normal yy Pelvis: Flared, hypoplastic ilia; trident acetabular roof yy Extremities: Precocious femoral epiphysis ossification generalized shortening of bones; cone-shaped epiphysis

Chondroectodermal dysplasia (Ellis-van Creveld syndrome)

yy Thorax: Small; moderately short ribs yy Pelvis: Hypoplastic ilia; trident acetabula yy Spine: Normal yy Extremities: Generalized shortening with mesoacromelia yy Hands: Post axial polydactyly, extra carpal bone yy Feet: Polydactyly

Diastrophic dysplasia group Diastrophic dysplasia

yy Head: Pinna calcification yy Thorax: Moderately small yy Spine: Progressive scoliosis, kyphosis, odontoid hypoplasia yy Extremities: Micromelia; short tubular bones; extra carpal bones

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PEDIATRICS ...Contâ&#x20AC;&#x2122;d

Multiple epiphyseal dysplasia (MED)

yy Pelvis: Hip dysplasia (quarter moon-shaped) yy Knee: Double layered patella on lateral X-ray knee

Type 2 collagenopathies Spondyloepiphyseal dysplasia congenita

yy Thorax: Small; short ribs yy Spine: Oval vertebral bodies (newborn); platyspondyly (later on) yy Pelvis: Absent pubic ossification (newborn and infancy) yy Extremities: Shortened long bones with delayed ossification (nonossified calcaneus/talus in newborn)

Kniest dysplasia

yy Thorax: Normal to small yy Spine: Coronal clefts (newborn/infancy) yy Extremities: Dumb bell femurs, ossification delay; mega epiphysis in childhood

Multiple epiphyseal dysplasia and pseudoachondroplasia group Multiple epiphyseal dysplasia

yy Spine: Disc herniation into vertebral end plates yy Extremities: Small, irregular epiphyseal centers

Pseudoachondroplasia

yy Skull: Normal yy Thorax: Mild anterior rib widening yy Spine: Rounded vertebral bodies yy Pelvis: Hypoplastic rounded iliac wings yy Extremities: Moderate-to-severe generalized epiphyseal dysplasia, metaphyseal irregularity in knees

Chondrodysplasia punctata group Rhizomelic chondrodysplasia punctata

yy Spine: Coronal cleft, anteriorly rounded bodies yy Extremities: Stippling, symmetric, bilateral shortening of femur/humerus

Metaphyseal chondrodysplasia group Jansen type

yy Skull: Brachycephaly, platybasia, small mandible yy Thorax: Small, expanded anterior rib ends yy Extremities: Metaphysis expanded and widely separated from epiphysis

McKusick type

yy Thorax: Anterior rib flaring yy Spine: Small square vertebral bodies yy Extremities: Flaring, cupping, fragmentation of metaphysis esp. of knees. Hands small with cupping and coning of metacarpals and phalanges yy Pelvic bones: Normal

Schmid type

yy Thorax: Same as above yy Spine: Transient changes in mid childhood yy Extremities: Hands normal; rounded femoral epiphysis, coxa vara present

Decreased bone-density group Osteogenesis imperfecta

yy Skull: Decreased ossification, Wormian bones yy Thorax: Small, narrow chest yy Spine: Collapsed vertebrae yy Extremities: Osteoporosis, pathological fractures

Increased bone-density group Osteopetrosis

yy Generalized increased in bone density yy Skull: Thickened, increased density esp. basilar yy Spine: Sandwich vertebral bodies yy Extremities: Bone in bone appearance, dense metaphyseal bands

Defective mineralization group Hypophosphatasia

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yy Skull: Decreased ossification yy Thorax: Thin, wavy, fractured ribs yy Spine: Osteopenic vertebrae, butterfly-shaped vertebral bodies yy Extremities: Generalized osteopenia, chromosome-shaped femur, irregular cupped metaphysis yy Clavicles: Normal

Indian Journal of Clinical Practice, Vol. 26, No. 10, March 2016

PEDIATRICS ÂÂ

Diaphyseal involvement can be widening, cortical thickening, marrow space widening/restriction.

ÂÂ

Look for fractures in all segments.

Step 3 (Differentiation of Normal Variants from Pathological Abnormalities) ÂÂ

Look for pathognomonic findings which point towards a specific diagnosis.

ÂÂ

Clues for radiographic diagnosis of skeletal dysplasia.

Table 3 highlights important radiological diagnostic features of different skeletal dysplasias.

Biochemical Investigations They are not routinely indicated and should be guided by the clinical features. Mucopolysaccharidoses and mucolipidoses are the two classic dysplasias diagnosed by urine metabolite screening and specific enzyme assay on leukocytes and fibroblasts. Table 4 shows selected biochemical tests indicated in skeletal dysplasias.

Genetic Analysis The continued advancements in the field of molecular biology has enabled us to bridge the missing link between the underlying molecular defect and the consequent clinical and biochemical changes in many of the skeletal dysplasias.

Molecular diagnosis can be used to confirm a clinical and radiological diagnosis, predict carrier status in at risk families and allow for prenatal diagnosis in at risk fetuses. Chromosomal analysis is indicated in dysplasias associated with malformations and/or developmental delay.

Table 5 shows the underlying molecular pathogenesis in selected dysplasias.

Bone/Cartilage Histology Although not commonly used, histology can be a useful test in evaluation of dysplasias, where the molecular defect is unknown. Histology is indicated in evaluation of lethal skeletal dysplasias, in suspected fibrous dysplasia and in disorders of bone mass and turnover.

PRENATAL DIAGNOSIS OF SKELETAL DYSPLASIA Ideally, the diagnosis of skeletal dysplasia should be made in the prenatal period for planning management of the affected newborn. This should include parental counseling in lethal cases. Many prenatal cases are detected during the second trimester ultrasound for

Table 4. Biochemical Tests for Dysplasias Clinical clue

Test

Disorder of bone density

Serum calcium, phosphate, albumin, alkaline phosphatase, vitamin D, CBC

Suspected IEM

Urine amino acid, organic acid, glycosaminoglycans

Stippled epiphysis on X-ray VLCFA and sterol analysis Suspected lysosomal storage disorder

Leukocyte enzyme analysis

Table 5. The Molecular/Genetic Basis of Selected Skeletal Dysplasias Molecular defect

Gene/protein involved Phenotype

yy Structural cartilage protein

yy Type 2 collagen (COL2A1 gene)

yy Kniest dysplasia

yy Cartilage metabolic pathways

yy Diastrophic dysplasia sulfate transporter (DTDST gene)

yy Diastrophic dysplasia

yy Regulators of cartilage growth

yy Fibroblast growth factor receptor 3

yy Achondroplasia, thanatophoric dysplasia

yy RNA processing

yy Mitochondrial RNA processing endoribonuclease

yy Metaphyseal dysplasia

yy PTHrP receptor protein

Table 6. Parameters Helpful in Determining Lethality yy Ultrasound Chest: Abdominal ratio <0.7 Cardiothoracic ratio >50% Abdomen: Femur length <0.16 Femur: Foot ratio (normal ratio 1 for all gestational age) Increased nuchal thickness yy Molecular diagnosis of known lethal disorder

congenital anomalies. However, milder forms may be detected first in the third trimester or at birth.

Achondroplasia, spondyloepiphyseal dysplasia and nonlethal osteogenesis imperfecta frequently have normal long bone measurements in the second trimester, which fall off in the third trimester. Molecular screening panels for pregnant women are noninvasive diagnostic tests for precise diagnosis in a suspected case. It is important to determine in the prenatal or immediate natal period whether a particular diagnosed

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PEDIATRICS case is lethal or not; management of lethal cases may be limited to comfort care. Table 6 shows indices used to determine lethality.

CONCLUSION Skeletal dysplasias are a diverse group of genetic disorders, which on an individual level, are difficult to diagnose in day-to-day practice. However, a systematic approach involving history, physical examination and stepwise radiological assessment can identify set clinical patterns of presentation and help to clinch the diagnosis in many cases. Prenatal diagnosis is desirable for appropriate management of the conceptus including parental counseling. Increasing use of molecular tests helps in confirming suspected cases.

SUGGESTED READING 1. Unger S, Superti-Furga A, Rimoin DL. A diagnostic approach to skeletal dysplasias (Chap 16). Pediatric Bone.

2003. pp. 375-400.

2. Kulkarni ML, Samuel K, Bhagyavathi M, Sureshkumar C. Skeletal dysplasias in a hospital in southern India. Indian Pediatr. 1995;32(6):657-65.

4. Krakow D. Skeletal 2015;42(2):301-19, viii.

dysplasias.

Clin

Perinatol.

5. Warman ML, Cormier-Daire V, Hall C, Krakow D, Lachman R, LeMerrer M, et al. Nosology and classification of genetic skeletal disorders: 2010 revision. Am J Med Genet A. 2011;155A(5):943-68.

6. Lyford-Pike S, Hoover-Fong J, Tunkel DE. Otolaryngologic manifestations of skeletal dysplasias in children.

Otolaryngol Clin North Am. 2012;45(3):579-98, vii.

7. Chen H, Bowman J, Windie ML, Flannery D, Petry PD, Buehler B. Skeletal Dysplasia Clinical Presentation.

Medscape Reference. August 11, 2011.

