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Volume 23, Number 11

April 2013, Pages 681-780

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

Volume 23, Number 11, April 2013 from the desk of group editor-in-chief

685 The Savitri Mantra

Community Health

686 World Record in Hands-only CPR 10

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

IJCP Editorial Board Obstetrics and Gynaecology Dr Alka Kriplani Dr Thankam Verma, Dr Kamala Selvaraj Cardiology Dr Praveen Chandra, Dr SK Parashar Paediatrics Dr Swati Y Bhave Diabetology Dr CR Anand Moses, Dr Sidhartha Das Dr A Ramachandran, Dr Samith A Shetty ENT Dr Jasveer Singh Dentistry Dr KMK Masthan Dr Rajesh Chandna Gastroenterology Dr Ajay Kumar Dermatology Dr Hasmukh J Shroff Nephrology Dr Georgi Abraham

KK Aggarwal

American Family Physician

689 Practice Guidelines cardiology

694 Evaluation of Cardiac Status of Patients with Sickle Cell Disease by 2D Echocardiography with Specific Reference to Pulmonary Hypertension

Jaya Pathak, M Vadivelan, Cinosh Mathew

698 A Study on Prevalence of Diastolic Dysfunction in Normotensive Obese Young Adults

Praveen Kumar H, Monika Maheshwari, HC Badjatiya

Critical Care

701 A View on Combination Antiplatelet Agents in Ischemic Stroke

Bhargava M Vyasa, RD Dave, PS Daniel, IS Anand, CN Patel

Dentistry

707 Periodontal-Restorative Interactions: A Review

Shaveta Sood, Shipra Gupta

Dermatology

714 A Study of Beetle Dermatitis

Asit Mittal, Sharad Mehta, Anubhav Garg, Lalit Gupta, CM Kuldeep, Ashok Kumar Khare, Sarin Nistha

Diabetology

717 Study of Serum Magnesium and HbA1C in Diabetic Patients along with Changes in their Lipid Profiles

Asha S Khubchandani, Hiren Sanghani

Drugs and Devices

Neurology Dr V Nagarajan Journal of Applied Medicine & Surgery Dr SM Rajendran, Dr Jayakar Thomas Anand Gopal Bhatnagar Editorial Anchor Advisory Bodies Heart Care Foundation of India Non-Resident Indians Chamber of Commerce & Industry World Fellowship of Religions

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721 Efficacy and Tolerability of Meroplan S (Meropenem 1 g and Sulbactam 0.5 g) (ETIOS) in the Management of Lower Respiratory Tract Infections caused by Gramnegative Pathogens in Adults: A Post Marketing Observational Study

Lisa Braganza, Prashant Khandeparkar, Qayum Mukkadum

ENT

728 Basaloid Carcinoma: An Unusual Presentation

Sanjana V Nemade, VV Rokade

Gastroenterology

735 An Observational Study of Essentiale-L in the Treatment of Patients with Fatty Liver Disease

L Padma, Qayum Mukaddam, Abhijit Trailokya

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

740 Bacterial Vaginosis in Pregnancy (<28 Weeks) and its Effect on Pregnancy Outcome: A Study from a Western UP City

Abhilasha Gupta, Priyanka Garg, Shipra Nigam

745 Rupture of Term Noncommunicating Rudimentary Horn of Uterus

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Padma Shukla, M Bhargava, PK Shukla

Orthopedics and Rheumatology

748 What is the Etiopathogenesis of OA?

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Ahmad Javaid

Pediatrics

750 Management of Juvenile Idiopathic Arthritis in Adolescents

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Donald E Greydanus, Mary D Moore

760 Malnutrition: A Daunting Problem for India’s Spectacular Growth

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768 Forthcoming Events eMedinewS Inspiration

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Confederation of Medical Associations in Asia and Oceania

770 Be Human Stop Child Abuse Around the Globe

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

Padma Shri and Dr BC Roy National Awardee Sr. Physician and Cardiologist, Moolchand Medcity, New Delhi President, Heart Care Foundation of India Group Editor-in-Chief, IJCP Group and eMedinewS National Vice President, Elect, IMA Chairman Ethical Committee, Delhi Medical Council Director, IMA AKN Sinha Institute (08-09) Hony. Finance Secretary, IMA (07-08) Chairman, IMA AMS (06-07) President, Delhi Medical Association (05-06) emedinews@gmail.com http://twitter.com/DrKKAggarwal Krishan Kumar Aggarwal (Facebook)

The Savitri Mantra

he history of cardiopulmonary resuscitation (CPR) goes back to Indian mythology when Savitri fought with Yamraj and saved the life of her husband Satyavan. According to the story, the Rishi Munis had predicted at the time of their wedding that Satyavan was prone to get sudden cardiac death in future and so the marriage might not last long. But Savitri insisted for marriage and stood by his side throughout and one day when he died suddenly, also saved him from Yamraj. The only medical explanation for this is that some form of CPR was available in that era, which was successfully done by Savitri who then saved the life of Satyavan. Way back in 1987 when I returned from the US, I brought one CPR manikin with me. Since then, 1 have been training people in CPR. But, this training was more of a demonstration of the CPR technique rather than one-to-one training. The recommendations of CPR have now changed from conventional CPR to hands-only CPR in which mouth-to-mouth breathing is not required. Hands-only CPR 10 is based on the concept that brain remains alive for the first 10 minutes and if the heart can be revived within this period, life can be brought back to the dead person. Last year my friend, Mr. P. Vivek from UK sent me an international dipping where attempts were made to train people in CPR at Seoul. He sent me the address of the company providing CPR manikins. We purchased 200 manikins and later bought 200 more manikins but this time, we chose another company as the manikins from the first vendor were not durable and long-lasting and probably were not suitable for Indian environment. With 400 dummies, we started training people and are now on the verge of completing 50,000 CPR trainings. On 6th April, 2013, Saturday, on the eve of World Health Day, we created a World Record of training 11,459 people in one day surpassing the previous record of 7,909 by Singapore Heart Foundation in the year 2011. During the last four months, multiple lives have been saved by successful CPR 10 done by the public who have been trained by us. In two cases that were successfully revived, one by a 16-year-old girl and another by a 30-year-old school teacher, both said that they could remember to do CPR only because it was taught in the form of a Mantra - “Marne ke dus minute ke bheetar (jitna jaldi utna behtar) kam se kam agle dus minute tak (jitni der tak ho utna behtar) apni chhati peeine ke badle mare hue vyakti ki chhati peeto.” Perhaps it was this last phrase “apni chhati peetne ke badle mare hue vyakti ki chhati peeto” that proved to be catchy and made it easier for people to recall the mantra. In both the above situations, they could recollect the mantra only because of this last phrase. The English version of this Mantra “Within 10 minutes of death (earlier the better) for the next 10 minutes (longer the better) continuously and effectively compress the center of the chest of the deceased person” has not been successful because it had low recall value. On 6th April, 2013, we named this Mantra as Savitri Mantra similar to the Gayatri Mantra. Savitri Mantra, therefore, teaches us how to save life after a cardiac arrest. I personally feel that Savitri Mantra, which has a scientific basis, should be adopted by the medical community and should be recited in sdiools whenever there is an opportunity when large number of students are present to listen such as in school assemblies. I wonder if one of my readers can convert this Mantra into a poetry/rhyme.

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Community Health

World Record in Hands-only CPR 10 KK Aggarwal

Abstract Heart Care Foundation of India, a not for profit NGO created a world record on the eve of the World Health Day on 6th April 2012 when the Foundation through its President Dr KK Aggarwal, Padma Shri & Dr BC Roy National Awardee trained 11,459 people in hands-only Cardiopulmonary Resuscitation (CPR 10) in one day surpassing the previous record of training 7909 people in one day by Singapore Heart Foundation. The training was organized at Dr Sampumanad Sarvodaya Kanya Vidyalaya No. 1, C-l, Block-C, Yamuna Vihar, East Delhi. The records were: Maximum number of people trained in hands-only CPR in one day by an individual and by an NGO and also the first to reach a training target of 10,000 in one day by an individual and by an NGO.

Keywords: CPR, hands-only CPR, cardiopulmonary resuscitation, records, medical record

udden cardiac arrest (SCA) refers to the sudden cessation of cardiac mechanical activity with hemodynamic collapse, most frequently due to sustained ventricular tachycardia/ventricular fibrillation. These events mostly occur in patients with structural heart disease (that may not have been previously diagnosed), particularly coronary heart disease. The event is referred to as SCA (or aborted sudden cardiac death) if an intervention - hands-only CPR or defibrillation or spontaneous reversion restores circulation. The event is called sudden cardiac death, if the patient dies. The administration of CPR by a layperson bystander (bystander CPR or bystander-initiated CPR) is important in determining patient outcome after out-ofhospital SCA. Survival after SCA is higher among those who have bystander CPR when compared with those who initially receive CPR from EMS personnel. Also, early restoration or improvement in circulation is associated with better neurologic function among survivors.1 For adults with sudden out-of-hospital cardiac arrest, compression-only bystander CPR (without rescue breathing) has equal or possibly greater efficacy compared with standard bystander CPR (compressions plus rescue breathing).

Padma Shri & Dr BC Roy National Awardee President Heart Care Foundation of India E-mail: emedinews@gmail.com

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The 2010 American Heart Association (AHA) guidelines for CPR recommend that bystanders perform compression-only CPR to provide high-quality chest compressions prior to the arrival of emergency personnel.2,3 Initial observational studies that evaluated the delivery of compression-only CPR versus standard CPR including rescue breathing found no significant

Community Health differences in survival or long-term neurologic function between the two groups, suggesting that compressiononly CFR could be safely delivered.4,7 METHODS AND OBSERVATIONS The Foundation planned a ‘CPR Utsav’ (festival) on the eve of World Health Day falling on 7th April, 2013 with a target of training 10,000 people in a day. Four hundred manikins were arranged. A school was identified in East Delhi as the hot school. A total of 32 schools were earmarked for the day of the event. Prior permission was taken from the Dept. of Education, Government of Delhi. A pre-event sensitization was done for all schools and their principals. Pre-event confirmation of students was taken from various schools. A total of 13,000 entries were received. A dropout of 10% was envisaged. On the day of event, a total of 11,459 students and teachers were trained. To make the event lively, every session of CPR was intermixed with the presence of a celebrity that included politicians, bureaucrats, administrators and heads of medical association, etc. Children were trained in batches of 400 each with single-rescuer CPR training or 800 each with two-rescuer CPR training. Complete training was provided to all students. Every child who underwent training signed an attendance sheet. Two independent observers certified the whole event apart from multiple celebrities, who also certified the number and the process. Over a hundred manikins were damaged in the intense heat. The mantra taught was “Marne kc dus minute ke bheetar (jitna jaldi utna behtar) kam se kam agle dus minute tak (jitni der tak ho utna behtar) apui chhati -peeine ke badle mare hue vyakti ki chhati peeto.” It was this last phrase “apni chhati peetne ke badle mare hue vyakti ki chhati peeto” that proved to be catchy and made it easier for people to recall the Mantra. When the children were interviewed after the training, more than 80% could recall the mantra only because of this last phrase. The English version of this Mantra “Within 10 minutes of death (earlier the better) for the next 10 minutes (longer the better) continuously and effectively compress the center of the chest of the deceased person” has not been successful due to its low recall value. On 6th April 2013, on the day of the Utsav, we named this Mantra as Savitri Mantra similar to the Gayatri Mantra. Savitri Mantra, therefore, teaches us how to save life after a cardiac arrest.

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Community Health Heart Association Guidelines improves outcomes after out-of-hospital cardiac arrest. Heart Rhythm 2010;7(10):l357-62.

DISCUSSION With proper planning and execution, it is possible to conduct any big awareness-cum-training event in the country. One should always anticipate a 10-20% drop¬out and plan accordingly. Records are always made to be broken but if you are the first to cross 10,000 mark, this type of record will always remain intact. LESSONS LEARNT DURING SUCH A CAMP ÂÂ

ÂÂ

Imported manikins do not last long in Indian circumstances. Either they get heated up in summer or they break early in the cold weather. Children should be taught and emphasized not to practice CPR 10 on live people as it can break the ribs and harm the heart health. This was the commonest question asked by the cliildren in the Utsav (Can they practice at home?).

CONCLUSION The word CPR 10 has been so created so that the people find it easy to remember and is also based on the fact that chances of reversibility of a cardiac arrest victim are maximum in the first 10 minutes. I personally feel that Savitri Mantra, which has a scientific basis, should be adopted by the medical community and should be recited in schools in assembly or when a large number of students are available to listen, REFERENCES 1. Aufderheide TP, Yannopoulos D, Lick CJ, Myers B, Romig LA, Stothert JC, et al. Implementing the 2005 American

2. Sayre MR, Berg RA, Cave DM, Page RL, Potts J, White RD; American Heart Association Emergency Cardiovascular Care Committee. Hands-only (compression-only) cardiopulmonary resuscitation: a call to action for bystander response to adults who experience out- ofhospital sudden cardiac arrest: a science advisory for the public from the American Heart Association Emergency Cardiovascular Care Committee. Circulation 2008;117(16):2162-7. 3. Field JM, Hazinski MF, Sayre MR, Chameides I. Schexnayder SM, Hemphill R, et al. Part 1: executive summary: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010;122(18 Suppl 3): S640-56. obrow BJ, Spaite DW, Berg RA, Stolz U, Sanders AB, Kem 4. B KB, et al. Chest compression-only CPR by Iay rescuers and survival from out-of-hospital cardiac arress. JAMA 2010;304(] 3):1447-54. 5. SOS-KANTO study group. Cardiopulmonary resuscitation by bystanders with chest compression only (SOS-KANTO): an observational study. Lancet 2007;369(9565):920-6. 6. Iwami T, Kawamura T, Hiraide A, Berg RA, Hayashi Y, Nishiuchi X et al. Effectiveness of bystander-initiated cardiac-only resuscitation for patients with out-ofhospital cardiac arrest. Circulation 2007;116(25):2900-7. 7. Bohm K, Rosenqvist M, Herlitz J, Hollenherg J, Svensson L. Survival is similar after standard treatment and chest compression only in out-of-hospital bystander cardiopulmonary resuscitation. Circulation 2007;116(25):2908-12.

Heart Care Foundation President Trains Over 11,000 People in CPR HT Correspondent Hindustan Times New Delhi, April 08, 2013 First Published: 00:26 IST(8/4/2013) 1 Last Updated: 00:27 IST(8/4/2013) By training more than 11,000 people in cardiopuLmonary resuscitation (CPR) in a single day, Dr KK Aggarwal, president, Heart Care Foundation of India, created a world record on Sunday. In all, 11,459 people were trained that mostly comprised school children. The earlier record was,of training 5,000 persons. The event was organized at the Dr Sampurnanand Sarvodaya Kanya Vidyalaya, Yamuna Vihar, on the occasion of World Health Day. “CPR 10 is based on the mantra - “Within 10 minutes of death (earlier the better) for the next at least 10 minutes (longer the better), compress the centre of the cliest of the victim with a speed of 10x10=100 per minute,” said Dr Aggarwal, who ! has trained 35,000 people so far. More than 24 lakh people die in our country every year with sudden deaths and 18 lakh of thern die before reaching the hospital. Around 12 lakh people can be saved if CPR 10 can be taught to even 1 per cent of the society.

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American Family Physician

Practice Guidelines

ACC and AHA Update on Chronic Heart Failure Guidelines In 2009, the American College of Cardiology (ACC) and the American Heart Association (AHA) published a focused update of the ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult. The guidelines writing committee reviewed recent trial data and other clinical information in the revision process for the 2009 update. The 2005 guidelines described four stages (i.e., stages A, B, C, and D) in the development of heart failure (Figure 1). Patients in stages A and B do not have heart failure, but have risk factors that predispose them toward the development of heart failure. Patients in stage C comprise the majority of patients with heart failureâ&#x20AC;&#x201D;those who have current or past symptoms of heart failure associated with underlying structural heart disease. Patients in stage D have refractory heart failure and may be eligible for specialized, advanced treatments (e.g., mechanical circulatory support, fluid removal procedures, continuous inotropic infusions, cardiac transplantation) or end-of-life care, such as hospice.

Updated Recommendations Updates to the 2005 guidelines are included in sections about the evaluation of patients presenting with heart failure; patients with reduced left ventricular ejection fraction (LVEF); patients with refractory end-stage heart failure; and the treatment of special population groups (e.g., blacks). The updated guidelines also contain a new section with recommendations about heart failure in the hospitalized patient. Evaluation of Heart Failure Updates to the section on the evaluation of patients presenting with heart failure were made to clarify the role of functional assessment beyond the New York Heart Association (NYHA) classification, and to expand on the use of brain natriuretic peptide (BNP) and N-terminal prohormone brain natriuretic peptide (NT-proBNP) testing for patient evaluation. According

to the update, patients with left ventricular dysfunction or heart failure generally present in one of three ways: with a syndrome of decreased exercise tolerance; with a syndrome of fluid retention; or with no symptoms, or symptoms of another cardiac or noncardiac disorder. 2009 updated recommendation: Measurement of natriuretic peptides (i.e., BNP and NT-proBNP) can be useful in the evaluation of patients presenting in the urgent care setting in whom the clinical diagnosis of heart failure is uncertain. Measurement of natriuretic peptides can be useful in risk stratification. (Level of Evidence: A) The 2005 guidelines also recommended measurement of BNP for evaluating patients who present in the urgent care setting with possible heart failure; the 2009 update expanded this recommendation to include the measurement of NTproBNP. The level of evidence remained the same for this recommendation. The 2009 update warns that, although elevated natriuretic peptide levels may help confirm a suspected diagnosis of heart failure, the results of this testing alone should not be used to confirm or exclude a heart failure diagnosis. Reduced LVEF The section of the guidelines on patients with reduced LVEF included minor updates on recommendations about the use of angiotensin-II receptor blockers (ARBs) and exercise testing. 2009 updated recommendation: Use of ARBs is recommended in patients with current or previous symptoms of heart failure and reduced LVEF who have an intolerance to angiotensinconverting enzyme (ACE) inhibitors. (Level of Evidence: A) For this recommendation, the 2009 update modified the text in the 2005 guidelines by eliminating mention of specific agents tested. 2009 updated recommendation: Maximal exercise testing with or without measurement of respiratory gas exchange is reasonable to facilitate prescription of an appropriate exercise program for patients presenting with heart failure. (Level of Evidence: C)â&#x20AC;ŻThe 2009 update changed the class of recommendation from class I (i.e., treatment should be performed) to class IIa (i.e., treatment is reasonable to perform).

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American Family Physician

At risk of heart failure

Management of Patients who have or are at Risk of Heart Failure Stage A: At high risk of heart failure, but without structural heart disease or symptoms of heart failure Includes patients with: Atherosclerotic disease Diabetes mellitus Hypertension Metabolic syndrome Obesity Or patients: Using cardiotoxins With a family history of cardiomyopathy

Therapy Goals: Control metabolic syndrome Discourage alcohol intake and illicit drug use Encourage regular exercise Encourage smoking cessation Treat hypertension Treat lipid disorders Drugs: ACE inhibitors or ARBs in appropriate patients for vascular disease or diabetes

Structural heart disease

Stage B: Structural heart disease but without signs or symptoms of heart failure Includes patients with: Asymptomatic valvular disease Left ventricular remodeling, including left ventricular hypertrophy and low ejection fraction Previous myocardial infarction

Therapy Goals: All measures under stage A Drugs: ACE inhibitors or ARBs in appropriate patients Beta blockers in appropriate patients Devices in selected patients: Implantable cardioverter-defibrillators

Development of symptoms of heart failure

Heart failure

Stage C: Structural heart disease, with previous or current symptoms of heart failure Includes patients with: Known structural heart disease and Shortness of breath and fatigue, reduced exercise tolerance

Therapy Goals: Drugs in selected patients: All measures under stages A and B Aldosterone antagonists Restrict dietary sodium ARBs Digitalis Drugs for routine use: Hydralazine/nitrates ACE inhibitors Beta blockers Devices in selected patients: Diuretics for fluid retention Biventricular pacing Implantable cardioverterdefibrillators

Refractory symptoms of heart failure at rest

Stage D: Refractory heart failure requiring specialized interventions Includes patients who have marked symptoms at rest despite maximal medical therapy (e.g., those who are recurrently hospitalized or cannot be safely discharged from the hospital without specialized interventions)

Therapy Goals: All measures under stages A, B, and C Decide appropriate level of care Options: Compassionate end-of-life care, hospice Extraordinary measures (e.g., chronic inotropes, experimental drugs or surgery, heart transplant, permanent mechanical support)

Figure 1. Algorithm of the stages in the development of heart failure, with recommended therapy for patients by stage. ACE = Angiotensin-converting enzyme; ARB = Angiotensin-II receptor blocker.

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American Family Physician The section on patients with reduced LVEF also included several changes to recommendations concerning implantable cardioverter-defibrillator therapy and cardiac resynchronization therapy. 2009 updated recommendation: Implantable cardioverterdefibrillator therapy is recommended for the primary prevention of sudden cardiac death to reduce total mortality in patients with non-ischemic dilated cardiomyopathy or ischemic heart disease at least 40 days after myocardial infarction (MI); an LVEF of 35 percent or less; and NYHA functional class II or III symptoms while receiving chronic optimal medical therapy, and who have reasonable expectation of survival with a good functional status for longer than one year. (Level of Evidence: A) This recommendation was modified in the 2009 update to be consistent with the 2008 Device-Based Therapy guidelines from the ACC, AHA, and Heart Rhythm Society (HRS). It replaces recommendations from the 2005 guidelines on implantable cardioverter-defibrillator therapy for patients with ischemic heart disease at least 40 days after MI (2005 Level of Evidence: A) or nonischemic cardiomyopathy (2005 Level of Evidence: B) with an LVEF of 30 percent or less, and for patients with an LVEF of 30 to 35 percent of any origin (2005 Level of Evidence: B). In two of the major trials reviewed by the guidelines committee, no survival benefit was observed from implantable cardioverter-defibrillator therapy until after the first year of recovery from an acute coronary event. Patients with heart failure and low ejection fraction are typically older than 70 years, although this patient population was not well represented in the trials. Physicians should consider common comorbidities in older adults (e.g., previous stroke, chronic pulmonary disease, arthritic conditions) when discussing this type of therapy with patients. Medication may substantially improve LVEF; therefore, consideration of implantable cardioverterdefibrillator therapy should follow documentation of sustained reduction of LVEF despite a course of beta blockers and ACE inhibitors or ARBs. Implantable cardioverter-defibrillator therapy is not warranted in patients with refractory heart failure (stage D) or in those with concomitant diseases that would shorten their life expectancy independent of heart failure. Before implantation, physicians should inform patients of the effectiveness, safety, and mortality risks of implantable cardioverter-defibrillator therapy; of the morbidity associated with an implantable cardioverterdefibrillator shock; and that the therapy does not improve clinical function or delay progression of heart

failure. 2009 updated recommendation: Patients with LVEF of 35 percent or less, sinus rhythm, and NYHA functional class III or ambulatory class IV symptoms despite recommended, optimal medical therapy and who have cardiac dyssynchrony (i.e., a QRS duration of 0.12 seconds or more) should receive cardiac resynchronization therapy, with or without an implantable cardioverter-defibrillator, unless contraindicated. (Level of Evidence: A) The 2009 recommendation was updated to clarify that cardiac resynchronization therapy may be indicated for patients with or without an implantable cardioverter-defibrillator. Evidence shows that cardiac resynchronization therapy can improve symptoms, exercise capacity, quality of life, LVEF, and survival; it can also decrease hospitalizations in patients with persistently symptomatic heart failure receiving optimal medical therapy who have cardiac dyssynchrony. The use of an implantable cardioverterdefibrillator in addition to cardiac resynchronization therapy should be based on the indications for implantable cardioverter-defibrillator therapy. End-stage Heart Failure The section of the guidelines on patients with refractory end-stage heart failure (stage D) included a modified recommendation on intermittent infusions. 2009 updated recommendation: Routine intermittent infusions of vasoactive and positive inotropic agents are not recommended for patients with refractory end-stage heart failure. (Level of Evidence: A) The 2009 update changed the level of evidence from B to A for this recommendation, based on evidence from an additional multicenter trial. Intermittent outpatient infusions of vasoactive medications (e.g., nesiritide) or positive inotropic medications have not been shown to improve symptoms or survival in patients with advanced heart failure.

New Recommendations Hydralazine/Nitrates New recommendation to 2009 update: The combination of hydralazine and nitrates is recommended to improve outcomes for patients with reduced LVEF whose ethnicity is self-described as African American and who have moderate to severe symptoms on optimal therapy with ACE inhibitors, beta blockers, and diuretics. (Level of Evidence: B) Analysis of vasodilator trials showed effectiveness of treatment with isosorbide dinitrate and hydralazine in black participants. Adding these medications to standard therapy with an ACE inhibitor, a beta blocker, or

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American Family Physician both proved to be beneficial in a subsequent trial. Accordingly, this combination is recommended for black patients who remain symptomatic despite optimal medical therapy. However, patient compliance with this combination may be low because of the large number of tablets required and the high incidence of adverse reactions. The combination treatment should not be prescribed in patients who have not previously used an ACE inhibitor, nor should it be substituted for ACE inhibitors in those who are tolerating them without difficulty. It is unclear if this combination is beneficial in non-black patients. Atrial Fibrillation and Sinus Rhythm New recommendation to 2009 update: It is reasonable to treat patients who have atrial fibrillation and heart failure with strategies to maintain sinus rhythm or to control ventricular rate alone. (Level of Evidence: A)â&#x20AC;ŻFour trials evaluated the effectiveness and safety of restoring and maintaining sinus rhythm in patients with atrial fibrillation. There were equivalent outcomes for restoring and maintaining sinus rhythm by electrical or pharmacologic conversion compared with controlling ventricular rate in patients with atrial fibrillation. Most patients quickly relapse to atrial fibrillation unless they are treated with a class I or III antiarrhythmic medication, but patients with heart failure are not likely to respond favorably to class I medications. Class III antiarrhythmic medications (e.g., sotalol, dofetilide, amiodarone) can maintain sinus rhythm in some patients, although treatment is associated with an increased risk of organ toxicity (amiodarone) and proarrhythmia (dofetilide). Cardiac Resynchronization Therapy New recommendations to 2009 update: For patients who have LVEF of 35 percent or less, a QRS duration of 0.12 seconds or more, and atrial fibrillation, cardiac resynchronization therapy, with or without an implantable cardioverter-defibrillator, is reasonable for the treatment of NYHA functional class III or ambulatory class IV heart failure symptoms on optimal recommended medical therapy. (Level of Evidence: B) Cardiac resynchronization therapy is reasonable for patients with LVEF of 35 percent or less with NYHA functional class III or ambulatory class IV symptoms who are receiving optimal recommended medical therapy and who have frequent dependence on ventricular pacing. (Level of Evidence: C)â&#x20AC;ŻCardiac resynchronization therapy recommendations were added to be consistent with the ACC/AHA/HRS 2008 Guidelines for DeviceBased Therapy of Cardiac Rhythm Abnormalities. New Section: The Hospitalized Patient The 2009 update includes a new section on the evaluation and treatment of heart failure in patients

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who are hospitalized. Patients may require hospitalization if they develop acute or progressive symptoms of heart failure. Generally there are three clinical profiles for these patients: those who have volume overload (manifested by pulmonary and/ or systemic congestion and often precipitated by an acute increase in chronic hypertension); those with profound depression of cardiac output (manifested by hypotension, renal insufficiency, and/or a shock syndrome); and those with signs and symptoms of fluid overload and shock. Patients with heart failure and preserved LVEF are just as likely to be admitted to the hospital as those with heart failure and low LVEF. Patients are usually admitted to the hospital following a concomitant cardiovascular or cerebrovascular event, and admission often is related to medical or dietary noncompliance. Other common factors that precipitate hospitalization for heart failure include acute myocardial ischemia; uncorrected high blood pressure; atrial fibrillation and other arrhythmias; recent addition of negative inotropic medications; pulmonary embolus; use of nonsteroidal anti-inflammatory drugs; excessive alcohol or illicit drug use; endocrine abnormalities (e.g., diabetes mellitus, hyperthyroidism, hypothyroidism); and concurrent infections (e.g., pneumonia, viral illnesses). Inpatient Evaluation and Diagnosis The diagnosis of heart failure in hospitalized patients should be based primarily on signs and symptoms, including volume status, the adequacy of circulatory support or perfusion, and consideration of precipitating factors or comorbidities. Many of the evaluation steps are identical to those used in the initial evaluation of heart failure. For an uncertain diagnosis of heart failure, plasma BNP or NT-proBNP concentrations should be considered in patients being evaluated for dyspnea who have signs and symptoms compatible with heart failure. In patients who have already been diagnosed with heart failure, it is important to understand what has caused the clinical symptoms to worsen. Acute MI is an important cause of worsening or new-onset heart failure, and criteria for an acute coronary event that might indicate the need for further intervention may be present in up to 20 percent of patients hospitalized for heart failure. However, several other patients may have low levels of detectable troponins that do not meet criteria for an acute ischemic event, but that are typical of chronic heart failure with an acute exacerbation. For patients with newly discovered heart failure, physicians should keep in mind the causative role of coronary artery disease in heart failure and be certain that coronary

American Family Physician structure and function are well delineated. Therefore, coronary visualization may be an important step in the evaluation of patients hospitalized with heart failure. Inpatient Treatment A careful review of each patientâ&#x20AC;&#x2122;s maintenance medications for heart failure is important, and medication adjustments may be necessary as a result of the hospitalization. The majority of patients should continue taking their medications during hospitalization, and most are able to tolerate the continuation of beta blockers, which results in better outcomes. Patients with substantial fluid overload on hospital admission should be treated with loop diuretics, initiated upon arrival to the emergency department. After admission, careful and frequent evaluation and monitoring are important and include assessing volume status and circulatory support; monitoring daily weight and vital signs; managing daily fluid input and output; and assessing daily electrolyte levels and renal function, which should be performed while intravenous diuretics or active heart failure medication titration is being done. Optimal dosing of diuretics should produce a rate of diuresis that will benefit volume status and relieve signs and symptoms of congestion without inducing an excessively rapid reduction in intravascular volume, possibly resulting in hypotension, renal dysfunction, or both. Limiting sodium intake and dosing the diuretic multiple times daily can enhance diuresis effectiveness. Patients who present with congestion and moderate to severe renal dysfunction may have a blunted response to diuretics, requiring higher initial doses. If all diuretic strategies are unsuccessful, ultrafiltration or another renal replacement strategy may be considered, as well as consultation with a kidney subspecialist. Intravenous vasodilators may be added to the treatment regimen in patients who have adequate blood pressure and ongoing congestion that does not adequately respond to diuretics and standard oral therapy. The goals of vasodilator therapy include a more rapid resolution of congestive symptoms; relief of anginal symptoms while awaiting coronary intervention; control of hypertension; and improvement of hemodynamic abnormalities before beginning oral medications for heart failure. Patients presenting with predominantly low output syndrome or combined congestion and low output

may be considered for intravenous inotropes (e.g., dopamine, dobutamine, milrinone), which may help relieve symptoms caused by poor perfusion and preserve end-organ function in those with severe systolic dysfunction and dilated cardiomyopathy. These medications are most beneficial in patients with relative hypotension and who have intolerance or no response to vasodilators and diuretics. However, the use of inotropes indicates a poor prognosis, and a thorough hemodynamic assessment is necessary. There is no evidence of benefit for routine use of these agents in patients with acute heart failure caused by congestion only; therefore, inotropes should be limited to carefully selected patients with low blood pressure and reduced cardiac output, who will require close monitoring of blood pressure and heart rhythm. Routine invasive hemodynamic monitoring is not indicated for most patients hospitalized with symptoms of worsening heart failure, but should be considered in those whose volume and filling pressures are uncertain or who are refractory to initial therapy, particularly when filling pressures and cardiac output are unclear. Routine invasive hemodynamic monitoring also may be beneficial in patients with clinically significant hypotension (i.e., systolic blood pressure typically less than 90 mm Hg or symptomatic low systolic blood pressure) or worsening renal function during initial therapy. Invasive hemodynamic monitoring should be performed in patients with presumed cardiogenic shock that requires escalating pressor therapy and consideration of mechanical support; those with severe clinical decompensation in whom therapy is limited by uncertainty regarding relative contributions of elevated filling pressures, hypoperfusion, and vascular tone; those with apparent dependence on intravenous inotropic infusions after initial clinical improvement; or those with persistent, severe symptoms despite adjustment of recommended treatments. As patients stabilize and volume status normalizes, oral therapy for heart failure should be initiated or resumed. Caution should be used when starting beta blockers in patients who were treated with inotropes while hospitalized, or when initiating ACE inhibitors in patients who had marked azotemia. Before discharge, patients should be fully transitioned off all intravenous therapy, and oral therapy should be adjusted and maximized. Patients should be given written discharge instructions or educational materials that address activity level, diet, discharge medications, follow-up appointments, weight monitoring, and what to do if symptoms worsen.

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cardiology

Evaluation of Cardiac Status of Patients with Sickle Cell Disease by 2D Echocardiography with Specific Reference to Pulmonary Hypertension Jaya Pathak*, M Vadivelan**, Cinosh Mathew†

Abstract Aims: To evaluate the cardiac status in patients with sickle cell anemia and sickle cell trait by 2D echocardiography (2D Echo) with specific reference to pulmonary hypertension (PH) and to assess prevalence and severity of PH in this population. Study design: A prospective, cross-sectional study was done in 50 patients with sickle cell disease in whom. 2D Echo was performed, which assessed their cardiac status with specific reference to PH. Material and methods: The study was conducted on outdoor and indoor patients of the Dept. of Medicine at Shri Sayajirao General (SSG) Hospital, Vadodara, Gujarat. The study was conducted over a period of 18 months in 50 patients with sickle cell anemia as well as sickle cell trait. Results: The present study revealed that PH was present in one-third of patients with sickle cell disease. Conclusion: Pulmonary arterial hypertension is one of the leading causes of morbidity and increased mortality in adults with sickle cell disease.

Keywords: Sickle cell disease, pulmonary hypertension

emoglobinopathies are disorders affecting the structure, function or production of hemoglobin. The most common hemoglobinopathy is sickle cell disease. In India, the highest prevalence of this disease is seen in Odisha (1-44%) and Madhya Pradesh (1-40%), while the prevalence in Gujarat is 1-31.4% amongst tribes.1

Studies from tertiary care referral centers suggest a prevalence of pulmonary hypertension (PH) in sickle cell disease patients ranging from 20 to 40%. Pulmonary hypertension (PH) develops in most forms of hereditary and chronic hemolytic anemia suggesting that there is a clinical syndrome of hemolysis-associated PH. This complication has been reported with increasing frequency in patients with sickle cell disease.

*Associate Professor **Assistant Professor †Ex-Resident Doctor, Dept. of Medicine Medical College and Shri Sayajirao General Hospital, Vadodara Address for correspondence Dr M Vadivelan B-290, Saurabh Park, Behind Samta Flats, Subhanpura, Vadodara - 390 023, Gujarat E-mail: mevadivelan@hotmail.com

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Pulmonary arterial hypertension (PAH) is a silent complication of sickle cell disease. 2D echocardiography (2D Echo) is a good noninvasive screening method to detect sickle cell patients with PAH so that therapy can be started at an earlier stage to reduce morbidity and mortality. AIMS OF STUDY ÂÂ

To evaluate the cardiac status in patients with sickle cell anemia and trait by 2D Echo with specific reference to PH.

ÂÂ

To assess prevalence and severity of PH in this population.

ÂÂ

To correlate differences in severity of PH between patients with sickle cell anemia and sickle cell trait.

ÂÂ

To evaluate comorbidities associated with PH in form of clinical and laboratory parameters in patients with sickle cell disease.

MATERIAL AND METHODS In this prospective, cross-sectional study, 50 adult patients having sickle cell anemia and sickle cell trait attending outpatient medical department or admitted in indoor medical wards at Shri Sayajirao General

cardiology (SSG) Hospital, Vadodara, Gujarat were taken as the study group. 2D Echo was performed in all patients to know the alteration in their cardiac status with specific reference to PH.

Inclusion Criteria Adults above the age of 14 years who were previously diagnosed to have sickle cell anemia or trait and freshly detected cases on the basis of clinical grounds, and positive sickling test that was later confirmed by hemoglobin electrophoresis.

