Ijcp march 2013

Indexed with IndMED

ISSN 0971-0876

www.ijcpgroup.com

Volume 23, Number 10

March 2013, Pages 581-680

Peer Reviewed Journal

yy American Family Physician yy Cardiology

yy Critical Care yy Dentistry

yy Dermatology yy Diabetology

yy Drugs and Devices yy ENT

yy Gastroenterology yy Neurology

yy Obstetrics and Gynecology

yy Orthopedics and Rheumatology yy Pediatrics yy Renal

yy Medifinance yy Medilaw

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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

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 Neurology Dr V Nagarajan

Volume 23, Number 10, March 2013 from the desk of group editor-in-chief

585 HIV-infected Child Functionally Cured

KK Aggarwal

from the desk of guest editor

586 Preventing Malarial Deaths in Pregnancy

American Family Physician

587 Practice Guidelines Cardiology

590 ECG: A Simple Noninvasive Tool to Localize Culprit Vessel Occlusion Site in Acute STEMI

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

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

Biplab Ghosh, Manoj Indurkar, Mahendra Kumar Jain

596 Patterns of Extended Lipid Profile Abnormalities in Freshly Diagnosed Myocardial Infarction Patients of Bundelkhand Region

Deep Chandra Pant, Hema Pant

critical Care

601 Antimicrobial Therapy in the Intensive Care Unit

MS Krishna Sarin, M Vadivelan, Chanaveerappa Bammigatti

Dentistry

610 Maxillary Full Arch Fixed Prosthesis: Clinical Laboratory Procedures and Rehabilitation with Milled Titanium Prosthesis

Eldo Koshy, Sony Jacob Mevada, Sunitha Raj Philip

Dermatology

616 Varying Arrhythmias during Single Hospital Stay in a Case of Systemic Lupus Erythematosus

Jaishree Ghanekar, Sujata Khatal, Nikhila A Pachani, Reji John

Diabetology

619 Comparison of Insulin Glargine with Human Premix Insulin in Patients with Type 2 Diabetes Inadequately Controlled on Oral Hypoglycemic Drugs in a 24-week Randomized Study among Central Indian Population

Journal of Applied Medicine & Surgery Dr SM Rajendran, Dr Jayakar Thomas

Anita Kant

Abhishek Singhai, Subodh Banzal, Dolly Joseph, Rajesh Kumar Jha

dRUGS AND DEVICES

624 Drugs and Dreams

Sarita Goyal, Jyoti Kaushal, MC Gupta, Savita Verma

ENT

628 Congenital Facial Palsy with Bilateral Anotia

Geeta Gathwala, Jagjit Singh, Poonam Dalal

Gastroenterology

635 A Study of Clinical Profile and Outcome in Acute Viral Hepatitis E

Tejas N Modi, Shivani A Patel, Kiran M Mirani, Dharmesh R Vaghasiya, Gautam S Makadia, Jignesh Usdadiya

NEUROLOGY

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

638 Giant Asymptomatic Cystic Dilatation in Dandy-Walker Malformation

Amit Agarwal

OBSTETRICS AND GYNECOLOGY

640 Labetalol - An Emerging First-line Drug for Pregnancyinduced Hypertension

Printed at IG Printers Pvt. Ltd., New Delhi E-mail: igprinter@rediffmail.com, printer_ig@yahoo.com

Sushrut D, Girija

642 Ulipristal Acetate: The Latest in Emergency Contraception

Š Copyright 2013 IJCP Publications Ltd. All rights reserved.

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

Monica Soni, Prasoon Soni

645 Effect of Raised Mid-trimester Serum hCG and a-fetoprotein on Pregnancy Outcome

Editorial Policies

Preeti Dubey, Kiran Pandey, Shaily Agarwal, Sunita Jain, Neetu Singh, Shilpi Gupta

648 Pregnancy Following Laparotomy for Ruptured Interstitial Pregnancy

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Parneet Kaur, Bajwa Surjit Kaur, Harjinder Kaur, Balwinder Kaur, Satinder Kaur

ORTHOPEDICS AND RHEUMATOLOGY

651 An Unusual Swelling at Ankle: An Osteochondroma in Adult?

Vivek AN

PEDIATRICS

654 The Role of Clinical Signs in the Diagnosis of Late-onset Neonatal Sepsis and Formulation of Clinical Score

Subhranshu Sekhar Kar, Rajani Dube, Samarendra Mahapatro, Sitanshu Sekhar Kar

RENAL

661 Intrarenal Abscess: When to Suspect?

SL Margekar, N Singh, OP Jatav, P Kori

MEDIFINANCE

664 Financial Advisory Team

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

MEDILAW

666 What are the Pros and Cons of Death Penalty?

Which Method of Execution is Best?

EMEDINEWS INSPIRATION

670 A Promise is a Promise

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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)

HIV-infected Child Functionally Cured

A

two-year-old child born with human immunodeficiency virus (HIV) infection and treated with antiretroviral drugs beginning within 30 hours of life no longer has detectable levels of virus using conventional testing despite not taking HIV medication for 10 months, according to findings presented at The Conference on Retroviruses and Opportunistic Infections (CROI) in Atlanta by Dr Deborah Persaud, associate professor of infectious diseases at the Johns Hopkins Children’s Center in Baltimore, and Dr Katherine Luzuriaga, professor of pediatrics and molecular medicine at the University of Massachusetts Medical School in Worcester.

This is the first well-documented case of an HIV-infected child functionally cured of HIV infection, which means without detectable levels of virus and no signs of disease in the absence of antiretroviral therapy.

In July 2010, the child was born prematurely in Mississippi at 35 weeks, to an HIV-infected mother who had received neither antiretroviral medication nor prenatal care. The infant was started at 30 hours of age on liquid three anti-HIV drugs: Zidovudine, lamivudine and nevirapine. The newborn’s HIV was confirmed by polymerase chain reaction (PCR) testing on the second day of life.

The baby was discharged at one week of age on a combination zidovudine, lamivudine and co-formulated lopinavirritonavir.

Viral load tests performed over the first three weeks of life again indicated HIV infection. On Day 29, the infant’s viral load had fallen to <50 copies of HIV per milliliter of blood (copies/ml).

The baby remained on the prescribed drugs until 18 months of age when treatment was discontinued by the relatives. However, when the child was again seen five months later blood samples revealed undetectable HIV levels (<20 copies/ml) and no HIV-specific antibodies. Ultrasensitive viral RNA and DNA tests revealed extremely low viral levels. Presently the child is on no antiretroviral therapy with no identifiable levels of HIV. The case suggests that providing antiretroviral therapy within the very first few days of life to infants infected with HIV through their mothers via pregnancy or delivery may achieve a cure.

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Indian Journal of Clinical Practice, Vol. 23, No. 10 March 2013

585

from the desk of guest editor Dr Anita Kant Consultant Gynecologist Asian Institute of Medical Sciences Faridabad

Preventing Malarial Deaths in Pregnancy Pregnant travellers should defer travel to areas where risk of malaria is high until after delivery.

For nonimmune pregnant women who cannot defer travel, chemoprophylaxis with chloroquine and mefloquine depending on travel to areas with chloroquine-sensitive or resistant malaria is recommended.

For pregnant women from endemic areas, who due to prolonged exposure to malaria, have developed natural immunity: ÂÂ

Continuous prophylaxis is not practical

ÂÂ

One should go for Intermittent Preventive Treatment during pregnancy (IPTp) in areas with medium and high malaria transmission

WHO suggests IPTp with sulfadoxine pyrimethamine (SP) at each scheduled antenatal care visit in the second and third trimesters.

Four focused antenatal care visits as standard care: A first visit in the first trimester, a second visit at 24-26 weeks of gestation, a third visit at 32 weeks and a fourth visit at 36-38 weeks.

Each dose suppresses or clears existing asymptomatic infections from the placenta and provides upto six weeks of prophylaxis.

The previous recommendation was for only two doses of SP one month apart.

In a systematic review and meta-analysis of trials ≥3 dose regimens resulted in fewer low birth weight infants, less placental malaria and less moderate-to-severe maternal anemia compared to two dose regimen.

For pregnant women who reside in areas of medium and high malaria transmission one should give treatment with three doses of SP as IPTp, rather than two doses.

Source: Kayentao K, Garner P, van Eijk AM, et al. Intermittent preventive therapy for malaria during pregnancy using 2 vs 3 or more doses of sulfadoxine-pyrimethamine and risk of low birth weight in Africa: systematic review and meta-analysis. JAMA 2013;309:594.

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Indian Journal of Clinical Practice, Vol. 23, No. 10 March 2013

American Family Physician

Practice Guidelines

IDSA Releases Guidelines on Management of Cryptococcal Disease

for amphotericin B deoxycholate in patients with or predisposed to renal dysfunction.

Cryptococcosis is an invasive fungal disease associated with high rates of morbidity and mortality in areas with uncontrolled human immunodeficiency virus (HIV) disease and limited access to health care.

In medically developed countries, patients with newly diagnosed HIV infection and those receiving highdose corticosteroids, monoclonal antibodies, or other immunosuppressive agents account for most cases of cryptococcal disease. Despite access to advanced medical care and the availability of highly active antiretroviral therapy, patients with acute cryptococcal meningoencephalitis have a three-month mortality rate of approximately 20 percent.

Alternative regimens include the following (in order of preference):

The Infectious Diseases Society of America (IDSA) recently updated its guidelines on the management of cryptococcal disease. The new guidelines include a discussion of the management of cryptococcal meningoencephalitis in three risk groups: patients who are HIV-positive, organ transplant recipients, and non–HIV-infected and nontransplant hosts. The new guidelines also include specific recommendations for other high-risk groups, such as children, pregnant women, patients in environments with limited health care resources, and those with Cryptococcus gattii infection.

Patients Who are HIV-Positive Induction and Consolidation Therapy The preferred regimen for induction and consolidation therapy in patients who are HIV-positive is amphotericin B deoxycholate (0.7 to 1.0 mg per kg per day, intravenously) plus flucytosine (100 mg per kg per day, orally, in four divided doses) for at least two weeks, followed by fluconazole (400 mg [6 mg per kg] per day, orally) for at least eight weeks.

Lipid formulations of amphotericin B, including liposomal amphotericin B (3 to 4 mg per kg per day, intravenously) and amphotericin B lipid complex (5 mg per kg per day, intravenously), can be substituted

ÂÂ

Amphotericin B deoxycholate (0.7 to 1.0 mg per kg per day, intravenously), liposomal amphotericin B (3 to 4 mg per kg per day, intravenously), or amphotericin B lipid complex (5 mg per kg per day, intravenously) for four to six weeks. Liposomal amphotericin B has been administered safely at dosages of 6 mg per kg per day in patients with cryptococcal meningoencephalitis, and could be considered in the event of treatment failure or in patients with high–fungal burden disease.

ÂÂ

Amphotericin B deoxycholate (0.7 mg per kg per day, intravenously) plus fluconazole (800 mg per day, orally) for two weeks, followed by fluconazole (800 mg per day, orally) for at least eight weeks.

ÂÂ

Fluconazole (at least 800 mg per day, orally; 1,200 mg per day is preferred) plus flucytosine (100 mg per kg per day, orally) for six weeks.

ÂÂ

Fluconazole (800 to 2,000 mg per day, orally) for 10 to 12 weeks. A dosage of at least 1,200 mg per day is recommended if fluconazole is used alone.

ÂÂ

Itraconazole (200 mg twice per day, orally) for 10 to 12 weeks. However, the use of this agent is discouraged.

Maintenance and Prophylactic Therapy Maintenance therapy should be initiated after the induction and consolidation regimen is complete.

Ideally, maintenance therapy is begun when the results of cerebrospinal fluid yeast culture are negative, and it is continued until there is evidence of persistent immune reconstitution with successful highly active antiretroviral therapy.

Regimens include the following: ÂÂ

Fluconazole (200 mg per day, orally).

ÂÂ

Itraconazole (200 mg twice per day, orally; drug level monitoring is strongly advised).

Indian Journal of Clinical Practice, Vol. 23, No. 10 March 2013

587

American Family Physician ÂÂ

Amphotericin B deoxycholate (1 mg per kg per week, intravenously). This is less effective than azoles and is associated with intravenous catheter– related infections.

Highly active antiretroviral therapy should be initiated two to 10 weeks after the initial antifungal treatment is begun. Physicians should consider discontinuing immunosuppressive therapy in patients with a CD4 cell count of greater than 100 cells per mm3 (100 × 109 cells per L) and an undetectable or very low HIV RNA level sustained for at least three months (minimum of 12 months of antifungal therapy). Reinstitution of maintenance therapy should be considered if the CD4 cell count decreases to less than 100 cells per mm3.

A lumbar puncture should be performed and a blood culture obtained in patients with asymptomatic antigenemia. If results are positive, the patient should be treated for symptomatic meningoencephalitis or disseminated disease. If there is no evidence of meningoencephalitis, the patient should receive fluconazole (400 mg per day, orally) until immune reconstitution.

Primary antifungal prophylaxis for cryptococcosis is not routinely recommended in the United States and Europe, but it may be considered in areas with limited availability of highly active antiretroviral therapy, high levels of antiretroviral drug resistance, and a high disease burden.

Organ Transplant Recipients Cryptococcosis has been documented in an average of 2.8 percent of solid-organ transplant recipients.

The median time to disease onset is 21 months after transplantation; 68.5 percent of cases occur more than 12 months after transplantation. Approximately 25 to 54 percent of organ transplant recipients with cryptococcosis have pulmonary infection, and in 6 to 33 percent, the disease is limited to the lungs.

Patients with central nervous system (CNS) disease should be treated with liposomal amphotericin B (3 to 4 mg per kg per day, intravenously) or amphotericin B lipid complex (5 mg per kg per day, intravenously) plus flucytosine (100 mg per kg per day in four divided doses) for at least two weeks, followed by fluconazole (400 to 800 mg [6 to 12 mg per kg] per day, orally) for eight weeks, then a lower dose of fluconazole (200 to 400 mg per day, orally) for six to 12 months. If induction therapy does not include flucytosine, four to six weeks of therapy with liposomal formulations of amphotericin B should be considered. Liposomal amphotericin B

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Indian Journal of Clinical Practice, Vol. 23, No. 10 March 2013

(6 mg per kg per day) may be considered for patients with high–fungal burden disease or relapse.

Fluconazole (400 mg [6 mg per kg] per day) should be given for six to 12 months in patients with mild to moderate non-CNS disease. Those with moderately severe to severe non-CNS disease or disseminated disease without CNS involvement should be treated the same as those with CNS disease.

In the absence of clinical evidence of extrapulmonary or disseminated cryptococcosis, patients with severe pulmonary disease are treated the same as those with CNS disease. Fluconazole (400 mg [6 mg per kg] per day) should be used for six to 12 months in patients with mild to moderate symptoms without diffuse pulmonary infiltrates.

Because of the risk of nephrotoxicity, amphotericin B deoxycholate should be used with caution in transplant recipients and is not recommended as first-line therapy in these patients. If this medication is used, the tolerated dosage is uncertain, but 0.7 mg per kg per day is suggested, with frequent monitoring of renal function.

Non–HIV-Infected, Nontransplant Hosts Recommendations for immunocompetent hosts are limited because most patients in the two major studies of cryptococcal meningoencephalitis before the HIV epidemic were immunosuppressed. However, patients with less severe or variable host immune defects can still present serious therapeutic challenges.

In immunocompetent hosts, induction therapy is reserved for persons with meningoencephalitis without neurologic complications and negative cerebrospinal fluid yeast cultures after two weeks of treatment.

Amphotericin B deoxycholate (0.7 to 1.0 mg per kg per day, intravenously) plus flucytosine (100 mg per kg per day, orally, in four divided doses) is recommended for at least four weeks for induction therapy. Lipid formulations of amphotericin B can be substituted in the second two weeks. Induction therapy may extend to six weeks in patients with neurologic complications, and lipid formulations of amphotericin B may be given for the last four weeks. Consolidation therapy should then be initiated with fluconazole (400 mg per day) for eight weeks.

Liposomal amphotericin B (3 to 4 mg per kg per day, intravenously) or amphotericin B lipid complex (5 mg per kg per day, intravenously) can be used in patients who do not tolerate amphotericin B deoxycholate. If flucytosine is not given or treatment is interrupted, induction therapy with amphotericin B deoxycholate or

American Family Physician lipid formulations of amphotericin B can be extended for at least two weeks.

After induction and consolidation therapy, maintenance therapy should be started with fluconazole (200 mg [3 mg per kg] per day, orally) for six to 12 months.

Special Considerations Children Children with CNS or disseminated disease should receive induction and consolidation therapy with amphotericin B deoxycholate (1 mg per kg per day, intravenously) plus flucytosine (100 mg per kg per day, orally, in four divided doses) for two weeks, followed by eight weeks of fluconazole therapy (10 to 12 mg per kg per day, orally). Children who are not HIV-positive and have not had an organ transplant should follow the treatment length schedule for adults. Those who do not tolerate amphotericin B should be given liposomal amphotericin B (5 mg per kg per day) or amphotericin B lipid complex (5 mg per kg per day). After induction therapy, fluconazole (6 mg per kg per day) should be given as maintenance therapy. Children with cryptococcal pneumonia should receive fluconazole (6 to 12 mg per kg per day, orally) for six to 12 months.

Discontinuation of maintenance therapy in children receiving highly active antiretroviral therapy should be individualized.

with amphotericin B deoxycholate (1 mg per kg per day, intravenously) for two weeks, or amphotericin B deoxycholate (0.7 mg per kg per day, intravenously) plus fluconazole (800 mg per day) for two weeks.

Induction therapy should be followed by consolidation therapy with 800 mg of fluconazole per day for eight weeks. Maintenance therapy with fluconazole (200 to 400 mg per day, orally) should be given until immune reconstitution.

When other antifungal agents are not available, patients with CNS or disseminated disease should receive induction therapy with fluconazole (at least 800 mg per day; 1,200 mg per day is preferred) for at least 10 weeks or until cerebrospinal fluid culture results are negative. If flucytosine is available, it should be added at a dosage of 100 mg per kg per day, orally, and induction therapy should continue for two to 10 weeks.

Induction therapy should be followed by maintenance therapy (200 to 400 mg per day).