8. Krakow D, Rimoin DL. The skeletal dysplasias. Genet Med. 2010;12(6):327-41.

9. Song D, Maher CO. Spinal disorders associated with skeletal dysplasias and syndromes. Neurosurg Clin N Am. 2007;18(3):499-514.

10. Alanay Y, Lachman RS. A review of the principles of radiological assessment of skeletal dysplasias. J Clin Res Pediatr Endocrinol. 2011;3(4):163-78.

11. Unger S. A genetic approach to the diagnosis of skeletal dysplasia. Clin Orthop Relat Res. 2002;(401):32-8.

12. Savarirayan R, Rimoin DL. The skeletal dysplasias. Best Pract Res Clin Endocrinol Metab. 2002;16(3):547-60.

3. Kinning E, McDevitt H, Duncan R, Ahmed SF. A 13. Puri RD, Thakur S, Verma IC. Spectrum of severe multidisciplinary approach to understanding skeletal skeletal dysplasias in North India. Indian J Pediatr. dysplasias. Expert Rev Endocrinol Metab. 2011;6(5):731-43.

2007;74(11):995-1002.

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...Cont’d from page 960

8. Mathur P, Samantaray JC, Samanta P. Fatal haemophagocytic syndrome and hepatitis associated with visceral leishmaniasis. Indian J Med Microbiol.

2007;25(4):416-8.

9. Salgado Filho N, Ferreira TM, Costa JM. Involvement of the renal function in patients with visceral leishmaniasis (kala-azar). Rev Soc Bras Med Trop. 2003;36(2):217-21.

10. Dutra M, Martinelli R, de Carvalho EM, Rodrigues LE, Brito E, Rocha H. Renal involvement in visceral leishmaniasis. Am J Kidney Dis. 1985;6(1):22-7.

11. Daher EF, Evangelista LF, Silva Júnior GB, Lima RS, Aragão EB, Arruda GA, et al. Clinical presentation and renal evaluation of human visceral leishmaniasis (kala-azar): a retrospective study of 57 patients in Brazil. Braz J Infect Dis. 2008;12(4): 329-32.

12. Chappuis F, Rijal S, Soto A, Menten J, Boelaert M. A meta-analysis of the diagnostic performance of the direct agglutination test and rK39 dipstick for visceral leishmaniasis. BMJ. 2006;333(7571):723.

“Obese Children Lack Essential Nutrients”: AIIMS Study A study conducted by the Dept. of Pediatrics at All India Institute of Medical Sciences (AIIMS) has found that teenagers are consuming more of fast food (refined and processed foods), than healthy fruit and vegetables.

Even as their food intake is high, adds the study, obese adolescents lacked essential nutrients such as iron, zinc, fiber and vitamin D. The study showed that while requirement of fiber is approximately 25 g per day, the intake of the study participants ranged a mere 5.6-9.4 g. Similarly, while vitamin D requirement is 600 IU, the adolescents only got 0.15-0.3 IU. The study enrolled 134 adolescents in the age group 10-16 years. This hidden hunger forms a vicious circle in which the body needs more food but does not get the required amount of nutrients. (Food Navigator Asia)

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MEDILAW

Issues Involving Medical Negligence KK AGGARWAL

The court may prefer one opinion over the other.

Can this be considered negligence?

In the case of Jacob Mathew vs State of Punjab, the Supreme Court of India has observed: “Lord Scarman who recorded the leading speech with which other four Lords agreed quoted the following words of Lord President (Clyde) in Hunter vs Hanley 1955 SLT 213 at 217, observing that the words cannot be bettered “In the realm of diagnosis and treatment there is ample scope for genuine difference of opinion and one man clearly is not negligent merely because his conclusion differs from that of other professional men. The true test for establishing negligence in diagnosis or treatment on the part of a doctor is whether he has been proved to be guilty of such failure as no doctor of ordinary skill would be guilty of if acting with ordinary care.”

“Lord Scarman added - “A doctor who professes to exercise a special skill must exercise the ordinary skill of his speciality. Differences of opinion and practice exist, and will always exist, in the medical as in other professions. There is seldom any one answer exclusive of all others to problems of professional judgement.

A court may prefer one body of opinion to the other, but that is no basis for a conclusion of negligence.” His Lordship further added - “that a judge’s ‘preferences’ for one body of distinguished professional opinion to another also professionally distinguished is not sufficient to establish negligence in a practitioner whose actions have received the seal of approval of those whose opinions, truthfully expressed, honestly held, were not preferred.”

observed in a case: “Deviation from normal practice is not necessarily evidence of negligence. To establish liability on that basis, it must be shown: (1) that there is a usual and normal practice; (2) that the defendant has not adopted it; and (3) that the course adopted is no professional man of ordinary knowledge skill would have taken had he been acting with ordinary care.”

Reference 1. Jacob Mathew v. State of Punjab SC/0457/2005:(2005) 6 SCC 1.

If a decision is taken in good faith, can it amount to negligence?

A decision taken in good faith is not a crime. Defences are available to the doctors under Indian Penal Code (IPC) sections 88, 92 and 93. ÂÂ

The illustration along with this section is: “A, a surgeon, knowing that a particular operation is likely to cause the death of Z, who suffers under a painful complaint, but not intending to cause Z’s death and intending in good faith, Z’s benefit, performs that operation on Z, with Z’s consent. A has committed no offence.”

Reference 1. 334/2005/SCI/144-145 of 2004: Jacob Mathew vs State of Punjab and Anr: 5th day of August 2005 CJI R C Lahoti, G P Mathur, P K Balasubramanyan.

Can deviation from normal practice be termed medical negligence?

No, deviation from normal practice does not always mean negligence. The Supreme Court of India has

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

Section 88. Act not unintended to cause death, done by consent in good faith for person’s benefit: Nothing, which is not intended to cause death, is an offence by reason of any harm which it may cause, or be intended by the doer to cause, or be known by the doer to be likely to cause, to any person for whose benefit it is done in good faith, and who has given a consent, whether express or implied, to suffer that harm or to take the risk of that harm.

ÂÂ

Section 92. Act done in good faith for benefit of a person without consent: Nothing is an offence by reason of any harm which it may cause to a person for whose benefit it is done in good faith, even without that person’s consent, if the circumstances are such that it is impossible for that person to signify consent, or if that person is incapable of giving consent, and has no guardian or other

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MEDILAW person in lawful charge of him from whom it is possible to obtain consent in time for the thing to be done with benefit.

The illustration along with this section is: Z is thrown from his horse, and is insensible. A, a surgeon, finds that Z requires to be trepanned. A, not intending Z’s death, but in good faith, for Z’s benefit, performs the trepan before Z recovers his power of judging for himself. A has committed no offence. A, a surgeon, sees a child suffer an accident which is likely to prove fatal unless an operation be immediately performed. There is no time to apply to the child’s guardian. A, performs the operation in spite of the entreaties of the child, intending, in good faith, the child’s benefit.

A committed no offence. ÂÂ

Section 93. Communication made in good faith: No communication made in good faith is an offence by reason of any harm to the person to whom it is made, if it is made for the benefit of that person. Illustration A, a surgeon, in good faith, communicates to a patient his opinion that he cannot live. The patient dies in consequence of the shock. A has committed no offence, though he knew it to be likely that the communication might cause the patient’s death.

Can an emergency room error be termed medical negligence?

Errors can be made in an emergency even by experts and may not amount to negligence. In SCI: 3541 of 2002, dated 17.02.2009, Martin F. D’Souza vs Mohd.

Ishfaq, the Supreme Court of India has observed: “The higher the acuteness in an emergency and the higher the complication, the more are the chances of error of judgement.”

The patient was not getting cured. Can this be termed as medical negligence?

The Supreme Court of India has observed in Jacob Mathew v. State of Punjab SC/0457/2005: (2005) 6 SCC 1: “Simply because a patient has not favourably responded to a treatment given by a physician or a surgery has failed, the doctor cannot be held liable per se by applying the doctrine of res ipsa loquitur.”

Can an error of judgement be termed medical negligence?

In its judgement in Jacob Mathew v. State of Punjab SC/0457/2005: (2005) 6 SCC 1, Supreme Court of India

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Indian Journal of Clinical Practice, Vol. 26, No. 10, March 2016

has observed: “An error of judgement on the part of a professional is not negligence per se.”

When can a doctor be held liable for negligence?

In one of its judgements, the Supreme Court of India observed: “(3) A professional may be held liable for negligence on one of the two findings: Either he was not possessed of the requisite skill which he professed to have possessed, or, he did not exercise, with reasonable competence in the given case, the skill which he did possess. The standard to be applied for judging, whether the person charged has been negligent or not, would be that of an ordinary competent person exercising ordinary skill in that profession. It is not possible for every professional to possess the highest level of expertise in that branch which he practices.”

Reference 1. 334/2005/SCI/144-145 of 2004: Jacob Mathew vs State of Punjab and Anr: 5th day of August 2005 CJI R C Lahoti, G P Mathur, P K Balasubramanyan.

What is the difference between professional misconduct or negligence or deficiency of service?

A doctor is liable only for actions that occur as a result of a breach of duty of care. The adjudication of professional liability of a doctor is decided by the appropriate forum.

The Consumer Court usually examines cases of civil negligence or deficiency of service and/should refer to the Medical Council of India/State Medical Council any complaint of professional misconduct.

For willful or gross or criminal negligence that results in injury or serious harm to the patient, or even death of the patient on account of a rash or negligent act, there are criminal courts.