Exclusion Criteria Patients with ischemic heart disease or any structural heart disease and those with history of any pulmonary disease were excluded from the study. Each patient on admission was evaluated with complete blood count with peripheral smear examination, sickling test and hemoglobin electrophoresis. Transthoracic echocardiography was performed in all patients using the â&#x20AC;&#x2DC;ALOKAâ&#x20AC;&#x2122; Echocardiographic machine SSD 630 with CW and PW Doppler probe 3 mega vietz with single and dual elements. Later on, the patient was subjected to Doppler ultrasound examination on the same machine using appropriate modes. Tricuspid regurgitation was assessed in the parasternal right ventricular inflow, parasternal short-axis and apical four-chamber views and a minimum of three sequential complexes were recorded. Continuous-wave Doppler sampling of the peak regurgitant jet velocity was used to estimate the right-ventricular-to-right atrial systolic pressure gradient with the use of the Modified Bernoulli equation. PH was defined as a peak tricuspid regurgitant jet velocity of at least 2.5 meter per second (m/sec). Pulmonary artery systolic pressure (PASP) was calculated from the tricuspid regurgitation velocity (TRV) and the estimated right atrial pressure (RAP) using the Modified Bernoulli equation: PASP = 4 (TRV x TRV) + RAP

The age of patients ranged from 14 to 50 years. Majority of patients were in the age group of 14-20 years (46%). Out of 50 patients in the study, 34 were males (68%) and 16 were females (32%) (Table 1). Of the 50 patients included in the study, 36 (72%) were having sickle cell anemia while 14 (28%) were having sickle cell trait (Table 2). Both the sickle cell disease and trait groups had nearly the same distribution of patients in mild, moderate and severe anemia groups (Table 3). In the present study, PH was defined in patients with sickle cell anemia who had TRV >2.5 m/sec. Doppler defined PH was found in 34% patients. Twenty-seven percent patients with sickle cell anemia had PH while 50% of patients with sickle cell trait had PH (Table 4). Table 5 shows that the incidence of PH increased with the age of the patients in the study; 75% of patients in the age group of 31-40 years had PH, while 80% of patients in the above 40 years age group had PH. From Table 6, no significant difference was found in the incidence of PH with respect to gender or their hemoglobin genotypes i.e. sickle cell anemia or trait. Significant difference was noted in the incidence of Table 1. Age and Gender Distribution of Patients with Sickle Cell Disease Age (years)

Gender Male

Female

14-20 years

21-30 years

31-40 years

41-50 years

Table 2. Distribution of Patients with Sickle Cell Disease to Sickle Cell Anemia and Sickle Cell Trait Characteristic

No. of patients

% of patients (n = 50)

The mean RAP was calculated according to the degree of collapse of the inferior vena cava with inspiration: 5 mmHg for a collapse of at least 50% and 15 mmHg for a collapse of less than 50%.

Sickle cell anemia

Sickle cell trait

RESULTS

Hemoglobin

Total 50 patients of sickle cell disease admitted in medical wards and attending Medical OPD at SSG Hospital, Vadodara who satisfied the inclusion criteria were selected for the study.

Table 3. Analysis of Hematological Profile of Patients with Sickle Cell Disease Sickle cell anemia patients

Sickle cell trait patients

<5 g/dl

5.1-7 g/dl

>7.1 g/dl

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cardiology Table 4. Analysis of TRV of Patients with Sickle Cell Disease TRV (m/sec)

Sickle cell anemia

Sickle cell trait

Total

Parameter

No.

< 2.5

72.22

2.5-2.9

22.22

35.71

>2.9

5.55

14.28

Table 5. Analysis of PH with Respect to Age Groups Age (years) No. of patients in the age group

No.

17.39

21-30

33.33

31-40

>40

Table 6. Analysis of Pulmonary Hypertension with Respect to Gender, Genotype and Presence or Absence of Crisis No. of patients in the group

No.

PH present

Male

Female

Sickle cell disease

Sickle cell trait

Crisis present

Crisis absent

Gender

Genotype

History

Table 7. Analysis of Pulmonary Hypertension with Respect to Hemoglobin Levels PH present

PH absent

4.49

6.35

Hb F (mean)

12.52%

22.02%

Hb S (mean)

57.87%

65.68%

Mean Hb (gm%)

PH present

PH absent

LDH (Mean level-micro liter)

466.19

283.87

Reticulocyte count (Mean %)

2.94

2.73

dehydrogenase (LDH) while there was no significant difference between the two groups in terms of the reticulocyte count. DISCUSSION

PH present

14-20

Hemoglobin

Table 8. Analysis of PH with Respect to Markers of Hemolysis - LDH and Reticulocyte Count

PH in the patients who presented with crisis and those who did not.

Sickle cell disease is a genetically inherited disorder resulting from structural hemoglobinopathy that manifests as a chronic congenital hemolytic anemia. The cardiovascular system in sickle cell disease is stressed by chronic anemia, recurrent small pulmonary artery occlusions and myocardial hemosiderosis.2 The shunting of blood through infarcted, non-aerated segments of the lung compromises arterial oxygen saturation and sludging of sickled erythrocytes in small pulmonary arteries may result in PH.3 The term ‘pulmonary hypertension’ denotes various conditions in which mean pulmonary arterial pressure is elevated above 25 mmHg at rest or above 30 mmHg with exercise with normal pressure being 15 mmHg.4 The most useful diagnostic modality used to detect and/ or confirm PH is echocardiography.5 Echocardiography is noninvasive, can evaluate both right and left heart anatomy and function and is ideal for evaluating and excluding secondary causes of PH. Echocardiography is used to determine PH severity and is of prognostic utility. Doppler echocardiography is the cornerstone of screening for PH and provides a quantitative assessment on pulmonary artery pressures.6 The risk factors for PH in sickle cell disease include age, degree of hemolysis and iron overload. The risk for PH is not related to the level of Hb F or the frequency of vaso-occlusive crisis. Several mechanisms have been proposed for the pathogenesis of PH in patients with sickle cell disease. They include: ÂÂ

Intravascular hemolysis leading to nitric oxide (NO) deficiency.7

Table 7 shows that the mean hemoglobin level was lower in the group with PH. The level of fetal hemoglobin (Hb F) was lower in those with PH.

ÂÂ

Progressive interstitial fibrosis secondary to acute chest syndrome.

ÂÂ

Table 8 shows that patients with PH had a higher degree of hemolysis as evident from the level of lactate

Vasculopathy secondary to platelet activation and intimal thickening.

ÂÂ

Hypoperfusion of the pulmonary vascular bed.

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cardiology ÂÂ

Recurrent thromboembolic disease and in situ thrombosis.

The standard therapy for sickle cell disease complicated by PH remains to optimize disease treatment with hydroxy-urea and to use hydration and transfusions while employing standard PH therapy. (Oxygen, anti-coagulation and pulmonary vasodilator therapy.) Survival is decreased among patients whose SCD is complicated by PH.8 PH is associated with an increased risk of death in these patients.

Limitations ÂÂ

This cross-sectional, comparative study was conducted with only 50 patients inclusive of sickle cell anemia and trait and hence, could not derive proper boundaries for cardiac parameters. A larger sample strength would be needed to accurately decide the cut off points.

ÂÂ

Long-term follow-up studies needed to establish definitive implications of PH on mortality as implicated in international studies could not be carried out due to poor patient compliance.

ÂÂ

Quantification of certain important parameters like cardiac catheterization for accurate measurement of PH was not done due to lack of resources.

CONCLUSION Advances in healthcare of patients with sickle cell disease have led to an increase in the life expectancy of these individuals. As this population grows older, chronic complications of this disease tend to develop. One of these complications, PH, has become one of the leading causes of morbidity and mortality in adults with sickle cell disease. PH is seen in about one-third patients with sickle cell disease and is associated with increased mortality. PH in sickle cell disease is found

to be associated with increasing age, the presence of crisis, anemia and the level of LDH. It is not found to be associated with gender, sickle cell anemia or trait and the reticulocyte count. It can be easily detected by 2D Echo and remedial measures taken in the early stages of the disease helps to decrease morbidity and mortality in these patients. REFERENCES 1. Lehman H, Cutbush MC. Sickle cell disease in India. BMJ 1952;(1):404-7. 2. Lindsay J Jr, Meshel JC, Patterson RH. The cardiovascular manifestations of sickle cell disease. Arch Intern Med 1974;133(4):643-51. 3. Gerry JL, Bulkley BH, Hutchins GM. Clinicopathologic analysis of cardiac dysfunction in 52 patients with sickle cell anemia. Am J Cardiol 1978;42(2):211-6. 4. Simonneau G, Galie N, Rubin LG, Langleben D, Seeger W, Domenighetti G, et al. Clinical classification of pulmonary hypertension. J Am Coll Cardiol 2004;43(12 Suppl S): 5s-12s. 5. Yeo TC, Dujardin KS, Tei C, Mahoney DW, McGoon D, Seward JB. Value of a Doppler-derived index combining systolic and diastolic time intervals in predicting outcome in primary pulmonary hypertension. Am J Cardiol 1998;81(9):1157-61. 6. Raymond RJ, Hinderliter AL, Willis PW, Ralph D, Caldwell EJ, Williams W, et al. Echocardiographic predictors of adverse outcomes in primary pulmonary hypertension. J Am Coll Cardiol 2002;39(7):1214-9. 7. Ataga KI, Sood N, DeGent G, Kelly E, Henderson AG, Jones AG, et al. Pulmonary hypertension in sickle cell disease. Am J Med 2004;117(9):665-9. 8. Glad MD, Sachdev V, Jison ML, Shizukuda Y, Pleehn JF, Minter K, et al. Pulmonary hypertension as a risk factor for death in patients with sickle cell disease. N Engl J Med 2004;350(9):2521-2.

■■■■

Routine ECG does not Help In populations of older adults, prediction of coronary heart disease (CHD) events through traditional risk factors is less accurate than in middle-aged adults. It has been shown that electrocardiographic (ECG) abnormalities are common in older adults and might be of value for CHD prediction. However, performing routine ECG among asymptomatic adults is not supported by current evidence and is not recommended by the US Preventive Services Task Force and the American College of Cardiology Foundation/American Heart Association. The aim of this study by Auer and colleagues was to determine whether baseline ECG abnormalities or development of new and persistent ECG abnormalities are associated with increased CHD events.

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cardiology

A Study on Prevalence of Diastolic Dysfunction in Normotensive Obese Young Adults PRAVEEN KUMAR H*, MONIKA MAHESHWARI**, HC BADJATIYA†

Abstract In our study, 200 obese individuals with body mass index (BMI) >30 kg/m2 were evaluated by echocardiography. We conclude that young and otherwise healthy obese subjects also exhibit alterations in left ventricle (LV) structure and function manifested by concentric LV remodeling and impaired diastolic functions. These early abnormalities in LV structure and function may have important implications in explaining the increased cardiovascular morbidity and mortality associated with obesity.

Keywords: Obesity, LV remodeling, impaired diastolic functions, echocardiography

n India, the incidence and prevalence of obesity is increasing progressively in proportion due to the sedentary lifestyle and westernization. Obesity is an independent risk factor for the development of heart failure. The effects of long-standing obesity on left ventricle (LV) structure and function have been characterized as eccentric LV hypertrophy and diastolic dysfunction and occasionally systolic dysfunction.1 Controversy exists regarding the effects of obesity on the cardiac structure and function of young obese subjects.2 Aims and Objectives To study the prevalence of diastolic dysfunction in young obese normotensive, nondiabetic and nonischemic individuals. MATERIAL and METHODS The patients attending medical outdoor/indoor of JLN Medical College and Hospital, Ajmer were taken for the study. Two hundred obese subjects in the age group of 21-60 years of either sex with their weight of 130%

*3rd Year Resident **Assistant Professor †Professor and Unit Head JLN Medical College, Ajmer, Rajasthan Address for correspondence Dr Monika Maheshwari Navin Niwas, 434/10, Bapu Nagar, Ajmer, Rajasthan E-mail: opm11@rediffmail.com

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of upper limit of desirable weight for their height or body mass index (BMI) ≥30 were included.

Exclusion Criteria Diabetes mellitus, hypertension, ischemic heart disease, valvular heart disease and dyslipidemia. A detailed history and thorough physical examination was done including anthropometry examination (height, weight, BMI) and 2D-echo for assessing diastolic dysfunction. 2D-echo measurements included the LV end-diastolic, the LV percent fractional shortening (%FS) obtained from the parasternal short-axis and calculated as %FS = [(Ded-Des)/Ded] × 100, where Ded and Des are the LV mid-cavity dimensions at end-diastole and end-systole, respectively. The left ventricular mass (LVM) was determined using the area length method; the LVM index and LVM/height were calculated by dividing body surface area and by the height, respectively. The relative wall thickness (RWT) was calculated as RWT = [2 × PWth]/Ded, where PWth is posterior wall thickness at end-diastole. All measurements were performed according to the guidelines of American Society of Echocardiography. Pulsed-wave Dopplerderived transmitral inflow velocities were obtained with the transducer in the apical four-chamber view and sampling volume at the mitral valve leaflet tips. The early diastolic (E) and atrial (A) velocities were measured and the E/A ratio was calculated. The deceleration time (in ms) and the isovolumetric relaxation time (in ms) were also assessed.

cardiology Observation

Table 4. Diastolic Dysfunction in Relation with BMI

Table 1 describes the subject characteristics and hemodynamics. Distribution of BMI is depicted in Table 2.

BMI

RESULT Our study, echocardiographic findings are comparable to previous studies conducted by Peterson and Waggoner and show that young obese subjects exhibit abnormalities in LV structure and formation, including a pattern of LV concentric evidenced by increased LV wall thickness, increased RWT and normal LV chamber size. Table 1. Subject Characteristics and Hemodynamics Obese (n = 28)

Diastolic dysfunction

25-30

30-35

35-40

>40

Conventional load-dependent indices of LV diastolic function, such as E wave, E/A ratio decreased and deceleration time and isovolumetric relaxation time were also increased again suggestive of stage 1 (impaired relaxation) diastolic dysfunction. These early abnormalities in LV structure and function may have important implications in explaining the increased cardiovascular morbidity and mortality associated with obesity (Table 3 and 4).

Age (years)

34 ± 4

DISCUSSION

BMI (kg/m2)

36 ± 4

Heart rate (beats/min)

74 ± 8

Table 3. Left Ventricular Diastolic Function in Obese

Obesity is one of the most common disorders of metabolism in human beings. Obese persons are at greater risk of morbidity and mortality than their nonobese counterparts. The pioneer survey of Connectient Mutual Life Insurance Company in the year 1912, and the studies of Dublin in 19303 have emphasized the relationship between excess weight and increased mortality. The statistics of Metropolitan Life Insurance Company (1953)4 also showed 50% greater death rates between the ages of 20 and 64 years among overweight insured people. The Framingham heart study5 showed a marked increase in sudden death rate among men >20% overweight as compared to the normal weight and lesser degree of overweight individuals. Garrow and Webster et al6 have suggested that the BMI is the best marker of obesity. The severity of obesity is classified as follows:

Structure

Grade 0

Wt/Ht2 (kg/mt2)

<24.9

Grade I

Wt/Ht2

25-29.9

Grade II

Wt/Ht2 (kg/mt2)

30-39.9

Grade III

Wt/Ht2 (kg/mt2)

>40.0

SBP (mmHg)

118 ± 10

DBP (mmHg)

84 ± 8

Table 2. Distribution of BMI (Degree of Obesity) Degree of obesity

BMI (kg/m2)

No. of patients M

Total Percentage

High-risk

30-35

112

132

Very high-risk

35-40

>40

Extreme high-risk

Obese (n = 28) Normal range

LVED volume (ml)

96 ± 14

56-104

Posterior wall thickness (mm)

90 ± 10

60-90

Septal wall thickness (mm)

91 ± 12

60-90

LV mass (g)

158 ± 28

66-150

LV MI

(g/m2)

LV mass/height (g/m) RWT

80 ± 12

76 ± 13

96 ± 20

80 ± 12

0.40 ± 0.06

0.34 ± 0.03

Diastolic function 74 ± 10

79 ± 17

E/A ratio

E-wave (cm/s)

1.02 ± 0.4

2.01 ± 0.5

Deceleration time (ms)

220 ± 30

<220

IVRT (ms)

92 ± 14

88 ± 8

(kg/mt2)

al7

Kissebah et indicate that obesity correlated with abdominal fat and less well with lower body fat. Kirschner et al8 and Larsson et al9 correlated waist hip ratio (WHR) to health risks and observed that WHR >0.9 for men, and >0.8 for women is associated with increased risk for complications of obesity. A 12-year follow-up of 3,36,000 men and 4,19,000 women by the American Cancer Society showed that persons who are >40% overweight suffer increased morbidity and mortality from diabetes, coronary heart disease,

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cardiology hypertension, menstrual abnormalities, cholelithiasis, respiratory complications, malignancy i.e. endometrial cancer, breast cancer, prostate cancer and colon cancer. There are few other medical complications associated with obesity like acanthosis nigricans, fungal infections in skin folds, varicose veins, osteoarthritis of weightbearing joints, post-traumatic arthropathy, hyperuricemia and various types of hernia. Adiposity is also known to be associated with metabolic abnormalities. Commonest abnormality is in the glucose metabolism resulting from an acquired insulin resistance at the periphery. Disorders in triglycerides and free fatty acid metabolism are also significant. Sims et al10 demonstrated that virtually all metabolic disturbances tested are inducible with weight gain and are reversible after weight reduction. Peterson et al2 designed a study to determine the effects of obesity on LV structure and function in young obese women. Fifty-one women were evaluated; 20 were obese having BMI ≥30 kg/m2 and their LV structure and diastolic function were assessed by 2D-echo. The result showed that obese women had higher and diastolic septal and posterior wall thickness. Grandi et al11 evaluated the influence of obesity on LV diastolic function. They selected 32 obese newly diagnosed never treated hypertensives, 32 obese normotensives matched for age, sex and BMI. Results showed the main effect was found for obesity on LV diameter and LV mass, LV systolic function was normal in all the subjects and LV diastolic function was significantly reduced. They concluded that obesity is associated with a preclinical impairment of LV diastolic function in both normotensive and hypertensives; similar results were found in our study. Our study echocardiographic findings are comparable to previous studies conducted by Peterson and Waggoner and show that young obese subjects exhibit abnormalities in LV structure and formation, including a pattern of LV concentric evidenced by increased LV wall thickness, increased RWT and normal LV chamber size. Conventional load-dependent indices of LV diastolic function, such as E-wave, E/A ratio decreased and deceleration time and isovolumetric relaxation

time were also increased again suggestive of stage 1 (impaired relaxation) diastolic dysfunction. CONCLUSION We conclude that, young and otherwise healthy obese subjects also exhibit alterations in LV structure and function manifested by concentric LV remodeling and impaired diastolic functions. REFERENCES 1. Alpert MA. Obesity cardiomyopathy: pathophysiology and evolution of the clinical syndrome. Am J Med Sci 2001;321(4):225-36. 2. Peterson LR, Waggoner AD, Schechtman KB, Meyer T, Gropler RJ, Barzilai B, et al. Alterations in left ventricular structure and function in young healthy obese women: assessment by echocardiography and tissue Doppler imaging. J Am Coll Cardiol 2004;43(8):1399-404. 3. Health implications of obesity. National Institutes of Health Consensus Development Conference Statement. Ann Intern Med1985;103(1):147-51. 4. Metropolitan Life Insurance Company: Statistical Bulletin (1953): Quoted by Mayer. J Physiol 1953; Rev 33:472. 5. Kalkhoff R, Ferrou C. Metabolic differences between obese overweight and muscular overweight men. N Engl J Med 1971;284(22):1236-9. 6. Garrow GS. In: Recent advances in medicine. Vol. 18, Churchill Livingstone, 1981. 7. Kissebah AH, Vydelingum N, Murray R, Evans DJ, Hartz AJ, Kalkhoff RK, et al. Relation of body fat distribution to metabolic complications of obesity. J Clin Endocrinol Metab 1982;54(2):254-60. 8. Kirschner MA, Ertel N, Schneider G. Obesity, hormones, and cancer. Cancer Res 1981;41(9 Pt 2):3711-7. 9. Larsson B, Björntorp P, Tibblin G. The health consequences of moderate obesity. Int J Obes 1981;5(2):97-116. 10. Sims EA, Danforth E Jr, Horton ES, Bray GA, Glennon JA, Salans LB. Endocrine and metabolic effects of experimental obesity in man. Recent Prog Horm Res 1973;29:457-96. 11. Grandi AM, Zanzi P, Piantanida E, Gaudio G, Bertolini A, Guasti L, et al. Obesity and left ventricular diastolic function: noninvasive study in normotensives and newly diagnosed never-treated hypertensives. Int J Obes Relat Metab Disord 2000;24(8):954-8.

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STREAM: First Success for Fibrinolysis before Transport to PCI Fibrinolysis with tenecteplase and contemporary antithrombotic therapy given before transport to a PCIcapable hospital coupled with timely coronary angiography is as effective as primary PCI in STEMI patients presenting within three hours of symptom onset who cannot undergo primary PCI within one hour of first medical contact, the STREAM trial has shown. (Source: Medscape)

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Critical care

A View on Combination Antiplatelet Agents in Ischemic Stroke Bhargava M Vyasa*, RD Dave*, PS Daniel*, IS Anand*, CN Patel*

Abstract The evaluation of antiplatelet agents for prevention of ischemic stroke is being focused as a strategy for stroke reduction. The aim of this analysis was to focus specifically on the necessity of combination antiplatelet agents for secondary prevention of ischemic strokes. Aspirin, clopidogrel, ticlopidine and the combination of aspirin plus extended-release dipyridamole are all effective in reducing the risk of recurrent ischemic strokes and transient ischemic attack. Furthermore, the combinations of all above drugs show some merits and demerits in one or more condition. National guideline endorses any of these antiplatelet agents as appropriate treatment options but more research into this strategy is needed. Choosing a single antiplatelet agent or the combination must be tailored according to patient characteristics, cost, disease condition and tolerability. Other classes of antiplatelet drugs should undergo clinical trials to optimize antiplatelet therapy.

Keywords: Aspirin, clopidogrel, dipyridamole, ticlopidine, combination antiplatelet therapy, ischemic stroke

troke is a leading cause of death and the primary cause of serious, long-term disability worldwide. Roughly, 90% of all strokes are ischemic in nature, with the remaining resulting from intracerebral hemorrhage or subarachnoid hemorrhage. Nearly, 25% of patients who experience a stroke have sustained a previous stroke, making secondary prevention of recurrent stroke an important target of pharmacotherapy. The high rates of mortality and disability associated with ischemic stroke, coupled with its prevalence, necessitate good, long-term preventive strategies. Patients suffering from a transient ischemic attack (TIA) or stroke are particularly vulnerable to secondary stroke. Available antiplatelet therapies include aspirin, clopidogrel, dipyridamole and ticlopidine. Of these options, aspirin monotherapy has been the mainstay of treatment for secondary prevention of ischemic stroke or TIA. It has been studied extensively and is relatively safe and inexpensive. Unfortunately, aspirin monotherapy has its limitations. It has been suggested that aspirin alone produces only a 10-15% relative risk (RR) reduction in stroke recurrence compared

*Dept. of Pharmacology Shri Sarvajanik Pharmacy College, Mehsana, Gujarat Address for correspondence Dr Bhargava M Vyasa D/301, Ashutosh Apartments, B/h St. Xavierâ&#x20AC;&#x2122;s Loyola School Naranpura, Ahmedabad - 380 013 E-mail: bmvyasa_1986@yahoo.co.in

with placebo. Aspirin can also cause significant gastrointestinal discomfort and bleeding, and certain patients may be resistant to its antiplatelet effects. These findings have led investigators to consider alternatives to aspirin monotherapy, most notably, combination antiplatelet treatment. Combination antiplatelet therapy seeks to block platelet aggregation through multiple mechanisms. Aspirin inhibits the enzyme cyclooxygenase, thus preventing production of prostaglandins and ultimately the production of thromboxane A2. Clopidogrel acts on platelets by irreversibly binding the adenosine diphosphate (ADP) receptor, blocking the ADP-dependent activation of the glycoprotein IIbIIIa complex. This complex works as a receptor for fibrinogen on the surface of the platelet. Dipyridamole inhibits the uptake of adenosine into platelets, resulting in elevated local adenosine concentrations. Adenosine then acts on platelet A2 receptors, increasing the production of cyclic adenosine monophosphate. This mechanism prevents platelet-activating factor, collagen, ADP and other stimuli from activating platelet aggregation. By blocking platelet aggregation through multiple mechanisms, it is postulated that secondary ischemic stroke prevention can be enhanced. The American Heart Association (AHA) and the American Stroke Association (ASA) published joint guidelines in 2006 for treatment of patients with a history of stroke or TIA.

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Critical care Randomized trials have established combination antiplatelet therapy as a cornerstone for secondary stroke prevention. Results from these trials enhance the recommendations from the AHA-ASA and provide the foundation for the updates in the 8th ACCP guideline. To identify pertinent combination antiplatelet trials, we performed a medline search of the literature from 1967-2007. We identified two trials - Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management and Avoidance (CHARISMA) and the European-Australasian Stroke Prevention in Reversible Ischemia Trial (ESPRIT). Data from these two trials are important to current recommendations for secondary ischemic stroke and TIA prevention. Data from historic trials - the European Stroke Prevention Study (ESPS), the Second European Stroke Prevention Study (ESPS-2), the Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events trial (CAPRIE) and the Management of Athero-Thrombosis with Clopidogrel in High-risk Patients (MATCH) - are also important to consider, as they provided the background for the AHA-ASA and most recent ACCP guidelines (Table 1). In this article, we review the evidence from randomized trials for the effectiveness and safety of established combination antiplatelet therapies for secondary prevention of ischemic stroke and TIA. We have focused on trials and meta-analysis that included patients with stroke, TIA or peripheral artery disease. Aspirin Aspirin, the most commonly used antiplatelet agent, inhibits the enzyme cyclooxygenase, reducing

production of thromboxane A2, a stimulator of platelet aggregation. This interferes with the formation of thrombi, thereby reducing the risk of stroke. The dose of aspirin in secondary stroke prevention studies ranged between 20-1,300 mg. Most studies have found that 50-325 mg/day of aspirin is as effective as higher doses. Furthermore, lower doses within this range appear to provide the same benefit as higher doses. In the ESPS-2, 50 mg of aspirin daily reduced stroke risk by 18% compared with placebo (29 strokes prevented per 1,000 treated), an effect of comparable magnitude to the other trials cited above. This benefit seen with very low-dose aspirin is consistent with laboratory observations that 30 mg of aspirin per day results in complete suppression of thromboxane A2 production. In an analysis of data from 31 randomized, controlled trials, aspirin doses â&#x2030;¤200 mg/day were associated with a significantly lower rate of major bleeding events compared with higher doses. However, there was no difference in major bleeding when aspirin <100 mg/ day was compared with 100-200 mg/day. Aspirin <100 mg/day was associated with a lower risk compared with the 100-200 mg/day and >200 mg/day groups when the overall rate of bleeding complications (including major, minor and insignificant events) was considered. A later meta-analysis of 22 randomized trials of lowdose aspirin (75-325 mg/day) versus placebo for cardiovascular prophylaxis reached similar conclusions within the low-dose range. Compared with placebo, aspirin increased the RR of any major bleeding, major gastrointestinal bleeding and intracranial bleeding

Table 1. Trial Characteristics for Six Randomized Controlled Trials Trial

Subjects Treatment arms

Primary endpoints

Results (% RRR)

ESPS-1

2,500

ASA 330 mg q.d. + IR-DP 75 mg t.i.d. vs placebo

Stroke or death

33.5% reduction in stroke

ESPS-2

6,602

ASA 25 mg b.i.d. + ER-DP 200 mg b.i.d. or ASA 25 mg b.i.d., or ER-DP 200 mg b.i.d. vs placebo

Stroke

37% with aspirin-dipyridamole, by 18% with aspirin alone, and by 16% with dipyridamole alone vs placebo

CAPRIE

19,185

ASA 325 mg q.d. vs clopidogrel 75 mg q.i.d.

Ischemic stroke, MI or vascular death

8.7% RRR favored clopidogrel group

MATCH

7,599

ASA 325 mg q.d. + clopidogrel 75 mg q.d. vs clopidogrel 75 mg q.d.

Ischemic stroke, MI, vascular death or rehospitalization for an acute ischemic event

No significant difference; increased risk for bleeding in combination group

CHARISMA 15,603

Clopidogrel 75 mg q.d. + ASA 75-162 MI, stroke or death mg q.i.d. vs ASA 75-162 mg q.i.d.

No significant difference; increased risk for bleeding in combination group

ESPRIT

ASA 30-325 mg q.i.d. + DP 200 mg b.i.d. vs ASA 30-325 mg q.i.d.

20% RRR favored combination group

2,763

Death from vascular causes, nonfatal stroke or MI

ASA = Aspirin; IR = Immediate release; ER = Extended-release; DP = Dipyridamole; MI = Myocardial infarction; RRR = Relative risk reduction.

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Critical care Aspirin/ Dipyridamole Ticlopidine Clopidogrel

Relative risk reduction (%)

25 20

Dipyridamole is currently available in two forms: ÂÂ

An immediate-release form, usually given as 50100 mg three times per day.

ÂÂ

A proprietary formulation containing both extended-release dipyridamole (ER-DP) 200 mg and 25 mg aspirin, given two times per day.

15 10

The effectiveness of dipyridamole monotherapy for secondary stroke prevention was established by the following studies:

5 0

Stroke, MI, Vascular death

Stroke

Figure 1. Comparison of antiplatelet agents.

by 1.7- to 2.1-fold. However, the absolute annual increase in risk for any major bleeding episode (mostly gastrointestinal) and for intracranial bleeding was 0.13 and 0.03%, respectively. Furthermore, there was no evidence of an increased risk of bleeding with ‘high’ low-dose aspirin (>162-325 mg/day) compared with ‘low’ low-dose aspirin (75-162 mg/day) (Fig. 1). Clopidogrel Clopidogrel is a thienopyridine that inhibits ADPdependent platelet aggregation. The CAPRIE trial randomly assigned 19,000 patients with recent stroke, myocardial infarction (MI) or symptomatic peripheral arterial disease (divided roughly equally between these three enrolling diseases) to treatment with aspirin (325 mg) or clopidogrel (75 mg). The primary endpoint, a composite outcome of stroke, MI or vascular death, was significantly reduced with clopidogrel treatment compared with aspirin treatment (5.3 vs 5.8% annually, RR reduction 8.7%, 95% confidence interval [CI] 0.3-16.5%). The benefit of clopidogrel over aspirin in the CAPRIE trial varied based on enrolling disease. Most of the benefit was observed in patients with peripheral arterial disease, and the difference in composite outcome between clopidogrel and aspirin treatment in patients with recent stroke and MI was not significant. However, the strength of these observations are limited, since they are based on subgroup analyses.

The ESPS-2 trial randomly assigned 6,602 patients with a recent TIA or ischemic stroke to one of 4 groups: 200 mg ER-DP alone given twice-daily; 25 mg aspirin alone given twice-daily; 25 mg aspirin plus 200 mg ERDP given twice-daily and placebo. An independent and significant benefit for stroke risk reduction was observed for both ER-DP monotherapy (odds ratio [OR] 0.81, 95% CI 0.76-0.99) and aspirin monotherapy (OR 0.79, 95% CI 0.65-0.97) compared with placebo. The benefit of combination ER-DP plus aspirin was significantly greater still than the two components alone and significantly greater than placebo (OR 0.59, 95% CI 0.48-0.73). A subsequent meta-analysis of individual patient data from all available randomized trials found that dipyridamole alone was effective for reducing recurrent stroke compared with control (OR 0.82, 95% CI 0.68-1.0). Since, the ESPS-2 trial provided 57% of the data in this meta-analysis, it is possible that ESPS-2 was the primary driver behind the results. When ESPS2 data were excluded, the effectiveness of dipyridamole alone compared with control did not achieve statistical significance. Whether this is related to the lower doses and immediate-release formulation used in trials other than ESPS-2 remains unclear. Ticlopidine Ticlopidine is a thienopyridine with a chemical structure and mechanism of action similar to clopidogrel. Its role in stroke prevention has been evaluated in two major trials. ÂÂ

The CATS trial compared ticlopidine with placebo in patients who had suffered a significant stroke. At a mean of 24 months follow-up, the primary composite endpoint of stroke, MI and vascular death was significantly lower with ticlopidine compared with placebo (10.8 vs 15.3%, RR reduction 30%). Analysis by intention-to-treat gave a smaller estimate of RR reduction for stroke, MI or vascular death (23%).

ÂÂ

The TASS trial compared ticlopidine (500 mg/

Dipyridamole Dipyridamole impairs platelet function by inhibiting the activity of adenosine deaminase and phosphodiesterase, which causes an accumulation of adenosine, adenine nucleotides and cyclic adenosine monophosphate. Dipyridamole may also cause vasodilation.

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Critical care day) to aspirin (1,300 mg/day) in 3,069 patients with a recent TIA or mild stroke. At 3-year followup, ticlopidine was associated with a significant reduction in the primary endpoint (nonfatal stroke or death) compared with aspirin (17 vs 19%). Ticlopidine treatment was also associated with a significant reduction in the rate of fatal and nonfatal stroke compared with aspirin (10 vs 13%, respectively; RR reduction 21% [95% CI, 4-38]). Aspirin Plus Clopidogrel The combined use of aspirin and clopidogrel does not offer greater benefit for stroke prevention than either agent alone but does substantially increase the risk of bleeding complications. This conclusion is supported by results from the MATCH trial. This study enrolled 7,599 patients with stroke or TIA who also had some additional ‘high-risk’ feature, defined as prior MI, prior stroke (in addition to the index event), diabetes, angina or symptomatic peripheral artery disease (PAD). The primary endpoint was a composite of ischemic stroke, MI, vascular death or rehospitalization for acute ischemia. Patients were randomly assigned to the combination of clopidogrel (75 mg daily) plus aspirin (75 mg daily) versus clopidogrel (75 mg daily) alone. Follow-up was 18 months. The following observations were reported: ÂÂ

Aspirin plus clopidogrel treatment did not reduce the risk of major vascular events compared with clopidogrel alone (RR reduction 6.4%, 95% CI -4.6 to 16.3%).

ÂÂ

Aspirin plus clopidogrel was associated with a significant increase in life-threatening bleeding complications, mainly intracranial and gastrointestinal, compared with clopidogrel alone. Over the 18-month trial period, there was an absolute excess of 1.3% for life-threatening hemorrhage (95% CI 0.6-1.9) and an additional 1.3% for major hemorrhage in patients assigned combination therapy.

ÂÂ

Overall, treatment with aspirin and clopidogrel compared with clopidogrel alone might prevent 10 ischemic events per 1,000 treated (not statistically significant) at the cost of 13 life-threatening hemorrhages per 1,000 treated.

Several authors have noted limitations of MATCH. For instance, 54% of MATCH subjects qualified for trial entry because of a lacunar stroke, a stroke subtype that has the lowest recurrence risk. Furthermore, data

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regarding interaction between treatment and stroke mechanism were not reported, raising the question of whether combination therapy might still play a role in particular stroke subtypes. The combination of aspirin and clopidogrel has been shown to have benefit over aspirin alone in patients with acute coronary syndromes. However, there are important differences between patients with coronary and cerebrovascular disease, and between short-term therapy initiated in the acute setting, and longer term preventative therapy. The results of the MATCH trial serve to emphasize these differences. In contrast to the MATCH trial, which evaluated aspirin plus clopidogrel versus clopidogrel alone in patients with stroke or TIA, the CHARISMA trial evaluated aspirin plus clopidogrel versus aspirin alone in patients with symptomatic cardiovascular disease or asymptomatic multiple cardiovascular risk factors. In this patient population, the combination of aspirin plus clopidogrel was not more effective than aspirin alone for reducing the rate of MI, stroke or death from cardiovascular causes. CHARISMA enrolled 15,603 patients with either documented cardiovascular disease (coronary, ischemic cerebrovascular or peripheral arterial) or, in 21% of patients, multiple atherothrombotic risk factors (e.g., diabetes, hypertension, primary hypercholesterolemia, current smoking, asymptomatic carotid stenosis ≥70%) and randomly assigned them to low-dose aspirin (75-162 mg/day) plus either clopidogrel (75 mg/day) or placebo. The following observations were reported at a median of 28 months: ÂÂ

Combined aspirin plus clopidogrel treatment did not reduce the risk of the composite primary endpoint (MI, stroke of any cause or death from cardiovascular causes) compared with aspirin alone (6.8 vs 7.3%, RR 0.93, 95% CI 0.83-1.05)

ÂÂ

Combination therapy compared with aspirin alone was associated with a significant increase in moderate bleeding (2.1 vs 1.3%) and a nonsignificant increase in severe bleeding (1.7 vs 1.3%).