When primary fluconazole therapy is used for induction, drug resistanceâ&#x20AC;&#x201D;both primary and secondaryâ&#x20AC;&#x201D;may be an issue, and minimum inhibitory concentration testing is recommended. Patients with azole-resistant strains of cryptococcosis should be given amphotericin B deoxycholate (1 mg per kg per day, intravenously) until cerebrospinal fluid and blood are sterile.

Pregnancy

C. gattii Infection

Pregnant women with CNS or disseminated disease should be treated with amphotericin B deoxycholate or lipid formulations of amphotericin B, with or without flucytosine. Because flucytosine is a U.S. Food and Drug Administration pregnancy category C drug, its potential benefits must be weighed against its risks.

Patients with CNS or disseminated disease from C. gattii infection should receive the same induction, consolidation, and suppressive treatment as those with Cryptococcus neoformans infection. However, additional diagnostic radiology and follow-up are needed in patients with cryptococcomas and hydrocephalus caused by C. gattii infection. Surgery should be considered if there is compression of vital structures or failure to thrive, or if four weeks of therapy does not reduce the size of the cryptococcoma.

The use of fluconazole (also a pregnancy category C drug) should be avoided in the first trimester and carefully considered in the second and third trimesters, weighing its risks against the need for continuous antifungal drug exposure. Women with limited and stable pulmonary cryptococcosis should be followed closely and given fluconazole after delivery. Immune reconstitution inflammatory syndrome is a risk in the postpartum period, and patients should be monitored for this condition.

Environments with Limited Health Care Resources When flucytosine is not available, patients with CNS or disseminated disease should receive induction therapy

Patients with pulmonary cryptococcosis should be treated with the same regimen as those infected with C. neoformans. Those with a single, small cryptococcoma should receive fluconazole (400 mg per day).

In patients with large or multiple cryptococcomas, four to six weeks of combination therapy with amphotericin B deoxycholate and flucytosine should be considered, followed by fluconazole for six to 18 months, depending on whether surgery was performed.

Source: Adapted from Am Fam Physician. 2010;82(6):711-714.

Indian Journal of Clinical Practice, Vol. 23, No. 10 March 2013

589

Cardiology

ECG: A Simple Noninvasive Tool to Localize Culprit Vessel Occlusion Site in Acute STEMI Biplab Ghosh*, Manoj Indurkar**, Mahendra Kumar Jainâ&#x20AC;

Abstract Introduction: Various electrocardiogram (ECG) patterns can determine the site of occlusion in culprit coronary artery in ST-elevation myocardial infarction (STEMI) and the size of the myocardium that is jeopardized. Objectives: The aim of this study was to assess diagnostic accuracy of the ECG localization of culprit vessel occlusion site as compared to coronary angiographic findings. Material and methods: ECG criteria for localization of culprit vessel occlusion site were specified and patients with STEMI (n = 21) were divided into three groups: Groups I, II and III, according to the localization of culprit vessel occlusion site in left anterior descending (LAD), right coronary artery (RCA) and left circumflex (LCx) coronary arteries, respectively. Group I was further divided into four subgroups: Ia, Ib, Ic and Ib+c according to whether occlusion in LAD was proximal to both first septal (S1) and first diagonal (D1) branches, distal to S1 but proximal to D1 branches, distal to both S1 and D1 branches or distal to S1 branch, respectively. Group II was further divided into two subgroups: IIa and IIb according to whether occlusion in RCA was proximal or distal to RV branch, respectively. The results of coronary angiograms were compared with those predicted by ECG. Results: The positive predictive accuracy (PPA) and negative predictive accuracy (NPA) of ECG criteria for LAD, RCA and LCx coronary arteries were 90.91% and 100%, 90% and 100%, and undetermined and 90.48%, respectively. Among subgroups, the sensitivity of ECG criteria was maximum for groups Ib+c and IIb (100%) followed by Group IIa (71.43%), Group Ic (50%), Group Ia (42.86%) and least for Group Ib (0%). The specificity was maximum for Groups Ia and IIa (92.86%) followed by Group Ib (90%), Group IIb (89.47%), Group Ic (78.95%) and Group Ib+c (77.78%) in that order. The PPA and NPA for Groups Ia, Ib, Ic, Ib+c, IIa and IIb were 75% and 76.47%, 0% and 94.74%, 20% and 93.75%, 42.86% and 100%, 83.33% and 86.67% and 50% and 100%, respectively. Conclusion: The present study demonstrates that ECG is an easily and widely available inexpensive tool to localize site of occlusion in culprit vessel in acute STEMI.

Keywords: Culprit vessels, STEMI, ECG, coronary angiography

T

he standard 12 lead electrocardiogram (ECG) has long been a reliable clinical tool for diagnosis of acute myocardial infarction (AMI). Specific ECG patterns for the site of occlusion in culprit coronary artery has been well-recognized.1 Larger the area at risk, more aggressive should be the attempt to restore or improve perfusion of that area.

Objectives The aim of this study was to amalgamate various ECG criteria for localization of culprit vessel occlusion site *Senior Resident Dept. of Nephrology, Institute of Medical Sciences Banaras Hindu University, Varanasi, Uttar Pradesh **Associate Professor â&#x20AC; Professor Dept. of Medicine, Shyam Shah Medical College Rewa, Madhya Pradesh Address for correspondence Dr Biplab Ghosh Senior resident Dept. of Nephrology, Institute of Medical Sciences Banaras Hindu University, Varanasi - 221 005, Uttar Pradesh E-mail: dr.biplabghosh@gmail.com

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Indian Journal of Clinical Practice, Vol. 23, No. 10 March 2013

and to assess its diagnostic accuracy as compared to follow-up coronary angiographic findings.

Material and Methods The present study was carried out on patients admitted with AMI after application of the following exclusion criteria: Patients with history of previous myocardial infarction and previous coronary artery bypass graft (CABG) surgery; ECG evidence of left bundle branch block (LBBB), pre-excitation and paced rhythm. Written informed consent was obtained from each patient. AMI was diagnosed as per standard criteria.1 A detailed history and physical examination was carried out. ECG was recorded on admission and then 90 minutes and three hours after completion of thrombolysis, and if thrombolysis was not done, at four hours and 24 hours after admission. Besides these ECG was also recorded whenever symptoms and clinical situations demanded so.

In inferior wall, AMI right sided leads and posterior leads were also recorded. Patients were referred to other hospitals for coronary angiography and the results were noted on subsequent follow-up. A lesion

cardiology ECG Criteria to Identify Site of Occlusion in LAD (in AWMI) Criteria 1. Any one or more of the following i. Complete RBBB ii. ST ↑ V1 > 2.5 mm iii. ST ↑ aVR iv. ST ↓ V5 v. New onset LAHB 2. Q in aVL 3. Any one or more of the following

Occlusion site Proximal to S1

i. ST ↓ II ≥ 1.0 mm ii. Maximum ST ↑ appeared in V2 4. Q in V5 5. ST ↓ aVL 6. No ST ↓ III

Proximal to D1 Proximal to S1 and/or D1

Distal to S1 Distal to D1 Distal to S1 and/or D1

Group Ia had criteria 1, 2 and 3; Group Ib had criteria 2 and 4 without 1 and 5; Group Ic had criteria 4, 5, and 6; Group Ib+c was the combination of Group Ib and Ic.

ECG Criteria to Identify whether Site of Occlusion is in RCA or LCx (in IWMI) Criteria *1. ST ↑ III > ST ↑ II *2. ST ↓ aVL > ST ↓ I *3. ST ↓ V3/ST ↑ III ratio 4. Lead V4R 5. ST ↓ V1-V2

6. Max ST ↓ V2-V3 7. ST ↑ V7-V9

RCA Present Present

LCx Absent Absent

<1.2 T-wave upright

>1.2 Inverted T-wave Present

Absent (present in occlusion of dominant RCA causing posterior wall MI) Absent Absent (present if RCA dominant)

Present Present

*In case of discrepancy between criteria 1, 2 and 3, the localization was done as per criteria 1 and 2 rather than 3. Criteria 5 to 7 were used mainly for supportive evidence.

ECG Criteria for Site of Occlusion in RCA Criteria V4R ST ↑ V1 ST ↑ VR > ST ↑ in V1-V3 Ratio of ST ↓ V3/ST ↑ III AV nodal block Atrial infarction

Proximal to RV branch ST ↑ ≥1 mm Present Present

Distal to RV branch No ST ↑ Absent Absent

< 0.5

>0.5, but <1.2

Present Present

Absent Absent

was considered to be the culprit when it occluded or severely narrowed the artery and was ulcerated and/or contained thrombus. The results of coronary angiograms were compared with that predicted by ECG. Patients were divided into three groups: Groups I, II and III according to the localization of occlusion site in left anterior descending (LAD), right coronary artery (RCA) and left circumflex (LCx) coronary arteries, respectively. Group I was further divided into four subgroups: Ia, Ib, Ic and Ib+c according to whether occlusion in LAD was proximal to both first septal (S1) and first diagonal (D1) branches, distal to S1 but proximal to D1 branch, distal to both S1 and D1 branches or distal to S1 branch (irrespective of D1 branch), respectively. Group II was further divided into two subgroups: IIa and IIb according to whether occlusion in RCA was proximal or distal to right ventricular (RV) branch, respectively.

Results Demographic and clinical parameters of all 21 patients are shown in Table 1. According to ECG criteria, Groups I, II, III, Ia, Ib, Ic, IIa and IIb had 11 (52.38%), 10 (47.62%), 0 (0.0%), 4 (19.05%), 2 (9.52%), 5 (23.81%), 6 (28.57%) and 4 (19.05%) patients, respectively. The mean left ventricular ejection fraction (LVEF) in Groups Ia, Ib, Ic, IIa and IIb were 35.25%, 34.0%, 42.2%, 42.6% and 55.2%, respectively. Lowest LVEF was noted in two diabetic patients (22% and 24%). ECG criteria correlated with coronary angiography fully in 11 patients (52.38%) and partially in eight patients (38.10%) but not at all in two patients (9.52%). Angiography revealed occlusion of LCx in two patients who were misclassified by ECG in Groups Ia and IIa. Out of the eight patients in whom ECG correlated partially, seven had involvement of the same coronary artery but at a proximal location from that predicted by ECG and one had occlusion more distally. Correlation of ECG criteria with coronary angiography is shown in Table 2. The sensitivity of ECG to identify culprit vessel in AMI was 100% for both LAD coronary artery and RCA but 0% for LCx coronary artery. The specificity was maximum for LCx coronary artery (100%) followed by that for RCA (91.67%) and LAD coronary artery (90.91%).

The positive predictive accuracy (PPA) and negative predictive accuracy (NPA) for LAD, RCA and LCx coronary arteries were 90.91% and 100%, 90% and 100%, and undetermined and 90.48%, respectively. The sensitivity of ECG criteria to further localize the site of occlusion in a culprit vessel in AMI was maximum for

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cardiology which is the terminal portion of a ‘wraparound’ LAD.

Table 1. Demographic, Clinical and Laboratory Parameters (n = 21) Characteristic

Number (%)

Age, mean ± SD (years)

55.09 ± 10.08

Current smoker BMI ± SD

9 (42.86%)

(kg/m2)

22.56 ± 3.54

Diabetes mellitus (DM)

2 (9.52%)

Hypertension (HT)

6 (28.57%)

Family history of DM, HT and/or IHD

7 (33.33%)

No past and/or family history of DM, HT

11 (52.38%)

Presented < 3 hours of chest pain onset

8 (38.10%)

Presented >12 hours of chest pain onset

7 (33.33%)

Thrombolytic therapy given

8 (38.10%)

Single vessel disease

13 (61.90%)

Double vessel disease

4 (19.05%)

Triple vessel disease

4 (19.05%)

Groups Ib+c and IIb (100% each) followed by Group IIa (71.43%), Group Ic (50%), Group Ia (42.86%) and least for Group Ib (0%). The specificity was maximum for Groups Ia and IIa (92.86% each) followed by Group Ib (90%), Group IIb (89.47%), Group Ic (78.95%) and Group Ib+c (77.78%) in that order. The PPA and NPA for Group Ia, Ib, Ic, Ib+c, IIa and IIb were 75% and 76.47%, 0% and 94.74%, 20% and 93.75%, 42.86% and 100%, 83.33% and 86.67% and 50% and 100%, respectively.

Discussion In anterior wall myocardial infarction (AWMI), the occlusion is nearly always in the LAD coronary artery.

With inferior wall myocardial infarction (IWMI), however, either the RCA or the LCx coronary artery may contain the culprit lesion.1 Rarely, acute IWMI may result from occlusion of the recurrent LAD branch,

In AWMI, ST-segment elevation in leads V1, V2 and V3 indicates occlusion of the LAD coronary artery.

ST-segment elevation in these three leads and in lead aVL in association with ST-segment depression of >1 mm in leads II, III and aVF indicates proximal occlusion of the LAD artery. In this case, the ST-segment vector is directed upward, toward leads V1, aVL, aVR and away from the inferior leads. ST-segment elevation in leads V1, V2 and V3 without significant inferior ST-segment depression suggests occlusion of the LAD artery after the origin of the first diagonal branch.

ST-segment elevation in leads V1, V2 and V3 with elevation in the inferior leads suggests occlusion of the LAD artery distal to the origin of the first diagonal branch, in a vessel that wraps around to supply the inferoapical region of the left ventricle. New right bundle-branch block (RBBB) with a Q-wave preceding the R-wave in lead V1 is a specific but insensitive marker of proximal occlusion of the LAD artery in association with anteroseptal myocardial infarction.1 In IWMI, several ECG criteria identify RCA or LCx as the artery containing the culprit lesion. Each of these criteria is based on one of two anatomic facts.2 First, the myocardial distribution of the RCA is slightly rightward in the frontal plane, and consequently the current of injury resulting from its occlusion will be reflected more in lead III than lead II and ST↓ will be more in lead aVL than in lead I. Conversely, the distribution of the LCx is slightly leftward in the frontal plane, and the current of injury from its closure will be seen more in lead II than lead III. Similarly, the current of injury with RCA occlusion is more or less perpendicular to the axis of lead aVR, whereas the current of injury resulting from occlusion of the LCx has a mean vector that forms an obtuse angle with the axis of aVR. Therefore, significant

Table 2. Correlation of ECG Criteria with Coronary Angiography Groups by ECG

Sensitivity (%)

Specificity (%)

PPA (%)

NPA (%)

42.86

92.86

75.00

76.47

Ib

0.00

90.00

0.00

94.74

Ic

50.00

78.95

20.00

93.75

Ib+c

100.00

77.78

42.86

100.00

I

100.00

90.91

90.91

100.00

IIa

71.43

92.86

83.33

86.67

IIb

100.00

89.47

50.00

100.00

II

100.00

91.67

90.00

100.00

III

0.00

100.00

-

90.48

Ia

NPA: Negative predictive accuracy; PPA: Positive predictive accuracy.

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cardiology ST-segment depression in aVR is more likely to occur with LCx occlusion. An injury vector leftward enough to cause ST-segment elevation in lead I is common with LCx occlusion, but rare with RCA occlusion. Second, the RCA provides almost all of the blood supply to the right ventricle, which is rightward as well as anterior to left ventricle. When the RCA is occluded proximal to one or more of its major RV branches, ST-segment elevation is likely to be seen in lead V4R. Similarly, the ST-segment in lead V1 (V2R) may be elevated even when the more leftward precordial leads show ST-segment depression due to the posterior injury that so frequently accompanies acute IWMI. Evidence of acute RV infarction is important, not only because it identifies the RCA as harboring the culprit lesion, but especially because it predicts a greatly increased morbidity and mortality. Consequently, right precordial leads or at least lead V4R should be recorded in all patients with acute IWMI. ST-segment depression in V1 and V2 indicates posterior injury and is typical of LCx occlusion.

Mortality and morbidity in part are determined by the location of the occlusion. For example, in patients with inferior MI who have RV infarction, the culprit artery virtually always is the RCA. Such patients, including those in whom ECG evidence of RV MI is masked, are at increased risk for death, shock and arrhythmias, including atrioventricular block.2 Thus, identifying the culprit artery in acute IWMI helps define those in whom aggressive reperfusion strategies are likely to yield most benefit. Coronary arteriography is the best means of determining the culprit artery in acute IWMI. When both the RCA and LCx are severely diseased, however, deciding which one is the culprit can be difficult and having an independent predictor of the culprit artery, such as the ECG, can be very helpful.

Engelen et al in a study of patients with AWMI showed that for different ECG criteria we used in our study to localize LAD occlusion proximal to S1 and/or D1 (i.e., patients in group Ia and Ib in the present study), the sensitivity, specificity, PPA and NPA varied from 12% to 44%, 85 to 100%, 67 to 100% and 61 to 70%, respectively.3 Similar figures for ECG criteria to localize occlusion in LAD distal to S1 and/or D1 (i.e., patients in Group Ib and Ic in the present study) were 22-41%, 86-95%, 77-92% and 46-53%, respectively.

In a study by Herz et al in patients with inferior wall AMI, the sensitivity to localize RCA occlusion varied from 55% to 94%.4 The specificity, PPA and NPA varied from 71% to 100%, 88% to 100% and 29% to 75%, respectively. The sensitivity, specificity, PPA and NPA

for LCx coronary artery were 88%, 100%, 100% and 97%, respectively.4 Kosuge et al studied the criteria of ratio of ST ↓ V3/ST ↑ III in patients with acute IWMI and found the sensitivity, specificity, PPA and NPA for RCA occlusion proximal to RV branch to be 91%, 91%, 88% and 93%, respectively.5 The similar figure for RCA occlusion distal to RV branch were 84%, 93%, 91% and 88% and those for LCx coronary artery occlusion were 84%, 95%, 73% and 98%, respectively.5 Nair et al found that quantifying ST-segment depression in lead aVR distinguished a culprit LCx (≥1 mm) from a culprit RCA (<1 mm or no depression) as well or better than other criteria and the importance of lead V4R has been investigated by many authors.6,7 Diagnostic accuracy of different ECG criteria in different studies are given in Tables 3 and 4.

The ECG criteria used in these previous studies were combined and used in the present study. The findings in the present study were in agreement with those of the study by Engelen et al except for the higher sensitivity and NPA and lower specificity and PPA in Group Ib+c.