The Consumer Protection Act has defined deficiency of service as any fault, imperfection, shortcoming or inadequacy in the quality, nature or manner of performance that is required to be maintained by or under any law for the time being in force or has been undertaken to be performed by a person in pursuance of a contract or otherwise in relation to any service.

Deficiency of service is different from civil negligence.

It may or may not amount to negligence. For deficiency of service the court may award compensation.

MEDILAW DMC Rule 32 (1) of Delhi Medical Council Rules 2003 states about complaint against medical practitioner.

“The Council may inquire into complaint against medical practitioner either suo moto or on the basis of any complaint made to the Council in respect of misconduct or negligence of any medical practitioner for the purposes of the Act through the Disciplinary Committee. The proceedings shall be conducted by the Registrar in the presence of the Chairman, Disciplinary Committee and at least two members thereof sitting together.”

In one of the judgements by the National Consumer Forum, the following was observed: “…………denied that there was any deficiency in service or negligence in treatment ……………..” “Considering the evidence on record and the medical texts on the subject, it cannot be said that there was any deficiency on the part of the Opposite Party No. 1 in giving treatment to the deceased. Learned Counsel for the Complainants was not in a position to point out any deficiency in the treatment given to her.”1

Reference 1. National Consumer Disputes Redressal Commission: 250 of 1997, dated 24.10.2005, C.H. Jayaram & Ors vs Dr. Mallika Samuel & Anr, Justice M.B. Shah, President; Mrs Rajyalakshmi Rao, Member.

When is negligence a criminal negligence? ÂÂ To prosecute a medical professional for negligence under criminal law it must be shown that the accused did something or failed to do something which in the given facts and circumstances no medical professional in his ordinary senses and prudence would have done or failed to do. The hazard taken by the accused doctor should be of such a nature that the injury which resulted was most likely imminent.1 ÂÂ In the Jacob Mathew case, it has been stated that simple negligence may result only in civil liability, but gross negligence or recklessness may result in criminal liability as well. For civil liability only damages can be imposed by the court but for criminal liability the doctor can also be sent to jail (apart from damages which may be imposed

on him in a civil suit or by the consumer fora).

However, what is simple negligence and what is gross negligence may be a matter of dispute even among experts. ÂÂ

Also, as per Jacob Mathew case, negligence which is neither gross nor of a higher degree may provide a ground for action in civil law but cannot form the basis for prosecution.

ÂÂ

In Dr SG vs GNTCT of Delhi, the appellant doctor was accused under Section 304A IPC for causing death of his patient. The operation performed by him was for removing nasal deformity. The magistrate who charged the appellant stated in his judgement that the appellant while conducting the operation for removal of the nasal deformity gave incision in a wrong part and due to that blood seeped into the respiratory passage and because of that the patient collapsed and died. The High Court upheld the order of the magistrate observing that adequate care was not taken to prevent seepage of blood resulting in asphyxia. The Supreme Court held that from the medical opinions adduced by the prosecution the cause of death was stated to be ‘not introducing a cuffed endotracheal tube of proper size as to prevent aspiration of blood from the wound in the respiratory passage. The Supreme Court held that this act attributed to the doctor, even if accepted to be true, can be described as a negligent act as there was a lack of care and precaution. For this act of negligence he was held liable in a civil case but it cannot be described to be so reckless or grossly negligent as to make him liable in a criminal case.2 For conviction in a criminal case the negligence and rashness should be of such a high-degree, which can be described as totally apathetic towards the patient.3

References 1. 334/2005/SCI/144-145 of 2004: Jacob Mathew vs State of Punjab and Anr: 5th day of August 2005 CJI R C Lahoti, G P Mathur, P K Balasubramanyan.

2. Dr Suresh Gupta vs Government of N.C.T. of Delhi and another AIR 2004 SC 4091.

3. SCI: 3541 of 2002, dated 17.02.2009, Martin F. D’Souza vs Mohd. Ishfaq Bench: Markandey Katju and G S Singhvi.

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CONFERENCE UPDATE

53rd Annual Conference of Indian Academy of Pediatrics (PEDICON 2016) DEFINING PRIORITIES FOR CHILD HEALTH IN POST-MDG WORLD

CHILDREN, YOUTH AND NCDS IN THE POST-MDG WORLD

Dr Pramod Jog, President, IAP ÂÂ

Every pediatrician is BIG pediatrician with expertise in breastfeeding, immunization and growth development.

ÂÂ

Milk is like a combo vaccine. Every IAP must encourage breastfeeding from ½ hour to ½ year.

ÂÂ

Exclusive breastfeeding rates in India have increased only up to 46% in 2011 from 43% in 1995.

ÂÂ

Promote breast sutras. Breast crawl, relook into routines (suction, prelacteal feeds), express, attachment, support, training.

ÂÂ

IAP has intelligence, authenticity, pyar for children, what IAP does not have is infrastructure, so IAP should work at individual level, academy level and at peripheral level.

Dr Jonathan D Klein, AAP ÂÂ

We have made lot of progress in MDG Goal 4; child mortality rate has reduced by more than 50% from 90 to 43 deaths per 1,000 live births.

ÂÂ

SDGs are different from MDGs: SDGs are designed to apply to all countries leaving no one behind; focus on sustainable development, global partnerships and rights based approach.

ÂÂ

WHO adopted a global plan for prevention and control of NCDs covering 4 diseases: CVD, cancer, chronic pulmonary disease, DM and 4 risk factors: tobacco, unhealthy diet, physical inactivity, harmful alcohol use.

ÂÂ

NCDs affect all; they are the leading cause of death in low and middle income countries.

ÂÂ

Children need a different approach to prevent and treat NCDs vs adults. Goals shared with child survival, immunization.

ÂÂ

There is a need to train family physicians; HAIC syndrome (How am I concerned?).

ÂÂ

Every IAPIAN should become a champion IAPIAN.

ÂÂ

The best vaccine is HE i.e., health education.

ÂÂ

ÂÂ

COLD chain to maintain potency of knowledge: Continuous, observation, learning, delivery/ deliberation/dissipation.

As pediatricians, we can educate local and national govts about SDGs and help formulate plans in SDG implementation.

ÂÂ

Immunization is also related to NCD; hepatitis B and human papilloma virus vaccine are cancer preventing vaccines.

ÂÂ

We can continue advocacy at various levels.

ÂÂ

We have scientific knowledge, social strategies, we need political will to carry things forward and make our children healthier.

ÂÂ

Mission Indradhanush should be Pindradhanush i.e., it should be persistent all through the year.

ÂÂ

Infant mortality is due to NIDRA; neonatal, immunization/infections (VPDs), diarrhea, respiratory, AFB anomalies.

ÂÂ

We should develop IPL - Individual Pediatrician’s Leadership.

P-PRAMOD Proactive Positive attitude Ready to give time Ability to monitor own self, family, colleagues, acquaintances, KOLs Medically perfect Overlook wrinkles, commentators... take all along Dedication

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Indian Journal of Clinical Practice, Vol. 26, No. 10, March 2016

ROLE OF APPA IN CHILD HEALTH IN POST-MDG WORLD Dr Naveen Thacker, President, APPA ÂÂ

The Asia Pacific Pediatric Association has 21 members, yesterday two countries were included: Mongolia, North Korea.

ÂÂ

APPA region has the largest number of children and covers more than two WHO regions (SEAR and Western Pacific) with diverse child health problems.

CONFERENCE UPDATE ÂÂ

Investigative approach should be stepwise, doing the basic investigations first then considering the specific ones.

ÂÂ

Standard guidelines for management should be followed.

PRIORITIZING INVESTMENTS IN CHILD HEALTH IN INDIA Dr Rakesh Kumar, Joint Secretary RMNCH+A, MOHFW, Govt of India

ÂÂ

In Western Pacific region, NCDs, injuries are more prominent causes.

ÂÂ

Our focus should be on reducing newborn mortality and stillbirths, increasing equitable coverage of immunization and reducing preventable deaths, overcome the dual burden of under and overnutrition, prevention and control of birth defects.

ÂÂ

We have charted an action plan for 2016-18 with establishment of Technical Advisory Groups (TAG) for ECD, NCDs, immunization advocacy, birth defects, adolescent health among others.

ÂÂ

Pediatricians should be the agents of change in the implementation of action plan.

ÂÂ

Immunization advocacy workshop with participants designated as “APPA Child Health Ambassadors”.

ÂÂ

GAPPD (Global Action Plan for Pneumonia and Diarrhea) launched in 2013, still a long way to go.

ÂÂ

IAP has a very active TAG on ECD.

ÂÂ

Pediatricians can play a role at every level especially at level of national strategic plans.

ÂÂ

India is a story of large numbers with 26 million babies born each year; 5,72,000 are born dead, 748,000 die in the first month.

ÂÂ

There are inequities in the system; rural/urban, male/female, rich/poor, etc.

ÂÂ

India has the highest number of neonatal deaths in the world (7,48,000) followed by Nigeria, Pakistan, China and DR Congo.

ÂÂ

But India is also a success story in the making with 1,000 additional newborns saved each day; 8 out of 10 women deliver in a healthcare facility.

ÂÂ

There has been a 20% decline in neonatal mortality rate in the last 5 years vs. 16.5% global decline.

ÂÂ

Causes of neonatal deaths in India: Prematurity (major cause 33%), pneumonia and diarrhea 18%, sepsis 15%; birth asphyxia contributes to one-fifth of neonatal deaths.