Aspirin Plus Dipyridamole The beneficial effects of aspirin and dipyridamole for secondary stroke prevention appear to be additive such that the combination of aspirin and ER-DP is significantly more effective than aspirin alone for stroke prevention. The data supporting this conclusion come from the following randomized trials:

Critical care ÂÂ

ÂÂ

In a meta-analysis of six randomized trials with 7,648 patients, stroke risk was significantly reduced with aspirin plus dipyridamole (including immediate and extended-release formulations) compared with aspirin alone (RR 0.77, 95% CI 0.67-0.89). Nearly, 80% of the patients in this metaanalysis came from just two trials, ESPS-2 and ESPRIT. In the ESPS-2 trial, the stroke rate at 24 months of follow-up was significantly reduced in the aspirin plus ER-DP group compared with the aspirin alone group (9.9 vs 12.9%; RR reduction 23%, 95% CI 9.2-37.0). There was no significant difference in the risk of death between the two groups. The risk of bleeding complications was not significantly different between the aspirin plus ER-DP group and the aspirin monotherapy group, whereas both groups experienced a greater frequency of bleeding complications than the placebo group. In the later ESPRIT trial, 2,739 patients within six months of a TIA or minor stroke of presumed arterial origin were randomly assigned to openlabel treatment with aspirin (30-325 mg/day) alone or aspirin plus dipyridamole (200 mg twicedaily). The median aspirin dose was 75 mg/day in both treatment groups, and the dipyridamole formulation used by most patients (83%) was extended-release rather than immediate release. Over a mean follow-up of 3.5 years, the composite primary outcome (death from all vascular causes, nonfatal stroke, nonfatal MI or major bleeding complication) was significantly less frequent in the aspirin plus dipyridamole group than the aspirin group (13 vs 16%, hazard ratio 0.80, 95% CI 0.660.98, absolute risk reduction 1.0% per year).

ESPRIT included patients using aspirin doses ranging from 30 to 325 mg daily, allaying concerns that the very low aspirin dose (25 mg twice-daily) used in ESPS-2 was in part responsible for the benefit of combined aspirin plus ER-DP over aspirin alone. The specific dipyridamole preparation may be important. In the meta-analysis cited above, the combination of aspirin and immediate-release dipyridamole was nonsignificantly better than aspirin alone for secondary prevention of stroke (RR 0.83, 95% CI 0.59-1.15). In contrast, ER-DP was used in all or the vast majority of patients in the much larger ESPS-2 and ESPRIT trials, and aspirin plus ER-DP was associated with a significant reduction in stroke risk compared with aspirin alone (RR 0.76, 95% CI 0.65-0.89).

Table 2. A Semi-quantitative Evaluation of Antiplatelets for the Prevention of Stroke and other Vascular Events ASA Clopidogrel Ticlopidine

ASA/ Dipyridamole

Efficacy

↑↑

↑↑↑

↑↑↑↑

Tolerability

↑↑↑

↑

↑↑

Routine monitoring

Yes

Dosing frequency

o.d.

b.i.d.

↑

↑↑↑↑

↑↑

↑↑↑

Cost

Triple Therapy As we know that two antiplatelet agents are beneficial to single, then three agents with different modes of action might be better still, providing bleeding risk doesn’t become vulnerable. The efficacy of combining three antiplatelet drugs (aspirin, dipyridamole and clopidogrel) on inhibiting platelet aggregation, the formation of platelet-leukocyte conjugates and leukocyte activation has been demonstrated in vitro. However, in human beings, for prevention of secondary ischemic stroke, short-term triple therapy was no more effective. Recurrent cerebrovascular events ceased with triple therapy over a period of 5-23 months follow-up and no episodes of intracranial hemorrhage or major extracranial bleeding have occurred to date. Comparison of Antiplatelet Agents A semi-quantitative evaluation of antiplatelets for the prevention of stroke and other vascular events based on selected criteria and available evidence is shown in Table 2. All the antiplatelet agents except for ticlopidine are acceptable for initial therapy but because of its efficacy, safety and cost, ASA should probably be used first in most circumstances for ischemic stroke prevention. Alternatives to ASA for second choice would include clopidogrel or the combination of ASA/dipyridamole. The combination of ASA and clopidogrel cannot be recommended for long-term stroke prevention both because of a lack of efficacy and increased risk of intracranial hemorrhage. Conclusion Antiplatelet therapy has major role in secondary prevention of ischemic stroke is undeniable. Effectiveness of single drug aspirin in contrast to combination with other antiplatelet agents is questionable according

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Critical care to various studies. Further, the potential of newer antiplatelets and their combination for reducing ischemic stroke is to be explored before arriving at decisive relative effectiveness of various combinations. Suggested Reading 1. Vande Griend JP, Saseen JJ. Combination antiplatelet agents for secondary prevention of ischemic stroke. Pharmacotherapy 2008;28(10):1233-42. 2. Katzan IL. Antiplatelet agents in secondary stroke prevention. The Cleveland Clinic 2009. 3. Sprigg N, Gray LJ, England T, Willmot MR, Zhao L, Sare GM, et al. A randomised controlled trial of triple antiplatelet therapy (aspirin, clopidogrel and dipyridamole) in the secondary prevention of stroke: safety, tolerability and feasibility. PLoS One 2008;3(8):e2852. 4. Sacco RL, Elkind MS. Update on antiplatelet therapy for stroke prevention. Arch Intern Med 2000;160(11):1579-82. 5. Cucchiara B, et al. Antiplatelet therapy for secondary prevention of stroke. Up To Date 2009. 6. Leonardi-Bee J, Bath PM, Bousser MG, Davalos A, Diener HC, Guiraud-Chaumeil B, et al; Dipyridamole in Stroke Collaboration (DISC). Dipyridamole for preventing recurrent ischemic stroke and other vascular events: a meta-analysis of individual patient data from randomized controlled trials. Stroke 2005;36(1):162-8. 7. O’Donnell MJ, Hankey GJ, Eikelboom JW. Antiplatelet therapy for secondary prevention of noncardioembolic ischemic stroke: a critical review. Stroke 2008;39(5):1638-46. 8. Côté R, David M, Deveber G, Teal P, Roussin A, Sharma M. Prevention of ischemic stroke. The Thrombosis Interest Group of Canada. February 19, 2007.

9. Antiplatelet chemoprevention of occlusive vascular events and death. Int Soc Drug Bull Therapeut Lett 2000;37a-37b. 10. Hass WK, Easton JD, Adams HP Jr, Pryse-Phillips W, Molony BA, Anderson S, et al. A randomized trial comparing ticlopidine hydrochloride with aspirin for the prevention of stroke in high-risk patients. Ticlopidine Aspirin Stroke Study Group. N Engl J Med 1989;321(8):501-7. 11. Gent M, Blakely JA, Easton JD, Ellis DJ, Hachinski VC, Harbison JW, et al. The Canadian American Ticlopidine Study (CATS) in thromboembolic stroke. Lancet 1989;1(8649):1215-20. 12. Fong JK. Update on Secondary Ischemic Stroke Prevention. Med Bull 2004;9:5-7. 13. Thijs V, Lemmens R, Fieuws S. Network meta-analysis: simultaneous meta-analysis of common antiplatelet regimens after transient ischaemic attack or stroke. Eur Heart J 2008;29(9):1086-92. 14. Kirshner HS. Therapeutic interventions for prevention of recurrent ischemic stroke. Am J Manag Care 2008;14(6 Suppl 2):S212-26. 15. Kirshner HS. Secondary stroke prevention, and the role of antiplatelet therapies. Clinical Medicine: Therapeutics 2009;1:601-12. 16. Zhao L, Heptinstall S, Bath PM. Antiplatelet therapy for stroke prevention. Br J Cardiol 2005;12(1):57-60. 17. McCabe DJ, Brown MM. Prevention of ischaemic stroke antiplatelets. Br Med Bull 2000;56(2):510-25. 18. Cote R. Prevention of ischemic stroke. Canadian J CME 2001;193-8. 19. Flemming KD, Wiebers DO. Optimizing antiplatelet therapy to prevent ischemic stroke. Emerg Med 2002;34:28-37.

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Tamiflu Resistance may be Rising The pandemic H1N1 influenza A strain -- now circulating as seasonal flu - appears to be developing resistance to oseltamivir (Tamiflu) in Australia, a researcher is reporting at the annual meeting of the Australasian Society for Infectious Diseases. (Source: Medpage Today)

Postpartum Depression Underidentified, Undertreated Postpartum depression is increasingly common, new research suggests. In a study of 10,000 women who had recently given birth, 14% — or roughly 1 in 7 - screened positive for recurrent episodes of major depression. And of these, more than 19% reported having considered harming themselves. (Source: Medscape)

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Dentistry

Periodontal-Restorative Interactions: A Review Shaveta Sood*, Shipra Gupta**

Abstract The interrelationship of restorative dentistry and periodontics is a dynamic one. We have reviewed the various guidelines for performing periodontally compatible restorative dentistry. Using these basic guidelines, restorative care can be used to directly aid periodontal treatment by restoring an esthetically pleasing, comfortable and stable dentition. This article addresses the interactions between periodontal tissues and restorative procedures.

Keywords: Restorations, crowns, pontic, periodontal health, sulcus

he interrelationship of restorative dentistry and periodontics is a dynamic one. The interactions between restorative dentistry and periodontal health have been well-documented both clinically and histologicaly. Periodontal health at the restorativegingival interface continues to represent one of the most difficult challenges for the restorative dentist. Emphasis must be placed on the control of bacterial plaque, the coronal contour of a restoration, alloy sensitivity and the margin location of a restoration.1

adaptation, restoration contour and occlusal function. This article strives to review the various considerations to be kept in mind while placing a restoration.

ÂÂ

Gingiva shrinks after periodontal treatment.

The successful integration of periodontal and restorative dentistry for both natural teeth and implants requires knowledge and application of both mechanical and biological principles.2 The proper margin location of a restoration relative to the alveolar bone may be one of the most important parameters in managing to ensure long-term gingival health.3 Thus, it is imperative that close attention be paid to restorative procedures such as margin placement, contours of restorations as well as occlusal forces. Restorations that interfere with host defences will create sites where microorganisms thrive and cause destruction. There are four aspects of restoration design which have a direct effect on the periodontium. These are margin placement, margin

ÂÂ

The position of teeth is frequently altered in periodontal disease. Resolution of inflammation after treatment causes the teeth to move again, often back to their original position. Restorations designed for teeth before the periodontium is treated may produce injurious tensions and pressures on the treated periodontium.

ÂÂ

Inflammation of the periodontium impairs the capacity of abutment teeth.

ÂÂ

Discomfort from tooth mobility interferes with mastication and function.

ÂÂ

It is easy to obtain accurate impressions and make precise preparations on healthy gingiva than inflamed one4

ÂÂ

To minimize the risk of trauma to the gingival tissues during preparation and impression procedures.

*Senior Assistant Professor **Associate Professor Dept. of Periodontics Dr HS Judge Institute of Dental Sciences and Hospital Punjab University, Chandigarh Address for correspondence Dr Shipra Gupta H. No: 1472, Near Government Dispensary Sector 21, Panchkula, Haryana E-mail: teena1472@yahoo.in

Importance of Preparation of the Periodontium for Restorative Dentistry The reasons why periodontal disease must be eliminated prior to restorative dentistry are:

Periodontal Considerations It includes: ÂÂ

Phase 1 therapy/initial therapy

ÂÂ

Periodontal surgery

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Dentistry Phase 1 Therapy5 Control of periodontal inflammation during phase 1 therapy results in restorative procedures of a much higher quality than those carried out in an environment of gingival inflammation. The presence of an acute inflammatory response in the gingiva causes ulceration of epithelium that lines the gingival pocket and increase of vascularity and edema of the tissues immediately under this epithelium. Thus, plaque control, calculus removal and the removal of any inadequate dental restorations in the gingival environment should be important first order procedures.

Periodontal Surgery In some patients, periodontal surgery like crown lengthening is necessary. These periodontal surgical procedures should be carried out with due regard for the restorative needs of the patient i.e. need to be modified because of the restorative or prosthetic needs of the patient.

Crown Lengthening In situations in which a tooth has a short clinical crown deemed inadequate for retention of a required cast restoration, it is necessary to increase the size of the clinical crown using periodontal surgical procedures. These crown lengthening procedures enable the dentist performing the restoration to develop an adequate area for crown retention without extending the crown margins deep into the periodontal tissues, referred to as the biologic width. Restorative Considerations

Margin Placement Guidelines or Restorative Margin Location When determining where to place restorative margins relative to the periodontal attachment, it is recommended that the patientâ&#x20AC;&#x2122;s existing sulcus depth is used as a guideline in assessing the biologic width requirement for that patient. The extension of any restorative margin into the gingival sulcus should be considered a compromise,6-9 but esthetic or retentive demands often make it necessary. Hence, subgingival margins should be considered a compromise,10-16 and supragingival margins are preferred.17,18 The marginal fit should be optimal because rough restorations or open margins lead to an accumulation of bacterial pathogens that are associated with inflammatory periodontal diseases.19 Intracrevicular margins are defined as those confined within the gingival crevice.20,21

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Different studies have demonstrated conclusively that periodontal tissues show more signs of inflammation around crowns with intracrevicular or subgingival margins than those with supragingival margins.6,22 Orkin et al23 demonstrated that subgingival restorations had a greater chance of bleeding and exhibiting gingival recession than supragingival restorations. Renggli et al24 showed that gingivitis and plaque accumulation were more pronounced in interdental areas with well-adapted subgingival amalgam fillings compared to sound tooth structure. Flores-de-Jacoby et al25 studied the effects of crown margin location on periodontal health and bacterial morphotypes in human 6-8 weeks and 1 year postinsertion. Subgingival margins demonstrated increased plaque, gingival index score and probing depths. Furthermore, more spirochetes, fusiforms, rods and filamentous bacteria were found to be associated with subgingival margins. Silness26 evaluated the periodontal condition of the lingual surfaces of 385 fixed partial denture abutment teeth. He found that a supragingival position of the crown margin was the most favorable, whereas margins below the gingival margin significantly compromised gingival health. The base of the sulcus can be viewed as the top of the attachment and therefore variations in attachment height are accounted for by assuring that the margin is placed in the sulcus and not in the attachment. The first step in using sulcus depth as a guide in margin placement is to manage gingival health. Once the tissue is healthy, the following three rules can be used to place intracrevicular margins. Rule I If the sulcus probes 1.5 mm or less, place the restoration margin 0.5 mm below the gingival tissue crest. This is especially important on the facial aspect and prevents a biologic width violation in a patient who is at high-risk in that regard. Rule II If the sulcus probes >1.5 mm, place the margin onehalf the depth of the sulcus below the tissue crest. This places the margin for enough below tissue so that it is still covered if the patient is at higher risk of recession. Rule III If a sulcus >2 mm is found, especially on the facial aspect of the tooth, then evaluate to see whether a

Dentistry gingivectomy could be performed to lengthen the teeth and create a 1.5 mm sulcus. Then the patient can be treated as mentioned in Rule-I.

Various chemicals used for the treatment of chords include: ÂÂ

0.1% and 8% recemic epinephrine

Tissue Retraction

ÂÂ

100% aluminum solution (potassium aluminum sulfate)

ÂÂ

5% and 25% aluminum chloride solution

ÂÂ

Ferric subsulfate (Monsel’s solution)

ÂÂ

13.3% ferric sulfate solution

ÂÂ

8% and 40% zinc chloride solution

Retraction Cord

ÂÂ

20% and 100% tannic acid solution

Tissue management is achieved with gingival retraction cords, using the appropriate size to achieve the displacement required. Thin, fragile gingival tissues and shallow sulcus situations usually dictate that smaller diameter cords be chosen to achieve the desired tissue displacement.

ÂÂ

45% negatol solution.

Very often, the gingival margin of the restoration is intracrevicular. To enhance access, so that damage to the soft tissues is prevented during cavity preparation and impression making, it may be desirable to carry out some degree of gingival retraction.

For a Rule 1 margin, the cord such a way that the top of in the sulcus at the level where be established, which will be previously prepared margin.

should be placed in the cord is located the final margin will 0.5 mm below the

On the interproximal aspects of the tooth, the cord will usually be 1-1.5 mm below the tissue height because the interproximal sulcus is often 2.5-3 mm in depth. With this initial cord in place, the preparation is extended to the top of the cord, with the bur angled to the tooth so that it will not abrade the tissue. This process protects the tissue, creates the correct axial reduction and establishes the margin at the desired subgingival level. Second retraction cord is required to create space for final impression. The second cord is pushed so that it displaces the first cord apically and sites between the margin and the tissue. For the final impression, the top cord is removed, leaving the margins visible and accessible to be recorded with the impression material. The initial cord remains in place in the sulcus, until the provisional restoration is completed. For Rule 2 situations, where the sulcus is deeper, two larger diameter cords are used to deflect the tissue prior to extending the margin apically. The top of the second cord is placed to identify the final margin location at the correct distance below the previously prepared margin, which was at the gingival tissue crest level. The margin is lowered to the top of the second cord and then a third cord is placed in preparation for the impression.

These drugs diffuse in blood circulation through crevicular epithelium, which is nonkeratinized and semi-permeable and cause vasoconstriction which results in transient gingival shrinkage, cause transient ischemia and help to control seepage of blood or gingival fluid.27

Recent Advances ÂÂ

Merocel: Merocel retraction strips are made of a synthetic material that is specifically chemically extracted from a biocompatible polymer (hydroxylate polyvinyl acetate) that creates a net like strip (2 mm thick). This material is chemically pure, easily shaped, effective for absorption of intraoral fluids, soft and adaptable and free of fragments.28

ÂÂ

Expasyl: It is a paste for gingival retraction that not only opens the sulcus but also leaves the field dry, ready for impression making or cementation. It is mainly composed of micronized kaolin, aluminum chloride and water. The material is simple, rapid, safe, painless, hemostatic, economical and reliable.

Electrosurgical Means The use of electrosurgery has been recommended for enlargement of the gingival sulcus and control of the hemorrhage to facilitate impression making.4 As an alternative to additional retraction cords, electrosurgery can be used to remove any overlying tissue in the retraction process. The electrosurgery tip sits on the top of the retraction cord in place in the sulcus. This controls the vertical position of the tip and results in the removal of least tissue needed for access.29,30

Surgical Means Surgical removal of hyperplastic gingival tissues for apically positioning could be done to create a healthy,

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Dentistry safely manipulated and easily retracted free gingiva. It includes: ÂÂ

ÂÂ

Surgery with a knife is the preferred method for providing access to the margin of the preparation. The gingiva regenerates and is restored to its normal position, provided it was healthy when the preparation was started. Rotary curettage: It is troughing technique, which involves the preparation of the tooth subgingivally, while simultaneous curetting the inner lining of the gingival sulcus with a rotary diamond instrument. This technique is usually followed by insertion of retraction cord.

Cryosurgery It is used in cases of interfering and unneeded gingival tissues to be removed and also for apical repositioning of whole periodontal apparatus to create a healthy, retracted free gingiva. It uses a sharp, cold knife to remove the tissues conservatively.31

Lasers This is one of the recent methods used for the retraction of gingiva utilizing laser beams such as Argon laser, CO2 laser, Nd:YAG laser, Diode laser and Er:YAG laser. This is a convenient, painless method of preparing for accurate impressions and is an excellent substitute for retraction cord. The operative and postoperative bleeding with the laser therapy is significantly less.32

Impression Techniques Severe and painful periodontal reactions will occur if rubber-base impression material is introduced into the gingival tissues during impression procedures.4 Careful visual inspection of the impression for torn areas is needed and if evidence of tearing is detected, the clinician should immediately check the tissue to remove any remnant of the impression. Otherwise a foreign body of impression material can cause severe gingival inflammation and may be misdiagnosed at a subsequent appointment.

Provisional Restorations Provisional restorations must provide an environment conducive for maintenance of periodontal health.33 Provisional restorations that are poorly adapted at the margins, are overcontoured, undercontoured and have rough or porous surfaces can cause

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inflammation, overgrowth or recession of gingival tissues. The‑outcome can be unpredictable and lead to unfavorable changes in the tissue architecture that can compromise the success of the final restoration.

Crown Contour When the gingiva contacts a flat (noncontoured) tooth surface, there is a tendency to develop a thick free gingival margin. Overcontouring of restorations or faulty placement of contour is a much greater hazard to periodontal health than is lack of contour, since both supra- and subgingival plaque accumulation may be enhanced by overcontoured margins. The greater the convexity, the more difficult it is to remove the plaque.34 The facial or lingual surface of a restoration should not have >0.5 mm bulge adjacent to the gingival margin because this may interfere with adequate plaque removal.3 It has been hence opinioned that buccal and lingual crown contours should be ‘flat’, not ‘fat’ usually <0.5 mm wider than the cementoenamel junction, and those furcation areas should be ‘fluted’ or ‘barreled out’ to accommodate oral hygiene in these areas.

Interproximal Contacts and Embrasure Space Normally, there must be a positive contact relation mesially and distally of one tooth with another in each dental arch. The areas of contact are small and are areas and not mere points of contact. Contact areas keep food from being trapped between the teeth and help to stabilize the dental arches by the combined anchorage of all teeth in either arch in positive contact with each other. In order to maintain the healthy gingiva in the interdental areas, the contact points should be located incisially or occlusally and buccally.35 Proper contact and alignment of adjoining teeth will allow proper spacing between them for the normal bulk of gingival tissue attached to the bone and teeth.

Pontic Design Pontics should both esthetically and functionally replace lost teeth, and at the same time be nonirritating to the mucosa and allow effective plaque control.4 Classically, four options should be considered in evaluating pontic design: Sanitary, ridge lap, modified ridge lap and ovate designs. The restorative material for all four designs can be either glazed porcelain, polished gold or polished resin. There is no difference in biologic response of the tissue on contact with the restoration, regardless of the material chosen, as long

Dentistry as it has smooth surface finish.36 The sanitary and ovate pontics have convex undersurfaces that facilitate cleaning. The ridge lap and modified ridge lap designs have concave surfaces that are more difficult to access with dental floss. A modified ridge lap design can be given where there is inadequate ridge to place an ovate pontic. Whereas the facial aspect of the undersurface has a concave shape, adequate access for oral hygiene is allowed by the more open lingual form.37

ÂÂ

Conservative tooth preparation maintains as much of the remaining tooth as possible, but the resulting supragingival or minimally prepared subgingival finish lines require additional metal display in the final restoration.

ÂÂ

A cast post and core may be indicated to create an adequate foundation for the final restoration because the remaining roots are often very thin mesiodistally, it is difficult to cement prefabricated posts and have adequate bulk to place a foundation core on the mesial and distal of the post. This problem is avoided with the one piece cast post and core restoration.

ÂÂ

Another area of concern when restoring these teeth is the development of appropriate contours for hygiene access. Facially and lingually, the contours should be essentially a straight line from the margin coronally, whereas interproximally, the contour emerges from the margin as a straight line or is slightly convex as it slopes upto the contact point.

ÂÂ

The interpoximal areas of root amputated and hemisectioned teeth present with surface concavities on the root trunk, and these areas cannot be adequately cleaned with floss because it will bridge across the concavity. The gingival embrasure form created in the restoration must be fluted into these areas so that the surfaces can be accessed with an interdental brush.

ÂÂ

Esthetics is usually not a major concern unless the tooth in question is a maxillary molar with a mesiobuccal root amputation and the patient has a broad smile.

Cementation and Polishing of Restorations After cementation, all retained excess cement must be thoroughly removed. When restorations extend below the gingival margin, particles of cement within the sulcus are often overlooked and can cause damage to the periodontal tissues.38

Hypersensitivity to Dental Materials Only about 30% of those patients with a known nickel allergy develop a reaction to an intraoral nickelchromium dental alloy. ÂÂ

Phosphate cements and silicates are slightly irritants.

ÂÂ

Acrylic is highly irritant, although the material itself is not irritant when fully polymerized.

ÂÂ

Gingival tissues adjacent to composite resin restorations extended subgingivally will develop gingivitis even in the presence of good oral hygiene.

More importantly, tissues respond more to the differences in surface roughness of the material rather than its composition.39,40 The rougher, the surface of the restoration subgingivally, the greater the plaque accumulation and gingival inflammation. The permeability of the gingival epithelium enhances the penetration of leachable components and thus the potential for toxic and allergic reactions.41

Special Considerations: Root-resected Teeth Root resection may be indicated in multirooted teeth with Grade II to IV furcation involvements. Root resection may be performed on vital or endodontically treated teeth. However, it is preferred in endodontically treated tooth.42 If this is not possible, then the pulp should be removed, the patency of the canals determined, and the pulp chamber medicated before resection.43

Restoration of Root-resected Teeth ÂÂ

Structural challenges are created in restoring these teeth because of the amount of tooth structure lost in the resection process.

The solution is to create an artificial mesiobuccal root with normal crown contour coronal to it and a furcation made out of restorative material that is easily cleaned with an interdental brush.

Crown Preparation Whenever possible, crown margins should be placed supragingivally for ease of impressions, margin finishing and overall periodontal health. Intracrevicular margin placement may be required to cover portions of the root resected area. The crown margin should be apical to the pulpal chamber floor or root canal that was exposed by resection especially if these structures have not been sealed with amalgam. To prevent impingement on the biologic width; intracrevicular margins to cover the pulpal canal structures should be no closer than 3 mm to the alveolar crest. This may necessitate additional lengthening.

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Dentistry To preserve remaining tooth structure and encourage a better-fitting restoration, a less complicated preparation utilizing a knife-edge finish line or a chamfer is recommended. The preparation eliminates residual ledges, roots, furcation lips or horizontal components or the furcation. In maxillary molars this includes eliminating remaining internal furcation invasions (IFI).44

Crown Contours and Embrasures In lower molars the most dependable way to-carry out this procedure is to use the hemisection approach, in which the tooth is cut in half through the crown. If both parts of the tooth are to be retained, it is essential that an adequate embrasure space be created between the two halves of the tooth, which will allow passage of all oral hygiene device. When a lower molar is hemisected and one portion is extracted, the remaining portion often serves as an abutment for a 3-unit bridge. The contour of the final restoration should be a smoothly flowing line from the contact area down to the most apical portion of the tooth preparation. Crowns that are placed on upper molars that have undergone root resection must be contoured in a specific way to ensure that the patient has access for oral hygiene measures. When a mesiobuccal or distobuccal root has been resected, it is necessary to hollow out the crown contours in the area coronal to the area where the root was removed, so that adequate access is available for oral hygiene procedures. When palatal root has been resected it is important that the crown be recontoured over the area where the palatal root was previously present. This results in a much thinner crown buccopalatally, with emphasis on a groove running in the mid-palatal surface. In other words, the crown form of this tooth with a palatal root resection would be somewhat similar to that seen in a narrow lower molar.

Occlusion Occlusal outline mirrors the gingival margin outline. The occlusal table may require extension over the area of the missing root in the following instances: Establishing the contact with an adjacent tooth, when the bulk of metal is required for a solder joint and establishing centric stops, such as the lingual cusps of maxillary molar. Lateral forces are controlled by minimizing cuspal inclines on the resected molar and the teeth stabilizing it.

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Conclusion All phases of clinical dentistry are intimately related to a common objective: The preservation and maintenance of the natural dentition in health. In an integrated multidisciplinary approach to dental care, it is logical that periodontal treatment precede final restorative procedures. For restorations to survive long-term, the periodontium must remain healthy so that the teeth are maintained. For the periodontium to remain healthy, restorations must be critically managed in several areas so that they are in harmony with their surrounding periodontal tissues. The integration of periodontal considerations with restorative planning is now the standard of care. Direct and frequent communication between the periodontist and restorative dentist is a prerequisite for predictable and satisfactory results. References 1. Gracis S, Fradeani M, Celletti R, Bracchetti G. Biological integration of aesthetic restorations: factors influencing appearance and long-term success. Periodontology 2000 2001;27:29-44. 2. Goldberg PV, Higginbottom FI, Wilson TG Jr. Periodontal considerations in restorative and implant therapy. Periodontology 2000 2001;25:100-9. 3. Kois JC. The restorative-periodontal interface: biological parameters. Periodontology 2000 1996;11:29-38. 4. Ramfjord SP, Ash MM. Periodontal considerations in restorative and other aspects of dentistry - Periodontology and Periodontics: Modern Theory and Practice. 1st edition, Shiyako Euro America, Inc.: USA 1996:p.339-52. 5. Schmid MO. Preparation of the tooth surface. Clinical Periodontology, 8th edition, WB Saunders Co., Philadelphia 1996:p.486-92. 6. Valderhaug J. Periodontal conditions and carious lesions following the insertion of fixed prostheses: a 10-year follow-up study. Int Dent J 1980;30(4):296-304. 7. Valderhaug J. A 15-year clinical evaluation of fixed prosthodontics. Acta Odontol Scand 1991;49(1):35-40. 8. Valderhaug J, Birkeland JM. Periodontal conditions in patients 5 years following insertion of fixed prostheses. Pocket depth and loss of attachment. J Oral Rehabil 1976;3(3):237-43. 9. Valderhaug J, Heloe LA. Oral hygiene in a group of supervised patients with fixed prosthesis. J Periodontol 1977;48(4):221-4. 10. Bergman B, Hugoson H, Olsson CO. Periodontal and prosthetic conditions in patients treated with removable partial dentures and artificial crowns. A longitudinal two-year study. Acta Odontol Scand 1971;29(6):621â&#x20AC;&#x2018;38.

Dentistry 11. Reichen-Graden S, Lang NP. Periodontal and pulpal conditions of abutment teeth. Status after four to eight years following incorporation of fixed reconstructions. Schweiz Monatsschr Zahnmed 1989;99(12):1381-5. 12. Valderhaug J. Margin of restorations - from the viewpoint of crown and bridge making. Nor Tannlaegeforen Tid 1972;82(7):386-90. 13. Silness J. Periodontal conditions in patients treated with dental bridges. J Periodontal Res 1970;5(1):60-8. 14. Silness J. Periodontal conditions in patients treated with dental bridges. II. The influence of full and partial crowns on plaque accumulation, development of gingivitis and pocket formation. J Periodontal Res 1970;5(3):219-24. 15. Silness J. Periodontal conditions in patients treated with dental bridges. III. The relationship between the location of the crown margin and the periodontal condition. J Periodontal Res 1970;5(3):225-9. 16. Silness J, Ohm E. Periodontal conditions in patients treated with dental bridges. V. Effects of splinting adjacent abutment teeth. J Periodontal Res 1974;9(2):121-6. 17. Mormann W, Regolati B, Renggli H. Gingival reactions to well-fitted subgingival proximal gold inlays. J Clin Periodontol 1974;1(2):120-5. 18. Renggli HH. The effect of cervical subgingival restoration margins on the degree of inflammation of the neighboring gingiva (a clinical study). SSO Schweiz Monatsschr Zahnheilkd 1974;84(1):1-18. 19. Lang NP, Kaarup-Hansen D, Joss A, Siegrist B, Weber HP, Gerber C, et al. The significance of overhanging filling margins for the health status of interdental periodontal tissues of young adults. Schweiz Monatsschr Zahnmed 1988;98(7):725-30. 20. Chiche GJ, Pinault A. Esthetics of anterior fixed prosthodontics. Chicago: Quintessence Publishing, 1994: Chapter 7. 21. Maynard GJ, Wilson RD. Physiologic dimensions of the periodontium fundamental to successful restorative dentistry. J Periodontol 1979;50:107. 22. Newcomb GM. The relationship between the location of subgingival crown margins and gingival inflammation. J Periodontol 1974;45(3):151-4. 23. Orkin DA, Reddy J, Bradshaw D. The relationship of the position of crown margins to gingival health. J Prosthet Dent 1987;57(4):421-4. 24. Renggli HH, Regolati B. Gingival inflammation and plaque accumulation by well-adapted supragingival and subgingival proximal restorations. Helv Odontol Acta 1972;16(2):99-101. 25. Flores-de-Jacoby L, Zafiropoulas GG, Cianco S. The effect of crown margin location on plaque and periodontal health. Int J Periodontics Restorative Dent 1989;9(3): 197-205.

26. Silness J. Fixed prosthodontics and periodontal health. Dent Clin North Am 1980;24(2):317-29. 27. Shillingburg HT, Hobo S, Whitsett LD, Jacobi R. Fluid control and soft tissue management - fundaments of fixed prosthodontics. 3rd edition, Quintessence Publishing Co., Inc., Chicago 1997:p.257-80. 28. Ferrari M, Cagidiaco MC, Erocli C. Tissue management with a new gingival retraction material: a preliminary clinical report. J Prosthet Dent 1996;75(3):242-7. 29. Azzi R, Tsao TF, Carranza FA Jr, Kenney EB. Comparative study of the gingival retraction methods. J Prosthet Dent 1986;50(4):561-5. 30. Coelho DH, Cavoliaro J, Rothchild LA. Gingival recession with electrosurgery for impression making. J Prosthet Dent 1975;33(4):422-6. 31. Bradley PF. Tissue changes. In: Cryosurgery of the Maxillofacial Region: General Principles and Clinical Applications of Benign Lesions (Volume 1). Whittaker DK, CRC Press, Inc.: BocaRaton, Florida 1986:p.35-76. 32. Bader HI. Use of lasers in periodontics. Dent Clin North Am 2000;44(4):779-91. 33. Yuodelis RA, Faucher R. Provisional restorations: an integrated approach to periodontics and restorative dentistry. Dent Clin North Am 1980;24(2):285-303. 34. Yuodelis RA, Weaver JD, Sapko S. Facial and lingual contours of artificial complete crowns and their effects on the periodontium. J Prosthet Dent 1973;29(1):61-6. 35. Wheeler’s Dental Anatomy, Physiology and Occlusion. 7th edition, WB Saunders Co. 1993:p.102-27. 36. Podshadley AG. Gingival response to pontics. J Prosthet Dent 1968;19(1):51-7. 37. Spear FM, Cooney JP. Periodontal-Restorative Interrelationships. In: Carranza’s Clinical Periodontology. 9th edition, WB Saunders Co., Philadelphia 2003:p.949‑65. 38. Bral M. Periodontal considerations for provisional restoration. Dent Clin North Am 1989;33(3):457-75. 39. Adamczyk E, Speichowics E. Plaque accumulation on crowns made of various materials. Int J Prosthodont 1990;3(3):285-91. 40. Swartz ML, Phillips RW. Comparison of bacterial accumulation on rough and smooth surfaces. J Periodontol 1957;28:304-7. 41. Anvasavice KJ. Phillip’s science of Dental Materials. 11th edition, Saunders Publishing; 196-7. 42. Harrington GW. The Perio-endo question: differential diagnosis. Dent Clin N Am 1979;23(4):673-90. 43. Ammons WF, Harrington GW. Furcation: the problem and its management. In: Carranza’s Clinical Periodontology. 9th edition, WB Saunders Co.: Philadelphia 2003:p.825-31. 44. Malone WFP. Tylman’s Theory and Practice of Fixed Prosthodontics. 8th edition 1997:p.71-112.

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Dermatology

A Study of Beetle Dermatitis Asit Mittal*, Sharad Mehta**, Anubhav Garg**, Lalit Gupta*, CM Kuldeep†, Ashok Kumar Khare‡, Sarin Nistha¶

Abstract Background: Beetle dermatitis is a common condition seen in regions with warm and tropical climate. The condition causes significant morbidity and can be misdiagnosed. Aim: The study was conducted to know the clinical profile of beetle dermatitis and to increase awareness among nondermatologist physicians about this condition. Methods: All clinically diagnosed cases of beetle dermatitis were included in the study. Detailed history was taken and a thorough clinical examination was conducted in all the cases. Clinical photographs were taken in all the cases. Results: A total of 70 cases comprising of 46 males and 24 females were studied. The age of the patients ranged from 5 to 60 years. Majority of the cases presented during the post monsoon months (September-November), indicating a distinct seasonal trend. Morphology of lesions was mainly linear, but kissing and bizarre lesions were also observed. Head, neck and upper extremities were the most commonly involved sites. Fever and malaise was observed in a few cases. Conclusion: Beetle dermatitis should be included in differential diagnosis while examining erythematous vesicular lesions of sudden onset, especially on exposed parts during rainy and post rainy season. Awareness of this condition and its clinical features among the physicians will prevent misdiagnosis. Preventive measures can be undertaken based on the behavioral pattern of this beetle.