The results were similar to that of the study by Herz et al except for the lower sensitivity for LCx and greater NPA for RCA in the present study. The present series also agreed with the findings by Kosuge et al except for the lower sensitivity and lower NPA in Group IIa, and higher sensitivity and NPA as well as lower PPA in Group IIb. The lower specificity and PPA in Group Ib+c (distal to S1 branch occlusion of LAD) in the present study was because of the fact that ECG was false positive for five patients in that group with four of them having severe degree of occlusion proximally in LAD (three had single vessel disease) and one had LCx disease by coronary arteriogram (CART). As pre-existing severe stenosis in these patients could have made collateral circulation to develop adequately so as to minimize the amount of myocardium jeopardized even when the occlusion was in the proximal segment of LAD, ECG might have falsely mimicked that of distal LAD occlusion. The lower PPA in Group IIb in the present study might be because of the same reason as two of the four patients in that group had occlusion more proximally. The small sample size could be the possible explanation for lower sensitivity in Group III, which inherently also has a low sensitivity due to inability of ECG to localize LCx coronary artery occlusion as posterior and lateral wall supplied by the artery is poorly represented in the standard surface ECG. When patients were divided into six subgroups, ECG did not correlate fully with CART in 10 patients all of

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593

cardiology Table 3. Diagnostic Accuracy of Different ECG Criteria in AWMI (Engelen et al3) IRA

ECG criteria

Sensitivity

LAD distal to S1

NPA

ST ↑ aVR*

43

95

86

70

36

100

100

68

ST ↓ III ≥1.0 mm

60

71

60

71

ST ↓ III ≥2.5 mm

33

97

88

67

ST ↓ aVF ≥1.0 mm

52

84

71

71

ST ↓ aVF ≥2.0 mm

26

97

85

64

cRBBB*

14

100

100

62

ST ↓ V5 ≥1.0 mm*

17

98

88

62

ST ↑ V1 ≥2.5 mm*

12

100

100

61

ST ↓ II ≥1.0 mm*

34

98

93

68

ST ↓ III ≥1.0 mm

66

75

64

76

ST ↓ III ≥2.5 mm

32

95

81

67

ST ↓ aVF ≥1.0 mm

54

85

71

72

ST ↓ aVF ≥2.0 mm

27

97

85

66

Q aVL*

44

85

67

69

Absence of ST↓ II

67

74

78

62

Absence of ST↓ III*

34

86

77

49

Absence of ST↓ aVF

45

90

87

54

Q V6

17

100

100

47

Q V 5* Q V4

LAD distal to D1

PPA

ST ↓ II ≥1.0 mm*

LAD proximal to S1

LAD proximal to D1

Specificity

24

93

82

47

55

69

71

53

Absence of ST↓ II

66

73

78

60

Absence of ST↓ III*

41

95

92

53

Absence of ST↓ aVF

44

90

87

53

ST↓aVL*

22

95

87

46

*Criteria used in the present study; AWMI: Anterior wall myocardial infarction; IRA: Infarct related artery; NPA: Negative predictive accuracy, PPA: Positive predictive accuracy, ST↑: ST-segment elevation; ST↓: ST-segment depression.

Table 4. Diagnostic Accuracy of Different ECG Criteria in IWMI in Different Studies Studies Herz et

al4

Kosuge et

al5

Verouden et al8 Verouden et

al8

Zimetbaum et al9

ECG criteria

IRA

Sensitivity

Specificity

PPA

NPA

Various criteria

RCA

55-94

71-100

88-100

29-75

LCx

88

100

100

97

RCA proximal to RV branch (<0.5)

91

91

88

93

RCA distal to RV branch (>0.5, <1.2)

84

93

91

88

LCx (>1.2)

84

95

73

98

RCA

70

72

-

-

Ratio of ST ↓ V3/ST ↑ III

ST ↑ III >II, ST↓I or aVL >1 mm Above + ST deviation >18.5 mm

RCA

90

-

-

-

ST ↑ in III>II and I and/or aVL <-1 mm

RCA

70

72

90

39

Chia et al10

ST ↑ in III>II and any ST↓ in I

RCA

76

66

89

42

Bairey et al11

ST ↓ in I

RCA

79

61

89

44

Bairey et al11

ST ↓ in aVL

RCA

95

24

82

56

IRA: Infarct related artery; IWMI: Inferior wall myocardial infarction; NPA: Negative predictive accuracy; PPA: Positive predictive accuracy, ST↑: ST-segment elevation; ST↓: ST-segment depression.

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Indian Journal of Clinical Practice, Vol. 23, No. 10 March 2013

cardiology whom had severe degree of obstruction. Among them one each was in Group Ia and IIa, two each in Group Ib and IIb and four in Group Ic. One patient each from Group Ia and IIa had occlusion in LCx coronary artery, which were not diagnosed by ECG, which is a known poor tool to diagnose such occlusion. One patient in Group Ib had more distal occlusion in LAD coronary artery (i.e., Group Ic by CART). Though, the occlusion was in distal LAD, he had diseased posterior descending artery (PDA) and thus the amount of myocardium jeopardized might have been substantial by virtue of the severity of disease in other artery and hence less chance of good collateral circulation. Rest of the seven patients had more proximal lesion by CART but in the same artery as predicted by ECG. The more proximal lesions in these cases were of severe degree and all patients had single vessel disease. Thus, the possible collateral circulation that might have developed long before the AMI in such cases could have led to better myocardial salvage in spite of a proximal lesion giving rise to false ECG diagnosis of distal lesion.

Conclusion The present study demonstrates that ECG is an easily and widely available inexpensive tool to localize site of occlusion in culprit vessel in acute STEMI.

Limitation The present study has two major limitations. Its sample size is small and coronary angiography was not done immediately on presentation but at a later date in other referral centers. Sometimes it becomes difficult to incriminate a lesion as the culprit one if angiography is done later in the course especially if there is multivessel disease or thrombolytic therapy has been given.

2. Fiol M, Cygankiewicz I, Carrillo A, Bayés-Genis A, Santoyo O, Gómez A, et al. Value of electrocardiographic algorithm based on “ups and downs” of ST in assessment of a culprit artery in evolving inferior wall acute myocardial infarction. Am J Cardiol 2004;94(6):709-14.

3. Engelen DJ, Gorgels AP, Cheriex EC, De Muinck ED, Ophuis AJ, Dassen WR, et al. Value of the electrocardiogram in localizing the occlusion site in the left anterior descending coronary artery in acute anterior myocardial infarction.

J Am Coll Cardiol 1999;34(2):389-95.

4. Herz I, Assali AR, Adler Y, Solodky A, Sclarovsky S. New electrocardiographic criteria for predicting either the right or left circumflex artery as the culprit coronary artery in inferior wall acute myocardial infarction. Am J Cardiol 1997;80(10):1343-5.

5. Kosuge M, Kimura K, Ishikawa T, Hongo Y, Mochida Y, Sugiyama M, et al. New electrocardiographic criteria for predicting the site of coronary artery occlusion in inferior wall acute myocardial infarction. Am J Cardiol 1998;82(11):1318-22.

6. Nair R, Glancy DL. ECG discrimination between right and left circumflex coronary arterial occlusion in patients with acute inferior myocardial infarction: value of old criteria and use of lead aVR. Chest 2002;122(1):134-9.

7. Wellens HJ. The ECG in localizing the culprit lesion in acute inferior myocardial infarction: a plea for lead V4R? Europace 2009;11(11):1421-2.

8. Verouden NJ, Barwari K, Koch KT, Henriques JP, Baan J, van der Schaaf RJ, et al. Distinguishing the right coronary artery from the left circumflex coronary artery as the infarct-related artery in patients undergoing primary percutaneous coronary intervention for acute inferior myocardial infarction. Europace 2009;11(11):1517-21.

9. Zimetbaum PJ, Josephson ME. Use of the electrocardiogram in acute myocardial infarction. N Engl J Med 2003;348(10):933-40.

References

10. Chia BL, Yip JW, Tan HC, Lim YT. Usefulness of ST elevation II/III ratio and ST deviation in lead I for identifying the culprit artery in inferior wall acute myocardial infarction.

Am J Cardiol 2000;86(3):341-3.

1. Gorgels AP, Engelen DJ, Wellens HJ. The electro cardiogram in acute myocardial infarction. In: Hurst’s the Heart. 11th edition, Fuster V, Alexander RW, O’Rourke RA (Eds.), McGraw-Hill: New York 2004:p.1351-60.

11. Bairey CN, Shah PK, Lew AS, Hulse S. Electrocardiographic differentiation of occlusion of the left circumflex versus the right coronary artery as a cause of inferior acute myocardial infarction. Am J Cardiol 1987;60(7):456-9.

■■■■

Omontys Safety still a Problem for Nondialysis Patients The anemia drug peginesatide (Omontys) in chronic kidney disease patients not undergoing hemodialysis may carry an increased risk of cardiovascular events, results of two paired trials suggested. (Source: Medpage Today)

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cardiology

Patterns of Extended Lipid Profile Abnormalities in Freshly Diagnosed Myocardial Infarction Patients of Bundelkhand Region Deep Chandra Pant*, Hema Pant**

Abstract Introduction: Coronary artery disease (CAD) in Indian population occurs a decade earlier, is more advanced at presentation and have different patterns of dyslipidemia compared to western population.1,2 Role of nonconventional lipid markers like apolipoprotein A (ApoA), apolipoprotein B (ApoB), lipoprotein a (Lpa) were studied in the present study. Material and methods: Thirty-six consecutive patients of acute myocardial infarction (AMI) were included in the study. Patients with risk factors for dyslipidemia like diabetes mellitus, hypothyroidism, liver failure, renal failure or those already on lipid lowering therapy were excluded from study. Extended lipid profile in fasting state was studied for all patients including apolipoproteins and Lpa within 12 hours of chest pain. The study was duly approved by hospital ethics committee. Results: Total cholesterol and LDL cholesterol values were within normal range for most of the patients (average value 155 ± 21 mg% and 90 ± 16.7, respectively).

The major abnormality found in lipid profile was high triglyceride (164 ± 51 mg%), low HDL (33 ± 6.5 mg%), high Lpa (mean value 25 ± 10.3 mg%) and high incidence of unfavorable ApoA/ApoB ratio (i.e ratio <1.00). 41.7% (15/36) patients had high Lpa value (i.e. >30 mg%). Percentage of patients having unfavorable ApoA1/ApoB ratio was 92%. Comprehensive lipid tetrad index was 19286. Percentage of patients with truncal obesity (i.e. waist-hip ratio >1.00) was 36% (13/36). Percentage of current smokers in study was 42% (15/36). Conclusion: We observed high incidence of elevated Lpa and unfavorable ApoA/ApoB ratio in AMI patients of this region. The role of these additional lipid markers needs to be studied in detail especially in subsets who have normal conventional lipid profile.

Keywords: Coronary artery disease, extended lipid profile, myocardial infarction, apolipoprotein A, apolipoprotein B, lipoprotein (a), HDL cholesterol, LDL cholesterol, waist-hip ratio

A

bnormalities in plasma lipoproteins and derangements in lipid metabolism are one of the best established risk-factors for atherosclerosis and coronary artery disease (CAD). Studies have shown that apolipoprotein A1 (ApoA1): Apolipoprotein B (ApoB) ratio distinguishes unequivocally between patients with and without CAD.3 Role of other lipid parameters like lipoprotein a (Lpa) in causation of atherosclerosis and CAD is yet to be established clearly. It is a known fact that CAD in Indians occurs at levels of dyslipidemia much lower than western populations and many Indian patients with coronary artery have lipid parameters that are much lower then their western counterparts.1,4-6

Asian Indians tend to have higher levels of triglycerides, lower high-density lipoprotein (HDL) levels and higher Lpa.8-11. The role of studying nontraditional lipid risk factors like ApoA1: ApoB ratio and Lpa in Indian CAD patients especially in patients with normal lipid parameters is not clear.

Studies are needed in Indian patients to evaluate the role of extended lipid profile parameters including the above nontraditional risk factors described above, especially when the patterns of dyslipidemias in Indian patients are different from their western counterparts.

Aims and Objectives To study the patterns of extended lipid profile abnormalities in CAD patients of Bundelkhand region.

Material and Methods

*Associate Professor Dept. of Cardiology **Assistant Professor Dept. of Pathology UFHT Medical College, Haldwani Nainital, Uttarakhand

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Indian Journal of Clinical Practice, Vol. 23, No. 10 March 2013

This study has been conducted on 36 freshly diagnosed CAD patients presenting on first instance with first episode of freshly diagnosed acute myocardial infarction (AMI). Inclusion criteria were:

cardiology ÂÂ

All patients of AMI were not previously known case of CAD.

ÂÂ

Patients found to have confounding factors for dyslipidemia were excluded from the study (confounding factors included presence of systemic hypertension, diabetes mellitus, hypothyroidism, liver diseases, kidney disease and those on statins).

ÂÂ

The diagnosis of MI was made by combination of history, physical examination, ECG, troponin bedside test, cardiac enzymes. Patients with evidence of old MI on ECG were also excluded from the study.

Examination History: Name, age, sex, weight, height, body mass index (BMI), waist-hip ratio, history of smoking and detailed medical and treatment history was taken.

Physical Examination: Patient full general examination was done to look for any signs of hyperlipidemia, thyroid swelling, pulse rate, blood pressure and detailed cardiovascular examination was done. Body weight, height, BMI, waist-hip ratio was taken.

Investigations General Routine Investigations ÂÂ

Hemogram, total and differential count

ÂÂ

Fasting and 2-hour postprandial blood glucose measurements to rule out diabetes mellitus.

ÂÂ

Liver function tests (serum glutamic pyruvic transaminase [SGPT], serum glutamic oxaloacetic transaminase [SGOT] serum bilirubin and serum alkaline phosphate) to rule out liver disease.

ÂÂ

Renal function tests including blood urea and serum creatinine to rule out renal disease.

ÂÂ

Routine urine microscopy was also done for all patients.

Extended Lipid Profile Fasting venous sample was taken for all patients within 12 hours of onset of chest pain for following lipid parameters: Total cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, HDL cholesterol, VLDL, LAa, ApoA1, ApoB, ApoA/ApoB ratio. The blood samples received were sent with due precautions to Lal’s Laboratory Pvt. Ltd., New Delhi, immediately for analysis. This Lab is approved by WHO and Center

Technique employed for lipid profile measurement at the laboratory: Lipoproteins (a)

Latex enhanced nephelometry

Apolipoprotein A1 and

Immunoturbidimetry

Apolipoprotein Total cholesterol

Spectrophotometry

HDL cholesterol Spectrophotometry

LDL cholesterol, VLDL, Electrophoresis lipoprotein Spectrophotometry for Disease Control, Atlanta, Georgia, USA and is a laboratory of international repute Analysis The results of extended lipid profile was pooled and patterns of lipid abnormalities studied using relevant statistical methods.

Results

Age-wise Distribution of Patients The average age of the patient was 55.86 years (25-78 years). Percentage of patients with age <60 years was 75% (27/36); percentage of patients with age <30 years was 2.77% (1/36). Maximum clustering of AMI was seen in the age group 40-59 years which included 70.22% patients (26/36).

Total Cholesterol Levels The average total cholesterol in the study group was 155 ± 21 mg%. Maximum clustering of total cholesterol levels were seen in the range group 140-159 mg% (16/36;44.4%). Only one patient had total cholesterol value of >200 mg%. The range of total cholesterol was 106-207 mg%.

LDL Cholesterol The average value of LDL cholesterol in the study group was 90.4 ± 16.7 mg%. Only 25% patients of the study group had LDL cholesterol value >200% (9/36). The range of LDL cholesterol value was 56.4-141 mg%.

Triglycerides The average value of triglyceride in the study group was 164 ± 52 mg%; 18 patients (50%) had triglycerides

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597

cardiology >150 mg%. The range of triglyceride value was 67-354 mg%.

HDL Cholesterol Mean value of HDL cholesterol in the study group was 33.0 ± 6.5 mg%; 32/36 (90%) patients had HDL cholesterol value <40 mg%.

VLDL Cholesterol The average value of VLDL cholesterol in the study group was 32.6 ± 10.9 mg%; percentage of patients having unfavorable VLDL levels >41 mg% was 18.4% (7/36).

The range of VLDL cholesterol was 14.42-58.2 mg%.

Lipoprotein A The average Lpa for the patients in the study group was 24.9 ± 10.29 mg%. Percentage of patients having high Lpa levels (i.e. >30 mg%) was 41.67% (15/36). The range of Lpa was 10.3-45.0 mg%.

Apolipoprotein A1 The average ApoA1 levels in the study group was 85 ± 14.62 mg%. The desirable ApoA1 level is in the range 104-202 mg%. Percentage of patients having ApoA1 <104 mg% (i.e. desirable levels) was 86.11% (31/36). The range of ApoA1 is 59-110 mg%.

Apolipoprotein B The average ApoB in the study group was 89 ± 14.09 mg%. The desirable range of ApoB is 66-133 mg%.

The range of ApoB was 59-118 mg% in our study group.

ApoA1/ApoB1 Ratio Percentage of patients having unfavorable ApoA1/ApoB ratio (ratio <1.00) was 49.44% (16/36). The ApoA1/ApoB ratio varied between 0.61-1.52.

Total Cholesterol/HDL Ratio Total cholesterol/HDL ratio should be <5.00. For our study group this ratio varied between 2.75-9.0. Percentage of patients having undesirable total cholesterol/HDL ratio (i.e. >5.00) was 36.11% (13/36).

LDL/HDL Cholesterol Ratio The desirable LDL/HDL ratio should be <3.55. For our study group, this ratio varied between 1.556.13. Percentage of patients having unfavorable ratio (i.e. ≥3.55) was 11.11% (4/36).

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Indian Journal of Clinical Practice, Vol. 23, No. 10 March 2013

BMI The BMI of the study group varied between 19.7-31.25. The average BMI of the study group was 23.72.

Percentage of patients who were overweight were (i.e.

BMI >25) 22.2% (8/36). Percentage of patients who were obese was (i.e. BMI >30) were 2.78% (1/36).

Comprehensive Lipid Tetrad Index Proposed by Enas as the best estimate of total burden of dyslipidemia. It is derived as follows: Total cholesterol × triglycerides × Lpa/HDL (all in mg%) = 24.9 × 164 × 155.9/33.01 = 19286.

Rural/Urban Classification Of the study group, 23 patients were from rural background and 13 from urban background. Percentage of patients of: Rural background (63.88%) and urban background (36.11%).

Waist-hip Ratio The waist-hip ratio of the patient varied between 0.9-1.16. The average waist-hip ratio of the group was 0.99. Percentage of patient having unfavorable waisthip ratio (i.e. >1.00) was 36.1% (13/36).