ÂÂ

We need to prioritize our focus on 4 states (UP, Bihar, MP and Rajasthan) and adopt a ‘continuum of care’ practice across RMNCH+A and scale up high impact interventions.

ÂÂ

Quality ANCs has to be the top most priority.

Maternal nutrition is very important but we are missing out on this very important component.

ÂÂ

Govt Initiatives: Intensified Diarrhea Control Fortnight (IDCF) launched in 2014 on 28th July;

CHOOSING THE CORRECT INVESTIGATION Dr Jaydeep Choudhury, Kolkata ÂÂ

Confusion arises when the choice is plenty.

ÂÂ

Our aim is to do the minimal but most appropriate investigations, which cause minimum harm to the patient.

ÂÂ

The first step should be framing the relevant differential diagnosis of the case considering the clinical findings and common diseases prevailing in the region.

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CONFERENCE UPDATE Rashtriya Bal Swasthya Karyakram (Universal screening of children initiative), Mission Indradhanush.

HEADACHE: HOW TO INVESTIGATE AND TREAT?

ÂÂ

India achieved elimination of maternal and neonatal tetanus by May 2015.

ÂÂ

ÂÂ

Focus is on High Priority Districts across 29 states of India.

New headache classification by the International Headache Society (IHS) 3 is being utilized now for the classification. In addition to the primary headaches, migraine and tension type of headache, trigeminal autonomic cephalalgias are also included. During the diagnostic process for a single patient, multiple diagnoses can be given.

ÂÂ

For the acute treatment rather than going for the ‘stepped care through attack’ approach, a ‘stratified care approach’ is adopted now. In the ‘stepped care through attack’, treatment is started with mild analgesic like acetaminophen. In the second step, triptan and in the third step, a combination treatment is given. But currently in the stratified approach, depending on the severity, either acetaminophen, NSAID(s) or triptan(s) is given initially itself as pain duration can be reduced fast.

ÂÂ

Preventive treatment is required for patients who have been having more than two headache attacks per month or their attacks cannot be controlled easily with acute treatment. Drugs used are propranolol, flunarizine, topiramate or sodium valproate. Use of amitriptyline along with these drugs helps in better headache prevention.

ÂÂ

Episodic syndrome that may be associated with migraine is the new terminology used for the childhood periodic syndrome. They are cyclical vomiting, abdominal migraine, benign paroxysmal vertigo and benign paroxysmal torticollis as they can occur at any age.

ÂÂ

With the presence of red flag signs like focal neurological deficit, secondary headache can be diagnosed. Moreover, when a new headache occurs first time in temporal relation with existing headache syndrome, a secondary headache can be diagnosed.

ÂÂ

Headache hygiene with a healthy lifestyle is important for children in preventing recurrence of migraine headache.

Dr PA Mohammed Kunju, Trivandrum

MEDIA ADDICTION IN ADOLESCENTS Dr Swati Y Bhave, Editor-in-Chief, AJPP Moderator: Dr Swati Y Bhave Panelists: Sunny Kurian, Piyali Bhattacharya, Garima Saikia, Chitra Dinkar, Rakesh Bhardwaj ÂÂ

Due to easy access to internet connectivity with smart phones and difficulty in monitoring by parents, media addiction is on the rise.

ÂÂ

Media addiction can take away valuable time from academic and sport pursuits and adversely affect the psychosocial development and future adult personality.

ÂÂ

Also, the sedentary lifestyle can lead to obesity and associated metabolic syndrome and other NCDs. Parents and teachers need to be aware of the various ill-effects of media addiction and educate, and monitor their children.

ÂÂ

The various problems are cyberbullying, sexting, pornography, victims and blackmailing of sexual abuse, online gaming.

ÂÂ

Internet addiction can lead to inability to form relationships in the real world, depression and substance abuse and various mental disorders.

ÂÂ

Treatment is same as that of any addiction like alcohol and gambling.

ÂÂ

But on the flip side playing educative video games for limited hours can help in positive way.

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Various apps can be an acceptable way of connecting with teens for many problematic issues and have been successfully used as therapy such as learning disorders, etc.

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CONFERENCE UPDATE

46th Annual Conference of the Indian Society of Nephrology (ISNCON 2015) “JEEVANDAN” DECEASED DONOR TRANSPLANTATION PROGRAM: A SUCCESS STORY

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The main center was kept in Nizam’s Institute of Medical Sciences (NIMS). The Awareness programs were allocated to Gandhi Hospital, Transplant Coordinator Training Program to Osmania Hospital.

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Awareness programs involving film personalities and other eminent public figures have been conducted in 25 hospitals. Coordinator program was conducted 10 times. The organ allocation is done depending on the sub-committee report and donor cards issued.

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Plan for Donor Families: Planting a Tree, honoring them with certificates and felicitating them during the awareness programs.

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But there are deficiencies in the program which need to be worked upon. Brain death has not been made mandatory in the executive orders. Because of lack of good infrastructure and inertia in the govt. setup, there is a bias towards corporate setup, with very few transplants in govt. hospitals.

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Very recently, for the first time, a heart transplant was done free of cost in NIMS, a State-run hospital in Telangana State under Jeevandan Scheme (The Hindu).

Dr Pradeep Deshpande, President, Indian Society of Nephrology Our scripture, the Bhagwad Gita says “What is the end of life for a caterpillar is a new life for butterfly.” Also, as it is often said, don’t take your organs to heaven, we need them here… ÂÂ

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In 1995, Legislative Assembly of United Andhra Pradesh ratified the Human Organ Transplant Act (HOTA). A Draft Committee formulated to suggest the government about encouraging the Deceased Donor Transplantation Program submitted its draft to the CM on 27th April 2010, who issued the orders on 16th August 2010.

Advisory bodies under the scheme are: Cadaver Transplant Advisory Committee (CTAC) - the final authority, Appropriate Authority for Cadaver Transplantation (AACT), AP Network for Organ Transplantation (APNOS), Organ Transplant Centers as well as Nontransplantation Organ Harvesting Centers (NTOHC).

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In the Tamil Nadu Model, declaration of brain death for cadaver transplantation is compulsory.

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The organs are allocated strictly as per the guidelines framed by the sub-committees. Based on these guidelines, the NIC has designed the web portals. Patients are registered through the concerned hospital, and they can see the details of the recipients through user ID and password.

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Three subcommittees: Heart and Lung, Liver and Pancreas and Kidney.

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Also in the offing are NOTTO (National Organ and Tissue Transplant Organization) and SOTTO (State Organ and Tissue Transplant Organization).

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A total of 761 organs have been donated from 2013 till 30.11.15. Heart transplants have picked up.

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Budgetary provisions have been made: Heart transplant (10 lakhs), liver transplant (10.5 lakhs) and kidney transplant (1.5-2.5 lakh) under Aarogyasri Scheme.

Tableau on 26th January 2012 During the Republic Day Parade

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CONFERENCE UPDATE The word ‘jeevandan’ translates as ‘gift of life’. It is the combined effort of all stakeholders including administrators, academicians that has crafted this success story. And now this program is making strides…

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Biodegradable Maturation Enhancing Stent (bMES) for early AVF failure could be placed at the time of fistula creation. It increases flow and diameter, optimizes anatomy and hemodynamics and improves vascular function. Also, avoids longterm effects of foreign body → successful AVF maturation.

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Far Infra-Red Therapy: It tries to change vascular biology and improves AVF maturation, access flow.

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Percutaneous fistula creation involves catheter insertion, magnet activation and radiofrequency energy blast to create a connection.

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About 80% incident hemodialysis patients start dialysis with a catheter. There is lot of evidence that shows significant mortality if dialysis with TDC and not fistula. A functional AVF → marked ↓ in morbidity and mortality.

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Factors that influence successful AVF: Early referrals, meet institutional program, good surgeon (decision), not long waiting list, AVF follow-up at 4-6 weeks, expert cannulator.

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There are huge process barriers in early referrals and good surgeons. If there is to be a battle for dialysis vascular access, it should be done before dialysis begins and not after patient starts dialysis.

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Judgment calls of the surgeon: Wisdom to make a judgment call about being able to place the right access in the right patient at right time.

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What we need to do in the future is to stratify patients based on clinical and biological parameters.

Individualize vascular access care by pairing specific therapies with clinical and biological phenotypes.

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About 70% of problems associated with vascular access are due to process of care issues providing opportunities for process of care innovations.

DIALYSIS VASCULAR ACCESS: A TALE OF BIOLOGY, TECHNOLOGY AND PROCESS OF CARE Dr Prabir Roy-Chaudhury, USA ÂÂ

The current modalities and therapies for dialysis vascular access are not very effective resulting in widespread use of TDC with the associated morbidity and mortality.

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Perianastomotic stenosis causes AVF nonmaturation and stenosis at the graft vein anastomosis causes graft thrombosis leading to dysfunction of dialysis vascular access.

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Even though neointimal hyperplasia is important it is important to remember that it is the combination of vascular neointimal hyperplasia with inward/ negative remodeling or lack of outward/positive remodeling that results in dialysis access stenosis.

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Flow pattern and shear stress are important determinants of endothelial function. Nonlaminar flow with oscillatory shear stress → inward remodeling, neointimal hyperplasia, failed dialysis access. Laminar flow with laminar stress → outward remodeling, no neointimal hyperplasia, successful dialysis access.