Keywords: Beetle dermatitis, kissing lesion

eetle dermatitis is a specific form of acute irritant contact dermatitis caused by a vesicant chemical present in the body fluid of the beetle belonging to the order coleopteron.1 The beetle does not bite or sting but accidental brushing against or crushing over the skin provokes the release of its coelomic fluid, which is a potent vesicant.1 The disease is characterized by sudden onset of erythematous, vesiculobullous lesions on the exposed body parts and associated with burning, stinging and itching.2 The dermatitis is most commonly seen in regions with warm tropical climate3 and is common in various parts of India, but may not be easily diagnosed by nondermatologists due to lack of awareness and familiarity about this condition. There have been reports of outbreak of beetle dermatitis from various

*Associate Professor **Assistant Professor †Professor ‡Professor and Head ¶Dept. of Dermatology, Venereology and Leprosy RNT Medical College, Udaipur, Rajasthan Address for correspondence Dr Asit Mittal Associate Professor, Dept. of Dermatology, Venereology and Leprosy, RNT Medical College, Udaipur, Rajasthan - 313 001 E-mail: asitmittal62@gmail.com

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regions of India.3,4 We undertook this study to know the various clinical patterns of beetle dermatitis and to raise the awareness about this entity among medical professionals. Material and Methods This study was carried out at the Dept. of Skin and VD, RNT Medical College and Associated Group of Hospitals, Udaipur, Rajasthan. A total of 70 cases of beetle dermatitis were seen over a period of three months from September to November. A detailed history was taken regarding age, sex, occupation, locality (rural or urban), duration, symptoms like itching, burning, pain, fever, malaise, living conditions, sleeping habits, history of exposure to insects, etc. A thorough clinical examination was done to record the sites, distribution, morphology of lesions, residual post inflammatory pigmentary changes and systemic features, if any. Clinical photographs of all cases were taken. Patients were treated according to severity of lesions. Mild cases were treated with topical corticosteroidantibiotic combination and oral antihistamines. For severe cases, oral corticosteroids were prescribed. Where secondary infection was seen, systemic antibiotics were also added.

Dermatology Results A total of 70 cases of beetle dermatitis were included in this study. Age of the patients ranged from 5 to 60 years. Out of 70 cases, 46 (65.71%) were males and rest 24 (34.29%) were females. Duration of lesions was less than one week in 60 (85.71%) patients. Maximum number of patients 55 (78.57%) had burning and itching at the site of lesion, while 15 (21.43%) cases were asymptomatic. Systemic features such as fever and malaise were observed in 10 (14.29%) cases. Face was the commonest site in 32 (45.71%) patients. Other sites of involvement were trunk, upper extremities and lower extremities (Table 1). Maximum number of patients 40 (57.14%) showed linear pattern (Table 2).

Figure 1. Kissing lesion over cubital fossa.

All cases responded well to therapy; however, residual hyperpigmentation and persistent exfoliation (Fig. 3), which were very distressing to the patient, were seen in a few cases. Discussion Beetle dermatitis is a distinctive seasonal vesicobullous skin disorder caused by three major families of blister beetles of the order coleoptera: Meloidae, edemeridae and staphylinidae. The vesicant chemical Table 1. Sites of Involvement of Beetle Dermatitis Sites of involvement

No. of cases

% (n = 70)

Face

45.71

Upper extremities

25.71

Trunk

14.29

Lower extremities

14.29

Total

100

Figure 2. Beetle dermatitis mimicking herpes zoster.

Table 2. Pattern of Lesions of Beetle Dermatitis Morphology of lesions

No. of cases

% (n = 70)

Linear

57.14

Kissing (Fig.1)

17.14

Bizarre

14.29

Herpetiform (Fig. 2)

11.43

Total

100

Figure 3. Persistent exfoliation.

in both meloidae and edemeridae is cantharidin, while it is pederin in the third family staphylinidae, which includes the genus Paederus.1 The genus paederus consists of more than 622 species, which are widely

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Dermatology distributed.2 Cantharidin dermatitis is characterized by noninflammatory vesicle and bullae whereas, Paederus dermatitis is characterized by vesicle and pustules arising from intensely inflamed skin.2 Blister beetle can fly but they prefer to run and live in moist habitats, and may appear in large numbers following heavy rains and hot weather.1 They are attracted to white light at night, a feature that commonly brings them into contact with humans. In our study, exposed body parts such as head, neck and upper extremities were most commonly affected. A similar observation was made in a study on 77 cases of beetle dermatitis in Punjab by Handa et al3 and in a study on 54 cases at Jodhpur by Kalla et al.4 Most common pattern of lesions seen in our study was linear. Similar pattern has been reported in other studies also.2-5 The lesions are commonly linear due to crushing and whipping an insect off the skin. Mirror image or ‘kissing lesions’ are seen in skin flexures where an insect has been inadvertently crushed with transfer of chemical to the opposing surface.5-7 Ocular involvement was seen in a few of our patients. It is usually secondary to transfer of toxic chemicals by fingers from elsewhere on skin. Ocular involvement as a relatively common finding was also reported by Zargari et al.2 We observed diffuse and persistent exfoliation (desquamative lesions) as an uncommon finding in a few of our patients. Such atypical variants of beetle dermatitis have been reported in other studies also.2,8 Clinically beetle dermatitis mimics many common skin conditions like herpes simplex, herpes zoster, thermal burns, bullous impetigo, phyto-photodermatitis and acute allergic or irritant contact dermatitis.2,6-9 Herpes zoster is particularly a condition often confused with beetle dermatitis on account of symptom of burning, pain and vesico-bullous lesions. Grouped vesicles and bullae strictly in a dermatomal pattern is characteristic of herpes zoster. The diagnosis of beetle dermatitis should be suspected by the sudden onset of linear and mirror image lesions, predominant involvement of exposed sites and seasonal incidence.

Conclusion Awareness about this condition amongst the medical practitioner will aid in early diagnosis and prompt treatment and prevent the sequelae of persistent hyperpigmentation, which can be particularly distressing in some patients. Therefore, an early diagnosis and treatment would prevent this complication. In addition awareness among the public at large may also help decrease the incidence of beetle dermatitis. The patients should also be counseled about the benign and self-limiting nature of the disease. Various preventive measures like changing the light source, using kerosene or petrol to kill the larva in stagnant water and spraying pesticides and insecticides particularly in breeding areas are often helpful.8 References 1. Nicholls DS, Christmas TI, Greig DE. Oedemerid blister beetle dermatosis: a review. J Am Acad Dermatol 1990;22 (5 Pt 1):815-9. 2. Zargari O, Kimyai-Asadi A, Fathalikhani F, Panahi M. Paederus dermatitis in northern Iran: a report of 156 cases. Int J Dermatol 2003;42(8):608-12. 3. Handa F, Sharma P, Gupta S. Beetle dermatitis in Punjab (a study of 77 cases). Indian J Dermatol Venereol Leprol 1985;51(4):208-12. 4. Kalla G, Batra A. Blister beetle dermatitis. Indian J Dermatol Venereol Leprol 1996;62(4):267-8. 5. Vegas FK, Yahr MG, Venezuela C. Paederus dermatitis. Arch Dermatol 1996;94:175-83. 6. Banney LA, Wood DJ, Francis GD. Whiplash rove beetle dermatitis in central Queensland. Australas J Dermatol 2000;41(3):162-7. 7. Kamaladasa SD, Perera WD, Weeratunge L. An outbreak of paederus dermatitis in a suburban hospital in Sri Lanka. Int J Dermatol 1997;36(1):34-6. 8. Singh G, Yousuf Ali S. Paederus dermatitis. Indian J Dermatol Venereol Leprol 2007;73(1):13-5. 9. Gnanaraj P, Venugopal V, Mozhi MK, Pandurangan CN. An outbreak of Paederus dermatitis in a suburban hospital in South India: a report of 123 cases and review of literature. J Am Acad Dermatol 2007;57(2):297-300.

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Umbrellas may Shield you from more than Rain: Study If it’s streaming sunshine outdoors and the sunscreen isn’t handy, an umbrella could help shield skin from ultraviolet (UV) rays, according to a new study by dermatologists at Emory University in Atlanta. They found that any fully-functioning handheld umbrella can block more than three-quarters of UV light on a sunny day. Black ones seem to do the job especially well, blocking at least 90% of rays. (Source: Medscape)

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Original Article diabetology

Study of Serum Magnesium and HbA1C in Diabetic Patients along with Changes in their Lipid Profiles Asha S Khubchandani*, Hiren Sanghani**

Abstract The aim of this study was evaluation and comparison of serum magnesium and glycosylated hemoglobin (HbA1C) level in patients of diabetes mellitus and normal healthy control along with changes in their lipid profile. A cross-sectional study was conducted in 75 subjects, 25 diabetics without complications (Group I), 25 diabetics with complications (Group II) and 25 normal healthy controls (Group III). Blood sugar levels, magnesium, HbA1C (%), cholesterol and triglyceride level were measured from plasma and serum. Serum magnesium levels were found low in Group II and Group I as compared to Group III. We found significant correlation between HbA1C and magnesium levels in our study. The results also indicate that the patients with diabetic complications have significant rise in serum cholesterol and triglycerides. Probably hypomagnesemia and increased serum cholesterol and triglyceride levels are responsible for micro- and macrovascular complications in diabetes. Thus, the purpose of this study was to gather information about the degree of control of diabetes and magnesium status.

Keywords: Hypomagnesemia, diabetes, complications

iabetes mellitus is a highly prevalent disease worldwide. Diabetes and its complications are a significant cause of mortality, morbidity and increased economical burden to countryâ&#x20AC;&#x2122;s health sector. At present in India, about 30 million people are suffering from diabetes. Many microelements have been evaluated as potential preventive and therapeutic measures in diabetes. Hypomagnesemia has long been associated with diabetes mellitus.1 Serum magnesium levels wide ranging impact on diabetic control and complications. Low level of serum magnesium has been reported in children with insulin-dependent diabetes.2,3 Historically, glycosylated hemoglobin (HbA1C) has been recommended only for the determination of glucose control among persons who are known diabetics. New clinical practice recommendations from the American Diabetes Association advocate the use of HbA1C in the diagnosis of diabetes, largely on the basis of the established association between HbA1C and microvascular disease.4 In type 2 diabetes mellitus, lipid

*Associate Professor **2nd Year Resident Dept. of Biochemistry, BJ Medical College, Ahmedabad Address for correspondence Dr Asha S Khubchandani Associate Professor Dept. of Biochemistry BJ Medical College, Civil Hospital, Ahmedabad, Gujarat E-mail: ashakhub@yahoo.com

abnormalities are almost the rule. Typical findings are elevated total cholesterol, very low-density lipoprotein (VLDL) cholesterol and triglyceride concentration. Triglyceridemia has been associated with increased risk of coronary heart disease in diabetic patients.5 Material and Methods The study was conducted in BJ Medical College and Civil Hospital, Ahmedabad with 75 subjects (50 patients with diabetes and 25 normal healthy controls) during February to July 2011. Fifty diabetic patients, who were attending the diabetic clinic, with history of diabetes for 14-20 years were included in study. They were screened for the presence of micro- or macrovascular complications like, retinopathy, peripheral vascular disease and coronary heart disease. On the basis of screening, 50 patients were divided into two groups: Group I (25 diabetic patients without complications) and Group II (25 patients with micro- or macrovascular complications). Group III include the normal healthy controls matched by age and gender with the patient groups. All the 75 subjects were in the age group of 45-60 years. Those who were hypertensive, chronic alcoholics, had adverse renal function or were taking diuretics were excluded from the study. Fasting plasma and serum sample of each subject were collected and serum magnesium, HbA1C and their lipid profiles were measured. Serum magnesium

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diabetology was measured by Calmagite endpoint method.6,7 Serum cholesterol was estimated by cholesterol oxidase method and serum triglyceride by glycerol peroxidase method on Erba XL640 Auto Analyzer. HbA1C estimation was done by ion exchange resin method.8 Statistical analysis was done by using ‘t’ test. Results and Observations The average serum magnesium level were measured as 1.94 ± 0.26, 1.32 ± 0.28 and 2.47 ± 0.24 in Group I, Group II and Group III, respectively (Table 1). Diabetic patients in Group I and Group II showed hypomagnesemia. Patients in Group II showed more hypomagnesemia as compared to Group I. The average HbA1C (%) values were measured as 7.80 ± 0.65, 10.60 ± 1.0 and 4.99 ± 0.43 in Group I, Group II and Group III, respectively (Table 2). The HbA1C (%) values were found to be significantly higher. And the values of HbA1C (%) were positively correlated with blood glucose level. The average serum cholesterol levels were measured as 216.88 ± 16.90, 270.92 ± 14.28 and 164.16 ± 15.58 in Group I, Group II and Group III, respectively. The serum cholesterol values were significantly higher in Group II (p < 0.001) and Group I (p < 0.01) as compared to Group III. The average serum triglyceride levels were 152.08 ± 8.93, 177.44 ± 13.47 and 119.96 ± 10.19 in Group I, Group II and Group III, respectively. The serum triglyceride values were significantly higher in Group II (p < 0.001) and Group I (p < 0.01) as compared to Group III.

Discussion Magnesium, the second most common intracellular cation, plays a fundamental role as a cofactor in various enzymatic reactions involving energy metabolism. It is also involved at multiple levels in insulin secretion, binding and activity. Cellular magnesium deficiency can alter the activity of membrane bound sodiumpotassium ATPase9 which is involved in maintenance of gradients of sodium, potassium and in glucose transport. The almost universal involvement of magnesium in a wide variety of cellular processes critical to glucose metabolism, insulin action and cardiovascular functions has been well-appreciated. The incidence of subclinical magnesium deficiency is common in diabetes and cardiovascular disorders. Our observations revealed a definite lowering of serum magnesium in diabetic patients, especially in patients who had complication. These observations correlate well with previous studies.10 Consequently, we suggest hypomagnesemia as a possible risk factor in development and progress of diabetic complications. Exact cause of diabetic hypomagnesemia is still unknown but an increased urinary loss of magnesium may contribute to it.11,12 HbA1C is formed through the nonenzymatic binding of circulating glucose to hemoglobin. Higher levels of glucose in the blood contribute to more binding and consequent higher levels of HbA1C. HbA1C reflects average plasma glucose over the previous 8-10 weeks. HbA1C levels measured in 60 diabetic patients were found higher than in normal healthy controls. Also, it was higher in diabetics with complications than those without any complications.13

Table 1. Showing Mean ± SD of Serum Magnesium, Cholesterol and Triglyceride in Different Groups Group

Magnesium (mg%)

Cholesterol (mg%)

Triglyceride (mg%)

I (Diabetes without complication)

1.94 ± 0.26

216.88 ± 16.90

152.08 ± 8.93

II (Diabetes with complication)

1.32 ± 0.28

270.92 ± 14.28

177.44 ± 13.47

III (Normal healthy control)

2.47 ± 0.24

164.16 ± 15.58

119.96 ± 10.19

Group I versus Group III, p < 0.01 and Group II versus Group III, p < 0.001

Table 2. Showing Mean ± SD of HbA1C and Blood Glucose in Different Groups Group

FBS (mg %)

PPBS (mg %)

HbA1C (%)

I (Diabetes without complication)

172.00 ± 15.96

204.80 ± 10.67

7.80 ± 0.65

II (Diabetes with complication)

235.44 ± 18.04

268.48 ± 15.62

10.60 ± 1.0

III (Normal healthy control)

93.80 ± 10.94

132.20 ± 9.57

4.99 ± 0.43

Group I versus Group III, p < 0.01 and Group II versus Group III, p < 0.001

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diabetology Study results also shows positive correlation of HbA1C with fasting blood glucose level as reported in earlier studies.14 Previous studies showed that higher level of HbA1C increases risk for development of microangiopathy15 and macroangiopathy16 in diabetics. Measurement of HbA1C is not only useful for monitoring of diabetic patients but also provides a conceptual framework for the pathogenesis of secondary sequelae of diabetes. The patients with diabetes have a higher degree of atherosclerosis burden due to dyslipidemia than people without diabetes.17 Statistical correlation was found between HbA1C and serum cholesterol and triglycerides during our study. Diabetic patients showed higher level of serum cholesterol and triglycerides as compared to healthy controls. Dietary supplementation with magnesium in addition to classical therapies for diabetes may help in prevention or delaying of diabetic complication. Some studies have documented that oral magnesium supplementation improves insulin sensitivity and metabolic control in type 2 diabetics with lower serum magnesium levels.18 It has also been shown that it has beneficial effect on lipid profile of diabetic patients. References 1. Mather HM, Nisbet JA, Burton GH, Poston GJ, Bland JM, Bailey PA, et al. Hypomagnesaemia in diabetes. Clin Chem Acta 1979;95(2):235-42. 2. Fort P, Lifshitz F. Magnesium status in children with insulin-dependent diabetes mellitus. J Am Coll Nutr 1986;5(1):69-78.

bound ‘calmagite’ of magnesium is human blood serum. Clin Chem 1971;17:662. 7. Tietz NW. Textbook of Clinical Chemistry. 3rd edition, Burtis CA, Ashwood ER (Eds.), WB Saunders 1999:p. 1034-36, et. 1408-10. 8. Trivelli LA, Ranney HM, Lai HT. Hemoglobin components in patients with diabetes mellitus. New Engl J Med 1971;284(7):353-7. 9. Peterson CM, Jones RL. Minor hemoglobin, diabetic “control” and diseases of postsynthetic modification. Ann Intern Med 1977;87(4):489-91. 10. Ishrat K, Jaweed S, Bardapurkar J, Patil V. Study of Mg, glycosylated Hb and lipid profile in diabetic retinopathy. Indian J Clin Bio 2004;19(2)124-7. 11. Linderman RD, Adler S, Yeingst MJ, Beard ES. Influence of various nutrients on urinary divalent cation excretion. J Lab Clin Med 1967;70(2):236-45. 12. Lennon EJ, Lemann J Jr, Piering WF, Larson LS. The effect of glucose on urinary cation excretion during chronic extracellular volume expansion in normal man. J Clin Invest 1974;53(5):1424-33. 13. Gonen B, Rubenstein A, Rochman H, Tanega SP, Horwitz DL. Haemglobin A1: An indicator of the metabolic control of diabetic patients. Lancet 1977;2:734-7. 14. Davis RE, Nicol DJ, McCann VJ, Calder JS. Glycosylated hemoglobin levels in patients with diabetes. J Lab Clin Med 1978;70:236-45. 15. Rohlfing CL, Little RR, Wiedmeyor HM, England JD, Madsen R, Harris MI, et al. Use of GHb (HbA1C) in screening for undiagnosed diabetes in the U.S. population. Diabetes Care 2000;23(2):187-91.

3. Ewald U, Gebre-Medhin M, Turemo T. Hypomagnesemia in diabetic children. Acta Paediatr Scand 1983;72(3): 367-71.

16. Khaw KT, Wareham N, Luben R, Bingham S, Oakes S, Welch A, et al. Glycated haemoglobin, diabetes, and mortality in men in Norfolk cohort of European prospective investigation of cancer and nutrition (EPICNorfolk). Bmj 2001;322(7277):15-8.

4. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2010; 33 Suppl 1:S62-9.

17. Mohsin R, Badar B, Saeed A, Rehman A. Type 2 diabetes: the relationship between the serum cholesterol and triglycerides. Professional M Ed J 2007;14:337-43.

5. Hu FB, Stamfer MJ, Haffner SM, Solomon CG, Willett WC, Manson JE. Elevated risk of cardiovascular disease prior to clinical diagnosis of type 2 diabetes. Diabetes Care 2002;25(7):1129-34. 6. Glindler EM, Hetti DA. Colorimetric determination with

18. Rodriguez-Moran M, Guerrero-Romero F. Oral magnesium supplementation improves insulin sensitivity and metabolic control in type 2 diabetic subject: a randomized double-blind controlled trial. Diabetes Care 2003;(4):1147-52.

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Weight Gain in Smokers who Quit is OK for the Heart Weight gained after someone quits smoking has no effect on the cardiovascular benefits of butting out, at least among people without diabetes, researchers reported. (Source: Medpage Today)

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Drugs and devices

Efficacy and Tolerability of Meroplan S (Meropenem 1 g and Sulbactam 0.5 g) (ETIOS) in the Management of Lower Respiratory Tract Infections caused by Gram-negative Pathogens in Adults: A Post Marketing Observational Study Lisa Braganza*, Prashant Khandeparkar**, Qayum Mukkadum†

Abstract Background: The rapid and ongoing spread of antimicrobial-resistant bacteria throughout all healthcare institutions is considered a critical medical and public health issue. Gram-negative bacteria are resistant to multiple drugs and are increasingly resistant to most available antibiotics. Given the high mortality rates caused by drug-resistant Gram-negative bacteria such as Klebsiella, Acinetobacter, Pseudomonas aeruginosa and Escherichia coli and the difficulty of developing new potent antibiotics to target the problematic pathogens, combination regimens are under ardent evaluation as new strategies to overcome increasing drug resistance. Carbapenems such as meropenem have assumed an important antibiotic niche for therapy of various multidrugresistant Gram-negative infections with good safety profile. However, the percentage of carbapenem-resistant enterobacteriaceae (CRE) increased by 4-fold over the last decade and that one particular form of CRE, a resistant form of Klebsiella pneumoniae, has increased 7-fold. Extended-release beta-lactamases (ESBL) production is one of the main bacterial resistance mechanisms to carbapenem antibiotics. The use of ESBL inhibitors like sulbactam combined with carbapenem antibiotics allows the inactivation of ESBLs produced by Gram-negative pathogens. Additionally, sulbactam has an intrinsic antimicrobial activity against penicillin binding proteins. By restoring or expanding the activity of meropenem, the combination with sulbactam offers a new approach to the management of lower respiratory tract infections caused by Gram-negative pathogens. A post marketing observational study was undertaken to evaluate the efficacy and tolerability of (Meropenem 1 g and Sulbactam 0.5 g) injection in the management of lower respiratory tract infections caused by Gram-negative pathogens in adults.

Keywords: Meropenem, sulbactam, post marketing observational study, lower respiratory tract infections, Gramnegative pathogens

OBJECTIVE To evaluate the efficacy and tolerability of (Meropenem 1 g and Sulbactam 0.5 g) injection in the management of lower respiratory tract infections caused by Gramnegative pathogens in adults. STUDY DESIGN Post marketing observational study.

ELIGIBILITY

Inclusion Criteria ÂÂ

Adults >18 years of age suffering from signs and symptoms of lower respiratory infections caused by Gram-negative bacteria.

ÂÂ

Willingness to follow-up.

Exclusion Criteria

METHODS

ÂÂ

Inability to follow-up

Sample

ÂÂ

Pregnant women or nursing mothers

ÂÂ

Diabetics, hypertensives and patients with other coexisting serious/life-threatening medical conditions.

Duration of the study: 7 days

ÂÂ

*Medical Advisor, Abbott Truecare **Chief Manager Medical Services, Abbott Healthcare †Director, Abbott Healthcare

Patients with any other clinically significant disorder, which needed treatment or serious systemic illness.

ÂÂ

Known hypersensitivity sulbactam.

No. of patients: 32 No of doctors: 12

meropenem

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and

721

Drugs and devices STUDY ASSESSMENTS

Concomitant Medication

History

The patients were permitted to take concomitant medications (e.g. paracetamol) as felt necessary by the doctor. The dose and frequency of these concomitant medications were noted at each follow-up visit.

After careful history and examination, patients were included in this post marketing study at Visit 0 (Day 0). The type of lower respiratory tract infection was noted (e.g., pneumonia, acute exacerabation of chronic bronchitis [AECB], etc.).

Efficacy Parameter Evaluation Symptoms and signs like fever, cough, dyspnea, wheezing, rhonchi, sore throat or any other were noted on a 4 point scale: 0 = Absent; 1 = Mild; 2 = Moderate and 3 = Severe. Body temperature (fever) was recorded as actual reading.

Tolerability Parameters Evaluation The side effects if any, were noted at each followup visit on a 4 point scale: 0 = Absent; 1 = Mild; 2 = Moderate and 3 = Severe.

Global Assessment for Efficacy by Doctor and Patient At the end of the study i.e. seven days the global assessment for efficacy was done by both doctor and patient and was graded as: 4 = Excellent, 3 = Good, 2 = Fair and 1 = Poor.

Global Assessment for Tolerability by Doctor and Patient At the end of the study i.e. 7 days the global assessment for tolerability was done by both doctor and patient and was graded as good, moderate and poor.

Compliance Compliance is a very important aspect of treatment. Compliance was judged by open questioning, criteria being if > 80% of drug was consumed, it was considered to be compliant.

Dosage and Administration The patient were prescribed a fixed-dose combination (FDC) of Meropenem 1 g + Sulbactam 0.5 g for injection, which was given as an IV bolus injection over approximately five minutes, or by IV infusion over approximately 15-30 minutes, using the specific available diluents, every eight hours. The duration of treatment depended on the severity of illness.

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STATISTICAL ANALYSIS The evaluable study population was the intention-totreat (ITT) population. The ITT population included all patients who had taken at least one dose of study medication. This population was used for the analysis of the primary efficacy endpoint and safety evaluation.

Descriptive Analysis Data describing categories or nominal data were expressed as numbers with percentages.

Tests of Significance Paired t-test statistical analysis was performed to assess the statistical significance of the difference between the baseline and follow-up visits for measurement data. For ranking data, Wilcoxon test was used. A p value <0.05 was considered statistically significant. OBSERVATIONS and RESULTS Total data available:

Data not analyzed:

Data used for analysis: 32

Demography (n = 32) The demographic details of the subjects are given in Table 1 and Figure 1.

Diagnosis and Baseline Data (n = 32) The diagnosis and baseline data of patients enrolled in the study is given in Table 2 and Figure 2. Table 1. Demography of Patients Enrolled (n = 32) No.

Male

75.00

Female

25.00

Mean

51.26

15.77

Gender

Age (years)

Drugs and devices Table 3. Concomitant Medication Received by Patients

Gender distribution (%, n = 32)

No. of Pts.

% of Pts.

Reason for use

Linezolid

21.88

Infection/Sepsis

Levofloxacin

15.63

Infection/Sepsis

Paracetamol

12.50

Fever

Amikacin

9.38

Infection/Sepsis

Meropenem

9.38

Infection/Sepsis

Insulin

6.25

Diabetes

Moxifloxacin

6.25

Infection/Sepsis

Pantoprazole

6.25

Stress ulcer

Teicoplanin

6.25

Infection/Sepsis

Albumin

3.13

Protein supplementation

Amoxycillin

3.13

Infection/Sepsis

Female, 8 (25.00%)

Male, 24 (75.00%)

Figure 1. Gender distribution of the patients enrolled (%, n = 32).

Table 2. Diagnosis and Baseline Data of Patients Enrolled (n = 32) No.

Pneumonia

59.38

Azithromycin

3.13

Infection/Sepsis

Bronchitis

6.25

Bronchodilators

3.13

AECB*

9.38

Respiratory symptoms

Others

25.00

Clindamycin

3.13

Infection/Sepsis

Mean

Colistin

3.13

Infection

Diagnosis

Parameter Cough score

2.25

0.89

Dalteparin sodium

3.13

DVT prophylaxis

102.13

1.09

Dyspnea score

2.18

1.02

Methyl prednisolone

3.13

Infection

Wheezing score

2.04

1.17

Metronidazole

3.13

Infection/Sepsis

Ronchi score

1.78

1.25

Pazufloxacin

3.13

Infection/Sepsis

Others

6.25

Body temperature (ยบF)

*AECB: Acute exacerbation of chronic bronchitis

Patients Presenting with Symptoms

Diagnosis of patients (%, n = 32)

The patients presenting with symptoms at baseline, Day 1, Day 3 and Day 7 are given in Table 4.

Others, 8 (25.00%)

MEAN SYMPTOM SCORES AT BASELINE AND DURING STUDY PERIOD

AECB, 3

Pneumonia,

(9.38%)

19 (59.38%)

Bronchitis 2 (6.25%) Figure 2. Diagnosis of the patients enrolled (%, n = 32).

Concomitant Medication Received by Patients The list of concomitant medication received by patients and reasons for their use are given in Table 3.

Cough The mean scores for cough and change from baseline during study period are given in Table 5. The mean scores for cough and percentage change in cough scores from baseline during study period are shown in Figures 3 and 4. It as seen that there was 11.11%, 38.70% and 82.22% improvement in symptom score at Day 1, Day 3 and Day 7, respectively.

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Drugs and devices Table 4. Patients Presenting with Symptoms Baseline No.

Day 1 %

No.

Day 3 %

Day 7

No.

Cough

96.88

78.13

71.88

15.63

Fever

100.00

96.88

43.75

9.38

Dyspnea

90.63

81.25

59.38

31.25

Wheezing

84.38

68.75

59.38

31.25

Ronchi

78.13

62.50

50.00

25.00

Table 5. Mean Score for Cough and Change from Baseline during the Study Period Mean

Mean ch.

% ch.

Baseline

2.25

0.89

Day 1

2.00

1.05

-0.25

-11.11

Day 3

1.38

0.90

-0.87

-38.70

Day 7

0.40

0.65

-1.85

-82.22

Mean score for cough

3.5

Body Temperature The mean body temperature and change from baseline during study period is given in Table 6. The mean body temperature and percentage change in body temperature from baseline during study period are shown in Figures 5 and 6. It as seen that there was 0.71%, 2.38% and 3.50% improvement in body temperature at Day 1, Day 3 and Day 7, respectively. Table 6. Mean Body Temperature (ยบF) and Change from Baseline during the Study Period

3.0 2.5

2.25 2.00

2.0

1.38

1.5 1.0 0.5

0.40

Mean

Mean ch.

% ch.

Baseline

102.13

1.09

Day 1

101.40

1.24

-0.73

-0.71

Day 3

99.70

1.93

-2.43

-2.38

Day 7

98.55

0.54

-3.57

-3.50

0.0 -0.5

Baseline

Day 1

Day 3

Day 7

Figure 3. Mean scores for cough. % change in cough score from baseline 0 -20 -40

Day 1

Day 3

Day 7

-11.11 -38.70

-60 -80 -100

-82.22

Figure 4. Change from baseline in mean cough score.

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Mean body temperarure (ยบF) 104 103 102 101 100 99 98 97 96 95

102.13 101.40 99.70 98.55

Baseline

Day 1

Figure 5. Mean body temperature.

Day 3

Day 7

Drugs and devices % change in dyspnea score from baseline

% change in body temparature from baseline Day 1

0 -1

Day 3

Day 7

Day 1

Day 3

Day 7

-20

-0.71

-23.50

-40

-2 -2.38

-3

-46.45

-60 -80

-3.50

-4

-81.97

-100

-5 Figure 6. Change from baseline in mean body temperature.

Figure 8. Change from baseline in mean dyspnea score.

Dyspnea

Wheezing

The mean scores for dyspnea and change from baseline during study period are given in Table 7. The mean scores for dyspnea and percentage change in mean dyspnoea score from baseline during study period are shown in Figures 7 and 8. It as seen that there was 23.50%, 46.45% and 81.97% improvement in symptom score at Day 1, Day 3 and Day 7, respectively.

The mean scores for wheezing and change from baseline during study period are given in Table 8. The mean scores for wheezing and percentage change in mean wheezing score from baseline during study period are shown in Figures 9 and 10. It as seen that there was 21.05%, 43.86% and 81.11% improvement in symptom score at Day 1, Day 3 and Day 7, respectively.

Table 7. Mean Score for Dyspnea and Change from Baseline during the Study Period Mean

Mean ch.

% ch.

Baseline

2.18

1.02

Day 1

1.67

1.03

-0.51

Day 3

1.17

1.02

Day 7

0.39

0.57

3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 -0.5

Table 8. Mean Score for Wheezing and Change from Baseline during the Study Period Mean

Mean ch.

% ch.

Baseline

2.04

1.17

-23.50

Day 1

1.61

1.13

-0.43

-21.05

-1.01

-46.45

Day 3

1.14

0.93

-0.89

-43.86

-1.79

â&#x20AC;&#x201C;81.97

Day 7

0.38

0.50

-1.65

-81.11

Mean score for dyspnea

Mean score for wheezing

3.5 3.0 2.5

2.18

2.0

1.67 1.17

2.04 1.61

1.5 0.39

1.14

1.0 0.5

0.38

0.0 Baseline

Day 1

Figure 7. Mean scores for dyspnea.

Day 3

Day 7

-0.5

Baseline

Day 1

Day 3

Day 7

Figure 9. Mean scores for wheezing.

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Drugs and devices % change in wheezing score from baseline Day 1

0 -20

Day 3

% change in rhonchi score from baseline

Day 7

Day 1

0 -20

-21.05

-40

Day 3

Day 7

-12.50

-40 -43.86

-60

-47.92

-60

-80

-81.11

-100

-80.53

-100

Figure 10. Change from baseline in mean wheezing score.

Figure 12. Change from baseline in mean ronchi score.

Rhonchi

Global Efficacy (n = 32)

The mean scores for rhonchi and change from baseline during study period are given in Table 9. The mean scores for rhonchi and percentage change in mean rhonchi score from baseline during study period are shown in Figures 11 and 12. It as seen that there was 12.5%, 47.52% and 80.53% improvement in symptom score at Day 1, Day 3 and Day 7, respectively.

At the end of the study i.e., seven days the global assessment for efficacy was done by both doctor and the patient. Sixteen patients (50%) found the treatment excellent, 10 (31.25%) found it moderate, 5 (15.63%) found it good and 1 (3.13%) found it fair. Seventeen doctors (53.13%) found the treatment excellent, 11 (34.38%) found it moderate and 4 (12.50%) found it good (Table 10 and Fig. 13).

Table 9. Mean Score for Rhonchi and Change from Baseline during the Study Period Mean

Mean ch.

% ch.

Baseline

1.78

1.25

Day 1

1.56

1.19

-0.22

-12.50

Day 3

0.93

0.92

-0.85

-47.92

Day 7

0.35

0.56

-1.43

-80.53

1.5 0.5

0.35

0.0 Baseline

Day 1

Day 3

Day 7

Figure 11. Mean scores for rhonchi.

726

3.13

0.00

15.63

12.50

Moderate

31. 25

34.38

Excellent

50.00

53.13

0.93

Indian Journal of Clinical Practice, Vol. 23, No. 11, April 2013

1.56

1.0

No.

Good

Global efficacy (% of patients, n = 32) 50.00

31.25

20 1.78

By Doctor

Fair

2.5

-0.5

By Patient No.

3.0 2.0

Scale

Mean score for rhonchi

3.5

Table 10. Global Efficacy Assessment (n = 32)

15.63

53.13

34.38

12.50

3.13 0.00

Fair

Good

Moderate

Excellent

Figure 13. Global efficacy assessment (% of patients, n = 32).

Global Tolerability (n = 28) At the end of the study i.e, seven days the global assessment for tolerability was done by both doctor

Drugs and devices and patient and was graded as good, moderate and poor. Fourteen patients (50%) reported excellent tolerability, 2 (7.14%) reported moderate tolerability and 12 (42.86%) reported good tolerability. Fourteen doctors (50%) reported excellent tolerability, 3 (10.71%) reported moderate tolerability and 11 (39.29%) reported good tolerability (Table 11 and Fig. 14). Table 11. Global Tolerability Assessment (n = 28) Scale

By Patient

By Doctor

No.

idiosyncracy. Overall adverse events were observed in 7 (21.88) patients (Table 12). Table 12. Adverse Effects Reported (n = 32) Adverse event

No.

GI disturbances

18.75

Mild (3), moderate (3)

Diarrhea

12.50

Mild (2), moderate (1)

Allergy

6.25

Mild (1), moderate (1)

Headache

3.13

Mild (1)

Idiosyncracy

3.13

Moderate (1)

Good

42.86

39.29

Total patients

Moderate

7.14

10.71

Day 1

21.88

Excellent

50.00

Day 3

12.50

Day 7

9.38

Overall

21.88

60 50 40

Global tolerability (% of pts., n = 28) 50.00 42.86

50.00

CONCLUSION

39.29

30 20 7.14

10 0

Good

10.71

Moderate

Severity

Excellent

Figure 14. Global tolerability assessment (% of patients, n = 28).

Adverse Effects Reported (n = 32) The adverse effects observed were generally mildto-moderate and included gastrointestinal (GI) disturbances, diarrhea, allergy, headache and

It was concluded that the FDC of (Meropenem 1 g and Sulbactam 0.5 g) injection has excellent efficacy, and good tolerability in the management lower respiratory tract infections caused by Gram-negative pathogens in adults. Also, the adverse effects observed were generally mild-to-moderate and included GI disturbances, diarrhea, allergy, headache and idiosyncracy.

Acknowledgment We would like to thanks the doctors who participated in the study: Dr Abhijit Pureholi, Dr BS Gaba, Dr Bharat Mehrotra, Dr Gurpreet Singh, Dr NP Singh, Dr Pradeep Jain, Dr Ram Babu, Dr Sanjay Kucheria, Dr Deepak Alviya, Dr Arshad Ahmed, Dr GC Singhal and Dr JS Khushwah.

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ENT

Basaloid Carcinoma: An Unusual Presentation Sanjana V Nemade*, VV Rokade**

Abstract Basaloid squamous cell carcinoma (BSCC), an uncommon tumor, is a distinct variant of squamous cell carcinoma because of its unique histological features and highly aggressive malignant behavior. We report a case of pedunculated, nonaggressive basaloid cell carcinoma of the posterior pharyngeal wall in a middle-aged female treated successfully with wide local excision and postoperative radiotherapy.