Discussion The present study has shown that conventional lipid parameters were normal for majority of patients in the study group. The main abnormalities found in the extended lipid profile of the patients with freshly diagnosed MI were high triglyceride, low HDL, high Lpa and high incidence of unfavorable ApoA1: ApoB ratio (<1.00).

A study5 by Gupta et al at Monilek Hospital and Research Centre, Jaipur, found out that total cholesterol levels were not significantly higher in CAD patients compared to healthy age-matched controls. This finding in our study is in conformity with our observation of near normal cholesterol levels (mean = 155.9 ± 21 mg%) for most of the patients.

Another study at Louisiana State University Medical College Center, New Orleans, evaluating risk factors for CAD and levels of Lp a in Asian Indians of USA found average total cholesterol to be 218.9 ± 39.0 mg% compared to 155.9 ± 21 mg% for our study. 1,4 Percentage of patients of MI patients having LDL cholesterol >100 mg% was only 25%. This value is in agreement with study by Gupta et al, which found

cardiology out that level of LDL cholesterol was not significantly higher in CAD patients when compared to normal healthy age-matched controls.

However, another study,4,7 of risk factor for CAD in Asian Indians of USA found average LDL cholesterol to be 117.8 ± 35.1 mg% compared to 90.4 ± 16.7 mg% in our study. This study was conducted on 110 Asian Indian physicians residing in United States. However, it is pertinent to mention here that study subject’s profile was different in our study, because all patients were freshly diagnosed MI patients and who did not have any confounding factors for dyslipidemia so that a direct link of fresh MI without previous known CAD with dyslipidemia could be studied.

A study by Austin2 et al recently described atherogenic lipoprotein phenotype B characterized by moderate hypertriglyceridemia, a high proportion of smalldense LDL, a high level of ApoA1 and HDL. It can inherited as a single gene trait. Atherogenic phenotype B can be differentiated from benign phenotype A by simple measurements of serum triglycerides and HDL. A triglyceride value of 95 mg/dl discriminates the two phenotypes in 83% cases, whereas an HDL value of 39 mg/dl separates the two groups in 72% of cases.

When a triglyceride level of >95 mg/dl was used; 75% of Asian Indian men in the CAD among Indians study demonstrated this phenotype. This figure when using serum triglyceride >95% with HDL cholesterol <35 mg% to identify atherogenic phenotype B was found to be 91.8% in our study.

The role of newer lipid parameter Lpa in atherogenesis is still to be proven; Lpa levels may be related to both atherogenesis and thrombosis and may be a key link between lipids and thrombosis.12 The levels of Lpa were found to be three times higher in the Asian Indians than among whites in United States in the CAD among Indians Study.7,13 A study12 of Lpa levels of 110 Asians physicians residing in United States found average value of Lpa to be 18.5 ± 20.0 mg%. This value is close to Lpa levels found in our study (24.9 ± 10.29 mg%). In the same study, levels of Lpa (mean = 20.0 mg%) among Indians were comparable to findings of Lpa values of Asian Indians in Singapore (20.1 mg%). The Lpa levels and high Lpa levels (>30 mg%) in males from this study (18.5 mg% and 20%) were also comparable to findings from male Indian physicians who migrated to US (19.6 mg% and 24%, respectively).

In our study group, 49.44% (16/36) patients had unfavorable ApoA1/ApoB ratio (i.e. <1.00). One important observation was that none of the patients had this ratio in the high-risk range of 0.00-0.50.

Studies15 have shown that ApoA1:ApoB ratio distinguishes unequivocally between persons with and without CAD. Therefore, ApoA1 and B studies are superior to conventional total cholesterol, HDL and LDL cholesterol studies for predicting risk for atherosclerosis.

A study4 of 110 Asian physicians residing in USA for risk factors for CAD found average level of ApoAI and B to be 131 ± 24 mg% and 147 ± 28%, respectively.

The composite ApoA1/ApoB ratio for this population group was 0.89 which is comparable to ApoA1 by ApoB ratio obtained in our study (i.e. 0.95).

A study13 conducted on lipid profile of patients with microvascular angina in Greece, found the average level of ApoB to be 146 ± 32 mg/dl in patients of CAD vs 89 ± 14.1 mg% in our study.

Hence, we conclude by saying that although the absolute values of ApoA1 and ApoB were not comparable in above two studies the more important discriminator of severity of atherosclerosis i.e ApoA1/ApoB ratio was comparable to value found in our study.

Conclusion Following conclusion can be derived from our study: ÂÂ

Total cholesterol and LDL cholesterol values were within normal range for most of the patients (average 155.9 ± 21.05 mg% and 90.4 ± 16.7 mg%, respectively).

ÂÂ

The major abnormality found in the extended lipid profile of MI patients was high triglyceride, low HDL, high Lpa and high incidence of unfavorable ApoA1 by ApoB ratio (i.e. ratio <1.00).

ÂÂ

Patient having atherogenic phenotype B as described

by Austin and defined as serum triglyceride >95 mg% and HDL cholesterol values <35% was found in 60.1% patients (22/36).

ÂÂ

Percentage of patient having high Lpa values was 41.66%.

ÂÂ

Percentage of patient having unfavorable ApoA1/ ApoB ratio (i.e. <1.00) was 91.8.

ÂÂ

Comprehensive lipid-tetrad index as defined by Enas was 1928.6

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599

cardiology ÂÂ

Unfavorable total cholesterol by HDL ratio (i.e. >5.00) was found in 36.11%(13/36) of patients.

based case-control studies. Indian Heart J. 2001;52(3): 332-6.

ÂÂ

Unfavorable LDL cholesterol by HDL cholesterol ratio (i.e. >3.55) was found in 11.11% (4/36) patients.

ÂÂ

Percentage of patients who were overweight (BMI >25) was 25% (9/36).

6. Chuang CJ, Subramaniam PN, Legardeur by, Lopez A. Risk factors for coronary artery disease and levels of lipoprotein(a) and fat-soluble antioxidant vitamins in Asian Indians of USA. Indian Heart J. 1998;50(3): 285-91.

ÂÂ

Percentage of patients who had objective evidence of truncal obesity (i.e. waist-hip ratio >1.00) was 36.11% (13/36).

ÂÂ

Percentage of female patients was 16.6% (6/36).

ÂÂ

Patients of MI had average age of 55.86 years.

Percentage of patients who were <50 years was 25 (9/36). Maximum percentage of MI patients was seen in the age group 40-59 years, which included 70.22% patients (26/36).

ÂÂ

Rural urban division of the patients was as follows: Rural background - 63.88% (23/36), urban background - 36.11% (13/36).

ÂÂ

Percentage of smokers in the study group was 41.7% and percentage of tobacco chewers were 5.6%.

Suggested Reading 1. Enas A, Yusuf S, Mehta JL. Prevalence of coronary artery disease in Asian Indians. Am J Cardiol 1992;70(9): 945-9.

2. McKeigue PM, Miller GJ, Marmot MG. Coronary heart disease in south Asian’s: a review. J Clin Epidemiol 198942(7):597-609.

3. Stamler J, Wentworth D, Neaton JD. Is the relationship between serum cholesterol and risk of premature death from coronary heart disease continuously graded?

Findings in 356,222 primary screenees of the Multiple Risk Factor Intervention Trial (MRFIT). JAMA 1986;256(20): 2823-8.

4. Enas EA, Mehta J; CADI Study. Malignant coronary artery disease in young Asian Indians: thoughts on pathogenesis, prevention, and therapy Clin Cardiol 1995;18(3): 131-5.

5. Gupta R, Kaul V. Prakash H, Saran M, Gupta VP. Lipid abnormalities in coronary heart disease: a population-

7. Mishra A, Reddy RB, Reddy KS, Muhan A, Bajaj JS. Clustering of impaired glucose tolerance, hyperinsulinemia and dyslipidemia in young North Indian patients with coronary heart disease: a preliminary case-control study. Ind Heart J 1995;51:275-89.

8. Gupta R, Gupta VP, Sarna M, Bhatnagar AS, Thanvi J, Sharma V, et al. Prevalence of coronary heart disease and risk factors in an urban Indian population: Jaipur Heart Watch. Indian Heart J 2002;54(1):59-66.

9. Anand S, Yusuf S, Vuksan V, Devanesen S, Teo K, Montague AA, et al. Differences in risk factors, atherosclerosis and cardiovascular disease between ethnic groups in Canada: the Study of Health Assessment and Risk in Ethnic Groups (SHARE). Lancet 2000;356: 279-84.

10. Haffner SM, D’Agostino R Jr, Goff D, Howard B, Festa A, Saad MF, et al. LDL size in African Americans, Hispanics and non-Hispanic whites: the insulin resistance atheroslerosis study. Arterioscler Thromb Vasc Biol 1999;19(9):2234-40.

11. Enas EA, Jacob S. Coronary artery disease in Indians in the USA. In: Coronary Artery Disease in Indians: A Global Perspective. Sethik, (Ed.), Cardiological Society of India; Mumbai 1998:32-43.

12. Misra A, Luthra K, Srivastava LM. Lipoprotein (a): biology and role in atherosclerotic vascular diseases. Curr Sci 1999;76:1553-60.

13. Stadmpfer MJ, Saxcks FM, Simonetta S. A prospective study of cholesterol, apolipoprotein and risk of myocardial infarction. N Engl J Med 1998;47:2008-111.

14. Joseph A, Kutty AR, Soman CR. High risk for coronary heart disease in Thiruvanthapuram city: a study of serum lipids and other risk factors. Indian Heart J 2000;52(1):29-35.

15. Bahl VK, Vaswani M, Tlatadi D, Wasir HS. Plasma level of apolipoprotein A1 and B in Indian patients with angiographically defined CAD. Int J Cardiolo 1994;46(2):143-9.

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critical Care

Antimicrobial Therapy in the Intensive Care Unit MS Krishna Sarin*, M Vadivelan**, Chanaveerappa Bammigatti**

Abstract Severe sepsis and septic shock in the intensive care unit (ICU) needs emergent coverage with empirical broad-spectrum antibiotics, with a commitment to de-escalation once the organism and its susceptibility to a particular antibiotic becomes known. The dose and duration of antibiotic must be optimized according to standard guidelines to prevent emergence of resistant pathogens. Strategies of using Procalcitonin measurements in guiding the duration of antibiotic treatment and aerosolized antibiotics are helpful in optimizing antibiotic usage. Efforts are needed to prevent emergence of antibiotic resistance by pathogens, as the antibiotic pipeline is dwindling and the number of newly discovered multidrug-resistant (MDR) pathogens is increasing. Prevention of infection must be given top priority by strict adherence to asepsis measures.

Keywords: Septic shock, intensive care unit, procalcitonin, aerosolized antibiotics, multidrug-resistant pathogens

T

he intensive care unit (ICU) is a place where patients with complex medical problems are crowded into a small area. The acute nature of critically ill patients necessitates the use of broadspectrum antibiotics frequently.

Fever in a patient in the ICU must be considered significant when the body temperature is >38.3°C (101°F) and a detailed evaluation must be carried out to ascertain whether infection is present or not.1 A lower threshold of fever must be used in immunocompromised patients.

However, as many as 50% of ICU patients with fever have no apparent infection. Fever is a sign of inflammation, not infection. Hence, noninfectious causes of fever must be ruled out before subjecting the patient to a number of costly and invasive diagnostic procedures.

Noninfectious causes of fever in ICU ÂÂ

Postoperative fever: Fever on the first day following major surgery is reported in 15-40% of patients.2

*Junior Resident **Assistant Professor, Dept. of Medicine Jawaharlal Institute of Post Graduate Medical Education and Research (JIPMER), Pondicherry Address for correspondence Dr M Vadivelan Q.No.: E-2, JIPMER Quarters, JIPMER Campus, Dhanvantari Nagar Pondicherry - 605 006 E-mail: mevadivelan@hotmail.com

ÂÂ

Procedures: Hemodialysis, bronchoscopy, blood transfusions.

ÂÂ

Endocrine disorders: Thyrotoxicosis, adrenal crisis.

ÂÂ

Myocardial infarction, stroke and venous thromboembolism.

ÂÂ

Drug fever: Common offending drugs are cephalosporins, penicillins and amphotericin B and phenytoin.

Infectious causes of fever in ICU ÂÂ Sinusitis ÂÂ Catheter-related bloodstream infection (CRBSI) ÂÂ Ventilator-associated pneumonia (VAP) ÂÂ Catheter-associated urinary tract infection (UTI) ÂÂ Wound infections Sepsis without an Obvious Focus In critically ill patients, the source of infection may not be apparent at the time of admission to the ICU. In such patients, empirical antibiotics must be started intravenously as early as possible within the first hour of recognition of severe sepsis and septic shock.

Each hour of delay will decrease the survival by 7.6% approximately.3 A rough guide to the choice of empirical antibiotics when the focus of infection is unknown is presented in Table 1.4 Empirical coverage for methicillin-resistant Staphylococcus aureus (MRSA) with vancomycin is required in the following situations:

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601

critical Care Table 1. Empirical Therapy for Severe Sepsis with no Obvious Focus Clinical condition

Antimicrobial regimens (IV therapy)

Immunocompetent adult

Piperacillin-Tazobactam/Meropenem/ Cefepime ± Vancomycin

Neutropenia Piperacillin-Tazobactam/Meropenem/ (<500 neutrophils/µl) Cefepime + Aminoglycoside ± Vancomycin Splenectomy

Cefotaxime/Ceftriaxone

IV drug user

Vancomycin

Subsequently, renal-modified dose of the drug can be given.

Sepsis with an Identified Focus of Infection

Ventilator-associated Pneumonia The diagnosis of VAP is made on the basis of a new infiltrate in the chest X-ray with two of the following: ÂÂ

Fever

ÂÂ

Leukocytosis Purulent tracheal secretions

ÂÂ

Patients with indwelling vascular catheters

ÂÂ

ÂÂ

If patient has received quinolone prophylaxis

VAP can be classified as:

ÂÂ

If the institution has a high incidence of MRSA infections.

ÂÂ

Early: If infection began within five days after hospital admission.

ÂÂ

If there is a high prevalence of MRSA isolates in the community.

ÂÂ

Late: If infection began more than five days after admission.

Indications for empirical antifungal drugs are: ÂÂ

If the septic patient has been neutropenic for five days or more

ÂÂ

If the patient has had a long-term central venous catheter

ÂÂ

If the patient has been hospitalized in an ICU and received broad-spectrum antibiotics for a prolonged period.

Amphotericin B is the drug of choice for all lifethreatening fungal infections and as empirical therapy in neutropenic patients with persistent fever.

Fluconazole is used for treatment of candidiasis in patients who are hemodynamically stable and are not immunocompromised. The echinocandins (e.g. caspofungin) can be used for invasive candidiasis as the drug provides improved coverage against all Candida species.

A combination of antibiotics is usually chosen for neutropenic sepsis and in patients with suspected Pseudomonas infections. The drugs which can be used in combination are ceftazidime or piperacillintazobactam or meropenem with an aminoglycoside.5 Indications for administering combination therapy with two drugs active against Pseudomonas are: ÂÂ

Neutropenic fever

ÂÂ

Severe sepsis and septic shock

ÂÂ

Presence of serious infections like pneumonia, endocarditis and meningitis.

All patients must receive the full loading dose of each antimicrobial irrespective of the renal function.

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Indian Journal of Clinical Practice, Vol. 23, No. 10 March 2013

Empirical therapy for early VAP is recommended using a single agent which can be any one of the following drugs:6 ÂÂ

Ceftriaxone

ÂÂ

Levofloxacin/Ciprofloxacin/Moxifloxacin

ÂÂ

Ampicillin + Sulbactam

ÂÂ

Ertapenem

Combination therapy is advised for late VAP and when VAP is suspected to be due to a multidrug-resistant (MDR) pathogen.6 The drugs used are: ÂÂ

Ceftazidime/Cefepime

ÂÂ

Imipenem/Meropenem

ÂÂ

Piperacillin-Tazobactam + an Aminoglycoside/ Fluoroquinolone + Vancomycin/Linezolid.

Optimum duration of therapy for VAP is eight days.

Catheter-related Bloodstream Infections The diagnosis of CRBSI depends on the demonstration, by culture, of the same organism from the catheter tip and blood culture. A colony count at least 3-fold greater for blood obtained from the catheter hub or a differential time to positivity (DTP) of at least two hours at the catheter hub also indicates CRBSI.7 The catheter must be removed in severe sepsis, suppurative thrombophlebitis, endocarditis and infections due to S. aureus, Pseudomonas aeruginosa, fungi or mycobacteria, and in a CRBSI that continues despite 72 hours of antimicrobial therapy to which the infecting microbes are susceptible.

critical Care CRBSI is treated with the combination of a fourthgeneration cephalosporin/carbapenem plus vancomycin to cover MRSA. An aminoglycoside is added if Pseudomonas is suspected. The duration of therapy depends on the infecting pathogen. Complicated CRBSI (i.e., CRBSI-associated with suppurative thrombophlebitis, endocarditis) requires at least 28 days of antibiotic therapy.

The recommended duration of antimicrobial treatment for patients with catheter-associated UTI who have rapid resolution of symptoms is 7 days and 10-14 days for those with a delayed response, regardless of whether the patient remains catheterized or not.8

Catheter-associated UTIs

Once the source of sepsis is known, the antimicrobial therapy should be tailored according to the possible infecting pathogens and their relative antibiotic susceptibilities. A summary of the possible etiologic agents according to the site of infection and the drug that can be used is given in Table 2.9

Catheter-associated UTIs are diagnosed when bacteriuria (10³ colony forming units/ml) is associated with symptoms compatible with UTI. Symptoms include fever with rigors, flank pain, renal angle tenderness, hematuria or pelvic discomfort.

These infections are often polymicrobial and are caused

by MDR pathogens. Urine culture results are required to guide treatment. Catheter has to be replaced if it has been in place for more than two weeks and if its use cannot be discontinued.