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The differential MCP1 expression between outer and inner curve of AVF is due to differences in shear stress.

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The surgical configuration – curved or straight influences shear stress profiles.

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The interaction between upstream and downstream determines if the fistula is going to be a success.

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Systemic therapies for dialysis access stenosis that do not work: Warfarin, aspirin, ACEIs, ARBs, CCBs, statins, fish oil, plavix, ticlopidine.

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Process of care innovation is best done via a team approach: VA coordinator, Dialysis unit, Surgeon and Interventionalist, Nephrologist.

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We have been largely unsuccessful because stenosis is a continuum of events from vascular injury to neointimal hyperplasia + negative vascular remodeling to stenosis to thrombosis. Most have worked in area of thrombosis, some in the area of stenosis, while almost nobody has worked on vascular injury and neointimal hyperplasia + negative vascular remodeling.

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Although we cannot fix the vast majority of these problems, we can fix their vascular access by combining biology/bioengineering and technology with clinical need or setting.

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If we do that then we can convert our dialysis units to factors of quality care and research and innovation and make a huge difference in survival and QoL.

Problems with AVF: Small vessels, hemodynamics, bad vascular pathology.

Dialysis vascular access is a multidisciplinary problem that can only be solved via a multidisciplinary approach…

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CONFERENCE UPDATE CKD: PREDICTION OF PROGRESSION AND THE POWER OF COHORT (AND OTHER) STUDIES Dr Adeera Levin, Canada, President, International Society of Nephrology ÂÂ

In CKD, we try to predict the population outcomes and individual outcomes, whether the CKD will progress to dialysis or will the patient get a CV event or death. Also, the time period: Shortterm (1-3 years), mid-term (3-5 years), long-term (5-10 years).

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Purpose: We need to counsel patients for decisionmaking about treatment choices, allocation of resources and we also need to enroll patients in clinical trials to test intervention outcomes.

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Prediction models used for different purposes clinical research, inform patients on prognosis, make decisions for treatment choices, resource allocation, decision support - require different characteristics.

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Predicting patient and kidney outcomes remains problematic due to the biological variability of disease process, need for multiple measurements, complex interaction of environment, exposures and biology, defining purpose of the model and reluctance of clinicians to replace clinical intuition with ‘mathematical’ models.

Possible events and outcomes of CKD patients can be kidney related (AKI, progression to dialysis or transplantation) or nonkidney-related (CVD, infection) and they may interact with each other.

Risk prediction models offer an opportunity to systematically quantify ‘clinical intuition’ and more uniformly predict outcomes for improved perceptions by patients and caregivers.

There is wide variability in GFR decline with age.

CKD progression in elderly also varies according to other conditions like DM. Men have faster decline than women.

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Different etiologies of CKD and comorbidities CKD predict different rates of decline.

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Asian patients have faster progression to ESRD, but have better survival.

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Small changes in creatinine (AKI) in CKD patients have profound impact on outcomes.

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2.1.2. Recognize that small fluctuations in GFR are common and are not necessarily indicative of progression (ungraded) (KDIGO-CKD Guideline).

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2.1.3. CKD progression based on ≥1 of the following (Not Graded): Decline in GFR category.

A drop in eGFR is defined as a drop in GFR category accompanied by ≥25% drop in eGFR from baseline.

Rapid progression is defined as a sustained decline in eGFR of >5 mL/1.73 m2/year (KDIGO-CKD Guideline).

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Newer biomarkers (cystatin C, troponin, NT proBNP, FGF 23, ADMA, TGF-b, CRP) may add to current prediction models: Identify those with/ without events with greater accuracy, therapeutic targets for intervention and identify new disease pathways.

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CanPREDDICT study: To determine if there is a biomarker profile/set of profiles, above and beyond the conventional risk factors, which predict risk for CKD progression, atherosclerotic events or heart failure, death.

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Other similar studies being conducted: CRIC study, Birmingham study, German CKD study, Queensland CKD study, Japan CKD, Beijing CKD. All have common themes: To describe phenotypes, biobanking, exploration of outcomes predictors.

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Ongoing studies are needed to better understand variability in biological processes and outcomes, how to use prediction models in clinical practice.

TOXIC ACUTE KIDNEY INJURY: LESSONS LEARNT FROM HAIR DYE POISONING Dr V Sivakumar, Tirupati ÂÂ

The kidney is the target of numerous xenobiotic toxicants, including environmental chemicals.

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Hair-dye poisoning is observed world over and may be intentional or accidental.

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Systemic injury was demonstrated in clinical and experimental methods.

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Kidney injury is associated with poor prognosis.

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Our study reiterates importance of public awareness, display of toxicity warnings on hairdye labels and control measures to prevent the over the counter sale.

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CONFERENCE UPDATE

56th Annual Conference of Indian Society of Gastroenterology (ISGCON 2015) “IT IS ALL ABOUT US” Dr Ajay C Anand, New Delhi In a brilliant Presidential address, Dr Ajay Anand gave his view from both sides of the fence-as a committed army man serving his country as he pursued his vocation to the commercial business-oriented practice that is prevalent today and which unfortunately most people in private practice have perforce become a part of.

Dr Anand reflected on the glorious 40 years serving in the army where there was life beyond medicine while working for the deserving in conditions incomprehensible by most doctors in the civilian arena.

The most valuable lesson learnt was that you must focus on the problems you face in your practice and find the best solution in solving them with the available recourses. Needless to say Dr Anand did a lot of research and opened up a liver transplant center of excellence. He also initiated a very successful organ donation movement in the army with a high rate of success.

Dr Anand then shifted his talk to perspectives gained during his Presidential Year in ISG. He was instrumental in initiating a number of reforms including e-voting and enhancing engagement of doctors across specialties as also setting up various committees to look into the affairs of ISG. According to him gastroenterology in India is like a wild stallion “raring to go” but needs proper handling and taming. Giving a real life story about a poor boy who through various ups and downs

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ultimately became a top business tycoon, Dr Anand brought out a few very disturbing facets of healthcare in India.

That Doctors are willing to give more than 25% of their fees as well as that of a procedure/operation fees to get more patients is a very alarming trend but more alarming is the perception that ethics is a matter for the medical professionals to think about while the businessmen go about commercializing healthcare.

“For the triumph of evil, it is only necessary for good men to do nothing” Edmund Burke. This is very apt in our scenario, said Dr Anand. There is public distrust towards doctors. The corporate environment is nudging doctors to overinvestigate and overtreat. He said, “I come from a background where commercialization and corruption had no place. I have seen life from both sides of the fence and I think it is all about ‘us’.

We should sit together and find a solution to this very serious problem, which threatens our very core value system- that of service to mankind. As an organization, isn’t it our duty to see that we as well as our patients are not unnecessarily victimized?”

Dr Anand received a much deserved standing ovation!

VASCULAR DISEASES OF THE LIVER: RECENT ADVANCES IN UNDERSTANDING AND MANAGEMENT Dr Deepak Amarapurkar, Mumbai ÂÂ

Vascular diseases in India up to 90s: Extrahepatic portal vein thrombosis predominantly disease in children: (No thrombophilia association); BuddChiari syndrome (Thrombophilia Association uncommon).

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Local risk factors for venous thrombosis: Liver cirrhosis, hepatobiliary malignancy, cholecystitis, pancreatitis, appendicitis, IBD, GI surgery.

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Systemic risk factors for venous thrombosis may be inherited (Factor V Leiden mutation, deficiency of protein C, S, antithrombin); acquired factors (antiphospholipid syndrome, PNH, OCs, malignancy, pregnancy or puerperium).

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JAK2(V617F) mutation occurs at high frequency in patients with idiopathic IAVT, so they should

CONFERENCE UPDATE be screened for latent MPD (Trop Gastroenterol.

2011;32:279-84). ÂÂ

IAVT: Low antithrombin, Protein C or S most likely acquired due to liver damage; but, if single defect & other coagulation factors synthesized by liver are normal, then inherited; do family studies in such cases to confirm that defects are inherited.

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Factor II gene mutation: Most frequent cause of hereditary thrombophilia, alone in combination with other risk factors (OCs, pregnancy).

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High levels of Factor VIII, IX, and XI have been recently recognized as new markers of prothrombotic risk; not known if inherited or acquired.

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To diagnose primary BCS, look at the hepatic veins and terminal IVC; good long-term outcome of BCS with a stepwise treatment approach (Hepatology. 2013).

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Cirrhosis, malignancy and MPN: Important in etiology of PVT (multifactorial).

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GI bleeding: Main complication of chronic PVT, but a rare cause of mortality.

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Anticoagulation should be individualized in chronic PVT.

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Prognosis depends on the underlying disorder and is good in patients without cirrhosis or malignancy.

Abdominal Venous Thrombosis: What do we Know in 2015? ÂÂ

A blood disease.

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Presenting features are protean vary from acute liver failure to mimicking cirrhosis and HCC.

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Currently treatable with a strategy of minimal invasiveness.

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Issues: Impact of treatment for underlying disorder? Expert centers for management? How to decrease bleeding on anticoagulation?

Both initial remission and long-term maintenance should be considered in treatment of severe UC with cyclosporine (J Gastroenterol. 2010;45(11):1129-37). ÂÂ

Cyclosporine A is an effective treatment to avoid immediate surgery (J Gastroenterol. 2010;45(11): 1129-37).