Keywords: Pedunculated basaloid carcinoma, nonaggressive, squamous cell carcinoma

asaloid squamous cell carcinoma (BSCC) is a high grade, aggressive variant of squamous cell carcinoma (SCC) with predilection for base of tongue, floor of mouth, larynx and tonsils. It appears biologically virulent, with a propensity to aggressive local behavior, early nodal and distant metastasis and subsequent poor survival. To the authorsâ&#x20AC;&#x2122; knowledge, pedunculated, nonaggressive basaloid cell carcinoma of the posterior pharyngeal wall without nodal and distant metastasis in middle-aged women has rarely been reported. Accurate diagnosis and appropriate treatment with surgery followed by radiotherapy gave a very good prognosis in this patient.

Case Report A 56-year-old female presented in the Dept. of ENT OPD with complaints of dysphagia to solid food since six months. There was no history of weight loss, change in voice or dyspnea or any abuse of tobacco or alcohol. No other significant history was noted.

was normal. All routine investigations were within normal limits. Computerized tomography (CT) showed a 1.5 x 1.8 cm moderately enhancing soft tissue lesion in posterior pharyngeal wall at the level of vallecula. There was no evidence of lymphadenopathy (Fig. 1). Patient was posted for excision of the mass under general anesthesia. Boyle Davis mouth gag was applied. Wide elliptical incision was taken around the pedicle of the mass and the mass was excised in toto (Fig. 2). The base was cauterized. The mass was sent for histopathological examination. Postoperative period was uneventful. Histopathological examination revealed a neoplastic infiltrate, predominantly pleomorphic, basaloid appearing cells with hyperchromatic nuclei and a variable amount of eosinophilic to clear-appearing

Routine throat examination was normal. On indirect laryngoscopy, a red, irregular, pedunculated mass 2 x 1 cm, was seen on the posterior pharyngeal wall at the level of vallecula. Rest of the ENT and neck examination

*Assistant Professor **Associate Professor and Head Dept. of ENT, Smt Kashibai Navale Medical College and General Hospital Ambegaon, Narhe, Pune Address for correspondence Dr Sanjana V Nemade C/o: R Manjarekar B-6/97, Shrikrishna Clinic, Vitthal Rakhumai Society Apte Colony, Sinhgad Road, Hingane Khurd, Pune - 411 051 E-mail: drsanjana31@yahoo.in

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Indian Journal of Clinical Practice, Vol. 23, No. 11 April 2013

Figure 1. CT scan showing moderately enhancing posterior pharyngeal wall at the level of vallecula.

ENT is frequently confused with adenoid cystic carcinoma histopathologically. The presence of lobules or cords of small, closely packed basaloid cells with scanty cytoplasm, with or without small cystic spaces and hyalinized stroma, as well as an associated abnormal squamous cell component differentiates this tumor from adenoid cystic carcinoma.6

Figure 2. Showing mass excised in toto.

cytoplasm. Tumor cells showed biphasic pattern with comedo type necrosis. Squamous differentiation was seen in focal areas. These features were suggestive of basaloid variant of SCC. After confirmation of diagnosis, CT brain and abdomen was done to rule out distant metastasis and it was normal. We referred the patient for radiotherapy after six weeks. Patient is on regular follow-up and without clinical or radiological evidence of recurrence for two years. Discussion Basaloid squamous cell carcinoma (BSCC), first described in 1986 by Wain et al for the head and neck region is a rare distinct variant of SCC. It shows predilection for upper aerodigestive tract especially base or tongue, floor of mouth, larynx and tonsils.1,2 It is known for its highly aggressive malignant behavior with early nodal (64%) and distant metastases (44%).3,4 Results of a case-control study by Soriano et al found a six times higher risk of distant metastasis compared to usual type of SCC.5 Absence of cervical metastasis cannot be considered as favorable prognostic sign as the tumor might have already spread to distant sites like liver, lungs, brain and skin. Hence, extensive workup in the form of whole body CT scan is mandatory in all cases of BSCC.2 By the time they are evaluated, most of the patients are in Stage III or IV. Our patient was in Stage I with no evidence of nodal or distant metastasis. Histological characteristics of BSCC have been described by Wain in 1986, and included in WHO classification in 2005. Prior to this, these cases were classified as adenoid cystic carcinoma, small cell undifferentiated carcinoma and poorly differentiated SCC and were treated on a case-to-case basis.4 BSCC

BSCC is usually seen in males after 60 years of age. In a series of cases reported by Ferlito et al, the average age of patients at their initial evaluation was 63.33 years.7 At 45 years of age, our patient was relatively young. It is usually seen in patients who have history or abuse of tobacco and heavy consumption of alcohol.8,9 Our patient had no history of abuse of tobacco or alcohol. Some reported cases of BSCC were associated with a second primary tumor,10 and rarely with previous irradiation.11 It is usually pedunculated and has benign papilloma-like appearance. The relationship of this tumor with viral agents, Epstein-Barr virus in BSCC of the nasopharynx,12 human papillomavirus in BSCC of external genitalia and anus13 has also been suggested by some authors. Treatment consists of surgery followed by radiotherapy as this tumor is more radiosensitive as compared to SCC. Chemotherapy might have role in patients with distant metastasis.2 BSCC is associated with poor outcome. The overall 3-year survival rate of BSCC has been estimated as 28.5%.14 Thus, our case is exclusive because of BSCC occurring in middle-aged female without history of abuse of tobacco, alcohol and without distant metastasis giving a very good prognosis. Our patient had no evidence of recurrence clinically or radiologically for two years after surgery. Conclusion The exact line of differentiation or pathogenesis of BSCC is still unknown. We strongly believe that every pedunculated papilloma-like mass of the upper aerodigestive tract should be considered to be BSCC unless proved otherwise and should be investigated for nodal and distant metastases. Surgery followed by radiotherapy is the standard line of treatment, however, close follow-up is mandatory. CT is recommended at baseline and every six months during follow-up. It is important for the otolaryngologist to be aware of this benign looking malignant tumor to improve the prognosis by accurate diagnosis and appropriate treatment.

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ENT References 1. Sah K, Kale A, Hallikerimath S. Basaloid squamous cell carcinoma involving floor of mouth. J Oral Maxillofac Pathol 2008;12(2):61-3. 2. Prasad KC, Kaniyur V, Devan PP, Kedakalathil J. Basaloid squamous cell carcinoma of larynx: report of a case. Ear Nose Throat J 2002;81(4):254-5. 3. Vasudev P, Boutross-Tadross O, Radhi J. Basaloid squamous cell carcinoma: two case reports. Cases J 2009;2:9351. 4. Thariat J, Badoual C, Faure C, de Mones E, Bucori C, Santini J, et al. Basaloid squamous cell carcinoma of head and neck. Bull Cancer 2009;96(10):989-1004. 5. Soriano E, Faure C, Lantuejoul S, Reyt E, Bolla M, Brombilla E, et al. Course and prognosis of basaloid squamous cell carcinoma of the head and neck: a case-control study of 62 patients. Eur J Cancer 2008;44(2):244-50. 6. Zhang XH, Sun GQ, Zhou XJ, Guo HF, Zhang TH. Basaloid squamous cell carcinoma of esophagus: a clinicopathological, immunohistochemical and electron microscopic study of sixteen cases. World J Gastroenterol 1998;4(5):397-403. 7. Ferlito A, Altavilla G, Rinaldo A, Doglioni C. Basaloid squamous cell carcinoma of larynx and hypopharynx. Ann Otol Rhinol Laryngol 1997;106(12):1024-35.

8. Coppola D, Catalano E, Tang CK. Elfenbein IB, Harwick R, Mohr R. Basaloid squamous cell carcinoma of floor of mouth. Cancer 1993;72(8):2209-305. 9. Paulino AF, Singh B, Shah JP, Huvos AG. Basaloid squamous cell carcinoma of the head and neck. Laryngoscope 2009;110(9):l479-82. 10. Seldman JD, Berman JJ, Yost BA, Iseri OA. Basaloid squamous cell carcinoma of die hypopharynx and larynx associated with second primary tumors. Cancer 1991;68(7):1545-9. 11. Wan SK,Chan JK, Tse KC. Basaloid-squamous carcinoma of the nasal cavity. J Laryngol Otol 1992;106(4):370-1. 12. Wan SK, Chan JK, Lau WH, Yip TT. Basaloid squamous cell carcinoma of nasopharynx. An Epstein-Barr virusassociated neoplasm compared with morphologically identical tumors occurring in other sites. Cancer 1995;76(10):1689-93. 13. Shroyer KR, Brookes CG, Markham NE, Shroyer AL. Detection of human papullomavirus in anorectal squamous cell carcinoma. Correlation with basaloid pattern of differentiation. Am J Clin Pathol 1995; 104(3):299-305. 14. Ereno C, Lopez Jl, Sanchez JM, Toledo JD. Basaloidsquamous cell carcinoma of larynx and hypopharynx. A clinicopathological study of 7 cases. Pathol Res Pract 1994;190(2):186-93.

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Tonsillectomy Helps Adults Too Adults who undergo a tonsillectomy have fewer symptoms of pharyngitis, visit their doctors with throat problems less often, and miss work less, researchers from the University of Oulu and Oulu University Hospital, both in Finland, reported in CMAJ (Canadian Medical Association Journal).

Tonsillectomy in Adults with Severe Recurrent Sore Throats may Benefit Some People Tonsillectomy may result in fewer severe sore throats and could benefit some adult patients, according to a randomized trial published in CMAJ (Canadian Medical Association Journal).

Light Shed on the Natural Mechanism that Protects Ears from Hearing Loss New research from the Massachusetts Eye and Ear, Harvard Medical School and Harvard Program in Speech and Hearing Bioscience and Technology may have discovered a key piece in the puzzle of how hearing works by identifying the role of the olivocochlear efferent system in protecting ears from hearing loss. The findings could eventually lead to screening tests to determine who is most susceptible to hearing loss. Their paper is published in the Journal of Neuroscience.

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Gastroenterology

An Observational Study of Essentiale-L in the Treatment of Patients with Fatty Liver Disease L Padma*, Qayum Mukaddam**, Abhijit Trailokyaâ&#x20AC;

Abstract Background: The most common forms of liver disease are alcoholic fatty liver disease and nonalcoholic fatty liver disease (NAFLD), which lead to cirrhosis, liver failure and death. Essential phospholipids play an important role in the management of these conditions. Polyenephosphatidylcholine (PPC) is a major active ingredient in essential phospholipids. It has a high bioavailability and affinity for cellular and subcellular membranes, and helps to maintain membrane fluidity and function. Essentiale-L comprises of PPC, which is a mixture of 94-96% of polyunsaturated phosphatidylcholine. It is prescribed in the management of viral hepatitis and fatty liver disease. Objective: There are only few recent clinical studies conducted in India regarding the role of Essentiale-L in the management of fatty liver disease therefore, we undertook this openlabel, nonrandomized, real clinical practice study, on adult patients diagnosed with fatty liver disease including NAFLD as well as alcoholic fatty liver disease (AFLD). Methods: All adult patients satisfying the inclusion and exclusion criteria were included in the study. Patients diagnosed with fatty liver disease including NAFLD as well as AFLD were treated for 90 days with Essentiale-L two capsules thrice-daily. Vital signs, adverse effects and laboratory evaluations (liver function tests, lipid profile and fasting blood glucose tests) were recorded at baseline (Day 0), Day 7, Day 21, Day 30, Day 60 and Day 90. Results: Essentiale-L showed a consistent improvement in both clinical as well as laboratory parameters in patients with fatty liver disease. The decrease in the liver enzyme levels from baseline was significant at Days 60 and 90 (p < 0.05). However, the decrease in serum total cholesterol, low-density lipoprotein (LDL) cholesterol and triglyceride levels was significant only at Day 90 (p < 0.05). The change in fasting blood glucose levels from baseline were not significant. Conclusion: Essentiale-L is a safe and effective option in patients with fatty liver disease. It can be safely recommended in patients with type 2 diabetes along with fatty liver disease since it did not alter the blood glucose levels significantly.

Keywords: Fatty liver disease, polyenephosphatidylcholine, liver function, lipid profile, blood glucose

he most common forms of liver disease are alcoholic fatty liver disease (AFLD) and nonalcoholic fatty liver disease (NAFLD), which lead to cirrhosis, liver failure and death. AFLD is seen in almost 90% of individuals who consume over 6 drinks per day.1 Some individuals develop alcoholic hepatitis and cirrhosis, which are more serious. About 50% of patients with alcoholic hepatitis have pre-existing cirrhosis and those who do not, are at high-risk, especially if they continue to consume alcohol.

risk factors for NAFLD are obesity, type 2 diabetes mellitus, metabolic syndrome and dyslipidemia. Other comorbidities associated with NAFLD include sleep apnea, polycystic ovary syndrome, hypothyroidism and hypopituitarism. AFLD and NAFLD have different risk factors and natural histories. In both these conditions the hepatocytes are characterized by macrovesicular steatosis, which is the accumulation of triglycerides as one large cytoplasmic globule that displaces the nucleus.1

NAFLD comprises of a spectrum of abnormal liver histology, ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis.1 The major

Essential phospholipids play an important role in the management of AFLD and NAFLD.

*Head, Dept. of Pharmacology Dr BR Ambedkar Medical College, Kadugondanahalli, Bangalore **Director Medical Services â&#x20AC; Abbott Healthcare Pvt. Ltd. Mulund (W), Mumbai Address for correspondence Dr Abhijit Trailokya Abbott Healthcare Pvt. Ltd. D-Mart Bldg, Goregaon - Mulund Link Road, Mulund (W), Mumbai - 400 080 E-mail: abhijit.trailokya@abbott.in

Essential phospholipids are highly-purified phosphatidylcholine fractions containing linoleic acid and other unsaturated fatty acids. Polyenephosphatidylcholine (PPC) is a major active ingredient in essential phospholipids. It has a high bioavailability and affinity for cellular and subcellular membranes, and helps to maintain membrane fluidity and function.2 Essentiale-L (Abbott Healthcare Pvt. Ltd., Mumbai, India), composed of essential phospholipids

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Gastroenterology extracted from soybeans is prescribed in India and other countries for treating viral hepatitis and other hepatocellular diseases.3 This product comprises of PPC, which is a mixture of 94-96% of polyunsaturated phosphatidylcholine. About half of this is the active compound, dilinoleoylphosphatidylcholine (DLPC). This plant phospholipid contains two unsaturated fatty acids in both 1 and 2 positions of the glycerol backbone, unlike mammalian phospholipids that have only one unsaturated fatty acid.4 It has a high bioavailability because of the reacylation of the unsaturated 1-acyllysophosphatidylcholine with additional unsaturated fatty acids during intestinal absorption.5 There have been several experiments demonstrating the hepatoprotective effects of PPC.6-8 Objective There are only few recent clinical studies conducted in India regarding the role of Essentiale-L in the management of fatty liver disease therefore, we undertook this study with the primary objective of evaluating the efficacy of Essentiale-L in fatty liver disease including NAFLD as well as AFLD. Patients and Methods This was an open-label, nonrandomized study, conducted on patients diagnosed with fatty liver disease including NAFLD as well as AFLD. The inclusion criteria were males and females aged 18 years or above diagnosed with fatty liver disease because of any etiology. NAFLD was defined as a raised ALT (>1.5 x upper limit of normal [ULN] in the screening period and on at least two other occasions in the previous 6 months). The patients also had to have ultrasound evidence of steatosis in the previous 12 months. Laboratory diagnosis was done based on three times above the normal levels of serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) (For patient to be taken for analysis, patient must be clinically positive and also positive by biochemical tests).

The efficacy variables included signs and symptoms of digestive discomfort liver enzymes, lipid profile and fasting blood glucose tests. Safety variables included all adverse effects and laboratory parameters. Vital signs, adverse effects and laboratory evaluations (liver function tests, lipid profile and fasting blood glucose tests) were recorded at baseline (Day 0), Day 7, Day 21, Day 30, Day 60 and Day 90. All illnesses (apart from fatty liver disease), which occurred during the course of the study were documented as intercurrent illness and same was done for adverse events along with the medication for the same. Efficacy analysis was done on patients completing the study period (per-protocol population), whereas safety analysis was done on all patients receiving study drug (intent-to-treat population). Descriptive analysis done with measurement data expressed as means with standard deviation (SD) and discrete data presented as counts with percentages. Change (mean and % change) in the laboratory parameters from baseline were calculated. Laboratory values at baseline and on Days 30, 60 and 90 were analyzed using One Way ANOVA with time as the main factor. Post-hoc analysis was done for comparison of individual visit values with baseline values. All testing was done using two-sided tests at alpha 0.05. Results The patient disposition is shown in Table 1. The baseline characteristics of the patients are shown in Table 2.

Signs and Symptoms At baseline, nausea (n = 219), loss of appetite (n = 205) and weakness (n = 199) were the commonest symptoms. Table 1. Patient Disposition Total enrolled Do not satisfy inclusion criteria

315 4

Patients with a diagnosis of hepatitis B and C, hepatotoxic drugs (steroids, estrogens, amiodarone, tamoxifen or other chemotherapeutic agents) and on weight-reducing diet for at least three months and pregnant women were excluded from the study.

Total patients satisfying inclusion criteria

311

Did not complete study

Completed study

293

Analyzed for efficacy (PP population)

293

The patients were treated for 90 days with Essentiale-L two capsules thrice-daily.

Analyzed for safety (ITT population)

315

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PP: Per protocol; ITT: Intention-to-treat

Gastroenterology 100 90 80 % of patients

70 60 50 40 30 20 10 0

Weakness

Nausea

Vomiting

Diarrhea

(n = 199)

(n = 219)

(n = 148

(n = 87)

Day 7

Day 21

Loss of appetite Abdominal pain Hepatomegaly Inflammation of (n = 205) (n = 190) (n = 197) liver (n = 152)

Day 30

Day 60

Day 90

Figure 1. Patients reporting improvement in signs and symptoms.

Laboratory Parameters

Table 2. Baseline Characteristics Age - years

43.47 ± 11.28

Male - no. (%)

229 (73.87)

Female - no. (%)

81 (26.13)

Diagnosis FLD

53 (18.50)

AFLD

148 (51.00)

NAFLD

43 (14.50)

NASH

36 (12.00)

Hepatitis

6 (2.00)

CLD

4 (1.00)

Others

3 (1.00)

Cause of fatty liver disease Excess weight

130 (41.80)

Alcoholism

145 (46.00)

Hypertriglyceridemia

74 (23.79)

Metabolic abnormality

56 (18.01)

Insulin resistance

47 (15.11)

Drugs

35 (11.25)

Hereditary disease

22 (7.07)

FLD: Fatty liver disease; AFLD: Alcoholic fatty liver disease; NAFLD: Nonalcoholic fatty liver disease; NASH: Nonalcoholic steatohepatitis; CLD: Chronic liver disease.

Other commonly encountered signs and symptoms included hepatomegaly, pain abdomen, inflammation of the liver, vomiting and diarrhea. There was a steady improvement in all the signs and symptoms on subsequent evaluations at Days 7, 21, 30, 60 and 90 (see Fig. 1).

Table 3 describes the change in the various laboratory parameters during the entire study period. There was also a decrease in the liver enzyme levels, which was significant at Days 60 and 90 (p < 0.05). This was the case with serum bilirubin levels also; however, the decrease in serum total cholesterol, low-density lipoprotein (LDL) cholesterol and triglyceride levels was significant only at Day 90 (p < 0.05). The change in levels of serum high-density lipoprotein (HDL) cholesterol and fasting blood glucose levels were not significant.

Global Efficacy and Tolerability Assessments A total of 246 (88.17%) of 279 physicians and 240 (86.96%) of 276 patients rated the efficacy of treatment with Essentiale-L as good, very good or excellent (Table 4). Tolerability was rated as good by 270 (93.43%) physicians and 268 (93.06%) patients (Table 5).

Safety Assessment A total of 11 patients reported a total of 15 adverse events on Day 7. Only one patient with dyspepsia reported the event as moderate in intensity, whereas all other events were mild in intensity. Dyspepsia was reported to be ‘probably related’ to Essentiale-L, whereas nausea was reported to be ‘possibly related’ to Essentiale-L in one patient. Diarrhea and headache was reported to be ‘not related’ to Essentiale-L in one patient each. No intervention was reported in any of the patients for management of adverse events. All the adverse events reported are shown in Table 6.

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Gastroenterology Table 3. Change in Laboratory Parameters during the Study Period SGOT

SGPT

ALP

HDL

LDL

FBS

98.04 ± 55.83

111.02 ± 81.70

176.74 ± 107.96

1.86 ± 1.78

232.58 ± 63.80

45.12 ± 20.35

120.56 ± 33.42

20519 ± 52.61

98.64 ± 22.23

Day 30

82.5 ± 36.71 (p > 0.05)

92.00 ± 68.36 (p > 0.05)

115.09 ± 88.45 (p > 0.05)

1.67 ± 1.75 (p > 0.05)

197.29 ± 24.82 (p > 0.05)

40.89 ± 4.08 (p > 0.05)

115.22 ± 32.91 (p > 0.05)

189.14 ± 39.78 (p > 0.05)

99.11 ± 22.93 (p > 0.05)

Day 60

66.25 ± 32.20 (p < 0.05)

71.58 ± 50.05 (p < 0.05)

144.90 ± 73.99 (p < 0.05)

1.33 ± 1.67 (p < 0.05)

188 ± 27.68 (p > 0.05)

39.73 ± 5.44 (p > 0.05)

110.08 ± 32.31 (p > 0.05)

179.08 ± 40.76 (p > 0.05)

94.54 ± 15,83 (p > 0.05)

Day 90

51.70 ± 29.21 (p < 0.05)

54.23 ± 32.60 (p < 0.05)

140.60 ± 78.57 (p < 0.05)

0.89 ± 0.50 (p < 0.05)

183.80 ± 34.19 (p < 0.05)

39.64 ± 5.42 (p > 0.05)

105.03 ± 30.66 (p < 0.05)

167.28 ± 35.41 (p < 0.05)

94.75 ± 15.02 (p > 0.05)

Baseline

SGOT: Serum glutamic oxaloacetic transaminase; SGPT: Serum glutamic pyruvic transaminase; ALP: Alkaline phosphatase; TB: Total bilirubin; TC: Total cholesterol; HDL: High-density lipoproteins; LDL: Low-density lipoproteins; TG: Triglycerides; FBS: Fasting blood sugar.

Discussion

Table 4. Global Efficacy Assessment Physicians’ assessment (n = 279)

Patients’ assessment (n = 276)

No. of patients (%) Excellent

53 (19)

53 (19.20)

Very good

93 (33.33)

89 (32.25)

Good

100 (35.84)

98 (35.51)

31 (11.11)

32 (11.59)

2 (0.72)

4 (1.45)

Satisfactory Poor

Table 5. Global Tolerability Assessment Physicians’ assessment (n = 279)

Patients’ assessment (n = 276)

No. of patients (%) Good

270 (93.43)

268 (93.06)

Moderate

18 (6.23)

18 (6.25)

Poor

1 (0.35)

2 (0.69)

Table 6. Adverse Events Reported by the Patients (n = 315) No. of patients

% of patients

Diarrhea

0.32

Dyspepsia

0.32

Headache

0.63

Nausea

1.59

Vomiting

0.95

Fever

0.95

Total events

4.76

Total patients

3.49

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To our knowledge, this is the first human trial reported on the use of Essentiale-L in literature. Essentiale-L has been shown to attenuate the ethanol-induced alterations in liver lipids and lipid metabolism.9,10 Dietary PPC prevented alcohol-induced fibrosis and cirrhosis in baboons.7 Additionally, it significantly attenuated ethanol-induced oxidative stress in baboons, which may at least partially explain its protective effect against alcoholic liver injury.11 Dietary PPC and DLPC had hypolipidemic effects in alloxan-diabetic rats and in cholesterol-fed rabbits.12,13 PPC also attenuated hepatic fibrosis-induced by CC14 or human albumin in rats and accelerated the regression of pre-existing fibrosis in another study conducted on rats.14 Our study demonstrated that treatment with Essentiale-L resulted in consistent improvement in both clinical as well as laboratory parameters in patients with fatty liver disease. Patients showed an improvement in all the signs and symptoms reported at baseline. There was decrease in the liver enzyme levels, which was significant at Days 60 and 90 (p < 0.05), with a steady decrease in all the parameters. The serum HDL and fasting blood glucose levels were the only parameters, which did not demonstrate a significant decrease. However, it has to be remembered that a decrease in serum HDL levels is actually detrimental to the health of the individual. Therefore, this can be considered as a positive outcome. The change in fasting blood glucose levels were not significant.

Gastroenterology Polyunsaturated lecithin prevents acetaldehyde-mediated hepatic collagen accumulation by stimulating collagenase activity in cultured lipocytes. Hepatology 1992;15(3): 373-81.

Conclusion Essentiale-L is a safe and effective option in patients with both AFLD and NAFLD. It can be safely recommended in patients with type 2 diabetes along with fatty liver disease since it did not alter the blood glucose levels. The limitations of this study are that it is an open-label, nonrandomized trial with no control arm. Therefore, it is important to conduct large-scale, randomized, controlled trials to further confirm the efficacy and safety of this drug in patients with fatty liver disease. References 1. Chalasani NP. Alcoholic and Nonalcoholic Steatohepatitis. Ch. 155. In: Goldman’s Cecil Medicine. 24th edition, Saunders 2011:p996-9. 2. Okiyama W, Tanaka N, Nakajima T, Tanaka E, Kiyosawa K, Gonzalez FJ, et al. Polyenephosphatidylcholine prevents alcoholic liver disease in PPARalpha-null mice through attenuation of increases in oxidative stress. J Hepatol 2009;50(6):1236-46. 3. Gundermann KJ. The “Essential” Phospholipids as a Membrane Therapeutic. European Society of Biochemical Pharmacology: Szczecin 1993:p.217-8. 4. Jayaraman T, Kannappan S, Ravichandran MK, Anuradha CV. Impact of Essentiale L on ethanol-induced changes in rat brain and erythrocytes. Singapore Med J 2008;49(4):320-7. 5. Zierenberg O, Grundy SM. Intestinal absorption of polyenephosphatidylcholine in man. J Lipid Res 1982;23(8):1136-42. 6. Li J, Kim CI, Leo MA, Mak KM, Rojkind M, Lieber CS.

7. Lieber CS, Robins SJ, Li J, DeCarli LM, Mak KM, Fasulo JM, et al. Phosphatidylcholine protects against fibrosis and cirrhosis in the baboon. Gastroenterology 1994;106(1): 152-9. 8. Cao Q, Mak KM, Lieber CS. DLPC and SAMe combined prevent leptin-stimulated TIMP-1 production in LX-2 human hepatic stellate cells by inhibiting HO-mediated signal transduction. Liver Int 2006;26(2):221-31. 9. Navder KP, Baraona E, Leo MA, Lieber CS. Oxidation of LDL in baboons is increased by alcohol and attenuated by polyenylphosphatidylcholine. J Lipid Res 1999;40(6): 983-7. 10. Turecky L, Kupcova V, Szantova M, Uhlikova E. Plasma lipid parameters in patients with alcoholic fatty liver after treatment with essential phospholipids. Bratisl Lek Listy 2003;104(7-8):227-31. 11. Lieber CS, Leo MA, Aleynik SI, Aleynik MK, DeCarli LM. Polyenylphosphatidylcholine decreases alcoholinduced oxidative stress in the baboon. Alcohol Clin Exp Res 1997;21(2):375-9. 12. Berliner JA, Heinecke JW. The role of oxidized lipoproteins in atherogenesis. Free Radic Biol Med 1996;20(5):707-27. 13. Buko V, Lukivskaya O, Nikitin V, Tarasov Y, Zavodnik L, Borodinsky A, et al. Hepatic and pancreatic effects of polyenoylphosphatidylcholine in rats with alloxaninduced diabetes. Cell Biochem Funct 1996;14(2):131-7. 14. Ma X, Zhao J, Lieber CS. Polyenylphosphatidylcholine attenuates non-alcoholic hepatic fibrosis and accelerates its regression. J Hepatol 1996;24(5):604-13.

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Obstetrics and Gynecology

Bacterial Vaginosis in Pregnancy (<28 Weeks) and its Effect on Pregnancy Outcome: A Study from a Western UP City Abhilasha Gupta*, Priyanka Garg**, Shipra Nigam

Abstract Introduction: Bacterial vaginosis (BV) is a vaginal infection involving a reduction in the amount of hydrogen-peroxideproducing Lactobacillus and an overgrowth of anaerobic and gram-negative or gram-variable bacteria. Its prevalence in pregnancy is upto 15-30% and it can have a bearing on pregnancy outcome. It has been associated with preterm labor and preterm delivery, premature rupture of membranes (PROM), amniotic fluid infections and postpartum endometritis. Material and methods: Five hundred antenatal patients admitted or attending antenatal outpatient clinic in Dept. of Obstetrics and Gynecology, LLRMMC and associated SVBP Hospital, Meerut, Uttar Pradesh in last one year were enrolled after a written and informed consent. Patients included were <28 weeks gestation and without any known risk factors for premature delivery. BV was diagnosed by Nugentâ&#x20AC;&#x2122;s criteria and correlated with occurrence of preterm labor, PROM and postpartum endometritis. Result: BV was found in 98 of the 500 patients studied. Twenty-three of the 98 BV patients had preterm delivery and this association was significant (p < 0.0001). Fourteen patients of BV had PROM and this association was also significant (p < 0.001). Six patients of BV also had postpartum endometritis. Conclusion: The above results suggest that screening for BV should start in early pregnancy and a high index of suspicion for preterm delivery should be kept in antenatal patients with BV.

Keywords: Preterm delivery, bacterial vaginosis, bacterial vaginosis in preganacy

acterial vaginosis (BV) is a polymicrobial, superficial vaginal infection. BV is characterized by a change from normal Lactobacillus dominated flora to a mixed flora consisting of Gardnerella vaginalis, Mycoplasma hominis, Mobiluncus species and other anaerobes.1,2 The majority of cases of BV are asymptomatic and remain unreported and untreated.3 BV when symptomatic presents as malodorous4,5 and increased amount of vaginal discharge, which can be grayish to homogenous white.6,7 Previously considered a benign condition, BV has been linked to many gynecological conditions like pelvic inflammatory disease (PID),8,9 posthysterectomy infections10,11 and postabortal PID.12,13 Certain obstetrical complications like preterm labor and preterm delivery,3,14-17 premature rupture of membranes (PROM),18 amniotic

*Professor and Head **Assistant Professor and Gynecology Laparoscopic Surgeon

Dept. of Obstetrics and Gynecology and Dept. of Microbiology, Lala Lajpat Rai Memorial Medical College and Associated Sardar Vallabhbhai Patel Hospital Meerut, Uttar Pradesh

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fluid infections19 and post partum endometritis20 have been linked to occurrence of BV during pregnancy. BV can be diagnosed using Amsel,21 Spiegel22 or Nugent criteria.23 Metronidazole is the drug of choice in the treatment of BV.24 Oral clindamycin has significant effect against anaerobic bacteria and G. vaginalis and is a good alternative to metronidazole.25 Intravaginal chlorhexidine, intravaginal metronidazole, clindamycin creams and lactate gels have also been found to be curative.26 Since, BV can be associated with pregnancy complications, we undertook this study to know the prevalence of BV in pregnant women attending antenatal clinic and its correlation with adverse pregnancy outcome. MATERIAL AND METHODS The study was conducted in Dept. of Obstetrics and Gynecology and Dept. of Microbiology in Lala Lajpat Rai Memorial Medical College (LLRMMC) and associated Sardar Vallabhbhai Patel (SVBP) Hospital, Meerut, Uttar Pradesh over a period of one year extending from October 2009 to September 2010. This study was conducted on 500 pregnant women.

Obstetrics and Gynecology Inclusion Criteria

ÂÂ

2+ = 1-5 morphotypes/100X field.

ÂÂ

Single pregnancy

ÂÂ

1+ = <1 morphotypes/100X field.

ÂÂ

Period of gestation <28 weeks as calculated by last menstrual period or first obstetrical ultrasound if the women was not sure of her last menstrual period.

ÂÂ

A scoring system based on quantification of different morphotypes on the Gram-stain slide as given in Table 1.

Exclusion Criteria ÂÂ

Women with history of previous preterm labor or threatened preterm labor.

ÂÂ

Women with known obstetrical complications, which can be a confounding factor for preterm labor such as antepartum hemorrhage, severe anemia, pregnancy-induced hypertension, essential hypertension, multiple gestation, existing kidney or heart disease, structural and functional abnormalities of the uterus and chronic documented urinary tract infection.

ÂÂ

Cases where preterm labor was induced for any obstetrical and medical condition.

Written and informed consent in patients own language was taken before enrolling patients for the study. Women with period of gestation <20 weeks and no BV at first visit were followed up again at 20 weeks and 28 weeks to assess for presence of BV. Those women with period of gestation between 20 and 28 weeks and no BV at first visit were followed up after their primary visit again at 28 weeks to assess for presence of BV. A detailed history and examination pertinent to an antenatal case was done in all the antenatal women. All women were subjected to routine antenatal investigations. Apart from the routine investigations, vaginal secretion/discharge were sent to detect BV by Nugent’s criteria.

Nugent’s Criteria for Diagnosis of Bacterial Vaginosis Interpretation from the Gram-stained slide was done using Nugent’s criteria. In this criterion, each Gram-stained smear was evaluated for the following morphotypes under oil immersion lens: ÂÂ

Large gram-positive rods: Lactobacillus morphotype.

ÂÂ

Small gram-negative rods: Gardnerella morphotype.

ÂÂ

Small gram variable rods: Bacteroides morphotype.

ÂÂ

Curved gram variable rods: Mobilincus morphology.

Each morphotype was quantified from 0 to 4+ with regard to the number of morphotypes per oil immersion field. ÂÂ

4+ = >30 morphotypes/100X field.

ÂÂ

3+ = 6-30 morphotypes/100X field.