Antibiotic Therapy Depending on the Site of Infection

Treatment of Mdr Pathogens MDR pathogens are a real and constant threat in the ICU environment. The six most common MDR pathogens encompassed in the eponymous ‘ESKAPE’

Table 2. Antibiotic Therapy Depending on the Site of Infection Site of infection

Bacteria

Suggested treatment

UTI

E. coli

Ceftriaxone or Ceftazidime ± Aminoglycoside

Severe acute pyelonephritis

P. aeruginosa Enterococcus species Staphylococcus species

Intra-abdominal sepsis

E. coli

Ertapenem

P. aeruginosa

Piperacillin-Tazobactam

Enterococcus species

Third- or fourth-generation cephalosporin (active against P. aeruginosa) + Metronidazole

Bacteroides species Nosocomial pneumonia

Enterobacteriaceae P. aeruginosa

β-lactam (active against P. aeruginosa) ± Aminoglycoside ± Glycopeptide (vancomycin)

S. aureus S. pneumoniae H. influenzae Pneumonia without risk factors for MDR Pseudomonas

S. aureus

Third-generation Cephalosporin ± Macrolide

S. pneumoniae H. influenzae Other gram-negative bacilli

Skin infections

CRBSI

Streptococcus species

β-lactam + β-lactamase inhibitor

Staphylococcus species

Piperacillin-Tazobactam

Gram-negative bacilli

Carbapenem

Staphylococcus species

Vancomycin + β-lactam with activity against P. aeruginosa

Enterobacteriaceae P. aeruginosa

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605

critical Care group are Enterococcus faecium, S. aureus, Klebsiella pneumoniae, Acinetobacter species, P. aeruginosa and the Enterobacter species.

Tables 3 and 4 summarize the treatment options for various MDR pathogens.

Newer Concepts in Antimicrobial Therapy

Procalcitonin as a Biomarker in Sepsis Procalcitonin is the best studied biomarker for guiding antibiotic treatment duration in the hospital setting.

Procalcitonin dynamics within 72 hours after onset of sepsis may be correlated both with appropriateness of the empirical antibiotic therapy and with overall survival.10 Procalcitonin measurements integrated in clinical algorithms have been shown to reduce the duration of antibiotic courses by 25-65% in hospitalized and more severely ill patients with CAP and sepsis.11

Pharmacokinetics in Drug-dosing Time/ Concentration-dependent Killing Antibiotics like b-lactams, quinolones and vancomycin exert their microbicidal activity depending on the duration for which the plasma drug levels remain above the minimum inhibitory concentration (MIC).

An appropriate strategy is to administer these antibiotics as a continuous infusion rather than as bolus doses.

On the other hand, aminoglycosides exert their action depending on the peak levels achieved in plasma. So, the appropriate strategy will be to give the entire daily dose as a single bolus injection.

The pharmacokinetics of antibiotics is modified in ICU patients owing to the large daily fluid balance, acute changes in body weight, hypoalbuminemia, edema and low hematocrit values that lead to a marked change in elimination half-life, volume of distribution and clearance. Sepsis increases capillary permeability

Table 3. Treatment Options for Resistant Gram-positive Bacteria Drug

Route of Activity against MRSA administration

Activity against resistant S. pneumoniae

Activity against vancomycinresistant Enterococci

Vancomycin

IV only

Yes

Yes

No

Daptomycin

IV only

Skin infection/Bloodstream infection

No

Yes

Linezolid

IV or oral

Pneumonia/Skin infection

No

Yes

Yes

No

Yes, against E. faecium

Quinupristin- IV only Dalfupristin Telavancin

IV only

Skin infection/Pneumonia

Yes

Yes

Tigecycline

IV only

Pneumonia/Skin infection

Yes

Yes

Ceftaroline

IV only

Pneumonia/Skin infection

Yes

No

Table 4. Treatment Options for Resistant Gram-negative Bacteria Organism Empirical therapy Monomicrobial infection

Polymicrobial infection

Directed therapy ESBL-producing Enterobacteriaceae

Carbapenemase-producing Enterobacteriaceae MDR P. aeruginosa

606

First-line therapy

Second-line therapy

Carbapenem

Piperacillin-Tazobactam

Tigecycline (not in UTIs) Âą Antipseudomonal agent Carbapenem + Vancomycin

Colistin

Tigecycline (not in UTIs) Âą Antipseudomonal agent

Colistin + Vancomycin

Carbapenem

Tigecycline (not in UTIs)

Piperacillin-Tazobactam

Fluoroquinolone

Tigecycline

Colistin Fosfomycin (parenteral formulation)

Colistin Meropenem

Colistin

Indian Journal of Clinical Practice, Vol. 23, No. 10 March 2013

Piperacillin-Tazobactam + Vancomycin

critical Care with third space sequestration resulting in higher antibacterial drug clearances.

Table 5. Practices Promoting the Optimization of Antimicrobial Use in the ICU Setting

Multiple organ dysfunctions cause a decrease in antibacterial drug clearance. Hence, monitoring of plasma drug concentrations needs to be performed whenever possible because these concentrations are difficult to predict in critically ill patients.

Provide adequate initial treatment of serious infections (e.g., pneumonia, bloodstream infections)

Aerosolized Antibiotics Intermittent aerosolization of antibiotics into the respiratory tract has been used in patients with P. aeruginosa pneumonia, particularly in the setting of cystic fibrosis. Tobramycin and colistin have been used in pneumonia caused by MDR Pseudomonas.

Recently, amikacin, nebulized with special devices has been used for MDR gram-negative pneumonia that was unresponsive to standard therapy.

Antimicrobial Resistance and Its Implications MDR pathogens are most frequently encountered in the ICU. The prime reason for the development of antimicrobial resistance is antibiotic misuse. Irrational antibiotic prescription for nondocumented infections in stable patients, prolonged use of broad-spectrum antibiotics without de-escalation, incorrect dosages and dosing intervals and continuation of the antibiotic course beyond the optimally recommended duration contribute to the development of resistance. Practices that promote optimization of antibiotic use in the ICU are summarized in Table 5.12

Awareness of predominant disease causing pathogens Up-to-date ICU-specific pathogen antibiograms Drainage of abscesses, empyema cavities, other infected fluid collections Removal of infected foreign bodies (e.g. central venous catheters) Monitor serum drug concentrations when appropriate to achieve therapeutic levels Avoid prolonged courses of empiric antibiotic therapy Consider de-escalation of antibiotics based on available microbiologic data and clinical course Use narrow-spectrum antibiotics when supported by clinical situation and culture data Establish appropriate thresholds for prescribing antibiotics Develop predetermined criteria for the discontinuation of antimicrobial therapy

Table 6. Predetermined duration of Antibiotic Therapy based on the IDSA Guidelines Site of infection

Duration of antibiotic therapy (days)

Lung infection CAP due to S. pneumoniae

8

VAP

8

VAP and immunodepression

14

Pneumonia due to Legionella pneumophila

21

The key point is to avoid antibiotic misuse by using them only in patients with documented infections except if the infections are life-threatening and avoiding the treatment of asymptomatic colonization.

De-escalation of broad-spectrum antibiotics based on clinical response and microbiological findings is needed to avoid the emergence of MDR pathogens.

Pneumonia with lung necrosis

≥28

Optimizing the duration of antimicrobial therapy by following a protocol-guided discontinuation if appropriate cultures are negative after Day 3 and prescribing the antibiotic course for the optimum duration will help to reduce the emergence of resistance. The optimum duration of antibiotic therapy for the commonly encountered infections in the ICU, according to the Infectious Diseases Society of America (IDSA) guidelines is given in Table 6. Certain practices may be helpful in controlling antibiotic resistance.

Postoperative meningitis due to S. epidermidis or Enterobacteriaceae

14

Meningitis due to Listeria monocytogenes

21

Postoperative meningitis due to S. aureus or P. aeruginosa

21

Brain abscess

≥28

Intra-abdominal infections Community peritonitis

<8

Postoperative peritonitis

14

CNS infections Meningococcemia Meningitis due to S. pneumoniae

5-8 10-14

Catheter-related bacteremia S. epidermidis or Enterobacteriaceae

<8

S. aureus/Candida species (uncomplicated)

14

S. aureus (complicated)

≥28

Indian Journal of Clinical Practice, Vol. 23, No. 10 March 2013

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critical Care Scheduled Changes in Antibiotic Therapy Periodic changes in the antibiotic preference in treating infections caused by the same pathogen (e.g., gramnegative infections treated with a cephalosporin for the first six months and a fluoroquinolone for the next 6 months) may help to reduce the emergence of resistance to either class.

ÂÂ

Give ‘sedation vacation’ and assess readiness to extubate daily.

ÂÂ

Use peptic ulcer disease prophylaxis.

ÂÂ

Use deep-vein thrombosis prophylaxis (unless contraindicated).

Prevention of UTIs

Antibiotic Class Cycling

ÂÂ

A class of antibiotic is withdrawn from use for a defined time period and reintroduced at a later point of time in an attempt to limit bacterial resistance to the antimicrobial agent.

Place bladder catheters only when absolutely needed (e.g. to relieve obstruction), not solely for the provider’s convenience.

ÂÂ

Use aseptic technique for catheter insertion and urinary tract instrumentation.

ÂÂ

Minimize manipulation or opening of drainage systems.

ÂÂ

Ask daily: Is the catheter needed? Remove catheter if not needed.

For any ICU, written protocols must be developed based on the local ecology of microorganisms and their pattern of resistance. This is best done in consultation with the Dept. of Microbiology. An infectious disease specialist consultation helps in improving the accuracy of the prescription of antimicrobial drugs.

Prevention of Infections in the ICU Simple measures to prevent infection and pathogen cross-transmission assume significance considering the huge expenses incurred in terms of patient morbidity and mortality as well as the indirect costs involved in treating a resistant infection. A summary of the recommendations made by the Centers for Disease Control is given below:13

Prevention of Central Venous Catheter Infections ÂÂ

Educate personnel about catheter insertion and care.

ÂÂ

Use chlorhexidine to prepare the insertion site.

ÂÂ

Use maximal barrier precautions during catheter insertion.

ÂÂ

Consolidate insertion supplies (e.g., in an insertion kit or cart)

ÂÂ

Use a checklist to enhance adherence to the bundle.

ÂÂ

Empower nurses to halt insertion if asepsis is breached.

ÂÂ

Cleanse patients daily with chlorhexidine.

ÂÂ

Ask daily: Is the catheter needed? Remove catheter if not needed or used.

Prevention of VAP ÂÂ

Elevate head end of bed to 30-45°.

ÂÂ

Decontaminate chlorhexidine.

608

oropharynx

regularly

with

Indian Journal of Clinical Practice, Vol. 23, No. 10 March 2013

Prevention of Surgical-site Infections ÂÂ

Choose a surgeon wisely.

ÂÂ

Administer prophylactic antibiotics within one hour before surgery; discontinue within 24 hours.

ÂÂ

Limit any hair removal to the time of surgery; use clippers or do not remove hair at all.

ÂÂ

Prepare surgical site with chlorhexidine-alcohol.

ÂÂ

Maintain normal perioperative blood glucose levels (cardiac surgery patients).

ÂÂ

Maintain perioperative normothermia (colorectal surgery patients).

Prevention of Pathogen Cross-transmission Cleanse hands with alcohol hand rub before and after all contacts with patients or their environments.

References 1. O’Grady NP, Barie PS, Bartlett JG, Bleck T, Carroll K, Kalil AC, et al; American College of Critical Care Medicine; Infectious Diseases Society of America. Guidelines for evaluation of new fever in critically ill adult patients: 2008 update from the American College of Critical Care Medicine and the Infectious Diseases Society of America. Crit Care Med 2008;36(4): 1330-49.

2. Fry DE. Fever in the ICU. The ICU Book 2008; 39(3):716.

3. Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, et al; International Surviving Sepsis Campaign Guidelines Committee; American Association of Critical-Care Nurses; American College of Chest Physicians; American College of Emergency Physicians;

critical Care Canadian Critical Care Society; European Society of Clinical Microbiology and Infectious Diseases; European Society of Intensive Care Medicine; European Respiratory Society; International Sepsis Forum; Japanese Association for Acute Medicine; Japanese Society of Intensive Care Medicine; Society of Critical Care Medicine; Society of Hospital Medicine; Surgical Infection Society; World Federation of Societies of Intensive and Critical Care Medicine.

Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med 2008; 36(1):296-327.

7. Mermel LA, Allon M, Bouza E, Craven DE, Flynn P, O’Grady NP, et al. Clinical practice guidelines for the diagnosis and management of intravascular catheterrelated infection: 2009 Update by the Infectious Diseases Society of America. Clin Infect Dis 2009;49(1):1-45.

4. Munford RS. Severe sepsis and septic shock. In: Harrison’s Principles of Internal Medicine. Volume 2, 2012;271(18):p.2229.

9. Textoris J, Wiramus S, Martin C, Leone M. Overview of antimicrobial therapy in intensive care units. Expert Rev Anti Infect Ther 2011;9(1):97-109.

5. Kanj SS, Kanafani ZA. Current concepts in antimicrobial therapy against resistant gram-negative organisms: extended-spectrum beta-lactamaseproducing Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae, and multidrug-resistant Pseudomonas aeruginosa. Mayo Clin Proc 2011;86(3):250-9.

6. American Thoracic Society; Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcareassociated pneumonia. Am J Respir Crit Care Med 2005;171(4):388-416.

8. Hooton TM, Bradley SF, Cardenas DD, Colgan R, Geerlings SE, Rice JC, et al; Infectious Diseases Society of America. Diagnosis, prevention, and treatment of catheter-associated urinary tract infection in adults: 2009 International Clinical Practice Guidelines from the Infectious Diseases Society of America. Clin Infect Dis 2010;50(5):625-63.

10. Schuetz P, Albrich W, Mueller B. Procalcitonin for diagnosis of infection and guide to antibiotic decisions: past, present and future. BMC Med 2011;9:107.

11. Harbarth S, Haustein T. Year in review 2009: Critical Care - infection. Crit Care 2010;14(6):240.

12. Kollef MH. Optimizing antibiotic therapy in the intensive care unit setting. Crit Care 2001;5(4):189-95.

13. Robert A. Weinstein. Health Care-Associated Infections.

Harrison’s Principles of Internal Medicine (Volume 1); 131(18):1114.

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Amyloid Imaging Guideline Issued Use of new, FDA-approved imaging technologies for beta-amyloid protein plaques in the brain should be limited to a relatively small subset of individuals, according to a new guideline issued jointly by the Alzheimer's Association and the Society for Nuclear Medicine and Molecular Imaging. According to the statement, PET scans with florbetapir (Amyvid) or other tracers now in the development pipeline are appropriate only for three patient presentations ÂÂ

Persistent or progressive and unexplained mild cognitive impairment

ÂÂ

Clinical diagnosis of ‘possible’ Alzheimer's disease because of an atypical clinical course or an etiologically mixed presentation

ÂÂ

Progressive dementia beginning at age 65 or younger. (Source: Medpage Today)

Breakthrough: First Digital Atlas of Brain Understanding the most complex human organ - the brain, has now become a lot simpler. In a major breakthrough, scientists at Berkeley Lab has made it possible to get a front row view into how the brain develops and functions and pinpoint which part of the organ is playing truant during neurological disorders like autism, epilepsy and schizophrenia. The scientists have created the world's first genome-wide digital atlas of gene enhancers in the brain - the switches that tell genes when and where they need to be switched on or off. This atlas completely documents the cerebrum - the region that is of critical importance for cognition, motor functions and emotion identifies and locates thousands of gene-regulating elements which are the underlying causes of neurological disorders. (Source: TOI)

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Dentistry

Maxillary Full Arch Fixed Prosthesis: Clinical Laboratory Procedures and Rehabilitation with Milled Titanium Prosthesis Eldo Koshy*, Sony Jacob Mevada**, Sunitha Raj Philip†

Abstract Maxillary teeth are the focal point of human smile. Restoring the edentulous maxilla with implant prosthetics is the most challenging area in implant dentistry. Several techniques have been described for the successful restoration of the edentulous mandible/maxilla. Fixed-detachable prostheses with either hybrid prosthesis design or conventional implant supported fixed partial dentures and implant-retained/supported over dentures are some examples. A clinical report is presented describing the clinical and laboratory procedures involved in the fabrication of a copy milled fixed full arch maxillary prosthesis. Similar procedures may be followed in the making of a fixed full arch copy milled mandibular prosthesis.

Keywords: Edentulous maxilla, implant prosthetics, fixed full arch maxillary prosthesis, copy milled mandibular

prosthesis

I

t is a challenge for the dentist to choose among the various materials and techniques available for fabricating an implant-supported prosthesis.

Every single step in fabricating an implant supported prosthesis influences the fit between the implants and the final prosthesis.1,3,11,18 There are many methods to construct a framework for a complete arch fixed implant prosthesis. Casting procedures as well as computeraided design/computer-aided manufacturing (CAD/ CAM) and milling procedures are among the reported techniques. Metal framework fabricated by conventional casting procedures inevitably result in discrepancies between the frameworks and the implants because of distortion in the casting process.4,12,16 Titanium and gold alloys are commonly used framework materials, and different cobalt-chrome alloys have been presented as alternatives because of low cost and favorable mechanical properties.6,13 Several alternative framework fabrication techniques have been presented, often aimed at reducing distortion problems.17

*Associate Fellow The American Academy of Implant Dentistry (AAID) Professor, Dept. of Prosthodontics and Implantology Royal Dental College, Challissery, Kerala, Cochin **Professor, Dept. of Oral Surgery Pariyaram Dental College, Kannur, Cochin Clinical Co-ordinator, Dr Koshy’s Dental Clinic, Cochin †Senior Lecturer, St. Gregorious Dental College Chelad, Kothamangalam, Kerala

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The term ‘copy mill’ comes from the key duplication business where an existing key is placed on one side of a machine and a blank on the other. As the key is traced by a probe, the other side moves a cutting instrument over the key blank. This creates an exact copy mill of the key. This was exemplified by the Celay milling machine and the term has since been adopted in dentistry. Here, wax ups of bars are created, scanned and digitized and then milled from that digitized file.

An advantage of copy milling in dentistry is the ability to obtain a true “what you see is what you get” design which sometimes may be hard to create or visualize on a screen. Additionally, the model work with fixture replicas and abutments are also scanned and the files are merged.2 Based on these studies, compared to milled frameworks in commercially pure (CP) titanium have been shown to have a better fit traditional cast gold alloy frameworks.10,12,15 Planning for implant placement for an implantsupported fixed denture also requires concern for occlusogingival dimension. To ensure an esthetic, phonetic, hygienic and mechanically robust prosthesis, an absolute minimum of 10 mm of occlusogingival dimension is recommended to accommodate 4 mm of incisor length above the metallic bar, 4 mm for the prosthetic cylinders, metallic bar and retaining screws and 2 mm to account for the transmucosal dimension of the abutment beyond the crest of bone. After examining mandibular casts mounted to oppose the established

Dentistry maxillary dentition at the correct vertical dimension of occlusion, any occlusogingival dimensional discrepancies should be addressed by consideration of an alveolectomy at the time of implant placement.