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EAI score post cyclosporine A therapy is one of good predictive markers for the risk of future total colectomy (J Gastroenterol. 2010;45(11):936-43).

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Oral tacrolimus therapy in patients with steroidrefractory UC shortened the acute phase and induced rapid mucosal healing (Inflamm Bowel Dis. 2012).

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Mucosal healing with oral tacrolimus is associated with favorable medium- and long-term prognosis in steroid refractory/dependent ulcerative colitis patients (J Crohns Colitis. 2013).

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ACTIVE: Efficacy and safety of tacrolimus vs. infliximab; multicenter randomized prospective study; enrollment started May 2013, end of study March 2017; clinical improvement rate at Week 10 (primary endpoint); clinical remission rate, DAI score, endoscopic remission rate at Week 10; partial DAI score at Weeks 2, 6; Lichtiger score, clinical remission rate, clinical improvement rate at Weeks 2, 6, 10 and surgical operation rate at Week 10 (secondary endpoints).

ESOPHAGEAL PHYSIOLOGY RELEVANT TO GERD Dr C Prakash Gyawali, USA

HOW TO USE CYCLOSPORINE AND TACROLIMUS IN IBD?

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Inappropriate relaxation of the lower esophageal sphincter is the most frequent mechanism for gastroesophageal reflux to occur.

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Presence of a hiatus hernia increases the frequency of inappropriate lower esophageal sphincter relaxation, and reduces resting pressure of the lower esophageal sphincter, thereby promoting reflux.

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Reduced esophageal motor function allows prolonged contact of the refluxed acid with the esophageal mucosa.

Dr Haruhiko Ogata, Japan ÂÂ

The Endoscopic Activity Index (EAI) is equivalent to other endoscopic indices and relatively more useful in choosing a treatment for patients with severe UC (J Gastroenterol. 2010;45(9):936-43).

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Reduction in saliva production from radiation therapy to the head and neck, smoking, and certain disorders and medications reducing saliva will increase the risk for esophagitis from reflux.

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Rapid endoscopic improvement is important for 1-year avoidance of colectomy but not for the longterm prognosis in cyclosporine A treatment for UC.

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Despite these mechanisms of reflux, treatment to reduce gastric acid production remains the most effective management for GERD.

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CONFERENCE UPDATE NEW-ONSET DIABETES: A POTENTIAL CLUE TO THE EARLY DIAGNOSIS OF PANCREATIC CANCER?

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This is the first objective evidence of marked immune-mediated mucosal injury in ‘mild enteropathy’, supporting the need of institution of GFD in them.

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There is a need of large multicenter studies, and randomized controlled trials to resolve this issue.

Dr Suresh T Chari, USA ÂÂ

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Long-standing type 2 DM is a modest risk factor for pancreatic cancer (PaC). The risk is not high enough to screen long-standing diabetics for PaC (Br J Cancer. 2005;92:2076-83).

When PaC patients are screened for DM by fasting glucose measurement or OGTT, the prevalence of DM is extremely high (45-65%)

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DM in PaC is mostly of recent onset (<2 years) (Chari et al. Gastroenterology. 2008;134(1):95-101).

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New-onset DM in PC is ameliorated by cancer resection (Pannala et al. Gastroenterology.

2008;134:981-7).

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If PC is diagnosed in subjects with asymptomatic new-onset DM, it will likely be resectable.

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Weight loss is greater in PC-DM than type 2 DM (Pannala et al. Gastroenterology. 2008;134:981-7).

Key Points ÂÂ Early PC: Resectable, small (<20 mm) or curable (Stage 1 or CIS). ÂÂ Detection of early PC will require screening of asymptomatic individuals using two “sieves”. ÂÂ New-onset DM in persons >50 years identifies a high-risk cohort. ÂÂ Ability to distinguish type 2 DM from PC-DM can lead to screening for sporadic PC.

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Dr Ashish Kumar, New Delhi ÂÂ

Although most international guidelines have recommended surveillance for cirrhotic patients for hepatocellular carcinoma (HCC), the evidence favoring this recommendation is very weak.

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Indian studies are scarce, but the two available studies do not support surveillance as it is not costeffective and even if HCC is detected early, many of them could not be offered curative treatments.

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Data from studies from other regions of the world cannot be applicable in India because the overall HCC prevalence is low in India; also, our etiological profile of cirrhosis is different from other countries.

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Even if surveillance has to be done, it should be done only for selected patients with good Child function (Child class A or B), and in those who can afford curative treatment.

EVALUATION OF DYSPHAGIA WITH A NORMAL UPPER GI ENDOSCOPY Dr C Prakash Gyawali, USA ÂÂ

A careful history is key in differentiating oropharyngeal from esophageal dysphagia.

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Dr Prasenjit Das, Dr GPS Gahlot, Dr Ritu Mehta, et al. AIIMS, New Delhi

Esophageal biopsies are performed at upper endoscopy to evaluate for eosinophilic esophagitis and PPI-responsive esophageal eosinophilia.

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Immune-mediated apoptotic enterocyte loss is as rampant in ‘mild enteropathy’, as that in ‘advanced enteropathy’ celiac disease.

An empiric trial of PPIs can be considered, as GERD-related esophageal lesions are the most common cause of esophageal dysphagia.

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Maintained crypt regenerative activity in the ‘mild enteropathy’ is responsible for maintenance of villous height.

Barium esophagograms, particularly with a solid bolus or barium tablet, can identify structural lesions, especially subtle strictures.

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A motor disorder causing dysphagia can be suspected if no structural etiology is found on endoscopy and barium studies.

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Empiric bougie dilation is an option if no structural or motor disorders are found.

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If all tests are negative, functional dysphagia can be considered and neuromodulators can be tried.

PATIENTS WITH MILD ENTEROPATHY HAVE APOPTOTIC INJURY OF ENTEROCYTES, SIMILAR TO THAT IN ADVANCED ENTEROPATHY IN CELIAC DISEASE: IMPLICATIONS ON THE TREATMENT

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HCC SURVEILLANCE IS INDICATED IN ALL PATIENTS WITH CIRRHOSIS IN INDIA

If extent of immune-mediated enterocyte loss, is as active in ‘mild enteropathy’ as that advanced disease, it raises a question mark on the existing practice of not treating patients with mild enteropathy.

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AROUND THE GLOBE

News and Views Obesity Affects Clinical Outcomes in Adult AML A pooled analysis from four CALGB (alliance) clinical trials has concluded that obesity has significant prognostic value for disease-free survival (DFS) and overall survival in patients with acute promyelocytic leukemia (APL), but not for non-APL acute myeloid leukemia (AML). Obesity was associated with worse DFS with hazard ratio of 1.53 and OS after adjusting for age, sex, performance status, race, ethnicity, treatment arm and baseline white blood cell count in APL patients. The study by Jorge J Castillo, from Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts and coauthors is published in the February issue of the American Journal of Hematology.

NAFLD and Metabolic Syndrome Together have a Bearing on Subclinical Atherosclerosis Results of a cross-sectional study published in February 2016 issue of the journal Clinical Endocrinology show the synergistic impact of nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS) on subclinical atherosclerosis. Ho Cheol Hong from The Division of Endocrinology and Metabolism, Dept. of Internal Medicine, College of Medicine, Korea University, Seoul, Korea and coresearchers found that the risk of subclinical atherosclerosis as defined by carotid intimamedia thickness (OR = 2.06, 95% CI = 1.13-3.74) or brachial-ankle pulse wave velocity (OR = 2.64, 95% CI = 1.46-4.76) was much more in patients, who had both NALFD and MetS than in normal subjects. Based on these results, the authors recommend CVD prevention strategies in these patients.

Kidney Disease in Moderate-to-severe Psoriasis Moderate-to-severe psoriasis is associated with an increased risk of moderate-to-advanced chronic kidney disease (CKD), independently of traditional risk factors.

This critical appraisal of kidney disease in moderateto-severe psoriasis is published online Feb 12 in the British Journal of Dermatology by ZK Jabbar-Lopez, from Dermatological Sciences, Institute of Cellular Medicine, Newcastle University, Framlington Place and Dept. of Dermatology, Royal Victoria Infirmary, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.

Simultaneous Living Donor Kidney and Parathyroid Allotransplantation Raquel Garcia-Roca, from the Division of Transplantation, Dept. of Surgery, University of Illinois at Chicago, Chicago, IL and co authors present the first case of a simultaneous living donor kidney and parathyroid allotransplantation in a 23-year-old women with endstage nephrocalcinosis secondary to congenital absence of parathyroid glands.

Her 25-year old sister had haploidentical human leukocyte antigen (HLA) and was ABO compatible; she underwent simultaneous left robotic-assisted donor nephrectomy and robotic single parathyroid excision via the transaxillary approach. The recipient received a kidney transplant and simultaneous single parathyroid gland transplant in the right iliac fossa. The parathyroid tissue was fragmented into several small portions and implanted in the rectus muscle during the exposure for kidney transplantation. The case is reported in an online publication Jan 12 in the journal Transplantation.

Assessment of a Combined Panel of Six Serum Tumor Markers for Lung Cancer A study reported in Feb 15 issue of the American Journal of Respiratory and Critical Care Medicine suggests that the combined assessment of a panel of six serum tumor markers (carcinoembryonic antigen, carbohydrate antigen 15.3, squamous cell carcinoma-associated antigen, cytokeratin-19 fragment, neuron-specific enolase and pro-gastrin-releasing peptide) is a more accurate marker for cancer of lung than each one individually.