Score: ÂÂ

0-3 = Normal/No BV

ÂÂ

4-6 = Intermediate

ÂÂ

7-10 = BV

Analysis of data The data was subjected to usual statistical analysis by employing the Chi-square tests. OBSERVATIONS AND RESULTS Vaginal microflora evaluation by Nugent’s criteria of the 500 women revealed that 350 (70%) women had normal vaginal flora, 52 (10.4%) had intermediate flora and 98 (19.6%) had BV. Out of the 98 women who had BV, 46 (46.9%) women were in the age group of 21-25 years, 33 (33.7%) were in the age group of 26-30 years, 16 (16.3%) belonged to the age group ≤ 20 years and three (3.1%) women were in the age group ≥ 31 years. The distribution of women with BV according to age was not significant (p = 0.23). Seventy-five (76.5%) antenatals with BV belonged to the lower socioeconomic class as opposed to 20 (20.4%) who belonged to the upper lower class and three (3.1%) who belonged to the lower middle class. This distribution shows that BV patients are significantly distributed in lower class (p < 0.0001). Fifty-three (54.1%) women with BV were in the gestation period between 11-20 weeks with the remaining 45 (45.9%) being in the gestation period between 21-28 weeks. This distribution was not significant. Sixty-six (67.3%) women with BV were nulliparous, 20 (20.4%) were primpara, seven (7.1%) were second para and the remaining five (5.1%) were para three and above. This shows that BV is significantly seen among nulliparous women (p < 0.001). Table 1. Morphotype

0 point

Lactobacillus

1 point 2 points 3 points 4 points 3+

Anerobic rods/ Gardnerella

Mobilincus

1+ - 2+

3+ - 4+

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Obstetrics and Gynecology Table 2. Distribution of Preterm Labor, PROM and Postpartum Endometritis Patients According to Vaginal Microflora Category

No. of women

Preterm delivery (%)

PROM (%)

Postpartum endometritis (%)

Normal flora

350

7 (2)

1 (0.3)

Intermediate

1 (1.9)

23 (23.5)

14 (14.3)

6 (6.1)

Total

500

Twenty-three (23.5%) of the 98 patients with BV had a preterm delivery (Table 2). Out of these 23, six delivered at 32 weeks gestation, five delivered at 33 weeks gestation, seven delivered at 34 weeks gestation and the remaining five delivered at 35 weeks gestation. None of the women who had intermediate flora had preterm delivery and only seven with normal vaginal flora had preterm delivery. The occurrence of preterm delivery in patients of BV is quite significant (p < 0.0001). Out of the 23 preterm deliveries in BV patients, 12 occurred in those where BV was diagnosed between 11-20 weeks period of gestation and remaining 11 in those where BV was diagnosed between 21-28 weeks period of gestation. This distribution was not significant (p = 0.2). PROM was seen in 16 patients (Table 2). Fourteen of them had BV. The remaining two patients had intermediate vaginal flora and normal vaginal flora, respectively. Only six patients had postpartum endometritis and all had BV. DISCUSSION Infection as a possible cause of preterm labor has caused much interest recently and most of the evidence relating to preterm labor is based on two observations, first, all types of infections relating to ascending bacterial invasions including funisitis, chorioamnionitis, neonatal sepsis and maternal endometritis are more commonly found in preterm births: Second, certain organisms in the vaginal flora are more often found in women with preterm labor or PROMs. According to a study by Lavett in 1995, BV is less common in pregnant than in nonpregnant women (23% vs 33%).27 Govender et al in 1996 found BV in 52% of the women studied at 30 weeks or more of gestation and was the commonest infection diagnosed.28 BV prevalence in Italian population of asymptomatic pregnant women was found to be 4.9% at 8th or 9th

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month of pregnancy by Cristiano et al in 1996.29 In our study, out of 500 antenatal women, 350 had normal vaginal flora, 52 (10.4%) had intermediate flora and 98 (19.6%) had BV. Our study showed a high prevalence of BV in pregnancy as compared to other studies. According to Gravett et al 1986, patient with and without BV did not differ significantly with respect to demographic factors.18 In our study, age of the women had no correlation with BV (p = 0.23). In a study by Bhalla et al 1994, BV showed a positive correlation with low socioeconomic status.30 Thakur et al 1986, found that colonization with G. vaginalis was more common among women of low socioeconomic status.31 In an article by Jenifer E Allsworth, 2007, the prevalance of BV in women between ages 14-49 years in USA was lower among those living well above the federal poverty level (24%) compared with those living at or near (34%) or lower (37%) the federal poverty level.32 In our study, prevalence of BV was most common in lower socioeconomic status (p < 0.0001) as seen in other studies. Gravett et al, 1986, also studied the relationship of obstetrical history to BV. Patient with BV did not differ significantly with respect to past reproductive performance and prenatal care but the history of prior first trimester abortions was more common among those with than those without BV (p < 0.05).18 In a study by Cristiano et al, 1996, incidence of BV was more common in primipara between gestational ages 11-20 weeks.29 In our study, occurrence of BV was more common in nullipara women (p < 0.001). Association of BV and prematurity in Indonesia was studied by Riduan et al, 1993. Four hundred ninety pregnant women were evaluated for BV at 16-20 weeks and 28-32 weeks and observed till delivery. They found significant differences between preterm delivery and BV diagnosed at 16-20 weeks gestation but not with BV diagnosed at 28-32 weeks gestation. The rates of preterm delivery were almost double for women who had BV in early pregnancy (20.5%) as compared to women who had BV only in late pregnancy (10.7%).14 In a study by Hay et al in 1994, 718 pregnant women attending antenatal clinics were studied. They concluded that pregnant women did not commonly develop BV after 16 weeks of gestation and if present, it remitted spontaneously in approximately half of those who reached term. They also noted that BV was associated with increased rate of preterm delivery. So, they opined that any treatment aimed at its eradication in pregnancy should be given no later than the beginning of second trimester of pregnancy.3

Obstetrics and Gynecology Kurki et al in 1992, observed that BV was associated with 2- to 6-fold increased risk for preterm labor, a 6.9-fold increased risk for preterm birth and a 7.3fold increased risk of preterm PROM.33 Sheehan et al, 1996, observed in their study on BV that it was the most common cause of vaginal infection and concluded that occurrence of BV in early pregnancy led to 5-fold increased risk of late miscarriage or preterm delivery.34 Govender et al, observed a significant difference in the outcome in women with BV (55 out of 88) compared to those who had infections other than BV (13 of 31) or no infection (5 of 9). This difference was for obstetrical complications (preterm delivery, PROM and intrauterine infection) but not for pregnancy losses and neonatal morbidity.28 In our study, preterm delivery occurred in 30 out of 500 women studied. Out of these 30 antenatal women, 23 had BV. This association was highly significant (p < 0.0001). In the study by Gravett et al, 1986, BV was significantly associated with PROM (odds ratio 2:4).18 In our study also, PROM occurred significantly among BV patients (p < 0.001). In our study, postpartum endometritis was seen in six women and all of them had BV. Our study further lays credentials to the fact that BV is associated with adverse pregnancy outcome and should be looked for early in pregnancy. REFERENCES 1. Muñoz Bellido JL, García Sánchez JE, García-Rodríguez JA. Epidemiological factors and vaginal flora changes in vaginal bacteriosis (bacterial vaginosis). Enferm Infec Microbiol Clin 1992;10(6):340-4. 2. Rosenstein IJ, Morgan DJ, Sheehan M, Lamont RF, TaylorRobinson D. Bacterial vaginosis in pregnancy: distribution of bacterial species in different gram-stain categories of the vaginal flora. J Med Microbiol 1996;45(2):120-6. 3. Hay PE, Morgan DJ, Ison CA, Bhide SA, Romney M, McKenzie P, et al. A longitudinal study of bacterial vaginosis during pregnancy. Br J Obstet Gynaecol 1994;101(12):1048-53. 4. Dinsmoor MJ. Common vaginal discharge. Med Aspects Hum Sexual 1991 May; 36-41. 5. Reamy KJ. Vaginitis. Clin Prac in Sexual 1992:23-6. 6. Pastorek JG. Bacterial vaginosis: current concepts of diagnosis and management. Infections in Medicine. January 1992:48 52. 7. Holst E. Bacterial vaginosis: clinical and microbiological findings. Vaginitis and Vaginosis. Wiley-Liss; 1991: p.115-20. 8. Eschenbach DA, Hillier S, Critchlow C, Stevens C,

DeRouen T, Holmes KK. Diagnosis and clinical manifestations of bacterial vaginosis. Am J Obstet Gynecol 1988;158(4):819-28. 9. Paavonen J, Teisala K, Heinonen PK, Aine R, Laine S, Lehtinen M, et al. Microbiological and histopathological findings in acute pelvic inflammatory disease. Br J Obstet Gynaecol 1987;94(5):454-60. 10. Soper DE, Bump RC, Hurt WG. Bacterial vaginosis and trichomoniasis vaginitis are risk factors for cuff cellulitis after abdominal hysterectomy. Am J Obstet Gynecol 1990;163(3):1016-21; discussion 1021-3. 11. Larsson PG, Platz-Christensen JJ, Thejls H, Forsum U, Påhlson C. Incidence of pelvic inflammatory disease after first-trimester legal abortion in women with bacterial vaginosis after treatment with metronidazole: a doubleblind, randomized study. Am J Obstet Gynecol 1992;166(1 Pt 1):100-3. 12. Møller BR, Ahrons S, Laurin J, Mårdh PA. Pelvic infection after elective abortion associated with Chlamydia trachomatis. Obstet Gynecol 1982;59(2):210-3. 13. Qvigstad E, Skaug K, Jerve F, Fylling P, Ulstrup JC. Pelvic inflammatory disease associated with Chlamydia trachomatis infection after therapeutic abortion. A prospective study. Br J Vener Dis 1983;59(3):189-92. 14. Riduan JM, Hillier SL, Utomo B, Wiknjosastro G, Linnan M, Kandun N. Bacterial vaginosis and prematurity in Indonesia: association in early and late pregnancy. Am J Obstet Gynecol 1993;169(1):175-8. 15. Platz-Christensen JJ, Larsson PG, Sundström E, Bondeson L. Detection of bacterial vaginosis in Papanicolaou smears. Am J Obstet Gynecol 1989;160(1):132-3. 16. Gravett MG, Nelson HP, DeRouen T, Critchlow C, Eschenbach DA, Holmes KK. Independent associations of bacterial vaginosis and Chlamydia trachomatis infection with adverse pregnancy outcome. JAMA 1986;256(14):1899-903. 17. McGregor JA, French JI, Richter R, Vuchetich M, Bachus V, Seo K, et al. Cervicovaginal microflora and pregnancy outcome: results of a double-blind, placebo-controlled trial of erythromycin treatment. Am J Obstet Gynecol 1990;163(5 Pt 1):1580-91. 18. Gravett MG, Hummel D, Eschenbach DA, Holmes KK. Preterm labor associated with subclinical amniotic fluid infection and with bacterial vaginosis. Obstet Gynecol 1986;67(2):229-37. 19. Hameed C, Tejani N, Verma UL, Archbald F. Silent chorioamnionitis as a cause of preterm labor refractory to tocolytic therapy. Am J Obstet Gynecol 1984;149(7):726-30. 20. Newton ER, Prihoda TJ, Gibbs RS. A clinical and microbiologic analysis of risk factors for puerperal endometritis. Obstet Gynecol 1990;75(3 Pt 1):402-6. 21. Amsel R, Totten PA, Spiegel CA, Chen KC, Eschenbach D, Holmes KK. Nonspecific vaginitis. Diagnostic criteria and microbial and epidemiologic associations. Am J Med 1983;74(1):14-22.

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Obstetrics and Gynecology 22. Spiegel CA, Amsel R, Holmes KK. Diagnosis of bacterial vaginosis by direct gram stain of vaginal fluid. J Clin Microbiol 1983;18(1):170-7.

28. Govender L, Hoosen AA, Moodley J, Moodley P, Sturm AW. Bacterial vaginosis and associated infections in pregnancy. Int J Gynaecol Obstet 1996;55(1):23-8.

23. Nugent RP, Krohn MA, Hillier SL. Reliability of diagnosing bacterial vaginosis is improved by a standardized method of gram stain interpretation. J Clin Microbiol 1991;29(2):297-301.

29. Cristiano L, Rampello S, Noris C, Valota V. Bacterial vaginosis: prevalence in an Italian population of asymptomatic pregnant women and diagnostic aspects. Eur J Epidemiol 1996;12(4):383-90.

24. McDonald HM, O’Loughlin JA, Vigneswaran R, Jolley PT, McDonald PJ. Bacterial vaginosis in pregnancy and efficacy of short-course oral metronidazole treatment: a randomized controlled trial. Obstet Gynecol 1994;84(3):343-8. 25. Lossick JG. Treatment of sexually transmitted vaginosis/ vaginitis. Rev Infect Dis 1990;12 Suppl 6:S665-81. 26. Holst E, Brandberg A. Treatment of bacterial vaginosis in pregnancy with a lactate gel. Scand J Infect Dis 1990;22(5):625-6. 27. Levett PN. Aetiology of vaginal infections in pregnant and non-pregnant women in Barbados. West Indian Med J 1995;44(3):96-8.

30. Bhalla P, Kaushika A. Epidemilogical and microbiological correlates of bacterial vaginosis. Ind J Dermatol Venereol Leprol 1994;60:8-14. 31. Thakur A, Bhalla P, Aggarwal DS. Incidence of Gardnerella vaginalis in non-specific vaginitis. Indian J Med Res 1986;83:567-74. 32. Allsworth JE, Peipert JF. Prevalence of bacterial vaginosis: 2001-2004 National Health and Nutrition Examination Survey data. Obstet Gynecol 2007;109(1):114-20. 33. Kurki T, Sivonen A, Renkonen OV, Savia E, Ylikorkala O. Bacterial vaginosis in early pregnancy and pregnancy outcome. Obstet Gynecol 1992;80(2):173-7. 34. Sheehan M, Lamont R. Bacterial vaginosis. Mod Midwife 19966(3):14-8.

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Tdap and Flu Vaccinations during Pregnancy The prevalence of pertussis in US is increasing. Infants younger than three months of age are at highest risk. Vaccination of the mother can decrease the risk of infant exposure, and placental transfer of maternal antibodies may additionally provide a degree of passive protection to the infant for 2-6 months. In 2013, the United States Advisory Committee on Immunization Practices (ACIP) has recommended that all pregnant women receive the tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccine during each pregnancy, optimally between 27 and 36 weeks of gestation, regardless of prior vaccination status. Previously, Tdap was recommended only for pregnant women who had not previously received the acellular pertussis vaccine during adulthood.1 Influenza vaccination is recommended in pregnancy as both mother and fetus are at increased risk. Maternal vaccination provides passive protection to the infant. The safety and efficacy of vaccination of pregnant women has been confirmed in a retrospective analysis of over 1,00,000 pregnancies during the 2009 influenza A (H1N1) pandemic in Norway.2 All women who are pregnant or will be pregnant during influenza season should receive the inactivated influenza vaccine, regardless of pregnancy trimester. References 1. A dvisory Committee on Immunization Practices (ACIP) Recommended Immunization Schedules for Persons Aged 0 through 18 years and Adults Aged 19 Years and Older — United States, 2013. http://www.cdc.gov/mmwr/preview/ mmwrhtml/mm62e0128a1.htm?s_cid=mm62e0128a1_e (Accessed on January 29, 2013). 2. H åberg SE, Trogstad L, Gunnes N, Wilcox AJ, Giessing HK, Samuelsen SO, et al. Risk of fetal death after pandemic influenza virus infection or vaccination. N Engl J Med 2013;368(4):333-40.

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Obstetrics and Gynecology

Rupture of Term Noncommunicating Rudimentary Horn of Uterus Padma Shukla*, M Bhargava**, PK Shukla†

Abstract Pregnancy in noncommunicating rudimentary horn is rare. It occurs following transperitoneal migration of sperms or zygote. Uterine rupture usually occurs in 70-80% cases in the second trimester by 20 weeks. Neonatal survival in rudimentary horn pregnancy is poor occurring in only about 11% of cases.

Keywords: Unicornuate uterus, noncommunicating rudimentary horn, pregnancy

regnancy in a noncommunicating rudimentary horn of a unicornuate uterus is rare.1 The incidence varies between 1/76,000-1/1,50,000 pregnancies.2 Pregnancy occurs following transperitoneal migration of sperms or zygote. Variable thickness of rudimentary horn musculature, dysfunctional endometrium and poor distensibility of the myometrium lead to rupture of the rudimentary horn. This complication is usually seen in the second trimester, resulting in hemoperitoneum and hemorrhagic shock. We report a case of rupture of noncommunicating rudimentary horn with unicornuate uterus at 37 weeks pregnancy.

Case Report A 21-year-old unbooked primigravida was admitted with amenorrhea since nine months, loss of fetal movement and pain in abdomen since three days. On general examination, the patient was of average built with marked pallor; pulse 120/min; BP 100/60 mmHg. Respiratory and cardiovascular system did not reveal any abnormality. On per abdominal examination, the height of uterus was 34 weeks; tenderness was present, lower pole was empty and fetal heart sound was absent. Os was closed and cervix long and uneffaced on per vaginum examination. Investigations showed hemoglobin (Hb) 5 g/dl; blood group AB-negative, bleeding time (BT) 2-minute 15 seconds and clotting time (CT) three minutes. *Assistant Professor **Professor and Head, Dept. of Obstetrics and Gynecology †Assistant Professor, Dept. of General Surgery Shyam Shah Medical College, Rewa, Madhya Pradesh Address for correspondence Dr Padma Shukla 12/145, Khutehi, Rewa - 486 001, Madhya Pradesh E-mail: shukladrpadma@gmail.com

Ultrasonography (USG) showed 37 weeks 2 days pregnancy with breech presentation and intrauterine death, low lying placenta covering the os with large collection near cervix 63 × 52 mm with no various liquor pocket (Fig. 1 a-d). A provisional diagnosis of 37 weeks pregnancy with intrauterine death and placenta previa/abruptio placenta/rupture uterus was made. Patient was taken for laparotomy on 13th November 2011. The fetus was found lying in the peritoneal cavity with 1.5 liter hemoperitoneum. Rupture was present in right fundolateral part of noncommunicating rudimentary horn. Nonpregnant unicornuate uterus was of 16 weeks size. Placenta was present in lower part to rudimentary horn with partial accreta. Right salpingo-ophorectomy with excision of rudimentary horn was done. The fetus measured 36 cm in length and specimen of horn measured 11 cm (Figs. 2-5). Postoperative recovery was uneventful. Discussion As per the available literature, 90% of rudimentary horns are noncommunicating to main uterine cavity. Pregnancy results from transmigration of ovum/sperms or zygote. Although corpus luteum is observed on the contralateral side in only 10% cases, in this condition rupture usually occurs in the second trimester before 20 weeks in 70-80% of cases.3 Diagnosis is only on suspicion by ectopic minded people. Because of functioning endometrium and hematometra, teenagers may give a history of spasmodic dysmenorrhea; married women may present with history of infertility, recurrent second trimester abortion during pregnancy, threatened abortion, preterm labor and/or malpresentation.

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Obstetrics and Gynecology

Figure 1 a and b. USG showing biparietal diameter. At the time of USG, fetus was inside the rudimentary horn and fetal abdomen.

Figure 1 c and d. USG showing placenta covering os and large collection near cervix 63 x 52 mm. This was left unicornuate uterus on laparotomy.

Bimanual palpation of a mass extending outside the uterine angle or displacement of fundus to contralateral side with rotation of uterus and elevation of the affected horn or deviation of uterus to one side with additional mass in pregnancy may indicate rudimentary horn.4

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In the nonpregnant stage, uterus is found deviated to one side with unilateral tubal block on hysterosalpingography (HSG). In USG, the gestational sac surrounded by myometrium is seen separate from the uterus with absent visual continuity in tissue surrounding the gestational sac, uterus and cervix or

Obstetrics and Gynecology

Figure 2. Rupture rudimentary horn with placenta accreta; near Doyenâ&#x20AC;&#x2122;s retractor left unicornuate uterus.

Figure 3. Fetus with excised rudimentary horn with tube and ovary. Length of specimen of horn measured 11 cm.

Figure 4. Fetus with excised rudimentary horn the length of fetus measured 36 cm.

Figure 5. Specimen of ruptured rudimentary horn.

a pseudopattern of an asymmetrical bicornuate uterus all indicate rudimentary horn pregnancy.5

References

Sensitivity of USG is 26%, which decreases with advancing age of pregnancy. Three-dimensional USG may be used for diagnosis of uterine anomalies. Laparoscopy is most accurate for diagnosis. Magnetic resonance imaging (MRI) is a useful noninvasive tool to detect uterine anomalies in gravid/nongravid uterus. Once the diagnosis is suspected, laparoscopy or laparotomy is a must. There have been case reports of fetal survival in late rupture of rudimentary horn. Neonatal survival in rudimentary horn pregnancy is poor, occurring in only 11% cases during the last half century.6 Evaluation of renal system is advised because of high incidence of urological anomalies.

1. Tufail A, Hashmi HA. Ruptured ectopic pregnancy in rudimentary horn of the uterus. J Coll Physicians Surg Pak 2007;17(2):105-6. 2. Ural SH, Artal R. Third-trimester rudimentary horn pregnancy. A case report. J Reprod Med 1998;43(10):919-21. 3. Goel P, Aggarwal A, Devi K, Takker N, Saha PK, Huria A. Unicornuate uterus with noncommunicating rudimentary horn - different clinical presentations. J Obstet Gynecol India 2005;55(2):155-8. 4. Bhattacharya TK, Sengupta P. Rudimentary horn pregnancy. Medical Journal Armed Forced India 2005;61(4):377-8. 5. Tsafrir A, Rojansky N, Sela HY, Gomori JM, Nadjari M. Rudimentary horn pregnancy: first-trimester prerupture sonographic diagnosis and confirmation by magnetic resonance imaging. J Ultrasound Med 2005;24(2):219-23. 6. Weitzner JS. Rudimentary horn pregnancy. J Reprod Med 1998;43(2):158-9.

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Original Article Orthopedics and Rheumatology

What is the Etiopathogenesis of OA? Ahmad Javaid

lthough osteoarthritis (OA) is a disease of the whole joint, the primary change is loss of articular cartilage. Bony remodeling, osteophyte formation and synovial, capsular, ligamentous and muscular changes are secondary.1 The key to healthy hyaline cartilage is the maintenance of the architecture and composition of the extracellular matrix (ECM), under the control of highly specialized cells, the chondrocytes. However, these cells are sparse and isolated, accounting for only 1% of cartilage volume. The matrix consists of a structural framework of macromolecules and tissue fluid. The former are the collagens, proteoglycans and noncollagenous proteins and glycoproteins. The tissue fluid contains water (80% wet weight of cartilage), small proteins, metabolites and a high concentration of cations that balance the negatively charged proteoglycans. The collagens form a fibrillar mesh that gives the cartilage its morphology and provides protection against tension and shear. There are two major classes of proteoglycan (polysaccharideprotein conjugate) in cartilage, namely large aggregating molecules (aggrecan) and smaller nonaggregating molecules, such as decorin, biglycan and fibromodulin. The aggrecan molecule contains a central core protein with approximately 100 glycosaminoglycan (GAG, polysaccharide chains consisting of repeating disaccharides, which contain an amino sugar) sidechains of chondroitin sulfate and keratan sulfate, each of which contains 80-100 negatively-charged groups. The aggrecan molecules form proteoglycan aggregates by linking with a long central hyaluronan molecule, resulting in a very large complex with several hundred thousand fixed, negatively charged groups. The loss of articular cartilage in OA may start as a focal lesion and progressively extend to involve specific joint compartments, thus inducing alterations in articulating surfaces2 and leading to progressive loss of cartilage3

Batth Bone Joint Clinic Manual Medicine Ergonomics Orthopedic Specialist Spine and RSI Specialist Clinical Ergonomics Bangalore, Karnataka

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Superficial fibrillation is associated with the loss of the small proteoglycans, decorin and biglycan, which are usually closely associated with the fibrils at the articular surface4 and the large proteoglycan aggrecan.5 Associated with the loss of these molecules, is an increased cleavage of type II collagen by collagenase,6 aggrecan cleavage7-9 and the degradation of small proteoglycans.10 Since, the degradation of the ECM exceeds its synthesis, there is a net decrease in the amount of cartilage matrix or even the complete erosion of the cartilage overlying the bone at the joint surface. This is thought to be caused by the increased proteolytic enzyme activity of the matrix metalloproteinases (MMP). The role of MMPs in the excessive matrix degradation that characterizes the cartilage degeneration of OA11 is supported by the increased expression of several MMPs in the cartilage of OA patients (e.g., MMP-3, MMP-13 and MMP-14). Recently, a group of MMP, called â&#x20AC;&#x2DC;aggrecanases,â&#x20AC;&#x2122; have been identified which are thought to play a major role in the breakdown of aggrecan (ADAMTS-1, ADAMTS-4 and ADAMTS-5).12 As the disease progresses, the local pH of the cartilage may fall and cathepsin B, cathepsin L and cathepsin K from the chondrocytes may participate in further cartilage destruction.13,14 A deficiency in the tissue inhibitors of MMP (TIMPs)15 clearly favors the excessive proteolysis seen in the diseased articular cartilage. It is thought that cytokines produced by the synovium and chondrocytes, especially interleukin (IL)-1 and tumor necrosis factor-a (TNF-a), play a significant role in the degradation of cartilage16 though prostaglandins (PG) and leukotrienes may also be involved. PGE2 is found to be increased in human OA-affected cartilage and reduces cell development and the induction of apoptotic processes in articular chondrocytes.17 The production of nitric oxide (NO), which is stimulated by proinflammatory cytokines, is involved in cartilage catabolism18 and also may induce the apoptosis of chondrocytes.19 The NO and PGE2 produced by activated chondrocytes in diseased cartilage may modulate disease progression in OA and should

Orthopedics and Rheumatology therefore be considered potential targets for therapeutic interventions.17 It is accepted that there is at least some synovitis in established OA.20 Inflammation may start earlier in post-traumatic OA; here, the synovial fluid concentration of MMP, such as stromelysin-1 (which is more likely to be derived from activated synovial cells than cartilage), rapidly increases. Like many other cells in the body, synovial cells actively synthesize and secrete hyaluronic acid (HA, hyaluronan), and the size of HA molecules and their concentration in synovial fluid decrease in OA.21 Similarly, the levels of cartilage oligomeric protein, which is synthesized by synovial cells and chondrocytes, are increased in patients with accelerated large joint degeneration.22 These associations suggest that joint inflammation may accelerate joint damage. C-reactive protein levels may be modestly raised in the serum of patients with OA.23 References 1. Buckwalter JA, Mankin HJ, Grodzinsky AJ. Articular cartilage and osteoarthritis. Instr Course Lect 2005;54:46580. 2. Lohmander LS, Lark MW, Dahlberg L, et al. Cartilage matrix metabolism in osteoarthritis: markers in synovial fluid, serum and urine. Clin Biochem 1992;25(3):167-74. 3. Dieppe P, Cushnaghan J, Young P, et al. Prediction of the progression of joint space narrowing in osteoarthritis of the knee by bone scintigraphy. Ann Rheum Dis 1993;52(8): 557-63. 4. Poole AR, Rosenberg LC, Reiner A, et al. Contents and distributions of the proteoglycans decorin and biglycan in normal and osteoarthritic human articular cartilage. J Orthop Res 1996;14(5):681-9. 5. Westacott CI, Webb GR, Warnock MG, et al. Alteration of cartilage metabolism by cells from osteoarthritic bone. Arthritis Rheum 1997;40(7):1282-91. 6. Billinghurst RC, Dahlberg L, Ionescu M, et al. Enhanced cleavage of type II collagen by collagenases in osteoarthritic articular cartilage. J Clin Invest 1997;99(7):1534-45. 7. Lark MW, Bayner EK, Flanagan J, et al. Aggrecan degradation in human cartilage. Evidence for both matrix metalloproteinase and aggrecanase activity in normal, osteoarthritic, and rheumatoid joints. J Clin Invest 1997;100(1):93-106. 8. Rizkalla G, Reiner A, Bogoch E, et al. Studies of the articular cartilage proteoglycan aggrecan in health and osteoarthritis: evidence for molecular heterogeneity and extensive molecular changes in disease. J Clin Invest 1992;90(6):2268-77.

9. Cs-Szabó G, Roughley PJ, Plaas AH, et al. Large and small proteoglycans of osteoarthritic and rheumatoid articular cartilages. Arthritis Rheum 1995;38(5):660-8. 10. Poole AR. Cartilage in health and disease. In: Arthritis and Allied Conditions. A Textbook of Rheumatology. 13th edition, Koopman WJ (Ed.), Williams and Wilkins: Baltimore, 1997. 11. Okimura A, Okada Y, Makihira S, et al. Enhancement of cartilage matrix protein synthesis in arthritic cartilage. Arthritis Rheum 1997;40(6):1029-36. 12. Nagase H, Kashiwagi M. Aggrecanases and cartilage matrix degradation. Arthritis Res Ther 2003;5(2):94-103. 13. Baici A, Hörler D, Lang A, et al. Cathepsin B in osteoarthritis: zonal variation of enzyme activity in human femoral head cartilage. Ann Rheum Dis 1995;54(4):281-8. 14. Konttinen YT, Mandelin J, Li TF, et al. Acidic cysteine endoproteinase cathepsin K in the degeneration of the superficial articular hyaline cartilage in osteoarthritis. Arthritis Rheum 2002;46(4):953-60. 15. Skiles JW, Gonnella NC, Jeng AY. The design, structure, and therapeutic application of matrix metalloproteinase inhibitors. Curr Med Chem 2001;8(4):425-74. 16. Sandell LJ, Aigner T. Articular cartilage and changes in arthritis. An introduction: cell biology of osteoarthritis. Arthritis Res 2001;3(2):107-13. 17. Amin AR, Dave M, Attur M, et al. COX-2, NO, and cartilage damage and repair. Curr Rheumatol Rep 2000;2(6):447-53. 18. Abramson SB, Amin AR, Clancy RM, et al. The role of nitric oxide in tissue destruction. Best Pract Res Clin Rheumatol 2001;15(5):831-45. 19. Pelletier JP, Martel-Pelletier J, Abramson SB. Osteoarthritis, an inflammatory disease: potential implication for the selection of new therapeutic targets. Arthritis Rheum 2001;44(6):1237-47. 20. Myers SL, Brandt KD, Ehlich JW, et al. Synovial inflammation in patients with early osteoarthritis of the knee. J Rheumatol 1990;17(12):1662-9. 21. Moreland LW. Intra-articular hyaluronan (hyaluronic acid) and hylans for the treatment of osteoarthritis: mechanisms of action. Arthritis Res Ther 2003;5(2):54-67. 22. Vilim V, Olejarova M, Machacek S, et al. Serum levels of cartilage oligomeric matrix protein (COMP) correlate with radiographic progression of knee osteoarthritis. Osteoarthritis Cartilage 2002;10(9):707-13. 23. Sharif M, Elson CJ, Dieppe PA, et al. Elevated serum C-reactive protein levels in osteoarthritis. Br J Rheumatol 1997;36(1):140-1.

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Pediatrics

Management of Juvenile Idiopathic Arthritis in Adolescents Donald E Greydanus*, Mary D Moore**

Abstract Many terms are used to describe juvenile rheumatoid arthritis and the term most used today is JIA or juvenile idiopathic arthritis. JIA is the most common rheumatoid disorder occurring in 0.5-2.0/1,000 children and adolescents. It is typically divided into oligoarticular, polyarticular (RF-positive and RF-negative) and systemic-onset (Stills disease). The laboratory testing is nonspecific and there is no single test or combination of tests that are pathognomonic for JIA. This discussion focuses on management of JIA that centers on nondrug treatment and drug treatment. JIA pharmacology centers on NSAIDs, corticosteroids, DMARDs (especially methotrexate) and if available various cytotoxic agents and biologic response modifiers. The proper use of nonpharmacologic and pharmacologic management can control pain, reduce inflammation as well as joint damage and improve the quality-of-life for adolescents with JIA.

Keywords: Arthritis, rheumatoid disorder, children

heumatoid diseases are disorders with inflammation and pain in connective tissues and supporting body structures - ligaments, joints, tendons and muscles.1,2 There is joint pain, swelling and stiffness (particularly morning stiffness) that leads to a myriad of disabilities with underlying autoimmune dysfunction. Rheumatoid diseases cause more activity limitation than diabetes mellitus, heart disease and cancer. The most common rheumatic disorders are juvenile idiopathic arthritis (JIA) and spondyloarthropathies; these are found in 0.5-2.0/1,000 children and adolescents. This discussion focuses on JIA and its management in adolescents.

Definition A number terms have been used to describe chronic inflammatory arthritis that have their onset prior to 16 years of age.3,4 These terms include juvenile rheumatoid arthritis (JRA) juvenile chronic arthritis (JCA), juvenile arthritis (JA) and the term often used today - JIA. JIA refers to arthritis that remains for over six weeks and involves joint swelling and/or painful joint

*Professor, Dept. of Pediatrics and Human Development **Pediatrics Program Michigan State University/Kalamazoo Center for Medical Studies Kalamazoo, Michigan, USA Address for correspondence E-mail: moore@kcms.msu.edu

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restricted movement.5 It is in contrast to arthralgia in which there is joint pain with or without inflammation. JIA is more common in females than males. JIA Types Table 1 lists disorders that may present with arthritis.1,4 Historically, three JIA have been identified by rheumatologists: Oligoarticular (former: Pauciarticular), polyarticular (rheumatoid factor [RF]-positive and RF-negative) and systemic-onset (Stills disease).6-8 The International League of Associations for Rheumatology (ILAR) classification for JIA also includes enthesitis-related arthritis, psoriatic arthritis, and undifferentiated arthritis. The evaluation rules out other causes of arthritis including post infectious arthritis, Lyme arthritis, septic arthritis, reactive arthritis and others.9 JIA usually presents in a child or adolescent with stiffness after a prolonged rest, whether developing after a nightâ&#x20AC;&#x2122;s sleep, prolonged day-time nap or other prolonged period of inactivity. The stiffness is accompanied by usually mild aching with joint swelling that varies greatly in amount. It is important to note that severe pain is not typical for JIA. Those with oligoarticular JIA are at increased risk of developing uveitis (iritis), which is gradual, insidious and often only found when specifically looked for on eye examination. Sometimes, the adolescent will present with overt eye symptoms such as eye redness, pain, photophobia

Pediatrics Table 1. Disorders that can Present as Arthritis Acute monoarthritis Enthesitis-related arthritis Hemophilia Leukemia Neuroblastoma Oligoarthritis Psoriatic arthritis Reactive arthritis Septic arthritis Trauma Chronic monoarthritis Enthesitis-related arthritis Episodic fever syndromes Hemophilia Hemangioma JIA Juvenile psoriatic arthritis Lyme arthritis Oligoarthritis Sarcoidosis Synovial chondromatosis Tuberculosis Villonodular synovitis

Polyarthritis Spondyloarthropathies Enthesitis-related arthritis Arthritis with inflammatory bowel disease Juvenile idiopathic polyarthritis Lyme disease (usually monoarticular) Malignancies Periodic fever syndromes Polyarthritis related to infection Psoriatic JIA Reactive arthritis Rheumatic fever (migratory joint involvement) Sarcoidosis Serum sickness Systemic juvenile idiopathic arthritis Systemic lupus erythematosis Vasculitis Viral arthritis

*Modified with permission from: Patel DR, Moore MD: Concepts of Rheumatology Ch. 25. In: Handbook of Clinical Pediatrics: An Update for the Ambulatory Pediatrician. Greydanus DE, Patel DR, Reddy VN, Feinberg AN, Omar HA. (Eds.), World Scientific, New Jersey 2010:p.702.

and/or changes in vision. Youth with polyarthritis are at reduced risk for chronic uveitis. The patient with oligoarthritis develops a nonpainful limp and swelling of four or less joints within 6 months of disease onset that is usually under eight years of age. In polyarticular JIA, the joint swelling is found in five or more joints within 6 months of disease onset and two classic age ranges are noted: 1-6 years of age and 11-16 years of age. Two classic subtypes of polyarticular arthritis are described: RF-negative and RF-position. In the latter, there is 2 or more positive RF tests during the first six months of disease-onset that are 3 months or more apart. In systemic-onset JIA, there is arthritis in one or more joints that develops or is preceded by fever with high spikes of two weeks or more duration, which is classically quotidian (daily) for 3 days or more.10 One or more of these findings are noted as well: Hepatosplenomegaly (one or both), generalized rash, recurrent rash (erythematous, evanescent) and/or serositis (peritonitis and/or pleuritis and/or pericarditis).

JIA Laboratory Testing Lab testing in JIA is either normal or mildly elevated. For example, the RF is negative in over 90% or more of JIA youth, while the antinuclear antibodies (ANA) titer is positive, usually in low titers, in upto 90%.11 There is no test nor combination of lab tests that are pathognomonic for JIA to differentiate it from other rheumatoid disorders or arthritides (Table 1). It is important to rule out such causes as malignancy or septic arthritis. Joint aspiration is very helpful in this regard and includes a Gram stain, culture, cell count, fluid glucose, fungal or acid-fast bacillus, cytology and crystal examination, where indicated. JIA Complications It is important to diagnose JIA as early as possible and to provide comprehensive management to reduce the potential complications of this chronic and recalcitrant rheumatoid disorder.12 These possible complications include inhibition of growth with shorted height, variable joint destruction, bony overgrowth, contractures, spinal cord compression that includes the cervical spine, chronic eye disease and even death.13 Eye complications include cataracts, secondary glaucoma, band keratopathy, posterior synechiae with papillary complications, vision compromise and even blindness.14 As noted the eye disease can be insidious and thus, all patients with JIA should have regular eye screening by ophthalmologists to reduce the chances for development of severe, progressive eye disease. These ophthalmologists should identify and manage the eye disease seen with JIA. Death from JIA may occur because of complications from potentially toxic drugs used to control JIA, infections, traumatic C-spine injury and the rare macrophage activation syndrome (MAS). MAS is a type of hemophagocytic lymphohistiocytosis syndrome stimulated by medications or viral infections.15,16 MAS can arise with fever, lymphadenopathy, petechiae, bleeding, pancytopenia and organomegaly; the erythrocyte sedimentation rate can lower very quickly and the ferritin levels can become elevated. Improvement may be seen with treatment that includes high-dose corticosteroids, cyclosporine, and tumor necrosis factor inhibitors. The death rate can be over 30%. MAS is most common in systemiconset JIA.

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Pediatrics JIA Management

General Adolescents with JIA require an individualized plan managed by a clinician with training and skill in the management of this condition seeking to improve the quality of care for these patients.17-21 A number of conservative measures can be utilized to help with JIA pain, such as use of moist heat, rest, appropriate physical activity and individualized joint support (i.e, splints, casts, canes or crutches). Non-narcotic analgesics are beneficial and narcotics should be used only very cautiously (if at all) for this chronic disorder. There remains no scientific evidence for the use of nutritional supplements in the treatment of JIA in children and adolescents. This includes such agents as chondroitin sulfate, glucosamine, S-adenosylmethionine (SAM-e) dehydroepiandrosterone (DHEA) or hyaluronic acid substitutes. A number of nonpharmacologic modalities are available and very useful, such as physical therapy, occupational therapy, hydrotherapy, heat and cold applications, transcutaneous electrical nerve stimulation (TENS) and others. Steroid intra-articular injections are helpful in those with only a few joints that are involved. Consultation with surgeons is important to provide needed arthroscopic surgery, osteotomy, bone fusion and arthroplasty. It is also important to provide appropriate management for potential comorbid conditions, such as mood disorders, anxiety disorders or sleep problems. Youth may find considerable help from online chat rooms.