Case Report A 53-year-old male nonsmoker patient with edentulous maxillary arch presented for treatment with a chief complaint of dissatisfaction with his existing maxillary complete denture because of the inconvenience of removing it every day. He was the director of a marketing company. He also encountered speech problems related to the full palatal coverage of the complete denture and lack of adaptability to its bulk. In addition, his upper denture lost retention many a times at some of his important business meetings causing him a lot of embarrassment. He would only be satisfied with a fixed, functionally stable and esthetically pleasing solution for his lost teeth.

After thorough intraoral examination, ridge mapping and treatment planning with articulated casts and orthopantograph and discussing with the patient about the advantages and disadvantages of various treatment modalities possible, it was decided to place eight implants in the maxilla and a fixed full arch copymilled titanium implant supported maxillary prosthesis 6-8 months later.

impression copings during the impression procedures, while transferring to the laboratory and during laboratory pouring procedures (Fig. 5).

An open tray impression was made in stiff elastomeric impression material after injecting light bodied impression material around the copings (Fig. 6) and the impression sent to the laboratory for pouring. After

Figure 1. Implant cover screws removed.

Seven regular platform and one wide platform (Nobel Biocare) implants were placed in the maxilla. Eight months later, at the second stage surgery, after assuring adequate osseointegration it was decided to carry out the prosthetic phase. The cover screws were removed (Fig. 1) and replaced with gingival formers (Fig. 2). A preliminary impression was made with alginate in a suitable stock impression tray with adequate depth.

The elevations of the gingival formers denoted the regions of the implants for making the special tray for an open tray impression, also recording the relationship of the implant to the adjacent soft tissue and functional sulci in order to aid in positioning the teeth and framework of the prosthesis. The impression was rinsed in water, sprayed with disinfectant and sent to the laboratory for pouring and making the special tray.

Patient was recalled after three weeks and open tray impression copings (Fig. 3) corresponding to the implant sizes was placed. The impression copings were linked to each other with dental floss (Fig. 4) and quick setting autopolymerizing resin (Pattern Resin, GC Company) placed on them assuring immovable stabilization of the

Figure 2. Healing caps placed.

Figure 3. Healing caps exchanged for open tray impression copings.

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Dentistry the impression is taken, healing caps were replaced and impression was send to the laboratory. In the lab, abutment replicas were placed on the copings, implant analogs attached to the copings and the impressions poured using die stone. The accuracy of the master cast was clinically established using a verification jig (check bar). The jig was placed on the copings of the

Figure 4. Impression copings linked by dental floss.

dummy abutments in the master cast initially. It was then verified by seating it intraorally by placing the copings in the bar over the abutments and the fixing screws partly inserted. One screw was tightened while the others remained slack. The fit of the copings were also checked clinically for any visible gaps. Thus, the verification jig returned from the laboratory was analyzed in the mouth, its passive fit and clinical stability ascertained and sent to the lab.

The maxillomandibular relation record was made by using a customized acrylic record base plate and wax occlusal rim and a facebow transfer done. The base that was constructed by incorporating holes over the abutments was secured by using the screws. The wax rims were contoured to establish lip support, incisal edge position, buccal corridor, midline and vertical dimension of occlusion.14 Teeth selection was done based on conventional principles. Proper verification of records was made in order to ensure that the teeth are in the most advantageous position prior to constructing the milled framework and that the teeth was positioned in a way that it could be linked to the underlying implants as well as be hygienically maintained along with controlling occlusal loads. A group function occlusal scheme was planned in this case.

The waxed up trial denture on the master cast was tried. It was ensured that both the patient and dentist were satisfied with the facial appearance, position of the teeth with the opposing dentition, underlying ridge and implants, space below prosthesis to maintain oral hygiene and with the accessibility to the fixture screws.

Figure 5. Self-cure (pattern resin) linking of the impression copings.

Figure 6. The open tray impression.

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The lab attached the teeth on to the milled titanium framework that comes from the milling center, using the previously made index as reference for the final try-in.

The framework (Figs. 7 [a] and [b]) was screwed into position intraorally (Figs. 8 [a] and [b]) and appearance checked for from all directions when the patient moved his lips, speaks and relaxes. Minor changes in the tooth position, extention of the gingival flanges and level of gingival margins were done at this stage. Examination of the surface contours of the prosthesis was done to check for obstruction of lip or tongue movement during swallowing and speaking. Occlusion and access for oral hygiene was also verified. The appliance was then sent to the laboratory for processing.

The final prosthesis (Fig. 9) was inserted after centering it over the abutments optimally initially tightening the screws lightly and sequentially. The fit of the framework, level of bone, position of the abutment and contact of the fixtures were ascertained before torquing

Dentistry

Figure 7. Copy-milled titanium full arch framework for try-in (a) labial view on cast and (b) palatal view on cast.

Figure 8. Intraoral try-in (a) labial view and (b) palatal view.

Figure 9. Finished prosthesis.

Figure 11. Postprosthetic OPG.

Figure 10. Copy-milled titanium full arch prosthesis in mouth.

Note the screw holes sealed with composite resin.

it to its final position. Examination of the occlusion using articulating paper was done with the appliance in the mouth. After the screws were fully torqued, the holes through which they were inserted were sealed using a silicone impression material and the access holes were sealed with light cure composite resin (Fig. 10). The patient was given oral hygiene instructions and discharged (Fig. 11). The patient was recalled after one week and a thorough examination of the prosthesis and surrounding tissues was made. Further recall appointments were given at six month intervals.

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Dentistry Discussion The clinical procedures and a brief description of the various laboratory procedures involved in the construction of a full arch maxillary prosthesis made of a copy-milled titanium frame is described here starting from the second stage surgery. In an edentulous patient, at least four and upto six or eight fixtures are required to support a fixed superstructure. The number of fixtures depends on the implant length, location, implant orientation, bone quality and the length of the cantilever.9 Though, the type of superstructure to be employed is made primarily on the basis of clinical examination and assessment of a trial or diagnostic denture, it is wise to caution the patient that even with careful assessment, the findings at implant insertion may dictate the number and location of implants which can be inserted and hence the type of prosthesis that may be used. Previous careful inspection of original study casts articulated with the trial dentures and comparison of the position of the healing abutments in relation to adjusted complete dentures will provide useful guidance on the choice of the type and length of the definitive abutments. In a majority of cases, the measured depth of the healed mucosal cuff plus 2 mm produces sufficient clearance beneath the fixed prosthesis.

Some of the factors must be evaluated when planning the treatment that would influence the final outcome are to analyze the bone anatomy - to see if sufficient bone depth and width is present to accommodate 4-5 fixtures,7 checking of the opposing prosthesis or natural teeth influences the choice of restoration. Also the prosthetic space, that is, the amount of resorption present should be looked for.7 For instance, in case of severe resorption, it would be advisable to give flanged prosthesis for lip support. The potential location of fixtures should be compatible with the positions of the teeth required to restore the appearance and occlusion without creating excessive leverage.7 Impression copings, which are implant specific, are necessary as they help in recording the position and orientation of the fixtures accurately. Linking of the impression copings is at the discretion of the clinician.

There are disparate school of thought regarding the linking of impression copings prior to the final impression recording. This is done to record the relationship between the fixtures and to produce an accurate impression which would not distort during its transit to the laboratory and during laboratory pouring procedures. The fixtures can be linked by use

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of dental floss, self-cure acrylic resin and by custom fabricated cast cobalt-chromium bar. It is said that this method of linking the copings with floss and selfcure can lead to considerable inaccuracies due to the curing shrinkage of acrylic.7 It is at the discretion of the clinician to decide the impression procedure. An impression may be recorded in a stiff elastomeric impression material without linking the copings. With an open tray impression technique, impression copings with long screws make it easier to remove the copings when the impression material has set. Closed trays or nonperforated trays are used along with tapered copings in areas with restricted access like in the more distal areas of the mouth.7 Here, the impression copings remain attached to the implants when the impression is removed from the mouth.

The advantages of copy-milled fixed prosthesis are that there is no need for soldering, welding, waxing or casting. As the framework is computer-milled, it is more accurate than other techniques. It has superior strength when compared to conventional techniques and has a passive fit and adaptability. No mucosal support is required here as the implant abutment unit supports the prosthesis. Hence, no potential tissue irritation due to prosthesis movement is caused.14 A few complications may arise in such fixed prosthesis.

Primary among these complications are bridge screw loosening and fracture, abutment screw loosening and fracture, prosthesis fracture and prosthetic tooth wear.

Tooth wear is a complication that must be addressed intermittently. The increased functional capacity imparted to the implant-supported fixed denture patient is clearly observed by prosthetic tooth wear.

The restoration of the occlusal and vertical dimension of occlusion for acrylic denture teeth should be considered approximately every 3-5 years. When oral hygiene may be questioned or restricted for physical reasons, the implant-supported fixed denture may be dissuaded in favor of an overdenture prosthesis.

Conclusion Clinicians should encourage patients to consider the potential use of endosseous dental implants as an effective means of improving their own perceptions of function, appearance and image. Harnessing the light weight of titanium and the precision obtained threedimensionally by CAD-CAM milling is the biggest blessing when using copy-milled titanium for the

Dentistry framework of fixed implant prosthesis. It eliminates the cumbersome casting procedures and the inherent casting distortion. It should however be remembered that adequate vertical space between the ridge crest and the occlusal plane is required to accommodate a zone for hygiene as well as the superstructure. Proper home care and regular monitoring of the maintenance of oral hygiene by the patient is mandatory for the long-term success of the restoration.

Suggested Reading

8. Lang NP, Berglundh T, Heitz-Mayfield LJ, Pjetursson BE, Salvi GE, Sanz M. Consensus statements and recommended clinical procedures regarding implant survival and complications. Int J Oral Maxillofac Implants 2004;19 Suppl:150-4.

9. Weinberg LA. Atlas of tooth and implant supported prosthodontics. Quintessence Books, 2006.

10. Ortorp A, Jemt T, Bäck T, Jälevik T. Comparisons of precision of fit between cast and CNC-milled titanium implant frameworks for the edentulous mandible. Int J Prosthodont 2003;16(2):194-200.

1. Assif D, Marshak B, Schmidt A. Accuracy of implant impression techniques. Int J Oral Maxillofac Implants 1996;11(2):216-22.

11. Phillips KM, Nicholls JI, Ma T, Rubenstein J. The accuracy of three implant impression techniques: a three dimensional analysis. Int J Oral Maxillofac Implants 1994;9:533-40.

2. Baba N, Watanabe I, Liu J, Atsuta M. Mechanical strength of laser-welded cobalt-chromium alloy. J Biomed Mater Res B Appl Biomater 2004;69(2):121-4.

12. Riedy SJ, Lang BR, Lang BE. Fit of implant frameworks fabricated by different techniques. J Prosthet Dent 1997;78(6):596-604.

3. Carr AB. Comparison of impression techniques for a fiveimplant mandibular model. Int J Oral Maxillofac Implants 1991;6(4):448-55.

13. Sertgöz A. Finite element analysis study of the effect of superstructure material on stress distribution in an implant-supported fixed prosthesis. Int J Prosthodont 1997;10(1):19-27.

4. Carr AB, Stewart RB. Full-arch implant framework casting accuracy: preliminary in vitro observation for in vivo testing. J Prosthodont 1993;2(1):2-8.

5. Ganeles J, Rosenberg MM, Holt RL, Reichman LH. Immediate loading of implants with fixed restorations in the completely edentulous mandible: report of 27 patients from a private practice. Int J Oral Maxillofac Implants 2001;16(3):418-26.

6. Helldén LB, Ericson G, Olsson CO. The Cresco Bridge and implant concept: presentation of a technology for fabrication of abutment-free, passively fitting superstructures. Int J Periodontics Restorative Dent 2005;25(1):89-94.

7. Hobkirk JA, Watson RA, Ktsson TA. Color Atlas and Text of Dental and Maxillofacial Implantology. Mosby-Wolfe, 1995.

14. Stevens PJ, Gress ML. Implant Prosthodontics: Clinical and Laboratory Procedures. Mosby, 2nd edition, 2000.

15. Takahashi T, Gunne J. Fit of implant frameworks: an in vitro comparison between two fabrication techniques. J Prosthet Dent 2003;89(3):256-60.

16. de Torres EM, Rodrigues RC, de Mattos Mda G, Ribeiro RF. The effect of commercially pure titanium and alternative dental alloys on the marginal fit of one-piece cast implant frameworks. J Dent 2007;35(10):800-5.

17. Van Roekel NB. Prosthesis fabrication using electrical discharge machining. Int J Oral Maxillofac Implants 1992;7(1):56-61.

18. Vigolo P, Millstein PL. Evaluation of master cast techniques for multiple abutment implant prostheses. Int J Oral Maxillofac Implants 1993;8(4):439-46.

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Mouthrinse Reduces Plaque and Gingivitis more than Toothbrushing Alone New research published in the January/February 2013 issue of General Dentistry, the peer-reviewed clinical journal of the Academy of General Dentistry (AGD), indicates that the use of a germ-killing mouthrinse in addition to regular toothbrushing can significantly reduce plaque and gingivitis, more so than brushing alone.

“It’s simple - mouthrinses can reach nearly 100% of the mouth’s surfaces, while brushing focuses on the teeth, which make up only 25% of the mouth,” says Christine A. Charles, RDH, BS, lead author of the study and director of Scientific and Professional Affairs, Global Consumer Healthcare Research and Development, Johnson & Johnson Consumer and Personal Products Worldwide. “Even with regular brushing and flossing, bacteria often are left behind.”

The General Dentistry study found that using a germ-killing mouthrinse twice a day, in addition to regular brushing, can significantly reduce the occurrence of plaque, as well as gingivitis - the beginning stage of gum disease.

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Dermatology

Varying Arrhythmias during Single Hospital Stay in a Case of Systemic Lupus Erythematosus Jaishree Ghanekar*, Sujata Khatal**, Nikhila A Pachani†, Reji John†

Abstract Cardiac involvement is present in more than half of the patients with systemic lupus erythematosus (SLE). However, studies on the prevalence of arrhythmias in this disease and laboratorial correlations predictive of their development do not exist.

Possible pathophysiological mechanisms include autoimmune process, atherosclerosis and adverse effects of the drugs especially chloroquine used for treatment of this disorder. We present a unusual case of SLE with varying arrhythmias during a single hospital stay.

Keywords: Systemic lupus erythematosus, autoimmune disorder, vasculitis, arrhythmias, chloroquine toxicity

S

ystemic lupus erythematosus (SLE) is a chronic inflammatory multisystemic autoimmune disorder of unknown etiology. It is probably multifactorial in origin, including a variable genetic predisposition and environmental factors that trigger the disease, characterized by the finding of antibodies directed against nuclear components. It is much common among certain races including Africans and Indians. Known environmental triggers include: Ultraviolet (UV) light and drugs such as hydralazine, chlorpromazine and methyldopa. The characteristic of SLE is the female predominance of approximately 9:1 and the onset during the reproductive years but has been known to occur in children as young as three years of age.

The disease is characterized by a widespread vasculitis affecting capillaries, arterioles and venules.

Any organ can be affected by SLE including heart.

Various symptoms pertaining to mucocutaneous, musculoskeletal, renal and central nervous system (CNS) along with nonspecific features such as fatigue, fever and weight loss dominate the clinical pictures, making the diagnosis difficult. Anti-double stranded DNA (dsDNA) antibodies and complement levels are used for diagnosis.

*Professor and Head **Associate Professor †Resident Dept. of Medicine, MGM Medical College and Hospital Kamothe, Navi Mumbai

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The American Rheumatism Association recommends four of following 11 revised criteria for the diagnosis of SLE: Malar rash, discoid rash, serositis, oral ulcers, arthritis, photosensitivity, renal, neurologic, hematologic or immunologic disorder on serologic testing, and antinuclear antibodies (ANA).

Case Report A 42-year-old female diagnosed case of DLE (ANA and anti-dsDNA - positive, confirmed on skin biopsy) and was on treatment with hydroxychloroquine (HCQ), admitted with history of high-grade fever for 20 days with altered behavior, maculopapular eruptions over face, neck and extremities along with tingling, numbness and radicular pain.

On admission, her general condition was poor. She was febrile and was looking toxic. Pulse was 98/min., irregularly irregular in rhythm. Blood pressure (BP) was 100/60 mmHg. RR was 18/min. and SpO2-99%.

On general examination, she had pallor, pedal edema, erythematous rash, bleeding oral ulcers (Fig. 1), digital gangrene, lymphadenopathy and raised jugular venous pressure.

Cardiovascular system examination revealed muffled heart sounds. On examination of CNS patient was drowsy with bilateral equal pupils reacting to light.

Plantar were bilateral flexors. RS examination suggested bilateral pleural effusion and on examination of P/A hepatosplenomegaly was present.

Laboratory investigations revealed anemia and pancytopenia (Table 1). Urine examination showed pro-

Dermatology

Figure 1. On Admission and On Discharge - suggesting improvement in general state of the patient after successful treatment.

Figure 2. Chest X-ray showing cardiomegaly.

Table 1. Investigations Investigation

26/11

30/11

6/12

12/12

Hemoglobin

7.9

6.6

9.7

8.0

Total count

3,400

2,400

5,100

4,700

Diff. count

P80 L20

P88 L12

P88 L8 E4

P70 L30

Platelet

65,000

1 lac

1 lac

1.23

Total bilirubin

0.69

-

-

-

SGOT

77.5

-

-

-

SGPT

14.8

-

-

-

Sr. albumin

1.9

2.92

2.2

2.6

Sr. creatinine

1.44

1.5

0.58

0.74

Sr. BUN

21.7

37.94

13.69

7.94

Sr. sodium

138

143

147

136

Sr. potassium

3.76

3.36

2.69

2.94

SGPT: Serum glutamic oxaloacetic transaminase; SGPT: Serum glutamic pyruvic transaminase; Sr.: Serum; BUN: Blood urea nitrogen.

teinuria and hematuria. Twenty-four hours urinary proteins was 1.5 g/day. However, all other biochemical parameters were within normal range. Pleural and pericardial fluids were transudative. Thyroid function test was normal. Chest X-ray showed cardiomegaly with bilateral pleural effusion (Fig. 2). 2D-echo revealed pericardial effusion, global hypokinesia, with left ventricular ejection fraction of 40% ultrasonography suggested hepatomegaly and bilateral pleural effusion.