Rafael Molina, from Laboratory of Biochemistry (Oncobiology Unit), Biomedical Diagnostic Center (CDB), Barcelona evaluated these six tumor markers in more than 3,000 individuals suspected of having lung cancer and observed that in patients with radiographic nodules <3 cm, the negative predictive value of the panel was 71.8%, hence providing some support for a more conservative diagnostic approach.

Study Implicates Fungal Microbiota in Pathogenesis of IBD According to findings published online Feb 3 in the journal Gut, patients with inflammatory bowel disease (IBD) show imbalance in their fungal intestinal

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AROUND THE GLOBE microbiota. Harry Sokol, Service de Gastroentérologie et Nutrition, Hôpital Saint-Antoine, Paris observed an alteration in the fungal microbiota in patients with IBD with an increase in Basidiomycota/Ascomycota ratio, decrease in Saccharomyces cerevisiae and an increase in Candida albicans compared with healthy subjects.

The study also identified disease-specific alterations in diversity, indicating that a Crohn’s disease-specific gut environment may favor fungi at the expense of bacteria.

WHO to Hold First Global Meeting of National NCD Program Directors and Managers WHO is organizing the First Global Meeting of National NCD Program Directors and Managers from 15 to 17 February 2016 in Geneva, at the WHO Executive Board Room.

The meeting will be devoted to supporting national NCD program directors and managers in their efforts to implement the four time-bound national commitments for 2015 and 2016 included in the 2014 UN Outcome Document on NCDs, taking into account the NCDrelated targets included in the proposed Sustainable Development Goals and the Addis Ababa Action Agenda on Financing for Development.

The meeting will provide a key opportunity for national NCD program directors and managers to exchange local insights and global perspectives on how to strengthen national NCD responses, in preparation for the third High-level Meeting of the United Nations General Assembly on NCDs in 2018… (WHO)

CDSCO Directs Manufacturers to Ensure ADR Label Changes on Package of FDC PiperacillinTazobactam Suja Nair Shirodkar reports in Pharmabiz, Feb 13 that the Central Drugs Standard Control Organization (CDSCO) has recently asked manufacturers of FDC piperacillin and tazobactam to ensure label change about adverse drug reactions. CDSCO took this step following strong recommendation by members of the signal review panel (SRP) of the Pharmacovigilance Program of India (PvPI) on adverse drug reaction. The committee has recommended that hypokalemia and bronchospasm should be included in the package insert and promotional literature.

New Guidelines on Care of Diabetic Foot Released Anil Hingorani, MD, of New York University Lutheran Medical Center, Brooklyn and colleagues have published the first diabetic foot guideline as a supplement to the February 2016 issue of the Journal of Vascular Surgery.

These clinical practice guidelines focus five areas, namely prevention of ulcer, off-loading, diagnosis of osteomyelitis and peripheral arterial disease and wound care. The Society for Vascular Surgery in collaboration with the American Podiatric Medical Association and the Society for Vascular Medicine have jointly worked on developing these guidelines.

The panel issued five recommendations for the care of the diabetic foot: ÂÂ

Adequate glycemic control, periodic foot inspection and patient and family education to prevent foot ulceration. Customized therapeutic foot wear is recommended for those patients who have significant neuropathy, foot deformities or previous amputation.

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Off-loading with a total contact cast or irremovable fixed-ankle walking boot is advised in patients with plantar diabetic foot ulcer, while specific types of pressure-relieving footwear are recommended for those with nonplantar wounds or healed ulcers.

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A probe-to-bone test and plain films is recommended in patients with a new diabetic foot ulcer, followed by MRI if a soft-tissue abscess or osteomyelitis is still suspected following the probeto-bone test.

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All infected ulcers should be debrided along with treatment of infections based on the 2012 Infectious Diseases Society of America (IDSA) guidelines.

Census 2011 Reveals Poor Sex Ratio in Small Families As per the Population Census of 2011 data, the overall population ratio in India 2011 is 940 females per 1000 of males. While the Sex Ratio 2011 shows an upward trend from the census 2001 data, it is still less than desired. The sex ratio was just 782 girls to every 1,000 boys born among women who had only one child, reports Subodh Varma in the Times of India, Feb 15.

This figure is much lower than the overall sex ratio of the population and even lower than the sex ratio for children aged up to 6 years (919). Among women with two children, the sex ratio has declined to 720 girls for every 1,000 boys. But, in women who have three children, it improves to 814. For women with four children, it improved further to 944 and by five children, it was 1,005 girls for 1,000 boys.

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AROUND THE GLOBE ÂÂ

Ankle-brachial index (ABI) measurement is recommended in all patients with diabetes starting at 50 years of age. High risk patients should undergo an annual vascular examination of the lower limbs and feet. Revascularization by either surgical bypass or endovascular therapy is recommended in patients with foot ulcer who have peripheral arterial disease.

CDC Report Highlights Negative Effects of Alcohol on Pregnancy The Center for Disease Control and Prevention (CDC) has released new information for women in their child-bearing years and the possible negative effects that alcohol consumption could have on pregnancy.

According to the CDC, alcohol use during pregnancy, even within the first few weeks and before a woman knows she is pregnant, can cause lasting physical, behavioral and intellectual disabilities that can last a child’s lifetime. These disabilities are known as fetal alcohol spectrum disorders. According to the latest CDC Vital Signs report, an estimated 3.3 million US women between the ages of 15 and 44 years are at risk of exposing their developing baby to alcohol because they are drinking, sexually active and not using birth control to prevent pregnancy.

Study Links Proton Pump Inhibitors to Dementia A pharmacoepidemiological claims data analysis has reported an association between dementia and regular use of proton pump inhibitors (PPIs) - drugs used in the treatment of acid related disorders of the digestive tract - in patients aged 75 years or older. Patients on regular PPI medication had a significantly increased risk of incident dementia as compared with the patients who were not taking PPI medication with hazard ratio of 1.44 [95% CI, 1.36-1.52]; p < 0.001).

Regular PPI use was defined in the study as at least one prescription per quarter in these intervals of omeprazole, pantoprazole, lansoprazole, esomeprazole or rabeprazole. Results of the study by Willy Gomm, PhD, from the German Center for Neurodegenerative Diseases, Bonn, Germany, and colleagues are published online Feb 15 2016 in JAMA Neurology.

Study Identifies an Association Between Lipids and Myeloma in One-third Patients Shiny Nair, PhD, from the Dept. of Medicine, Section of Hematology, Yale University School of Medicine, New Haven, CT and colleagues have identified a link between lipids and the origin of a third of all myelomas.

They have shown that long-term immune activation

by lysolipids may underlie both Gaucher’s diseaseassociated gammopathies and some sporadic monoclonal gammopathies. Myeloma clonal immunoglobulin associated with transformed plasma cells was found to be reactive against lysolipids, lysoglucosylceremide (LGL1) and lysophosphatidylcholine (LPC). Whether these findings published in the February 11 issue of the New England Journal of Medicine will alter treatment of myelomas still remains to be seen.

Subclinical Atherosclerosis High in Patients with Systemic Sclerosis Subclinical atherosclerosis is as frequent in patients with systemic sclerosis as in those with rheumatoid arthritis, says a new study published in the journal Arthritis Care & Research.

Haner Direskeneli, MD, of Marmara University’s medical school in Istanbul, and colleagues observed subclinical atherosclerosis on ultrasound evaluation in 19.1% of patients with systemic sclerosis vs. 21.8% of those with rheumatoid arthritis vs. only 5.9% of healthy controls.

The risk of subclinical atherosclerosis was found to be more than 3-fold higher for both systemic sclerosis and rheumatoid arthritis than in controls. The cardiovascular risk indices for general population are considerably insufficient to detect systemic sclerosis patients with atherosclerosis.

Second Generation LOTUS Valve is an Improvement on First-generation Valves A multicenter study from the United Kingdom has reported favorably about transcatheter aortic valve replacement (TAVR) using the second-generation Lotus valve. The largest published series on use of the LOTUS analyzed prospectively collected data relating to procedural and in-hospital outcome showed that the LOTUS device has a good safety profile and it was associated with a very low incidence of aortic regurgitation, very low in-hospital mortality (1.8%) rate; complication rates - cardiac tamponade (1.8%), conversion to sternotomy (1.3%), stroke (3.9%), vascular access-related (7.0%) and acute kidney injury (7.9%) - were also low with this device. However, the authors suggest further study of long-term safety and performance of this device. The study by Rajiv Rampat, from Sussex Cardiac Centre, Brighton and Sussex University Hospitals, Brighton, United Kingdom and colleagues is published in the Journal of the American College of Cardiology: Cardiovascular Interventions.

Indian Journal of Clinical Practice, Vol. 26, No. 10, March 2016

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INSPIRATIONAL STORY

Only One Move

A

10-year-old boy decided to study judo despite the fact that he had lost his left arm in a devastating car accident. The boy began lessons with an old Japanese judo master. The boy was doing well, so he couldn’t understand why, after 3 months of training the master had taught him only one move. “Sensei,”(Teacher in Japanese) the boy finally said, “Shouldn’t I be learning more moves?” “This is the only move you know, but this is the only move you’ll ever need to know,” the Sensei replied. Not quite understanding, but believing in his teacher, the boy kept training.