Rheumatoid Arthritis Drugs Drugs for JIA are typically prescribed to control pain, reduce inflammation as well as joint damage and decrease JIA symptoms in addition to reducing functional decline.1,4,22,23 These medications can slow the course of the JIA and/or limit or prevent ongoing destruction of joints or other body tissues. Cure is not possible by any medication despite claims made in various media or unscrupulous â&#x20AC;&#x2DC;experts.â&#x20AC;&#x2122; Cure may occur in some rheumatoid diseases such as by use of the correct antibiotics in infectious arthritis or Lyme arthritis. NSAIDs The most commonly prescribed medications for JIA around the world are the nonsteroidal anti-inflammatory drugs (NSAIDs).10,20 They have become very popular analgesics since ibuprofen was introduced to

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the drug market in the 1960s. The classic NSAIDs include ibuprofen, tolmetin sodium, naproxen, indomethacin, acetylsalicylic acid, sulindac and others.20 Commonly used NSAIDs are noted in Table 2 and potential adverse effects in Table 3. It is important to note that these medications do not affect the longterm outcome of JIA but are very helpful to control important JIA symptoms - pain, stiffness, swelling and fever. Thus, they are very beneficial for these youth if adverse effects do not restrict their use. A number of topical agents are also available in various formulations in different countries. However, some youth do not tolerate their texture or the burning sensation that they may cause. NSAIDs approved by the US Food and Drugs Administration (FDA) for use in children include aspirin, ibuprofen, naproxen, indomethacin, oxaprozin, meloxicam etodolac SR and celecoxib. Acetylsalicyclic acid (aspirin) has been of historical use as an analgesic in management of JIA but has been replaced by more traditional NSAIDs. Clinicians are concerned with the small but well-known risk of Reye syndrome and salicylates should be avoided in those who have an active infection with influenza or varicella. Salicylates (especially ASA) are the only NSAIDs that leads to less platelet aggregation with clinical relevance lasting 4-6 days from a small a dose as 80 mg. Salicylates have an increased adverse effect profile and more toxicity from an overdose in contrast to other NSAIDs. NSAIDs can also cause dizziness, lethargy and headaches that tend to cease with cessation of the specific drug.20 These medications are useful because they nonselectively inhibit cyclooxygenase 1 and 2 (COX-1 and COX-2) enzymes; however, this property also leads to various side effects since the COX-1 enzyme is expressed in the renal, hematologic (i.e., platelets), and gastrointestinal (GI) systems. The specific adverse effects depend on various factors such as the specific drug used, dosage, degree of COX-1 inhibition, co-morbid conditions and contribution of other prescribed medications. NSAID GI toxicity can be reduced by adding misoprostol or proton pump inhibitors and is especially useful for those at highrisk for GI side effects, such as those with a history of GI disorders or those also taking corticosteroids. Asthmatic youth who are aspirin-sensitive should not be taking NSAIDs. More recent selective COX-2 inhibitors (i.e., rofecoxib, celecoxib and valdecoxib) lead to less GI effects but

Pediatrics Table 2. Systemic Analgesics and Anti-inflammatory Drugs* Generic name

Adult dosage

Pediatric dosage

Diclofenac sodium

100-200 mg daily (2-4 divided doses)

2-3 mg/kg/day (2-4 divided doses)

*ER given 1-2x daily* Diclofenac potassium

100-200 mg daily (2-4 divided doses)

2-3 mg/kg/day (2-4 divided doses)

Diclofenac epolamine

180 mg patch every 12 hour

N/A

Etodolac

600-1,000 mg daily (2-3 divided doses)

20-30 kg: 400 mg daily 31-45 kg: 600 mg daily 46-60 kg: 800 mg daily >60 kg: 1,000 mg daily *Age 6-16 years* *Based on ER product*

Fenoprofen calcium

200-600 mg 3-4x/day

N/A

Max. 3,200 mg/day Flurbiprofen

200-300 mg daily

N/A

(2-4 divided doses) Ibuprofen Indomethacin

1,200-3,200 mg daily

4-10 mg/kg/dose 3-4x/day

(3-4 divided doses)

Max. 40 mg/kg/day

50-200 mg daily

1-2 mg/kg/day

(2-3 divided doses)

(2-4 divided doses) Max. 4 mg/kg/day, NTE: 150-200 mg/day *Age >2 years*

Ketoprofen

IR: 150-300 mg daily

N/A

(3-4 divided doses) ER: 100-200 mg daily Ketorolac tromethamine

20 mg initially, 10 mg 4x/day

N/A

Max. 5-day duration Meclofenamate sodium

200-400 mg daily

N/A

(3-4 divided doses) Mefenamic acid

500 mg initially, 250 mg every 6 hour as needed

N/A

(NTE: 1 week) Meloxicam

7.5-15 mg daily

0.125 mg/kg/day Max. 7.5 mg daily *Age â&#x2030;Ľ2 years*

Nabumetone

500-2,000 mg daily

N/A

Naproxen

Naproxen: 250-500 mg 2x/day

*Analgesia: 5-7 mg/kg/dose every 8-12 hours

Naproxen sodium: 200-500 mg 2x/day

*Inflammatory disease: 10-15 mg/kg/day (2 divided doses)

(1-2 divided doses)

Naproxen DR: 375-500 mg 2x/day

Max 1,000 mg/day *Age >2 years*

Contâ&#x20AC;&#x2122;d...

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Pediatrics ...Cont’d Generic name

Adult dosage

Pediatric dosage

Oxaprozin

600-1,200 mg daily

22-31 kg: 600 mg daily

Max. 1,800 mg daily (in divided doses)

32-54 kg: 900 mg daily ≥55 kg: 1200 mg daily *Age 6-16 years*

Piroxicam

10-20 mg daily

Sulindac

150-200 mg 2x/day

0.2-0.3 mg/kg/day Max. 15 mg daily 2-4 mg/kg/day (2 divided doses) Max. 6 mg/kg/day, NTE: 400 mg/day

Tolmetin sodium

600-1,800 mg daily

*Analagesia: 5-7 mg/kg/dose every 6-8 hours

(3 divided doses)

*Inflammatory disease: 15-30 mg/kg/day (3-4 divided doses)

Max. 2,000 mg daily

NTE: 1,800 mg/day *Age ≥2 years*

Celecoxib

100-400 mg daily

10-25 kg: 50 mg 2x/day

(1-2 divided doses)

>25 kg: 100 mg 2x/day *Age ≥2 years*

Diflunisal

500-1,000 mg daily

N/A

(2-3 divided doses) Max. 1,500 mg daily Magnesium salicylate

Novosal: 600 mg 3-4x day Max 4,800 mg daily

N/A

Doan’s: 934 mg every 6-hour as needed Salsalate

3,000 mg daily

N/A

(2-4 divided doses) Choline magnesium trisalicylate

500-1,500 mg 2-3x/day

30-60 mg/kg/day (3-4 divided doses)

IR = Immediate-release; ER = Extended-release; DR = Delayed-release, NTE = Not to exceed. *Used with permission from: Greydanus DE, Moore MD, Feucht C. Concepts of rheumatoid disorders (Chapter 11). In: Adolescent Medicine: Pharmacotherapeutics in Medical Disorders. Greydanus DE, Patel DR, Feucht C, Omar HA, Merrick J. (Eds.) 2012:p.333-55.

increase cardiovascular toxicity risks. Rofecoxib and valdecoxib have been removed from the market because of these cardiovascular adverse effects; celecoxib has been approved by the FDA in the United States for use in JIA. Selective COX-2 inhibitors do not reversibly inhibit platelet aggregation. Leukopenia may develop, which is usually mild and resolves with medication cessation; however, rarely it can be severe and chronic. Potential dermatologic adverse effects of NSAIDs are myriad and range from urticaria to Stevens-Johnson syndrome. Pseudoporphyria is a photosensitive rash particularly noted in fair complexioned individuals on chronic naproxen use and this may lead to chronic scarring.

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Approximately 3% of those taking NSAIDs (5% of those on chronic salicylate use) develop increased liver transaminases; overt liver toxicity is rare but can be fatal. Renal toxicity may develop and include proteinuria, hyperkalemia and interstitial nephritis. Aseptic meningitis has been reported while on NSAIDs, especially in those with systemic lupus erythematosus; medications in this regard include ibuprofen, naproxen, diclofenac, ketoprofen, tolmetin, sulindac and rofecoxib. A trial and error method is needed to see which NSAID provides the most benefit with the least or acceptable side effect profile for an adolescent with JIA.20 One that is taken once or twice a day is best for most to minimize problems in taking the medication in school and also

Pediatrics to improve overall compliance. Some NSAIDs are prepared in a liquid form and these include ibuprofen, naproxen, indomethacin, meloxicam and various salicylate preparations. Ketorolac and indomethacin are available as parenteral formulations while diclofenac is made in patch and topical gel forms. Youth taking chronic NSAIDs should get periodic (i.e. every 3 months) screening for GI, renal and hematopoietic toxicity. The clinician should screen for melena and abdominal pain and add a protonpump inhibitor if needed. Serum NSAID levels are not clinically helpful except when monitoring salicylate levels in those on chronic salicylate therapy. Corticosteroids Corticosteroids have become a very powerful tool in pharmacologic management of many disorders since the discovery of cortisone in 1949 by Edward Kendall, an American chemist at the Mayo Clinic (Rochester, Minnesota, USA) and physician Philip Hench.24 These drugs (i.e. prednisone, cortisone, hydrocortisone, methylprednisolone, others) are powerful anti-inflammatory agents that also suppress the immune system to help adolescents with JIA. They can be given in various forms: orally, intra-articularly, intramuscularly, intravenously or as topical agents. As noted with other powerful drugs, corticosteroids have much potential benefit but also many serious side effects and so must be used carefully and judiciously. Thus, they are used in youth with JIA with severe disease and used when disease complications arise, such as anemia or pericarditis. The lowest effective dose should be used and a typical manner of application is an alternative day schedule to reduce adverse effects (Tables 3 and 4). Oral doses can range from 0.5 to 3 mg/kg day; it should be tapered as rapidly as possible. Intra-articular corticosteroid injections are very helpful in youth with minimal joint disease and may keep the patient off regular systemic steroids as well as chronic NSAID therapy. The steroid dose varies with the size of the joint being injected and synovitis may be well-controlled for months after the steroid injection. Fluoroscopy or ultrasound assistance is suggested for injection of a large joint, such as the hip. Youth having considerable anxiety over this procedure may need a short-acting sedative and general anesthesia is suggested if several joints are being injected. It is best that an experienced clinician perform this procedure since it can be difficult because of such problems as local fibrosis, bony changes or infection. The presence of major synovial hypertrophy may limit the penetration

Table 3. Potential Side Effects of NSAIDs Headache Dizziness Bronchospasm Gastrointestinal Nausea, vomiting (indigestion, heartburn) Gastritis; peptic ulcer disease Gastrointestinal ulceration and bleeding Hepatotoxicity Rash Bruising Photosensitivity Hypersensitivity reactions Anaphylaxis Tinnitus Fluid retention or peripheral edema Hyperkalemia Suppression of bone marrow Acute renal insufficiency (interstitial nephritis) Increased risk of cardiovascular thrombotic events, myocardial infarction and stroke.

Table 4. Potential Acute (Reversible) Effects of Corticosteroids Swelling (sodium and fluid retention) Weight gain with moon facies; Cushinoid appearance Emotional instability Increased appetite Sleep dysfunction Steroid acne Psycyhosis (rare) Muscle weakness (severe; rare)

of steroid into the inflamed joint. Some atrophied changes may occur along the needle tract because of steroid leakage. Infections are potential side effects of steroid use and these include typical or common bacteria to increased incidence of a myriad of opportunistic infections as well as Mycobacterium tuberculosis. An adolescent taking corticosteroids on a chronic basis should be prescribed calcium and vitamin D supplementation in addition to counseling about the need for weight-bearing exercise. Clinician usually obtain annual bone density studies and may recommend bisphosphonates for prevention of osteoporosis in adolescents taking chronic steroids for JIA.

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Pediatrics Disease-modifying Antirheumatic Drugs Disease-modifiying antirheumatic drugs (DMARDs) are another class of drugs for JIA with potential benefit but also considerable side effects for youth with JIA. They do not cause reversal of existing damage but can result in reduced joint swelling, pain and destruction in JIA patients. The agent most frequently used by rheumatology experts is methotrexate, a drug first used by the famous Boston pediatric pathologist, Dr Sidney Farber, in the late 1940s to improve the high mortality rate of children with leukemia. It was approved by the US FDA in 1953, as an anticancer agent and has since been used in various serious illnesses, including JIA who have polyarthritis, oligoarticular disease that is resistant to other treatments, and also chronic, severe uveitis that is steroid-refractory.20,25 Other DMARDs that are used by experts include gold salts (intramuscular), sulfasalazine, hydroxychloroquine, D-penicillamine and leflunomide (Table 5). Gold salts are not used often due to severe toxicity. Leflunomide is also not used very often in adolescent females because of its long half-life and significant risk for teratogeneis. Methotrexate is used in moderate dosages in combination with other medications, such as hydroxychloroquine, sulfasalazine or biologic response modifiers (Table 6). Such combinations achieve better reduction in joint inflammation and destruction in dosages best determined by experts in this disease. Cytotoxic Agents These drugs are utilized occasionally to attempt treatment of rheumatoid disorders that have been resistant to other agents already discussed. They include azathioprine, chlorambucil and cyclophosphamide; sometimes they are part of treatment protocols for autologous bone marrow transplantation. Agents also used in such refractory situations include mycophenolate mofetil and cyclosporine. Reasons for not using these drugs more often include the availability of other drugs with normally good efficacy and also the high incidence of significant side effects to cytotoxic agents. It is important to avoid use of live vaccines in those taking cytotoxic agents; these attenuated â&#x20AC;&#x2DC;liveâ&#x20AC;&#x2122; viral vaccines include the measles vaccine, mumps vaccine, rubella vaccine, varicella vaccine, yellow fever vaccine nasal-spray influenza vaccine, rabies vaccine and others. Cytotoxic agents should only be used by experts in rheumatoid diseases.26 Cyclophosphamide is a nitrogen mustard alkylating agent, which can lead to nausea, emesis, anorexia,

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Table 5. Potential Effects from Chronic Corticosteroids (Can be Irreversible) Hyperglycemia Infections Osteoporosis Osteonecrosis of hips (2% for most; upto 25% in SLE) Hirsuitism Hypertension Pseudotumor cerebri Striae Growth failure Accelerated atherogenesis Dyslipidemias Cataracts Arterial damage

lethargy, diarrhea, rash, weakness, hair loss, bone marrow suppression, hemorrhagic cystitis, hematuria, proteinuria, amenorrhea, pigmentation (skin and nail), anaphylaxis, teratogencity and other side effects. Chlorambucil can lead to agitation, bone marrow suppression, tremor, confusion, hepatotoxicity, fertility impairment, teratogenicity and others. Azathioprine can lead to similar side effects including acute pancreatitis, increase risk for cancer, fertility impairment, teratogenicity and increased risk for serious infections. Cyclosporine can induce abdominal pain, headache, tremor, dizziness, acne, nephrotoxicity, hepatotoxicity, hypertension, malignancy, encephalopathy and others. Finally, mycophenolate can lead to cough, headache, back pain, rash, increased infection risk, reactivation of latent viral infections, anorexia, nausea, emesis, weakness, possible increased risk for lymphoma and other cancers, leukopenia, pure red cell aplasia and teratogenicity. There can be multiple drug interactions including decreased efficacy of oral contraceptives. Biologic Response Modifiers Biologic response modifiers or biologics are medications that are genetically engineered to block various immune system pathways that are implicated in the rheumatoid disease inflammatory processes.4,27-29 They can be particularly beneficial to adolescents with rheumatoid diseases with inflammatory joint disease as well as inflammatory bowel disease. They include medications such as rituximab, adalimumab, certolizumab pegol, tocilizumab, infliximab, abatacept, etanercept and golimumab. A potential severe adverse

Pediatrics Table 6. DMARDs for Rheumatoid Disorders* Generic name

Adult dosage

Adverse effects

Monitoring

Methotrexate

10-15/week; usually given IM or orally

Anorexia, nausea, emesis, abdominal cramps, hepatotoxicity, hepatic fibrosis, bone marrow suppression, allergic pneumonitis, opportunistic infections

LFTs, hepatitis B and C serologies for those with risk factors for infection, CBC with platelets, SCr

Add folic acid 1 mg daily

Teratogenic; abortifacient; avoid with renal insufficiency (CrCl <30 ml/min); increased toxicity if given with NSAIDs, trimethoprim, sulfamethoxazole/trimethoprim Leflunomide

Initial: 100 mg/day for 3 days Maintenance: 10-20 mg/day Add folic acid 1 mg daily

Diarrhea, nausea, reversible hair loss, rash, bone marrow suppression, hepatotoxicity, interstitial lung disease, peripheral neuropathy, anaphylaxis, severe dermatological reactions, weight loss Teratogenic

LFTs, CBC with platelets Drug elimination procedure: Stop leflunomide and administer cholestyramine 8 g 3x/day for 11 days Verify plasma level is <0.02 mg/l

Hydroxychloroquine

400-600 mg/day; maintenance is 200-400/per day; also used as antimalaria drug

Dermatological reactions including skin and mucosal pigmentation (blue/black), nausea, epigastric pain, retinal damage, blurred vision, keratopathy, central nervous system toxicity, hemolysis with G6PD deficiency

Ophthalmic exams, CBC with platelets, G6PD

Gold salts

IM: 10 mg as an initial dose, followed by 25 mg on Week 2, then 25-50 mg weekly until 1 g total dose achieved

Nausea, diarrhea, stomatitis, decreased appetite, exfoliative dermatitis, proteinuria, hepatitis, interstitial pneumonitis, enterocolitis, blood dyscrasias with bone marrow suppression

CBC with platelets, urinalysis

Gold sodium thiomalate

Maintenance: 25-50 mg every 2-4 ‘Nitroid’ reaction: Flushing, fainting, sweating and dizziness within 30 minutes of injection weeks Sulfasalazine

500 mg daily increasing to a maximum daily dose of 3,000 mg (in 2 divided doses) Consider adding folic acid 1 mg daily. Also used for inflammatory bowel disease

D-penicillamine

Initial: 125-250 mg/day, increase by 125-250 mg/day at 1-3 month intervals. Maintenance: 500-750 mg/day. Consider addition of pyridoxine 25 mg/day Also used to treat Wilson’s disease, cystinuria, arsenic poisoning

Nausea, anorexia (use enteric coated form to reduce), rash, headache, hepatitis, bone marrow suppression, hemolytic anemia with G6PD deficiency, oligospermia (reversible), aplastic anemia, hypersensitivity reactions, renal toxicity

CBC with platelets, LFTs, urinalysis, G6PD

Aplastic anemia, lupus-like syndrome, pruritus/rash, proteinuria, membranous glomerulonephritis, elastosis perforans serpiginosa, myasthenic syndrome, bone marrow suppression, drug fever, mouth ulcers, GI distress, altered taste, neuropathy, intrahepatic cholestasis

CBC with platelets, urinalysis, LFTs

Contraindicated during pregnancy Avoid in renal insufficiency Avoid concomitant use with gold therapy, antimalarial and cytotoxic agents Do not coadminister with antacids, iron or food

LFTs = Liver function tests; CBC = Complete blood count; SCr = Serum creatinine; CrCl = Creatinine clearance; G6PD = Glucose-6-phosphate dehydrogenase. *Used with permission from: Greydanus DE, Moore MD, Feucht C. Concepts of rheumatoid disorders (Chapter 11). In: Adolescent Medicine: Pharmacotherapeutics in Medical Disorders. Greydanus DE, Patel DR, Feucht C, Omar HA, Merrick J. (Eds.), 2012:p.333-5.

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Pediatrics effect of the immune blocking powers of these drugs is the stimulation of hepatitis B or reactivation of latent M. tuberculosis infection as well as post-drug increase in lymphoma and others cancers.30 These agents are used alone or in combination with DMARDs, especially methotrexate, for those with refractory disease including DMARDs. It is not recommended to use more than one biologic agent due to the failure of additive effect and the high-risk for severe side effects. A lower response rate to the agent may occur because of the development of antibodies to the drug. Patients on these agents should avoid use of attenuated, ‘live’ vaccines. These drugs are given as infusions in clinics or even injection in the patient’s home. Guidelines for their use are published by the American College of Rheumatology and these recommendations are based on various factors, such as disease duration, overall disease activity, and the presence or absence of factors indicating a poor outcome.2,3 They should be only be used by experts in rheumatology and they are extremely expensive in the United States healthcare system. CONCLUSION JIA is the most common rheumatoid disorder in children and adolescents. The term, ‘juvenile’ refers to the onset of symptoms before age 16 years. A number of nondrug treatments are helpful including physical therapy, occupational therapy, rest, moist heat, individualized joint support (i.e., splints, casts, canes or crutches) and others. Pain relief utilizes NSAIDs and corticosteroids (oral, topical, intraarticular, intramuscular, intravenous). Some adolescents need additional medications including DMARDs, especially methotrexate. Refractory situations may also benefit from various cytotoxic agents (azathioprine, cyclophosphamide, chlorambucil, mycophenolate mofetil and cyclosporine. Finally, resistant cases may respond to a new class of drugs called biologic response modifiers or biologics. These agents have considerable potential for severe side effects and should be managed by a clinician with training in this area. Much progress has been accomplished in management of JIA in adolescents and yet, many questions remain in the care of adolescents with JIA.31 REFERENCES 1. Moore MD. Rheumatic diseases. In: Essential Adolescent Medicine. Greydanus DE, Patel DR, Pratt HD (Eds.), McGraw Hill Med: New York (USA) 2006:p.201-34.

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2. Klippel JH, Crofford LJ, Stone JH, Weyand CM (Eds.). Primer on the Rheumatic Diseases. 12th edition, Arthritis Foundation, Atlanta: GA, 2001. 3. National Institute of Arthritis and Musculoskeletal and Skin Diseases. Arthritis and Rheumatic Diseases, National Institutes of Health Publication No. 08-4999, October 2008. Bethesda MD (USA): National Institutes of Health: United States Department of Health and Human Services. (www.niams.nih.gov). 4. Patel DR, Moore MD. Concepts of rheumatology. In: Handbook of Clinical Pediatrics: An Update for the Ambulatory Pediatrician. Greydanus DE, et al. (Eds.), World Scientific: New Jersey 2010;25:697-713. 5. Prakken B, Albani S, Martini A. Juvenile idiopathic arthritis. Lancet 2011;377(9783):2138-49. 6. Petty RE, Southwood TR, Manners P, Baum J, Glass DN, Goldenberg J, et al; International League of Associations for Rheumatology. International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol 2004;31(2):390-2. 7. Bader-Meunier B, Wouters C, Job-Deslandre C, Cimaz R, Hofer M, Pillet P, et al. Guidelines for diagnosis and treatment of oligoarticular and polyarticular juvenile idiopathic arthritis. Arch Pediatr 2010;17(7):1085-9. 8. Beresford MW. Juvenile idiopathic arthritis: new insights into classification, measures of outcome, and pharmacotherapy. Paediatr Drugs 2011;13(3):161-73. 9. Martini A, Lovell DJ. Juvenile idiopathic arthritis: state of the art and future perspectives. Ann Rheum Dis 2010;69(7):1260-3. 10. Singh S, Mehra S. Approach to polyarthritis. Indian J Pediatr 2010;77(9):1005-10. 11. Agarwal M, Sawhney S. Laboratory tests in pediatric rheumatology. Indian J Pediatr 2010;77(9):1011-6. 12. Hashkes PJ, Laxer RM. Medical treatment of juvenile idiopathic arthritis. JAMA 2005;294(13):1671-84. 13. Padeh S, Pinhas-Hamiel O, Zimmermann-Sloutskis D, Berkun Y. Children with oligoarticular juvenile idiopathic arthritis are at considerable risk for growth retardation. J Pediatr 2011;159(5):832-7. 14. Rabinovich CE. Treatment of juvenile idiopathic arthritisassociated uveitis: challenges and update. Curr Opin Rheumatol 2011;23(5):432-6. 15. Behrens EM. Macrophage activation syndrome in rheumatic disease: what is the role of the antigen presenting cell? Autoimmun Rev 2008;7(4):305-8. 16. Shigemura T, Yamazaki T, Hara Y, Ou JN, Stevens AM, Ochs HD, et al. Monitoring serum IL-18 levels is useful for treatment of a patient with systemic juvenile idiopathic arthritis complicated by macrophage activation syndrome. Pediatr Rheumatol Online J 2011;9(1):15.

Pediatrics 17. Hayward K, Wallace CA. Recent developments in antirheumatic drugs in pediatrics: treatment of juvenile idiopathic arthritis. Arthritis Res Ther 2009;11(1):216. 18. Beukelman T, Patkar NM, Saag KG, Tolleson-Rinehart S, Cron RQ, DeWitt EM, et al. 2011 American College of Rheumatology recommendations for the treatment of juvenile idiopathic arthritis: initiation and safety monitoring of therapeutic agents for the treatment of arthritis and systemic features. Arthritis Care Res (Hoboken) 2011;63(4):465-82. 19. Berard R, Laxer RM. Improving the quality of care in children with juvenile idiopathic arthritis: a step in the right direction. J Rheumatol 2011;38(5):789-90. 20. Greydanus DE, Moore MD, Feucht C. Concepts of rheumatoid disorders. In: Adolescent Medicine: Pharmacotherapeutics in Medical Disorders. Greydanus DE, Patel DR, Feucht C, Omar HA, Merrick J (Eds.), DeGruyter: Berlin, Germany 2012;12:p333-55. 21. Beresford MW, Baildam EM. New advances in the management of juvenile idiopathic arthritis - 1: nonbiological therapy. Arch Dis Child Educ Pract Ed 2009;94(5):144-50. 22. Stanley LC, Ward-Smith P. The diagnosis and management of juvenile idiopathic arthritis. J Pediatr Health Care 2011;25(3):191-4. 23. Kimura Y, Walco GA. Treatment of chronic pain in

pediatric rheumatic disease. Nat Clin Pract Rheumatol 2007;3(4):210-8. 24. Woodward RB, Sondheimer F, Taub D. The total synthesis of cortisone. J Amer Chem Soc 1951;73:4057. 25. Holzinger D, Frosch M, Föll D. Methotrexate in the therapy of juvenile idiopathic arthritis. Z Rheumatol 2010;69(6):496-504. 26. Quartier P. Current treatments for juvenile idiopathic arthritis. Joint Bone Spine 2010;77(6):511-6. 27. Lamot L, Bukovac LT, Vidovic M, Frleta M, Harjacek M. The ‘head-to-head’ comparison of etanercept and infliximab in treating children with juvenile idiopathic arthritis. Clin Exp Rheumatol 2011;29(1):131-9. 28. Kuo HC, Yu HR, Wu CC, Chang LS, Yang KD. Etanercept treatment for children with refractory juvenile idiopathic arthritis. J Microbiol Immunol Infect 2011;44(1):52-6. 29. Yokota S, Imagawa T, Takei S, Murata T, Tomiita M, Itoh Y, et al. Guidance on using tocilizumab for juvenile idiopathic arthritis. Mod Rheumatol 2011;21(6):563-71. 30. Ruperto N, Martini A. Pediatric rheumatology: JIA, treatment and possible risk of malignancies. Nat Rev Rheumatology 2011;7(1):6-7. 31. Mellins ED, Macaubas C, Grom AA. Pathogenesis of systemic juvenile idiopathic arthritis: some answers, more questions. Nat Rev Rheumatol 2011;7(7):416-26.

■■■■

ESA dose Predicts Death in Kids on Peritoneal Dialysis In children receiving chronic peritoneal dialysis (PD), anemia and high requirements for erythropoiesisstimulating agents (ESAs) independently predict mortality, according to results from a global cohort study published online March 7 in the Journal of the American Society of Nephrology. (Source: Medscape)

Breastfeeding won’t Ward off Obesity in Child An intervention designed to encourage longer and more exclusive breastfeeding among mothers failed to prevent obesity in their children, a large, randomized trial conducted in Belarus found. (Source: Medpage Today)

Parent Training Tops Meds in ADHD Parent behavior training (PBT) topped medication and other interventions for preschool children at risk of attention-deficit/hyperactivity disorder (ADHD), a systematic literature review showed. (Source: Medpage Today)

Prebiotics may Guard against Infant Eczema A prebiotic added to infant formula or breast milk may prevent eczema in infants up to 2 years old, but evidence is unclear about whether prebiotics help to prevent other infant allergic diseases, according to a study published online September 27 in the Cochrane Database of Systematic Reviews. (Source: Medscape)

“Disease” Tag Prompts Parents to want Tx for Healthy Babies Giving a baby’s minor symptoms the “disease” label may boost parents’ desire to medicate, even if told drugs won’t work, researchers found. (Source: Medpage Today)

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Pediatrics

Malnutrition: A Daunting Problem for India’s Spectacular Growth Vijayashree Mathad*, Shivprasad S

Abstract In the global campaign of health for all, promotion of proper nutrition was one of the eight elements of primary healthcare. Mother’s literacy has a much higher impact than father’s literacy on better nutritional status of children. Lower socioeconomic condition, higher birth order, lower birth interval and faulty feeding habits have adverse effects on nutritional status of children. Faulty feeding practices are commonly observed and diets of most children are not adequate for calories and proteins as per Indian Council of Medical Research (ICMR) guidelines. Hence, there is a urgent need for the government to strengthen the policies and invest more funds to combat malnutrition among under-five children.

Keywords: Nutrition, lower socioeconomic condition, faulty feeding practices

alnutrition is the principal cause of child deaths. Half of all child deaths in India could be prevented if this one issue is tackled. Children die because malnutrition lowers a child’s resistance to infection.

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1951 - Health for your child and world’s children.

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1979 - A healthy child a sure future.

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1984 - Children’s health tomorrows’ wealth.

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2005 - Make every mother and child count.

“Children are our future, and their mothers are its guardians”.1 Almost 11 million children will die before they reach the age of five; four million of them in the first month of life. A large number of them could be prevented by promoting their good health. In this country, almost one out of every 2 children goes to bed on an empty stomach.

PATHOPHYSIOLOGY

Malnutrition is one of the largest factors suppressing India’s spectacular growth. In a country of lunar missions, billionaires and nuclear power, a staggering 46% of all Indian children under five years old are still underweight. Malnutrition is widespread in rural, tribal and urban slum areas and it is a significant public health problem described as a silent killer, silent emergency, invisible enemy affecting those who cannot express their voice and have to depend upon others for their advocacy.1 Growing children are most vulnerable to its consequences. Their nutritional status is a sensitive indicator of community health and nutrition.2

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Undernutrition: Insufficient food intake over a extended period of time.

ÂÂ

Overnutrition: Excessive intake of food over a period of time.

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Imbalance: Disproportion among essential nutrients with or without absolute deficiency of any nutrient.

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Specific deficiency: Relative or absolute lack of an individual nutrient.

Realizing the importance of children, World Health Organization (WHO) had declared themes relating to children for the following years: *Lecturer Dept. of Public Health JNMC, KLE University, Belgaum, Karnataka

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Malnutrition is a pathological state resulting from a relative or absolute deficiency or excess of one or more essential nutrients.3 Forms of malnutrition

There are two clinical forms of protein energy malnutrition: Kwashiorkor and marasmus (Table 1). It is not only an important cause of childhood morbidity and mortality, but also leads to permanent impairment of physical and mental growth of those who survive. Diagnosis The current WHO recommendation is to use the Z-score or standard deviation (SD) system to grade

Pediatrics Table 1. The Two Clinical Forms of Protein Energy Malnutrition: Kwashiorkor and Marasmus Marasmus

Kwashiorkor

Obvious muscle wasting

Hidden edema may mask weight loss

Severe loss of subcutaneous fat

Some loss of fat

Severe malnutrition

Edema over legs, arms and face

Mental changes present quite apathetic

Irritable, apathetic and moaning

No skin changes

Skin changes: Flaky paint dermatosis

Less hair changes

Hair changes: Sparse, silky, easily pluckable

No organomegaly

Hepatomegaly + Low albumin, urea/creatinine

Good appetite

Poor appetite

History of loose stools +

History of diarrhea +

undernutrition. This system allows us to measure all the three indices and express the results in terms of Z scores or SD units from the median of the international reference population, developed from anthropometric data collected in the United States by the National Center for Health Statistics (NCHS). Although widely recommended, the Z scores have not been widely in use in India, especially in community-based studies.4 Indicators of Malnutrition Indicators

Nutritional status

Stunting (low heightfor-age)

Chronic undernutrition

Wasting (low weight-for height)

Acute undernutrition

Underweight (low weight-for-age)

Acute and chronic undernutrition

Upto -2SD: Normal

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<-2SD to -3SD: Moderate

ÂÂ

<-3SD: Severe

Epidemiology of malnutrition

Morbidity and Mortality In India, where everything is on a large scale malnutrition is daunting, an estimated 200 million children are underweight at any given time, with more than six million of those children suffering from the worst form of malnutrition, severe acute malnutrition. Experts estimate that malnutrition constitutes over 22% of India’s disease burden, making malnutrition one of the nation’s largest health threats.6 Prevalence of clinical protein energy malnutrition (PEM) in the form of marasmus was found to be more than kwashiorkor, while emaciation and vitamin A deficiency in the form of Bitot’s spots and vitamin B complex deficiencies in the form of angular stomatitis and cheilosis were seen in few children. Many children were found to be suffering from upper respiratory tract infection (URTI).2 According to National Family Health Survey (NFHS-3), a large number of children with diarrhea and acute respiratory infection are malnourished.7

Age

The classification can be summarized as follows: ÂÂ

Malnutrition in children depends on various factors like poor food quality, insufficient food intake and severe and repeated infectious diseases or most of the time the combination of all the factors. Assessment of growth thus not only serves as a means for evaluating the health and nutritional status of children, but also provides an indirect assessment of the quality-of-life of an entire population.5

Mid-upper Arm Circumference The degree of severity of malnutrition in children on the basis of mid-upper arm circumference (MUAC) is given below.

The prevalence of malnutrition was much higher in the lower age groups of 12-35 months and it decreased in the older age groups of 36-47 months and in the age groups of 48-60 months.8,9 In a study conducted in Coimbatore slums among under-fives, the prevalence of wasting seen among 0-11, 12-23, 24-35, 36-47 and 48-59 months age group was 32.1%, 23.8%, 31.8%, 36.1% and 20.7%, respectively.8 In a drought-affected district of Odisha, the prevalence of stunting was found to be high in 37-48 months age group.10 According to a study done in Kenya, stunting was maximum in 12-24 months age group children and was statistically significant.11

>14 cm: Normal

Sex

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12.5-14.0 cm: Mild/Moderate wasting

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<12.5 cm: Severe wasting

A study conducted among under-five children of rural area of Karnataka, who attended anganwadi, 70%

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Pediatrics of the children were malnourished. The prevalence of malnutrition was slightly more in females than in males.8,9 The mean MUAC among boys was higher than girls at all ages except five years. Significant sex differences were observed at ages 3 (p < 0.005) and 4 (p < 0.05) years.12

Religion According to NFHS-3, it is reported that Hindu and Muslim children are equally likely to be undernourished, but Christian, Sikh and Jain children are considerably better nourished. It is also reported that the prevalence of underweight and wasting among Hindu children was slightly more than that of Muslim children.7

Socioeconomic Status Fatherâ&#x20AC;&#x2122;s occupation had a significant bearing on the nutritional status of the child. The maximum prevalence of malnutrition was observed in children of laborers. In a study conducted in Uttar Pradesh, the prevalence of underweight was maximum among children of low socioeconomic status than among children of high socioeconomic status (p < 0.02).7,13

Literacy Status Literacy of mother displayed a significant (p < 0.001) relationship, with malnutrition being highest among children whose mothers were illiterate.14 In Karnataka, it was observed that children of illiterate mothers were severely stunted.7,15 In a study conducted in West Bengal, substantial difference was observed in the prevalence of malnutrition among children of illiterate fathers versus literate fathers, which were statistically significant (p < 0.05).15

Birth Order and Birth Interval A significant association (p < 0.001) was observed between birth order and the nutritional status of the child. Highest prevalence of malnutrition was observed in children with birth order 4 and above.14 Prevalence of underweight was more among children of birth interval <36 months, while it was significantly less (p < 0.05) in children with birth interval >36 months.15

Feeding Practices Only few children were put on breastfeeding within two hours of birth. Colostrum was not given to majority of children and exclusive breastfeeding was

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not done in many children. Many children started supplementary feeding by six months.2 In a study conducted at Varanasi, some of rural children had delayed breastfeeding by one day and the colostrum was discarded in majority children and prelacteal feeds were commonly given, like goatâ&#x20AC;&#x2122;s milk and boiled water with honey and sugar water.16 It has been observed that lack of exclusive breastfeeding upto six months is significantly associated with underweight.11

Calorie and Protein Intake An analysis of 24-hour dietary intake recall data revealed that undernourished children had significantly lower energy and protein intake than normal children (p < 0.05).17 The study undertaken in Ghaziabad revealed that the childrenâ&#x20AC;&#x2122;s diet was adequate for proteins but was deficient in energy.18 The caloric and protein intake was significantly (p < 0.001) lower among malnourished children. The caloric intake was <80% of RDA among majority of children and the protein intake was <80% of RDA among >90% children.14 Average calorie intake was 2271.7 kcals and nearly half of the studied families were getting <2,400 kcals.15 An ICMR study has observed that energy intakes are about 70% of RDA in children of 1-6 years age group, while the protein intake was found to be adequate.19 A study in a rural area near Mysore, Karnataka revealed that the nutrient intake was grossly inadequate.20

Immunization Status According to the results observed in a multicentric survey in Karnataka, few children were partially immunized and some children did not receive any vaccine among children.21

Malnutrition In studies conducted in an urban slum of Delhi and Jabalpur and evaluating the prevalence of underweight, stunting and severe underweight, it was observed that the prevalence stunting was more than that of wasting and severe wasting.11,17 In Karnataka, the prevalence of underweight, stunting and wasting was 43.9%, 36.6% and 20.0%, respectively and these are comparable to the results in our study.21 In a study conducted in a rural area in Faridabad district, malnutrition was detected in 27.2% of the

Pediatrics children by using mid-arm circumference. The sensitivity and specificity was found to be 34.1% and 80.8% and the authors concluded that this criterion detected moderately severe cases of malnutrition.22 In a study conducted at Vadodara city, among children’s <5 years attending Integrated Child Development Services (ICDS) anganwadis, the prevalence of malnutrition according to Indian Academy of Pediatrics (IAP) classification was 40.5%, 20.1% and 2.3%.13 The severe degree (below -3 SD) of underweight, stunting and wasting was 27.8%, 30.3% and 6.5%, respectively.2 RECOMMENDATIONS ÂÂ

Mothers should be advised to initiate breastfeeding within one hour of delivery.