On admission, ECG showed irregularly irregular rhythm s/o atrial fibrillation with low voltage complexes and left axis deviation (Fig. 3). She was treated with digoxin, amiodarone and b-blockers.

After five days her serial ECG showed sinus bradycardia, global ischemia (Fig. 4). After three days serial ECGs

Figure 3. ECG showing left axis deviation and atrial fibrillation.

Figure 4. ECG showing low voltage pattern, sinus bradycardia, global ischemia.

Figure 5. ECG showing short PR interval, δ-wave, suggestive of WPW syndrome.

showed short PR interval, δ-wave, suggestive of Wolff-Parkinson-White (WPW) syndrome (Fig. 5).

The ECG changes reverted back to normal with the treatment, however, chloroquine was continued. Thus, chloroquine was not the cause for various arrhythmias in our patient. During her hospital stay, she was treated with antibiotics, pulse steroid therapy with injectable

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Dermatology methylprednisolone, amiodarone, β-blockers, HCQ, topical steroids and emollients.

CONCLUSIONS

She also received fresh frozen plasma and blood transfusion. On discharge her ECG showed sinus rhythm, improved clinical status and improved skin lesions (Fig. 1).

The search to identify predictive factors of arrhythmia, especially of the conduction system, should be done in every SLE patient and identification and timely management of arrhythmias could prevent complications and sudden death.

DISCUSSION

REFERENCES

This is an unusual case of SLE with varying type of arrhythmias like atrial fibrillation, WPW syndrome, bradyarrhythmias developing in the patient during single hospital stay. Studies demonstrated that conduction disturbances could occur as a result side effect of drugs. Autoimmune process, atherosclerotic complications, seem to be the other pathophysiological mechanisms of these disturbances.1,2 Risk management algorithms of population do not suggest this and careful evaluation of conduction system disorders, should be included along with dyslipidemia.3 Chloroquine and glucocorticoids are common attributable drugs.4 The diagnosis of chloroquine toxicity can be confirmed by endomyocardial biopsy and ultrastructural study with transmission electron microscopy.5

1. James TN, Rupe CE, Monto RW. Pathology of cardiac conduction system in systemic lupus erythematosus. Ann Intern Med 1965;63(3):402-10.

Classical findings include vacuolated cells with numerous and enlarged secondary lysosomes with a dense material with lamellar structure, myelin and curvilinear bodies, and disorganized miofibrillar structure,6 with necrosis of cardiac myocytes. These changes, found mainly in the cardiac septum, could affect the cardiac conduction system. Recently, the magnetic resonance imaging has proven to be extremely useful in the detection of chloroquine-induced cardiomyopathy, representing an excellent noninvasive option for the diagnosis of this complication.7 Improvement of the cardiac dysfunction after withdrawal of the drug in patients who developed cardiomyopathy has been reported.5

5. Naqvi TZ, Luthringer D, Marchevsky A, Saouf R, Gul K, Buchbinder NA. Chloroquine-induced cardiomyopathyechocardiographic features. J Am Soc Echocardiogr 2005;18(4):383-7.

2. Fonseca E, Crespo M, Sobrino JA. Complete heart block in an adult with systemic lupus erythematosus. Lupus 1994;3(2):129-31.

3. Wajed J, Ahmad Y, Durrington PN, Bruce IN. Prevention of cardiovascular disease in systemic lupus erythematosus - proposed guidelines for risk factor management. Rheumatology (Oxford) 2004;43(1):7-12.

4. Kasamatsu Y, Yoshioka K, Miyashita T, Shibata M, Nakamura T, Yamagami K. Development of various arrhythmias and conduction disturbances following corticosteroid therapy for systemic lupus erythematosus with antiphospholipid syndrome. Mod Rheumatol 2010;20(4):401-4.

6. Teixeira RA, Borba EF, Bonfa E, Pedrosa A, Nishioka S, Martinelli FM. Evidence for antimalarial beneficial effect in cardiac arrhythmic events in a large systemic lupus erythematosus (SLE) cohort. Arthritis Rheum 2009;60(10) (Suppl):S585.

7. Reffelmann T, Naami A, Spuentrup E, Kuhl HP. Contrast enhanced magnetic resonance imaging of a patient with chloroquine-induced cardiomyopathy confirmed by endomyocardial biopsy. Circulation 2006;114(8):e357-8.

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Strain of Acne-Causing Bacteria Found to Actually Preserve Skin Everyone has acne-causing bacteria living on their skin, but researchers at the Washington University School of Medicine have identified that there are ‘good’ and ‘bad’ strains of the bacteria, which determine the frequency and severity of developing pimples.

The findings, which were published in the Journal of Investigative Dermatology, reveal that not all acne bacteria trigger pimples, they even identified one strain that can actually help maintain healthy skin.

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Diabetology

Comparison of Insulin Glargine with Human Premix Insulin in Patients with Type 2 Diabetes Inadequately Controlled on Oral Hypoglycemic Drugs in a 24-week Randomized Study among Central Indian Population Abhishek Singhai*, Subodh Banzal**, Dolly Joseph**, Rajesh Kumar Jha†

Abstract Objective: To compare the safety and efficacy of the long-acting analog insulin glargine and human premix insulin in patients with type 2 diabetes who were previously treated with oral hypoglycemic drugs alone but inadequately controlled. Research design and methods: A total of 750 subjects with type 2 diabetes who were receiving oral hypoglycemic drugs for diabetes control were randomized to receive insulin glargine once-daily (n = 370) or human premix insulin twice-daily (n = 380) for 24 weeks in an open-label, tertiary center study. Doses were adjusted systematically to obtain target fasting glucose <100 mg/dl.

Outcomes included fasting blood sugar, glycosyloted hemoglobin (HbA1C) levels, change in weight and insulin dose from study start to end. Results: At the start of study, age range was 30-70 years, BMI was 26.48 ± 6.3 kg/m2 and HbA1C was 11.9 ± 3.1% (mean ± SD) for both groups. The mean change (means ± SD) in HbA1C from baseline to endpoint was similar in the insulin glargine group (−3.0 ± 1.68%) and the human premix insulin group (−2.89 ± 1.79%) (p = 0.3861). The symptomatic hypoglycemic episodes were greater with human premix insulin than with glargine (significance level 0.00002). Subjects in the insulin glargine group experienced less weight gain than those in the premix human insulin group (0.4 vs 1.4 kg, p < 0.0001).

Conclusions: In patients with type 2 diabetes, once-daily bedtime insulin glargine is as effective as twice-daily human premix insulin in improving and maintaining glycemia control. In addition, insulin glargine demonstrates a lower risk of symptomatic hypoglycemia and less weight gain compared with human premix insulin. The treatments were associated with similar reductions in fasting glucose levels and HbA1C levels.

Keywords: Type 2 diabetes, insulin glargine, human premix insulin, oral hypoglycemic drugs

T

ype 2 diabetes is a progressive disorder of β-cell dysfunction. Patients using oral therapy for it seldom achieve and maintain the recommended 7% glycosylated hemoglobin (HbA1C) goal for glycemic control1,2 and are exposed to increasing risks of diabetic complications as control worsens over time.3,4 However, the majority of patients with a longer duration of diabetes remain poorly controlled with oral agents, and use of insulin, which could improve glycemic control, is often long delayed and not aggressive enough. The reluctance to initiate insulin *Assistant Professor **Associate Professor †Professor and Head Dept. of Medicine, Sri Aurobindo Medical College, Indore, MP Address for correspondence Dr Abhishek Singhai Assistant Professor Dept. of Medicine, Sri Aurobindo Medical College, Sanwer Road, Indore - 453 555, MP E-mail: drabhisheksinghai@gmail.com

therapy seems partly due to its perceived complexity, and fear of hypoglycemia, which may be the greatest barrier.5 A regimen that may make initiation of insulin simpler and more effective has been tested in several small studies.6-8 A single bedtime injection of long-acting (basal) insulin is added while prior oral agents are continued, and insulin is systematically titrated, seeking a defined fasting glucose target. Glargine, a long-acting insulin analog with a more favorable 24-hour timeaction profile (no pronounced peak) than long- or intermediate-acting human insulin preparations,9,10 may be especially suited to this regimen. We compared the abilities of glargine and human premix insulin to reduce HbA1C to 7% when added to ongoing oral therapy and the hypoglycemia accompanying this effort using a simple algorithm for insulin dosage titration seeking fasting blood glucose (FBG) target of 100 mg/dl.

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diabetology RESEARCH DESIGN AND METHODS Enrolled subjects were men or women aged 30-70 years, with type 2 diabetes and treated with stable doses of one or more oral hypoglycemic drugs (sulfonylurea, metformin or pioglitazone) for ≥6 months. There were no significant differences in the mean age, racial distribution, body mass index (BMI), admission blood glucose or HbA1C between treatment groups (Table 1). Inclusion criteria included BMI between 26 and 40 kg/m2, HbA1C >7.5 and FBG ≥140 mg/dl at screening. Exclusion criteria included prior use of insulin, current use of an α-glucosidase inhibitor or a rapid-acting insulin secretagogue, use of other agents affecting glycemic control (including systemic glucocorticoids, nonselective β-sympathetic blockers and antiobesity drugs), history of ketoacidosis or selfreported inability to recognize hypoglycemia, or serum creatinine (≥1.5 mg/dl for men and ≥1.4 mg/dl for women), and a history of drug or alcohol abuse.

This single center, randomized, parallel, 24-week comparative study was performed at Sri Aurobindo Medical College, Indore between January 2009 and September 2012.

Patients were randomized to either glargine (Lantus; Aventis) or human premix insulin (mixture of 30% neutral soluble insulin and 70% isophane insulin) to be administered subcutaneously at bedtime (glargine) or twice a day (human premix insulin), using a pen injector or insulin syringe as preferred by patient for 24 weeks.

Oral hypoglycemic drugs were continued at similar dosages. The starting dose of glargine insulin was 10 IU/day, and dosage was titrated weekly according to laboratory blood glucose levels or self-monitored capillary FBG measurements using meters (Accu-Chek Advantage; Roche Diagnostics) that provide values corresponding closely to laboratory measurements of plasma glucose. Dosages were titrated till target FBG of ≤100 mg/dl was achieved (Table 2).

Subjects visited center at baseline and 1, 3, 5, 7, 10, 12, 18 and 24 weeks and contacted telephonically on 2, 4, 6, 8, 9, 11, 13, 14, 20 and 22 weeks. Glucose values and insulin changes were recorded each time. Subjects were asked to test glucose whenever they experienced symptoms that might be related to hypoglycemia and to record the results. Subjects documenting hypoglycemia by glucose levels ≤70 mg/dl were asked to reduce insulin dose by 2 units. Insulin titration started after one week if symptoms of hypoglycemia did not recur.

Weight was measured, and venous blood for FPG was collected between 08:00 and 09:00 hours at each visit.

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Blood for HbA1C was collected at baseline and 12 and 24 weeks.

Results Of 750 patients screened, 370 were treated with glargine and 380 with human premix insulin. A total of five insulin glargine recipients and 15 human premix insulin recipients withdrew from the study after beginning of treatment. In three insulin glargine subjects and nine human premix insulin subjects, the reason was the subject’s desire to discontinue or loss to follow-up. Two insulin glargine subjects (0.54%) and six human premix insulin subjects (1.57%) discontinued treatment because of adverse events.

Figure 1 illustrates that the mean improvements in HbA1C were similar: −3.00 ± 1.68% for glargine and −2.89 ± 1.79% for human premix insulin (p = 0.3861).

The proportions of patients achieving HbA1C <7% were also similar (76.3 and 75.5%, respectively), but fewer human premix insulin than glargine-treated patients reached HbA1C <6.5% (14.6 and 26.7%, respectively).

Change in FBG from baseline was significant at endpoint in both groups (p < 0.0001). Similar proportions of subjects receiving insulin glargine (29.6%) and neutral Table 1. Baseline Characteristics of Subjects in the Study Glargine N Sex (F/M) (%) Age (years) Duration of diabetes (years) BMI

(kg/m2)

Human premix insulin

370

380

58/42

54/46

45 ± 9.5

46 ± 8.9

10 ± 5

9.0 ± 6

31.8 ± 3.63

32.2 ± 3.85

FPG (mg/dl)

188 ± 39

184 ± 47

HbA1C (%)

8.58 ± 0.7

8.46 ± 0.8

SU + metformin

24

27

SU + metformin + TZD

76

73

Prior therapy (%)

Table 2. Weekly Insulin Titration Start with 10 IU/day bedtime basal insulin and adjust weekly FBG values

Increase of insulin dosage (IU) day

>180 mg/dl

8

141-180 mg/dl

6

121-140 mg/dl

4

101-120 mg/dl

2

diabetology compared with subjects in the human premix insulin group who reported 42 episodes (significance level 0.00002).

10 9 8 7 HbA1C

6 5

Glargine

4

Human premix

3

Weight gain was significantly higher with human premix insulin versus glargine: 1.4 Âą 0.02 and 0.4 Âą 0.012 kg (p < 0.0001). Average glargine insulin dose was 0.26 IU/kg and average human premix insulin dose was 0.64 IU/kg (Fig. 3).

2

Discussion

1 0

0 12 24 Weeks of treatment

Figure 1. Mean HbA1C variation during study.

200

Fasting blood sugar (mg/dl)

180 160 140 120 100

Glargine

80

Human premix

60 40 20 0

0 3 5 7 9 11 13 18 22 Weeks of treatment

Figure 2. Mean HbA1C variation during study.

1

Insulin dose (IU/kg)

0.9 0.8 0.7 0.6 0.5

Glargine

0.4

Human premix

0.3 0.2 0.1 0

0

2

4

6 8 10 12 14 20

24

Weeks of treatment

Figure 3. Mean daily insulin dose during study.

protamine Hagedorn (NPH) (27.1%) achieved FBG <90 mg/dl by study endpoint (Fig. 2).

Risk of hypoglycemia was significantly higher with human premix insulin. We found that subjects in the insulin glargine group had 12 episodes of hypoglycemia documented by a blood glucose value <70 mg/dl,

Insulin glargine was developed as improved longacting, basal insulin. It is an analog of human insulin that is produced in a nonpathogenic strain of Escherichia coli. Insulin glargine differs from human insulin by the addition of two arginine amino acids to the C-terminus of the B-chain and the replacement of asparagine at position A21 by glycine. These changes shift the isoelectric point so that the molecule is soluble at an acid pH, but less soluble at neutral physiological pH levels. This results in a clear solution (pH 4.0) that when injected forms a precipitate in the subcutaneous tissue, which delays absorption and prolongs duration of action.11 The absorption characteristics of insulin glargine are not affected by the site of injection (arm, leg or abdominal regions). Furthermore, compared with NPH insulin, the absorption rate is significantly slower with approximately 50% of the injected dose of insulin glargine still detectable after 24 hours compared with approximately 20% of the NPH insulin dose.12 A potential major advantage of insulin glargine over NPH insulin and ultralente preparations is a lack of pronounced peaks in plasma insulin concentrations and a more constant delivery of insulin over a 24-hour period. This smooth profile was clearly shown in studies of insulin glargine versus NPH insulin in healthy volunteers and of insulin glargine versus NPH and ultralente insulin in patients with type 1 diabetes.13,14 In fact, in this later study, the delayed absorption of insulin glargine provided a consistent delivery of insulin that closely mimicked insulin delivery by continuous subcutaneous insulin infusion (CSII). Furthermore, in this study, interindividual variability in plasma insulin concentrations was lower with insulin glargine than with NPH or ultralente. These pharmacokinetic studies highlight the potential of insulin glargine to be a better insulin for patients with diabetes.

Riddle et al compared the addition of either insulin glargine or NPH insulin with existing regimens of one or two oral antidiabetic agents. This 24-week, randomized trial enrolled 756 patients. Although both basal insulins reduced FPG and HbA1C levels by similar

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diabetology amounts (FPG: 6.4 mmol/l vs 6.6 mmol/l; HbA1C: 6.96% vs 6.97% for insulin glargine and NPH insulin, respectively), 25% more patients attained a target HbA1C level of = 7% without experiencing nocturnal hypoglycemia with insulin glargine than with NPH insulin (p < 0.05). The overall rate of hypoglycemia, rate of symptomatic events, and rate of confirmed events in the insulin glargine group were reduced by 21%, 29%, and 41%, respectively.15 Yki-Jarvinenâ&#x20AC;&#x2122;s group designed a similar trial, but the treatment period was one year.

Again, insulin glargine and NPH insulin reduced HbA1C levels by a similar amount, but there was less nocturnal hypoglycemia (9.9% vs 24.0% of patients, p < 0.001) and insulin glargine was associated with better post-meal glucose control than NPH insulin (9.9 mmol/l vs 10.7 mmol/l, p < 0.002).16 While some studies have shown similar rates of hypoglycemia when compared with NPH insulin, there is also evidence that insulin glargine can maintain effective glucose control and reduce risk of hypoglycemia. Rosenstock et al randomized 518 patients with type 2 diabetes, who were already being treated with basal NPH insulin and regular insulin, to receive either insulin glargine or NPH insulin once- or twice-daily. While improvements in HbA1C were comparable, the group who switched to insulin glargine showed a 25% decrease in the rate of nocturnal hypoglycemia (26.5% vs 35.5%, p = 0.0136). A recent meta-analysis of four open-label, randomized trials of insulin glargine versus NPH insulin adds further weight to this assertion. In total, 2,304 patients were randomized and while glycemic control was similar between groups, there was a significant and consistent reduction in the risk of hypoglycemia.17 While in our study insulin glargine and human premix insulin were both associated with significant reductions in fasting blood sugar and HbA1C but hypoglycemia risk was lesser with insulin glargine.