Several months later, the sensei took the boy to his first tournament. Surprising himself, the boy easily won his first two matches. The third match proved to be more difficult, but after some time, his opponent became impatient and charged; the boy deftly used his one move to win the match. Still amazed by his success, the boy was now in the finals.

This time, his opponent was bigger, stronger and more experienced. For a while, the boy appeared to be overmatched.

Concerned that the boy might get hurt, the referee called a time-out. He was about to stop the match when the sensei intervened. “No,” the Sensei insisted, “Let him continue.” Soon after the match resumed, his opponent made a critical mistake: He dropped his guard. Instantly, the boy used his move to pin him. The boy had won the match and the tournament. He was the Champion. On the way home, the boy and Sensei reviewed every move in each and every match. Then the boy summoned the courage to ask what was really on his mind. “Sensei, how did I win the tournament with only one move?”

“You won for two reasons,” the Sensei answered. “First, you’ve almost mastered one of the most difficult throws in all of judo. And second, the only known defense for that move is for your opponent to grab your left arm.”

The boy’s biggest weakness had become his biggest strength. Sometimes, we feel that we have certain weaknesses and we blame God, the circumstances or ourselves for it but we never know that our weaknesses can become our strengths one day.

Each of us is special and important, so never think you have any weakness, never think of pride or pain, just live your life to its fullest and extract the best out of it!”

“If we wait until our lives are free from sorrow or difficulty, then we wait forever. And miss the entire point.”

—Dirk Benedict “It is good to have an end to journey toward; but it is the journey that matters, in the end.”

—Ursula K LeGuin ■■■■

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Indian Journal of Clinical Practice, Vol. 26, No. 10, March 2016

LIGHTER READING

DAUGHTER IN COLLEGE

TROUBLE ON THE ROOF

Did you hear about the banker who was recently arrested for embezzling $100,000 to pay for his daughter’s college education?

Mike and Rob were laying tile on a roof when a sudden gust of wind came and knocked down their ladder.

As the policeman, who also had a daughter in college, was leading him away in handcuffs, he said to the banker, “I have just one question for you. Where were you going to get the rest of the money?”

GETTING RID OF THE PROBLEM A farmhand is driving around the farm, checking the fences. After a few minutes he radios his boss and says, “Boss, I’ve got a problem. I hit a pig on the road and he’s stuck in the bull-bars of my truck. He’s still wriggling.

What should I do?” “In the back of your truck there’s a shotgun. Shoot the pig in the head and when it stops wriggling you can pull it out and throw it in a bush.” The farm worker says okay and signs off. About 10 minutes later he radios back. “Boss I did what you said, I shot the pig and dragged it out and threw it in a bush.”

“I have an idea,” said Mike. “We’ll throw you down, and then you can pick up the ladder.”

“What, do you think I’m stupid?” Rob replied.” I have an idea. I’ll shine my flashlight, and you can climb down on the beam of light.”

“What, do you think I’m stupid?” Mike answers. “You’ll just turn off the flashlight when I’m halfway there.”

FUNNY QUOTE ON A HUSBAND’S T-SHIRT All girls are devils, but my wife is the queen – – – of them.

QUOTE

“Determine what specific goal you want to achieve. Then dedicate yourself to its attainment with unswerving singleness of purpose, the trenchant zeal of a crusader.”

—Paul J Meyer

“So what’s the problem now?” his Boss snapped.

“The blue light on his motorcycle is still flashing!”

I’M CRAZY NOT BECAUSE I’M STUPID There was this man driving along in his car when he suddenly got a flat tire. When he pulled over he was at the fence of a mental hospital. When he got out of the car one of the patients came to the fence and asked “Can I help you?” And the man said “No, I need to figure out how to make it home with only 2 lugs on this wheel.” The patient asked again “Are you sure you do not need any help?” And the man said “No.” The man tried to figure it out when all of a sudden the patient said “If I were you I would take one lug off the other 3 wheels and put them on that wheel and you should be able to get home.” The man asked “How did you think of that?” The patient replied “I am in here because I’m crazy not because I’m stupid.”

Dr. Good and Dr. Bad SITUATION: A patient diagnosed with falciparum malaria came for prescription.

Take quinine plus tetracycline

Take artesunate

© IJCP Academy

HUMOR

Lighter Side of Medicine

LESSON: Artesunate (to be given in combination) is preferred over

quinine in combination with tetracycline in patients with uncomplicated falciparum malaria as it is more effective, better-tolerated and more cost-effective.

Indian Journal of Clinical Practice, Vol. 26, No. 10, March 2016

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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,

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Indian Journal of Clinical Practice, Vol. 26, No. 10, March 2016

name of the corresponding authors, acknowledgment of financial support and abbreviations used.

– The title should be of no more than 80 characters and should represent the major theme of the manuscript.

A subtitle can be added if necessary.

– A short title of not more than 50 characters (including inter-word spaces) for use as a running head should be included.

– The name, telephone and fax numbers, e-mail and postal addresses of the author to whom communications are to be sent should be typed in the lower right corner of the title page.

– A list of abbreviations used in the paper should be included. In general, the use of abbreviations is discouraged unless they are essential for improving the readability of the text.

Summary – The summary of not more than 200 words. It must convey the essential features of the paper.

– It should not contain abbreviations, footnotes or references.

Introduction – The introduction should state why the study was carried out and what were its specific aims/objectives.

Methods – These should be described in sufficient detail to permit evaluation and duplication of the work by others.

– Ethical guidelines followed by the investigations should be described.

Statistics The following information should be given: – The statistical universe i.e., the population from which the sample for the study is selected.

– Method of selecting the sample (cases, subjects, etc. from the statistical universe).

– Method of allocating the subjects into different groups.

– Statistical methods used for presentation and analysis of data i.e., in terms of mean and standard deviation values or percentages and statistical tests such as Student’s ‘t’ test, Chi-square test and analysis of variance or non-parametric tests and multivariate techniques.

–

Confidence intervals for the measurements should be provided wherever appropriate.

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

Discussion –

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

References These should conform to the Vancouver style. References should be numbered in the order in which they appear in the texts and these numbers should be inserted above the lines on each occasion the author is cited (Sinha12 confirmed other reports13,14...). References cited only in tables or in legends to figures should be numbered in the text of the particular table or illustration. Include among the references papers accepted but not yet published; designate the journal and add ‘in press’ (in parentheses). Information from manuscripts submitted but not yet accepted should be cited in the text as ‘unpublished observations’ (in parentheses).

At the end of the article the full list of references should include the names of all authors if there are fewer than seven or if there are more, the first six followed by et al., the full title of the journal article or book chapters; the title of journals abbreviated according to the style of the Index Medicus and the first and final page numbers of the article or chapter. The authors should check that the references are accurate. If they are not this may result in the rejection of an otherwise adequate contribution.

Examples of common forms of references are: Articles Paintal AS. Impulses in vagal afferent fibres from specific pulmonary deflation receptors. The response of those receptors to phenylguanide, potato S-hydroxytryptamine and their role in respiratory and cardiovascular reflexes.

Q. J. Expt. Physiol. 1955;40:89-111.

Figures – Two complete sets of glossy prints of high quality should be submitted. The labelling must be clear and neat.

– All photomicrographs should indicate the magnification of the print.

– Special features should be indicated by arrows or letters which contrast with the background.

– The back of each illustration should bear the first author’s last name, figure number and an arrow indicating the top. This should be written lightly in pencil only. Please do not use a hard pencil, ball point or felt pen.

– Color illustrations will be accepted if they make a contribution to the understanding of the article.

–

Do not use clips/staples on photographs and artwork.

–

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

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

Books

5. Special requests _____________________________

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

6. Suggestions for reviewers (name and postal address)

Articles in Books

2.____________ 2.________________

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

3.____________ 3.________________

4.____________ 4.________________

Tables –

These should be typed double spaced on separate sheets with the table number (in Roman Arabic numerals) and title above the table and explanatory notes below the table.

Legends – These should be typed double spaces on a separate sheet and figure numbers (in Arabic numerals) corresponding with the order in which the figures are presented in the text.

–

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

Indian 1.____________Foreign 1.________________

7. All authors’ signatures________________________ 8.

Corresponding author’s name, current postal and e-mail address and telephone and fax numbers __________________________________________

Online Submission Also e-Issue @ www.ijcpgroup.com For Editorial Correspondence

Dr KK Aggarwal

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

Indian Journal of Clinical Practice, Vol. 26, No. 10, March 2016

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In This Issue —

Asian Journal of Diabetology

Emerging role of Cardiac MRI in Ischemic and Non-ischemic Cardiomyopathy

—

Acute Renal Failure and Silent Myocardial Infarction Following Multiple Honey Bee Stings

—

Superficial Brachial Artery: Its Embryological and Clinical Significance

—

Glucose Tolerance in Nondiabetic Patients after First Attack of Acute Myocardial Infarction and its Outcome

—

A Case of Left Atrial Myxoma Presenting as Severe Pulmonary Hypertension

—

Double-Chambered Right Ventricle with Transient 2:1 Atrioventricular Block: A Rare Presentation

—

Cornary Artery Air Embolism

Volume 17, Number 5

more...

January-March 2015

Volume 1, Number 1

Asian Journal of OBS & Gynae Practice Asian Journal of Paediatric Practice

Volume 18, Number 3

Dr Swati Y Bhave

Dr KK Aggarwal

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