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Importance of exclusive breastfeeding for the first six months of baby’s life and proper weaning thereafter should be properly explained to mother.

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Nutritional education has to be imparted to the people regarding consumption of cost-effective nutritious diet. Special efforts have to be made to improve acceptance of family planning methods for limiting the family and to give adequate spacing between children.

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Environmental sanitation has to be promoted in reducing infection and breaking the vicious cycle of infection leading to undernutrition.

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Socioeconomic development among the rural masses needs to be ensured, which is the important factor to tackle malnutrition, mainly undernutrition.

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Government should allocate more money in health sector for integrated health packages and should ensure proper functioning of health programs.

CONCLUSION Faulty feeding practices were commonly observed and most of the children’s diet was not adequate for calories and proteins as per ICMR guidelines. The mean height and weight of the children were lesser than the WHO reference data. No child was found to be overweight or obese. Literacy of the mother had a much higher impact than father’s literacy on better nutritional status of children. Lower socioeconomic condition, higher birth order, lower birth interval and faulty feeding habits were found to have adverse effect on nutritional status of children. On the other hand, higher socioeconomic status, lower birth order, higher birth interval and proper feeding

habits had beneficial effects in protecting children from malnutrition. Among micronutrient deficiencies, nearly one-third of children were detected clinically to have anemia. One-tenth of children were found to have vitamin ‘A’ deficiency, which implies public health problem as per WHO criteria. Some children had vitamin ‘B’ complex deficiency while still lesser number of children were diagnosed to have rickets. REFERENCES 1. Lal S. Combating malnutrition in India through community efforts. Indian J Commun Med 2003;28(3):99-106. 2. Rao VG, Yadav R, Dolla CK, Kumar S, Bhondeley MK, Ukey M. Undernutrition & childhood morbidities among tribal preschool children. Indian J Med Res 2005;122(1): 43-7. 3. Park K. Park’s Textbook of Preventive and Social Medicine. 18th edition, M/s. Banarsidas Bhanot Publishers. Jabalpur 2005:p.416-7. 4. Seetharaman N, Chacko TV, Shankar SLR, Mathew AC. Measuring malnutrition: the role of Z scores and the composite index of anthropometric failure (CIAF). Indian J Commun Med 2007;32(1):35-9. 5. World Health Organization, Global database on malnutrition. Available at: http://www.who.int/ nutgrowthdb/en/ (Cited on 12-12-10). 6. Malnourished millions: Malnutrition in India. Available at: http://malnourishedmillions.blogspot.com/2010/02/ khargone-and-khandwa-difference.html (Assessed on 1507-2010). 7. National Family Health Survey. Available at: http://www. nfhsindia.org/data/ka-pre.pdf. (Cited on 24-12-2010). 8. Joseph B, Rebello A, Kullu P, Raj VD. Prevalence of malnutrition in rural Karnataka, South India: a comparison of anthropometric indicators. J Health Popul Nutr 2002;20(3):239-44. 9. Bhalani KD, Kotecha PV. Nutritional status and gender differences in the children of less than five years of age attending ICDS anganwadis in Vadodara city. Indian J Commun Med 2002;27(3):124-9. 10. Mohapatra A, Geddam JJ, Marai N, Murmu B, Mallick G, Bulliyya G, et al. Nutritional status of preschool children in the drought affected Kalahandi district of Orissa. Indian J Med Res 2000;111:90-4. 11. Bloss E, Wainaina F, Bailey RC. Prevalence and predictors of underweight, stunting, and wasting among children aged 5 and under in western Kenya. J Trop Pediatr 2004;50(5):260-70. 12. Mandal G, Bose K. Assessment of undernutrition by midupper arm circumference among pre-school children of Arambag, Hooghly District, West Bengal, India:

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Pediatrics An observational study.  Int J Pediatr Neonatol 2009;11 (1):1-4.

17. Saxena N, Nayar D, Kapil U. Prevalence of underweight, stunting and wasting. Indian Pediatr 1997;34(7):627-31.

13. Reddy DCs, Singh K, Tiwari IC. Epidemiology of nutritional deficiency disorders among tribal preschool children around Manikpur, Banda district, Uttar Pradesh. Indian J Prevent Soc Med 1984;15(1-2): 57-62.

18. Garg SK, Singh JV, Bhatnagar M, Chopra H. Nutritional status of children (1-6 years) in slums of Ghaziabad city. Indian J Commun Med 1997;22(2):70-3.

14. Verma R, Prinja S. Assessment of nutritional status and dietary intake of preschool children in an urban pocket. Int J Epidemiol 2008;6(1):1-5.

19. Gupta M, Jain A, Singh RN. Nutritional status of urban and rural preschool children in Western Rajasthan (in and around Bikaner City). II. Clinical study. Indian J Pediatr 1978;45(370):345-51. 20. Lakshmi AJ, Khyrunnisa B, Saraswathi G, Jamuna P. Dietary adequacy of Indian rural preschool children influencing factors. J Trop Pediatr 2005;51(1):39-44.

15. Ray SK, Biswas AB, Gupta SD, Mukherjee D, Kumar S, Biswas B, et al. Rapid assessment of nutritional status and dietary patterns in a municipal area. Indian J Commun Med 2000;25(1):14-8.

21. Singh P, Yadav RJ. Immunization status of children of India. Indian Pediatr 2000;37(11):1194-9.

16. Katiyar GP, Agarwal DK, Tripathi AM, Agarwal KN. Feeding practices in Varanasi district. Indian Pediatr 1981;18(1):65-70.

22. Sood AK, Kapil U. Anthropometry in detection of protein energy malnutrition. Indian Pediatr 1984;21(8): 635-9.

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GERD Label in Infants Encourages Parents to Medicate

Parents who were told that fussy infants had gastrointestinal reflux disorder (GERD) were more interested in giving them medications - even when told the drugs would likely be ineffective - than when the children were not diagnosed with a disease, according to a new study. (Source: Medscape)

Sleep Disordered Breathing Takes Toll on Kids

Children with sleep disordered breathing (SDB) are at significantly increased risk of behavioral problems, including hyperactivity, attention problems, aggressiveness, and reduced social competency, results of a longitudinal study showed. (Source: Medpage Today)

Air Pollution Linked to Neural Tube Defects

Early maternal exposure to high levels of air pollution can cause neural tube defects, according to new Stanford University research published online March 28 in the American Journal of Epidemiology. (Source: Medscape)

Whole-cell Pertussis Vaccine Shot Boosts Later Protection

Protection against whooping cough was better in the past, with an older whole-cell pertussis vaccine (wP), than it is now with a series of doses of acellular pertussis vaccine (aP), a new study shows. (Source: Medscape)

Older Fathers more Likely to have Autistic Grandchildren

Men who have children when they are older are more likely to have grandchildren with autism, according to a study which shows for the first time that risk factors for autism may build up over generations. Men who had a daughter when they were 50 or older were 1.79 times more likely to have a grandchild with autism than men between 20 and 24, and with sons the likelihood was 1.67 times. (Source: Medscape)

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Medifinance

Funding of Financial Goals

octors have studied hard to qualify, their earnings potential is significant, but right now money is likely to be tight. They may have student debts to repay, yet they may like to buy a house, not to mention have the occasional holiday. Most needs and aspirations call for a financial commitment. Providing for this commitment becomes a financial goal. Fulfilling the financial goal sets doctors on the path towards realizing their needs and aspirations. People experience happiness, when their needs and aspirations are realized within an identified time frame. Financial planning is a planned and systematic approach to provide for the financial goals that will help people realize their needs and aspirations, and be happy. Financial health check:

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Does one have a fund for emergencies?

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Is one’s income protected properly?

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Doctors have good earning potential - does their bank recognize that?

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How much does one need to save for a deposit on a property?

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Do doctors understand the different mortgage options?

Cash Flow Management Every successful business relies on a financial system to carefully control income and expenses. A business must have a system to know its present financial status, and more important, to plan for its future financial moves. A doctor’s personal financial situation is comparable to that of a business. Both have concerns for profit, income and expenses, and spending decisions affected by anticipated circumstances. Cash flow management is a mechanism, not a budget. It allows the doctor to assess his financial situation from a long-term, systematic perspective. It helps him understand that one move, such as a periodic tax payment, can affect his disbursements for several months prior to, and following, the actual payment. Budgets are too immediate in scope to allow you to relate a current income to an expense at a later date.

It is thus essential to begin a systematic savings and investment program to accomplish financial and retirement goals to control income and disbursements. Most doctors have not saved as much as they would have wished. The reason is not that they did not intend to save, but they did not have a system. Lacking a system makes it very easy to be distracted by the many opportunities to spend earnings. The financial needs and desires of doctors present unique situations, and so the system must be flexible enough to accommodate whatever they require. It should be tailored to their needs and not influenced by what their neighbor is doing. While his friends or neighbors might be managing cash flow to save for an overseas vacation, the doctor may need to direct cash flow towards current tuition for a degree. A doctor’s system should be flexible, but also disciplined enough to guide and point him in the right direction. If the cash flow system becomes a hindrance, it should not be abandoned but redesigned. With sensitive shaping to a doctors needs, it will allow financial freedom rather than acting as a financial barrier. A Personal Cash Flow Management System, if used consistently, can be of great value in helping to gain control of one’s personal financial situation. It will ensure that there is always cash available to pay bills as they come due. It will also help one to save more money in a systematic way. Time is a doctor’s greatest ally. The more time one has, then less money one will need to save and invest. The less time one has, then more money it will take. Replacing high-priority actions with tasks of lower priority, is a deadly enemy of a doctor’s goal to retire with financial dignity. Importance of Goals A cash flow plan functions best if it reflects a doctor’s goals, whether long-term or short-term. The purchase of a luxury sedan in three years or the decision to remodel your basement next winter should influence one’s cash flow plans.

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Medifinance The goals that one has already set will help one shape the personal version of this system. These should often be referred. As a doctor achieves some short-term goals, or begins to see significant progress towards long-term goals, his enthusiasm for this process will increase, and that will make the system even more effective for him. Establishing Your System There are four factors that will help a doctor establish control over money: ÂÂ

Income/Expense: Identify and isolate income and disbursements. Consider whether income is gross, or net.

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Category: Define the kinds of income one receives and the kinds of expense one incurs. Categorize them according to the fixed or flexible nature of the item.

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Time: The system should be based on a monthly structure. One should quantify his income and expense within a 12-month format.

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Amount: Income and expenses are expressed in rupees.

Controlling your Cash Flow Once a doctor has qualified all financial transactions, he will be well on the way to controlling his cash flow, rather than letting it control him.

Periodic Fixed Expenses Most people lose control over cash flow because they have no system to handle periodic known expenses of a substantial nature. Good examples of this type of expense might be a large real estate tax bill due every March, an income tax payment due by 15th September or a life insurance premium due in December. What people frequently do is remember the bill a month before it is due and start scrimping, but it is too late! So, what happens then? In the ensuing months, they start running behind on bills or they simply do not make the planned payment at all. Interest charges are then added, and their attitude starts to decline. The solution is to schedule these larger payments and start saving for them on a monthly basis. For example, for a small additional amount, an automatic bank deduction can be made regularly to cover these expenses as and when they are due. Save Regularly and Systematically It is important to assign a portion of each paycheck for the savings and investment program. Consider it an obligation just as important as any other monthly obligation. In addition to saving a portion of monthly income, it is equally important that any money saved by tax planning each year be invested the following year. This will give one an additional source of investment funds as well as a means of reducing income tax liability on a regular basis.

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Risk profiles are all about a person’s tolerance for risk, tolerance for loss and how a loss might emotionally affect him and the subsequent decisions the person may choose to make.

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Most medical professionals enjoy such a strong and consistent level of income that often only a minimal level of investment risk is required to achieve their objectives.

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Personal residences represent the bulk of many people’s fortunes, and have great sentimental value. A doctor’s personal residence is thus the most important asset, which needs to be protected from creditor claims.

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An alternative to an outright sale is the sale and leaseback of the residence to a friendly third-party on a deferred instalment note. This allows the doctor to transfer the ownership of the residence without having to move out.

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Assets owned by a doctor through an LLC or a limited partnership are not deemed owned by the doctor because these legal entities have their own separate legal existence.

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Forcing the plaintiff to pursue an ownership interest in an LLC or in a limited partnership is a lot more advantageous for the doctor because interests in LLCs and limited partnerships are not subject to attachment by a plaintiff.

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Medilaw

Proof of Age MC Gupta

Q. Why do the courts insist on school certificate etc. for proof of age instead of the scientific approach of bone ossification? There is a possibility that documents may be false. For example, a main accused in the recent Delhi gang rape case (Nirbhaya case) appears to be an adult by all appearances. Is it fair? Ans. ÂÂ

It is not a valid question. Courts are bound by law. They cannot import their own idea of fairness into their judgments in violation of law.

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The courts insist on school certificate, etc. for proof of age instead of the scientific approach of bone ossification because Rule 12(3) of the Juvenile Justice (Care and Protection of Children) Rules, 2007, reads as follows: “3) In every case concerning a child or juvenile in conflict with law, the age determination inquiry shall be conducted by the court or the Board or, as the case may be, the Committee by seeking evidence by obtaining–

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It is clear from the above that the ossification test can be done only when documentary evidence is not available.

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It is also clear that ossification test report cannot be given by a single doctor. It must be given by a duly constituted board. This is clear from a recent direction given by Delhi High Court as follows: “Allowing a plea, a bench of HC said, “The Juvenile Justice (Care and Protection of Children) Rules envisage that to determine the age of the offender based on the ossification test, the report must come from a duly constituted medical board and not from any single member team who alone may not be competent to give the correct opinion.” Therefore, HC said, this matter deserves to be remanded back to the trial court with a direction to call for a fresh report from a duly constituted medical board of a government hospital comprising a minimum of one dentist, one general physician and one radiologist.” (Times of India, 26 February 2013, http://timesofindia. indiatimes.com/city/delhi/HC-throws-out-bone-test-bysingle-doctors/articleshow/18683819.cms)

(a) (i) the matriculation or equivalent certificates, if available; and in the absence whereof;

(ii) the date of birth certificate from the school (other than a play school) first attended; and in the absence whereof;

(iii) the birth certificate given by a corporation or a municipal authority or a panchayat;

(b) and only in the absence of either (i), (ii) or (iii) of clause (a) above, the medical opinion will be sought from a duly constituted Medical Board, which will declare the age of the juvenile or child. In case exact assessment of the age cannot be done, the Court or the Board or, as the case may be, the

Committee, for the reasons to be recorded by them, may, if considered necessary, give benefit to the child or juvenile by considering his/her age on lower side within the margin of one year and, while passing orders in such case shall, after taking into consideration such evidence as may be available, or the medical opinion, as the case may be, record a finding in respect of his age and either of the evidence specified in any of the clauses (a)(i), (ii), (iii) or in the absence whereof, clause (b) shall be the conclusive proof of the age as regards such child or the juvenile in conflict with law.” http://wcd.nic.in/icpsmon/pdf/jjrules2007.pdf

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Advocate and Medicolegal Consultant, New Delhi

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Forthcoming events

Forthcoming Events 10th National Summit on “Stress Management " and Workshop on "How to be happy and Healthy" Date: Saturday 2 PM- Sunday 3 PM, 27-28 April 2013 Venue: Om Shanti Retreat Center, Bhora Kalan, Pataudi Road, Manesar Course Directors: Padma Shri and Dr B C Roy National Awardee Dr KK Aggarwal and BK Sapna Organizers: Heart Care Foundation of India, Prajapati Brahma Kumari Ishwariya Vidyalaya and eMedinewS Fee: Donation Rs 250 per person in favour of Om Shanti Retreat Center Facilities: Lodging and boarding provided (One room per family or one room for two persons). Limited rooms for first three hundred registrants. Course: Meditation, Lectures, Practical workshops, Atmosphere: Silence, Nature, Pyramid meditation, Night walk

a Dialogue on Life after Death Padma Shri and Dr BC Roy National Awardee Dr KK Aggarwal in conversation with His Holiness Sri Sri Swami Parmananda Bharti. Date: 28th April, 5 PM Venue: IMA AKN Sinha Auditorium, IMA House, Indraprastha Marg Near ITO, New Delhi Organizers: Heart Care Foundation of India and Bhartiya Vidya Bhavan Introductory remarks: Prof. Uma Devi (Ex-Delhi University) Registration: SMS - 9899974439 Contact: Prof Sunil Kumar, 9818532157 kumar2sunil@ yahoo.com RSVP: Dr Veena Aggarwal, Director HCFI (Seat limited, book your seats in advance, no fee)

Registration: SMS - Rekha 9899974439 rekhapapola@ gmail.com; SMS - BK Sapna 9650692204 bksapna@ hotmail.com ■■■■

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eMedinewS Inspiration

A Violin with Three Strings GM Singh

n Nov. 18, 1995, Itzhak Perlman, a violinist, came on stage to give a concert at Avery Fisher Hall at Lincoln Center in New York City.

If you have ever been to a Perlman concert, you know that getting on stage is no small achievement for him. He was stricken with polio as a child, and so he has braces on both legs and walks with the aid of two crutches. To see him walk across the stage one step at a time, painfully and slowly, is an awesome sight. He walks painfully, yet majestically, until he reaches his chair. Then he sits down, slowly, puts his crutches on the floor, undoes the clasps on his legs, tucks one foot back and extends the other foot forward. Then he bends down and picks up the violin, puts it under his chin, nods to the conductor and proceeds to play.

By now, the audience is used to this ritual. They sit quietly while he makes his way across the stage to his chair. They remain reverently silent while he undoes the clasps on his legs. They wait until he is ready to play. But this time, something went wrong. Just as he finished the first few bars, one of the strings on his violin broke. You could hear it snap - it went off like gunfire across the room. There was no mistaking what that sound meant. There was no mistaking what he had to do. We figured that he would have to get up, put on the clasps again, pick up the crutches and limp his way off stage – to either find another violin or else find another string for this one. But he didn’t. Instead, he waited a moment, closed his eyes and then signaled the conductor to begin again. The orchestra began, and he played from where he had left off. And he played with such passion and such power and such purity as they had never heard before.

Of course, anyone knows that it is impossible to play a symphonic work with just three strings. I know that, and you know that, but that night Itzhak Perlman refused to know that. You could see him modulating, changing, re-composing the piece in his head. At one point, it sounded like he was de-tuning the strings to get new sounds from them that they had never made before. When he finished, there was an awesome silence in the room. And then people rose and cheered. There was an extraordinary outburst of applause from every corner of the auditorium. We were all on our feet, screaming and cheering; doing everything we could to show how much we appreciated what he had done. He smiled, wiped the sweat from this brow, raised his bow to quiet us, and then he said – not boastfully, but in a quiet, pensive, reverent tone – “You know, sometimes it is the artist’s task to find out how much music you can still make with what you have left.” What a powerful line that is. It has stayed in my mind ever since I heard it. And who knows? Perhaps that is the definition of life – not just for artists but for all of us. Here is a man who has prepared all his life to make music on a violin of four strings, who, all of a sudden, in the middle of a concert, finds himself with only three strings; so he makes music with three strings, and the music he made that night with just three strings was more beautiful, more sacred, more memorable, than any that he had ever made before, when he had four strings. So, perhaps our task in this shaky, fast-changing, bewildering world in which we live is to make ‘music’, at first with all that we have, and then, when that is no longer possible, to make ‘music’ with what we have left.

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Confederation of Medical Associations in Asia and Oceania

Be Human Stop Child Abuse What is trafficking?

Trafficking violation of children rights

Trafficking is the moving, selling or buying of woman and children for prostitution within and outside a country for monetary or other consideration with or without the consent of the person subjected to trafficking. (SAARC Convention on Preventing and Combating Trafficking in Woman and Children for Prostitution)

They can roughly be divided in four categories:

Seventy-nine percent of the child abuse cases involve physical abuse An abused child has as much as 50% chances of undergoing further abuse and 10% chances of dying if abuse is not detected at the initial presentation.

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The right to life (art.6.1 CRC);

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The right to survival and development (art 6.2 CRC);

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The right to protection (from discrimination and punishment, (art. 2.2 CRC); from physical or mental violence, (art.19.1 CRC);from economic exploitation (art.32; from sexual exploitation (art. 34): 4)

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The right to participation (art.12)

Physical abuse in children ÂÂ

Physical neglect– Failure to provide adequate food, clothing, shelter, hygiene, protection; inadequate supervision with risk of harm to the child.

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Emotional neglect– Failure to provide love, affection, security, and emotional support; failure to provide psychological care when needed; spouse abuse in presence of the child.

Neglect It is the failure to provide for the child’s basic needs. Neglect can be physical, educational, or emotional. ÂÂ

Physical neglect can include not providing adequate food or clothing, appropriate medical care, supervision, or proper weather protection (heat or cold). It may include abandonment.

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Educational neglect includes failure to provide appropriate schooling or special educational needs, allowing excessive truancies.

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Psychological neglect includes the lack of any emotional support and love, never attending to the child, substance abuse including allowing the child to participate in drug and alcohol use.

Trafficking types

Medical Record A medical record is a medicolegal document. The statements of caretakers, detailed description and sketches or photographs of all of the child’s injuries, emotional status of all family members must be carefully documented. It is important to document ad verbatim everything the child says that is relevant to the diagnosis. Records are required for legal purposes and to refresh the memory in the event of court testimony, which may be required months or years later.

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Forced or bonded labour including domestic work

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Prostitution and Sex tourism

Documentation in the medical record should also include

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Drug trafficking

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History of previous injuries or accidents

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Forced employment in entertainment industries

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Developmental history

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Entertainment (camel jockeying)

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Begging

Procedures performed (skeletal survey, dilated fundus exam)

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Organ trade viz. sale of kidneys

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Purchase and sale of babies for adoption

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Pornography

Diagnosis (suspected child abuse, probable child abuse), followed by a descriptive summary of findings (multiple bruises of various ages)

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Fraudulent or forced marriage

Whether a child abuse/neglect report was made

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The final disposition of the child

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Around the Globe

News and Views Should Sanjay Dutt be pardoned? If the law is clear that under Section 25 (1 A) of the arms act that after the possession of arms without license, there is a minimum punishment of five year imprisonment, then why a long trial. As I understand the role of a judge is to look for the mitigating circumstances at the time of crime. The Supreme Court judges did use their discretion while giving the verdict by reducing the sentence of Sanjay Dutt from 6 to 5 years. Making this less than five years was not under the powers of Supreme Court of India. “Section 25 (1 A) of the Arms Act states that if a person has in his possession a prohibited weapon without a licence, he shall be awarded punishment of not less than 5 years imprisonment and not more than 10 years”. This mean the judges were convinced that the circumstances were not that he could be labeled as a criminal mentally, or a terrorist or had a link with them. In that case they could have given a sentence of not less than 10 years. The very face the court reduced the sentence from 6 to 5 years means the court took a positive and lenient stand in his favor. Only the President of India or the Governor can grant a pardon. Article 161 in the constitution of India 1949 defines the power of Governor to grant pardons, etc., and to suspend, remit or commute sentences in certain cases. The Governor of a State shall have the power to grant pardons, reprieves, respites or remissions of punishment or to suspend, remit or commute the sentence of any person convicted of any offence against any law relating to a matter to which the executive power of the State extends.

Even Bill Clinton was pardoned by the American Society. Hanumana was also pardoned by Ravana when he went to Lanka as an envoy of Lord Rama. He was not killed. Nanavati was pardoned by the government when he was facing murder charges. Harbhajan Singh was pardoned by the society when he spoke in an abusive manner about Symonds, which was mistaken by the Australian as racial remark and under the cover of racial discrimination remark; his abuse to Symonds was totally forgotten by the community. The society forgave Phoolan Devi and elected her to the Parliament. In our day to day life, we always pardon our children when they use filthy abusive language, tease girls or other such actions. I personally feel that everybody who wants to change and can show that he has changed should be given a special consideration and under the Constitution, if the case can be filed convincingly before the President of India or the Governor of the State, he or she should be pardoned. Sanjay Dutt has already been in the jail for over 18 months and now considering that he has totally reformed, one should take it positively. He may be given a suspended sentence under which he may be allowed to live a free life, provided he does not break the Law of the Land for next 3 ½ years for which he is being sentenced. In case he breaks any Law during this period he may be liable to go to prison for the law that he breaks + 3 ½ years.

Public is also supreme. The Public elects the government and government elects governors and the President of India. Both the governor and the President of India normally respect the sentiments of the people.

There are two types of suspended sentences. A judge may unconditionally discharge the defendant of all obligations and restraints. An unconditionally suspended sentence ends the court system’s involvement in the matter, and the defendant has no penalty. A Munich court recently handed an 18-month suspended sentence and a 200,000 Euro fine to former Force India driver Adrian Sutil after he was found guilty of injuring the chief executive of the then Renault Formula One team at a night club in China last year.

It is easy to say that the law should be equal and everybody should be punished but there are always grounds for a mercy. All of us make mistakes and seek pardon.

The purpose of giving punishment is to reform a person and as we all know Sanjay Dutt is already a reformed person so the very purpose of the punishment is defeated if he not pardoned.

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Around the globe This is my personal opinion and Vedic philosophy clearly talks that every personal opinion needs to be respected. Only if my opinion is agreed by 51% of my friends it will be called as a public opinion and 49% may still differ. Don’t use legal term ‘rape’ in medical reports: manual The Health Ministry has advised doctors not to use the word ‘rape’ in medical reports on sexual assault victims, and even in court depositions. ‘Rape is not a medical diagnosis, it is a legal definition, hence the word should not be used while forwarding opinion,’ says the latest Instruction Manual for Forensic Medical Examination Report of Sexual Assault (Victim) brought out by the Indian Council of Medical Research under the Department of Health Research (DHR). The victim must not be refused treatment and examination for want of police papers. The recommendations, which also carry a draft of a ToolKit for Psychological Support for Women Survivors of Sexual Assault, are open to public opinion. Importantly, the manual suggests that doctors should not identify a victim as ‘habituated to sexual intercourse’ on the basis of a ‘finger test.’ Such identification is an unlawful interference with her privacy and an unlawful attack on her honor and reputation and is violation of her human rights. “In a prosecution of sexual assault, where the question of consent is at issue, evidence of the character of the victim or of her previous sexual experience with any person is not relevant to the issue of consent or quality of consent.” As normal examination findings neither refute nor confirm forcible sexual intercourse, circumstantial and other evidence may be taken into consideration. The manual says forcible sexual intercourse is possible without leaving any medical evidence. Submission of the victim may be achieved by emotional manipulation, fear of violence or death or by verbal threats; the force used, or resistance offered, is insufficient to produce injury; bruises may not become apparent for 48 hours following an assault; a delay in reporting the incident will allow minor injuries to fade or heal, and the survivor becoming unconscious, under the effect of alcohol/drugs are some of the reasons cited for absence of injury. Such cases shall be registered in hospital as a medicolegal case (MLC), whether the patient comes on her own or is brought by the police. If the patient comes on her own, the decision to inform the police shall be taken after obtaining due consent from her or her guardian. The doctor should examine such cases if the

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survivor reports to the hospital first without a First Information Report. A victim may come to the hospital only for treatment of the effects of the assault. Under Section 39 of the Cr.PC, the doctor is not bound to inform the police of such cases. Informed refusal to inform the police should be documented. Neither the court nor the police can force the victim to undergo medical examination. It has to be done with her/parents/guardian’s informed consent (depending on age). The consent form will be signed by the person herself if she is above 12, the manual recommends. An important need identified by the DHR is making guidelines available to healthcare providers who work with victims of sexual violence. The manuals are meant, not to replace the standard textbooks, but to supplement them in such a way that these guidelines can be adapted easily to most healthcare provider situations in the country. Most countries which have well-developed services for women subjected to sexual assault have realised the need for psychological support and the need for a survivor support worker who will help the woman through all stages — from the initial contact at the police station or health facility, helping her handle medical examination, discussing an emergency contraception and STD/HIV prophylaxis and subsequently helping her with court proceedings and to normalise her life. The toolkit is meant to help nurses, doctors and counselors give psychosocial support to survivors of rape, help them with the consequences of the experience and through recovery from trauma. Describing rape and sexual assault as severely traumatic experiences often associated with immediate psychological reactions such as shock, shame, guilt, anger, numbing and psychological distress, the toolkit says women and young girls may not be able to discuss everything or reveal all details at the first contact at a police station or hospital. The clinical environment of a hospital or the alien atmosphere in a police station may add to the distress and often result in the survivor not revealing important information. ‘You are not to blame’ is the key message the survivor wants to hear. She should not be quizzed by too many professionals. ‘I believe you’ and ‘I understand your distress’ are two critical messages that will help a survivor in talking about her problem. The partner needs to be educated on the normal reactions to healing after sexual assault: how anger sometimes serves a function and how the partner may also need to talk about his own emotions with the counselor. (Source: The Hindu, March 10, 2013)

eMedi Quiz

Quiz Time Q1. Nurse Ted is administering IV fluids to an infant. Infants receiving IV therapy are particularly vulnerable to: a. Hypotension b. Fluid overload c. Cardiac arrhythmias d. Pulmonary emboli Q2. Nurse Claudine is reviewing a client’s fluid intake and output record. Fluid intake and urine output should relate in which way? a. Fluid intake should be double the urine output. b. Fluid intake should be approximately equal to the urine output. c. Fluid intake should be half the urine output. d. Fluid intake should be inversely proportional to the urine output. Q4. A client is frustrated and embarrassed by urinary incontinence. Which of the following measures should nurse Bea include in a bladder retraining program? a. Establishing a predetermined fluid intake pattern for the client b. Encouraging the client to increase the time between voidings c. Restricting fluid intake to reduce the need to void

d. Assessing present erythropoietin.

elimination

patterns

Q3. A male client comes to the emergency department complaining of sudden onset of sharp, severe pain in the lumbar region, which radiates around the side and toward the bladder. The client also reports nausea and vomiting and appears pale, diaphoretic and anxious. The physician tentatively diagnoses renal calculi and orders flatplate abdominal X-rays. Renal calculi can form anywhere in the urinary tract. What is their most common formation site? a. Kidney b. Ureter c. Bladder d. Urethra Q5. An infant, age 8 months, has a tentative diagnosis of congenital heart disease. During physical assessment, nurse Jasmine measures a heart rate of 170 beats/minute and a respiratory rate of 70 breaths/minute. How should the nurse position the infant? a. Lying on the back b. Lying on the abdomen c. Sitting in an infant seat d. Sitting in high Fowler’s position

Answers to eMedi Quiz Published in March 2013 Issue Q1. (C) Frequently observing for hoarseness, stridor and dyspnea. Q2. (A) Sit upright for at least 30 minutes after meals. Q3. (B) Medicate the patient for pain. Q4. (D) Fluid and electrolyte monitoring. Q5. (D) Leg cramps. Q6. (B) Inform the neurosurgeon of the patient’s status. Send your answers to the Editor-Indian Journal of Clinical Practice. E-mail: editorial@ijcp.com The correct answers will be published in the next issue of IJCP.

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Humor

Laugh-A-While

Doctor: I have some bad news and some very bad news. Patient: Well, might as well give me the bad news first. Doctor: The lab called with your test results. They said you have 24 hours to live. Patient: 24 HOURS! That’s terrible!! WHAT could be WORSE? What’s the very bad news? Doctor: I’ve been trying to reach you since yesterday.

A little girl was taken to the dentist. It was discovered that she had a cavity that would have to be filled. “Now, young man,” asked the dentist, “what kind of filling would you like for that tooth?” “Chocolate, please,” replied the youngster

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Indian Journal of Clinical Practice, Vol. 23, No. 11 April 2013

Doctor: You’re in good health. You’ll live to be 80. Patient: But, doctor, I am 80 right now. Doctor: See, what did I tell you.

Doctor: “Did you take the patient’s temperature?” Nurse: “No. Is it missing?”

lighter reading

Lighter Side of Medicine Quote

Make Sure

During Medical Practice A patient intolerant to penicillin was denied rheumatic prophylaxis.

“We are all travelers in the wilderness of the world, and the best that we can find in our travels is an honest friend.” −Robert Louis Stevenson

Mind Trivia Oh my God! Why was he not put on a sulfa drug?

1. What number comes next?

2, 2, 4, 12, 48, ___

2. What is the next number in this series?

1, 2, 6, 42, 1806?

11111121113122223222

Make sure that patients who cannot tolerate penicillin are put on sulfadiazine or sulfisoxazole. This antibiotic class is effective for preventing Group A streptococcal (GAS) infection although it cannot be used to achieve eradication. KK Aggarwal

Dr. Good & Dr. Bad Situation: A child presented with focal convulsions

with onset of high-grade fever.

These are not simple febrile convulsions

Lesson: Simple benign febrile convulsions are always

generalized.

Dr KK Aggarwal

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8, 5, 4, 9, 1, 7, 6, 10, 3, 2, 0

5. Which two numbers are missing and where do they go in the sequence?

8, 11, 5, 14, 1, 7, 6, 10, 13, 3, 12, 2

Ans. (1) 240. (2) To get the next number, multiply the previous number in the series by itself plus one: n * (n+1). For example, to get 6, multiply 2 * 2+1. To get 42 multiply 6 * 6+1. Thus, 1806 * 1807 = 3263442. (3) The syllables in the numbers from 1 to 20. (4) It’s the numbers 0 through 10 in alphabetical order. (5) The missing numbers are 4 and 9. The list is sorted alphabetically by the English spelling of the numbers, so four belongs after five and nine comes after fourteen.

ILLUSION

©IJCP Academy

These are simple febrile convulsions

4. What is special about the following number sequence?

Indian Journal of Clinical Practice, Vol. 23, No. 11 April 2013

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 –

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

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

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

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

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

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

Confidence intervals for the measurements should be provided wherever appropriate.

Results –

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

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Discussion –

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

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

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

Do not use clips/staples on photographs and artwork.

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

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

Books

5. Special requests _____________________________

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

Indian 1.____________Foreign 1._ _______________

Articles in Books

2.____________ 2._ _______________

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

3.____________ 3._ _______________

4.____________

Tables –

These should be typed double spaced on separate sheets with the table number (in Roman Arabic numerals) and title above the table and explanatory notes below the table.

Legends – These should be typed double spaces on a separate sheet and figure numbers (in Arabic numerals) corresponding with the order in which the figures are presented in the text. –

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

Indian Journal of Clinical Practice, Vol. 23, No. 11 April 2013

6. Suggestions for reviewers (name and postal address)

4._ _______________

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

R.N.I. No. 50798/90 Date of Publication 13th of Same Month Date of Posting 13-14 Same Month

DL (S)-01/3200/2012-2014 Posted in N.D. PSO New Delhi