Weight gain has long been an issue with insulin therapy. Insulin glargine has been associated with a mean weight gain of upto 2.02 kg in a 39-month study of 239 patients being treated in combination with oral antidiabetic agents, but many studies have reported no significant weight gain despite significant improvements in HbA1C.18 Some evidence suggests that insulin glargine may be associated with less weight gain than NPH insulin. In two studies, NPH insulin was associated with significantly more weight gain than insulin glargine.19,20 In a 16-week trial in patients with type 2 diabetes, weight gain was 0.4 kg with insulin glargine versus 1.4 kg with NPH insulin (p < 0.0007).17

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In contrast, one study reported similar gains in mean body weight following one year of treatment of patients with type 2 diabetes with insulin glargine (+2.6 kg, n = 214) and NPH insulin (+2.3 kg, n = 208).16 While in our study, weight gain was significantly higher with human premix insulin versus glargine: 1.4 Âą 0.02 and 0.4 Âą 0.012 kg (p < 0.0001).

Case reports of nausea and vomiting in patients receiving insulin glargine have been published,21 although these adverse events were not seen in our study.

Conclusion Managing diabetes with insulin is primarily based on the balance between the necessity of tight glycemic control and the risks associated with hypoglycemia.

Insulin glargine appears to improve this balance such that at least equivalent glycemic control can be achieved with a lower risk of hypoglycemia than traditional basal insulins. In patients with type 2 diabetes, the reduced risk of hypoglycemia with insulin glargine, combined with the flexibility of once-daily dosing at any time of the day, is likely to make insulin a more acceptable option, which may mean that patients are more open to start insulin earlier and to intensify their insulin sooner. In the long-term this may lead to improvements in HbA1C and thereby a reduction in the long-term complications of diabetes. Insulin glargine treatment was associated with significantly less weight gain than NPH insulin treatment (0.40 vs 1.40 kg).

Presumably, the difference in weight gain despite comparable improvement in glycemic control reflects the less frequent hypoglycemia seen with insulin glargine, the correction of which requires supplemental caloric intake.

References 1. Harris MI, Eastman RC, Cowie CC, Flegal KM, Eberhardt MS. Racial and ethnic differences in glycemic control of adults with type 2 diabetes. Diabetes Care 1999;22(3): 403-8.

2. Turner RC, Cull CA, Frighi V, Holman RR; UK Prospective Diabetes Study Group. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). JAMA 2005;281(21):2005-12.

3. Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull CA, et al. Association of glycemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ 2000;321(7258):405-12.

diabetology 4. Klein R, Klein BE, Moss SE. Relation of glycemic control to diabetic microvascular complications of diabetes mellitus.

Ann Intern Med 1996;124(1 Pt 2)90-6.

5. Hayward RA, Manning WG, Kaplan SH, Wagner EH, Greenfield S. Starting insulin therapy in patients with type 2 diabetes: effectiveness, complications, and resource utilization. JAMA 1997;278(20):1663-9.

6. Taskinen MR, Sane T, Helve E, Karonen SL, Nikkila EA, Yki-Jarvinen H. Bedtime insulin for suppression of overnight free fatty-acid, blood glucose, and glucose production in NIDDM. Diabetes 1989;38(5):580-8.

7. Riddle MC. Evening insulin strategy. Diabetes Care 1990; 13(6):676-86.

8. Shank ML, Del Prato S, DeFronzo RA. Bedtime insulin/ daytime glipizide: Effective therapy for sulfonylurea failures in NIDDM. Diabetes 1995;44(2):165-72.

9. Bolli GB, Owens DR. 2000;356(9228):443-5.

Insulin

glargine.

Lancet

10. Rosenstock J, Schwartz SL, Clark CM Jr, Park GD, Donley DW, Edwards MB. Basal insulin therapy in type 2 diabetes: 28-week comparison of insulin glargine (HOE 901) and NPH insulin. Diabetes Care 2001;24(4):631-6.

11. Bähr M, Kolter T, Seipke G, Eckel J. Growth promoting and metabolic activity of the human insulin analogue [GlyA21, ArgB31, ArgB32] insulin (HOE 901) in muscle cells. Eur J Pharmacol 1997;320(2-3):259-65.

12. Owens DR, Coates PA, Luzio SD, Tisbergen JP, Kurzhals R. Pharmacokinetics of 125-Ilabeled insulin glargine (HOE 901) in healthy men: comparison with NPH insulin and the influence of different subcutaneous injection sites.

Diabetes Care 2000;23(6):813-9.

13. Heinemann L, Linkeschova R, Rave K, Hompesch B, Sedlak M, Heise T. Time-action profile of the long-acting insulin analog insulin glargine (HOE901) in comparison with those of NPH insulin and placebo. Diabetes Care 2000;23(5):644-9.

14. Lepore M, Pampanelli S, Fanelli C, Porcellati F, Bartocci L, Vincenzo A, et al. Pharmacokinetics and pharmacodynamics of subcutaneous injection of long-acting human insulin analog glargine, NPH insulin, and ultralente human insulin and continuous subcutaneous infusion of insulin lispro. Diabetes 2000;49(12):2142-8.

15. Riddle MC, Rosenstock J, Gerich J; Insulin Glargaine 4002 Study Investigators. The treat-to-target trial: randomized addition of glargine or human NPH insulin to oral therapy of type 2 diabetic patients. Diabetes Care 2003;26(11):3080-6.

16. Yki-Jarvinen H, Dressler A, Ziemen M; HOE 901/300S Study Group. Less nocturnal hypoglycemia and better post-dinner glucose control with bedtime insulin glargine compared with bedtime NPH insulin during insulin combination therapy in type 2 diabetes. HOE 901/3002 Study Group. Diabetes Care 2000;23(8):1130-6.

17. Rosenstock J, Schwartz SL, Clark CM Jr, Park GD, Donley DW, Edwards MB. Basal insulin therapy in type 2 diabetes: 28-week comparison of insulin glargine (HOE 901) and NPH insulin. Diabetes Care 2001;24(4):631-6.

18. Dunn CJ, Plosker GL, Keating GM, McKeage K, Scott LJ. Insulin glargine: an updated review of its use in the management of diabetes mellitus. Drugs 2003;63(16): 1743-78.

19. Raskin P, Klaff L, Bergenstal R, Halle JP, Donley D, Mecca T. A 16-week comparison of the novel insulin analog insulin glargine (HOE 901) and NPH human insulin used with insulin lispro in patients with type 1 diabetes. Diabetes Care 2000;23(11):1666-71.

20. Garg SK, Paul JM, Karsten JI, Menditto L, Gottlieli PA. Reduced severe hypoglycemia with insulin glargine in intensively treated adults with type 1 diabetes. Diabetes Technol Ther 2004;6(5):589-95.

21. Dixon AN, Bain SC. Nausea and vomiting due to insulin glargine in patient with type 1 diabetes mellitus. BMJ 2005;330(7489):455.

■■■■

Alogliptin Wins FDA Go-ahead for Type 2 Diabetes After a long delay, the FDA approved the oral drug alogliptin (Nesina) for treatment of adults with type 2 diabetes, as well as two products combining alogliptin with other antidiabetic drugs. Approved simultaneously with Nesina were alogliptin combinations with metformin (Kazano) and with pioglitazone (Oseni). Alogliptin is the fourth dipeptidyl peptidase-4 inhibitor to win FDA approval, joining sitagliptin (Januvia), saxagliptin (Onglyza), and linagliptin (Tradjenta). (Source: Medpage Today)

Ranibizumab Fails to Beat Saline in Avoiding Vitrectomy Patients with vitreous hemorrhage from proliferative diabetic retinopathy (PDR) experienced about the same rates of vitrectomy by 16 weeks whether they received intravitreal injections of ranibizumab (Lucentis, Genentech) or saline. The results of this short-term study, published online January 31 in JAMA Ophthalmology, suggest little likelihood of a clinically meaningful difference on vitrectomy between the 2 interventions. Longer follow-up is planned. (Source: Medscape)

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dRUGS AND DEVICES

Drugs and Dreams Sarita Goyal*, Jyoti Kaushal**, MC Gupta†, Savita Verma‡

Abstract Dreams are a series of images, ideas, thoughts, emotions and sensations occurring involuntarily in the mind during certain stages of sleep. They have been described physiologically as a response to a neural process when the person is asleep while the psychological basis proposed is that they are because of reflection of the subconscious mind. Pharmacologists are of the view that medications, many hormones, neurotransmitters, herbs and supplements can alter dreams and make them more or less vivid.

Keywords: Oneirology, REM sleep, NREM sleep, neurotransmitters

D

reams are a series of images, ideas, thoughts, emotions and sensations occurring involuntarily in the mind during certain stages of sleep.1 The content and purpose of dreams are not fully understood although they have been a topic of interest since ages.

The scientific study of dreams is known as oneirology.1

Dreams have a long history. They have been a subject of controversy and disagreement as different individuals have tried to describe in their own manner. They have been described physiologically as a response to a neural process when the person is asleep while the psychological basis proposed is that they are because of reflection of the subconscious mind. The spiritual people ascribe them to as messages from Gods.

Pharmacologists are of the view that medications, many hormones, neurotransmitters, herbs and supplements can alter dreams and make them more or less vivid.2 Dreams can be of various forms i.e., pleasant dreams or frightening dreams. Frightening dreams can be either in the form of a nightmare or a night terror. A nightmare is a type of dream that arouses feelings of intense,

*Demonstrator **Professor †Senior Professor and Head ‡Associate Professor Dept. of Pharmacology Pt. BDS PGIMS, Rohtak, Haryana Address for correspondence Dr Sarita Goyal Demonstrator, Dept. of Pharmacology 14/9J, Medical Campus, PGIMS, Rohtak - 124 001 E-mail: drsaritagoyal@rediffmail.com

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inescapable fear, terror, distress or extreme anxiety that usually awakens the sleeper. It results in the dreamer waking with full or partial recall of the dream itself.

Recurrent nightmares can be because of post-traumatic stress disorders or due to other psychiatric illnesses.

Nightmares are more common in women and are associated with an increase in nocturnal awakenings, sleep-onset insomnia and day time memory impairment and anxiety following poor sleep.3 Night terror is an arousal disorder that usually occurs early in the sleep period. It is an episode of extreme fright during sleep without any recollection of a dream.

Both nightmares and night terrors strike children much more often than adults.3 Sleep Patterns and Dreams As indicated by Davidson, Duffy and Osselton, sleep may be divided into two alternative phases: Rapid eye movement (REM) sleep and nonrapid eye movement (NREM) sleep. Although, dreams can occur in both the phases, they primarily take place in the REM phase which is associated with low-voltage electroencephalogram (EEG).4 NREM sleep is further divided into four stages (stage 1 to stage 4). Stage 3 and 4 constitute the deep sleep. It is reported that 80% of persons have dreams during REM sleep and sleep onset (stages 1 and 2), while 20% persons have dreams during deep sleep.5 Patients report that dreams experienced during REM sleep tend to be bizarre and detailed, with storyline plot associations. Unpleasant or frightening dreams usually occur in this period.

In contrast, dreams experienced in deep sleep are more diffuse (e.g., dreams about a color or an emotion). Night terrors may occur at this time. The dreams of stages 1

drugs and devices and 2 are simpler, shorter and have fewer associations than the dreams of REM sleep.5 These phases of sleep, especially REM sleep, can be affected by a variety of drugs and hormones.6 A number of drugs used in various diseases can affect the sleep pattern and can cause dreams. Nightmares including night terrors are also associated with the use of medications, which affect the neurotransmitters e.g., adrenergic, cholinergic, dopaminergic, serotonergic and gabaminergic, etc. It has been observed that almost all psychiatric drugs can influence our dreams but even medications that would not seem suspect, such as drugs affecting blood pressure, may have an effect, some of them reducing nightmares and some increasing them.

Individual differences are of course always possible. Its not only the drugs used in pharmaco-therapeutics that lead to dreams, even drugs of abuse can be responsible for change in sleeping pattern and dreams.2

Pharmacotherapeutic Drugs and Dreams Prescriptions drugs used in various disease states can alter sleeping patterns leading to dreams by affecting one or the other neurotransmitters. Drugs influencing adrenergic, aminergic, dopaminergic and cholinergic neurotransmitters have a prominent role in dreams and nightmares.7 These neurotransmitters may function by modulation of the cardinal sleep stages - REM and NREM sleep.8

Antihypertensive Agents Antihypertensive agents, in general use, affect adrenergic receptors. β-blockers and adrenergic neuron blocking agents are responsible for 34% of clinical trials in which nightmares are reported as an adverse effect.8 β-blockers which cause nightmares or dreams are: Propranolol, atenolol, betaxolol, bisopropolol and labetalol. They are known to be NREM suppressants.

Adrenergic neuron blockers-guanethidine, and reserpine have probable association with nightmare reports. These drugs have been shown to affect REM sleep and thus cause dreams. Decrease in dream recall occurs with the use of both adrenergic neuron blockers (REM suppressant) and β-blockers (NREM suppressants).9 Other antihypertensive agents that may cause dreams are angiotensin-converting enzyme inhibitors (captopril, enalapril and quinapril), angiotensin receptor blocker (losartan) and calcium channel blocker (verapamil).8

Hypolipidemic Agents Nightmares may also be a rare class effect of the statins: Simvastatin, pravastatin, fluvastatin and atorvastatin, which may be linked to REM sleep suppression.8

Drugs used in Alzheimer’s Disease REM sleep is affected by pharmacological alteration of cholinergic activity in the central nervous system (CNS).8 Many lines of study support the hypothesis that brainstem cholinergic neurons can be excited to induce REM sleep.10 Cholinergic agents (anticholinestrases) such as donepezil, rivastigmine and tacrine are likely to increase the percentage of REM sleep, while cholinergic antagonists have a tendency to decrease REM sleep.11 Anticholinestrases affecting acetylcholine neuroreceptor system thus have a possible association with drug-induced nightmares.

Memantine, which is a N-methyl-d-aspartate (NMDA) receptor antagonist, may cause surreal or unpleasant dreams, sometimes nightmares.2

Antidepressants Agents All drugs that alter serotonin levels may affect sleep and dreaming. This effect is greatest for the monoamine oxidase inhibitors (MAOIs) followed by tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs).12 Intense visual dreaming and nightmares are associated with clomipramine; REM sleep rebound occurring after the withdrawal of these REM sleep suppressant agents.13 Fluoxetine, citalopram, as well as atypical antidepressant mirtazapine can also cause very peculiar, sometimes disturbing dreams.2

Antipsychotics Agents Antipsychotic (neuroleptic) drugs e.g.; chlorpromazine, thiothixene and clozapine can increase vividness of dream but often decrease dream recall.2

Antiparkinsonian Drugs Dopamine receptor stimulation may be another common mechanism resulting in drug-induced nightmares.

Dopamine agonists - levodopa, bromocriptine, pergolide, amantadine, selegiline and rasagiline, used to treat Parkinson disease may cause vivid dreams, sometimes of sexual nature.14

Antiepileptic Drugs Drugs known to affect the gamma-aminobutyric acid (GABA) receptor (agonist, modulators and reuptake

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drugs and devices inhibitors) can cause nightmares and abnormal dreaming. Gabapentin, valproic acid and tiagabine are few examples related to GABA neurotransmitter. Other antiepileptics like lamotrigine and ethosuximide also cause dreams.15

Sedative Hypnotic Drugs Nightmares and intense dreaming have been associated with the REM sleep rebound associated with withdrawal from REM sleep suppression agents such as barbiturates. Benzodiazepines (diazepam, flunitrazepam, nitrazepam) and nonbenzodiazepine hypnotic, zolpidem can also induce dreams and night terrors by increasing REM sleep.16

General Anesthetic Agents These agents may also induce nightmares. An increased incidence of pleasant dreams is reported with use of propofol,17 while thiopental, midazolam, isoflurane and ketamine have been reported to produce disordered dreaming and nightmares.18

Antihistamine Drugs Chlorpheniramine has been reported to induce nightmares suggesting a potential role for histamine as a modulator of dreaming.19

Antimicrobial and Immunosuppressant Agents Viral and bacterial infections can be associated with large increase in NREM sleep. In some studies, several agents like fleroxacin, erythromycin and ciprofloxacin, which are used for the treatment of bacterial infections, are reported to induce nightmares.19 Antiviral agents such as ganciclovir and amantadine may also lead to dreams.

Even gusperimus, which is an immunologic response suppressant, is also reported to induce nightmares.7

Analgesic Drugs

nitric oxide and neuropeptides may also be associated with varied dreams.20 Riluzole and dextromethorphan, which are NMDA receptor antagonists may lead to unpleasant dreams, sometimes nightmares. Drug used for smoking cessation i.e., vareniciline which is a nicotine receptor partial agonist may also be responsible for nightmares.2

Herbal Drugs Many herbal drugs influence dreaming, especially those with psychotropic effects like Kava-Kava, St. Johnâ&#x20AC;&#x2122;s Wort, Valerian, Licorice root, Jasmine, Lavender, Cardamom, Ginkgo biloba, Cinnamon, Marigold, Nutmeg, Peppermint and Passion flower.

The Ayurvedic herb Ashwagandha is also well-known for creating surreal dreams.2 Drugs of Abuse and Dreams There are many drugs, such as opium, cocaine, cannabis, coal tar products and alcohol, which have an abuse potential and may have an influence upon dreams. Dreams caused by such drugs are, however, influenced by the physiological action of the drug taken, the amount used, the idiosyncrasies of the individual and the mentality. Drugs as opium and cocaine, when taken in medicinal doses, produce a sense of well-being and comfort and so tend to promote pleasurable fancies. These drugs, when taken in sufficient doses, cause sleep dreams which are not remembered. Many persons are much distressed by these drugs and others, in place of awaking refreshed, awake tired and dimly conscious of disturbing dreams.21 CNS stimulant drugs e.g., amphetamines and caffeine may also lead to dreams. Amphetamines are associated with vivid and unpleasant dreams whereas caffeine has been used to induce lucid dreaming, because it makes one sleep lighter.22

Miscellaneous Drugs

Dreams are, thus, reflections of the subconscious mind and are caused by a variety of pharmacological agents.

These agents act via a variety of neurotransmitters i.e., adrenergic, cholinergic, dopaminergic, serotonergic and gabaminergic, etc. These drugs are either pharmacotherapeutic drugs prescribed for the treatment of various diseases or are the drugs of abuse. These drugs may be responsible for causation of dreams, which are either pleasant in nature or may be in the form of nightmares.

Other drugs modulating the various neurotransmitters i.e., orexin, adenosine, histamine, glycine, glutamate,

From the clinicianâ&#x20AC;&#x2122;s point of view, various strategies can be adopted for the management of varied types

People taking opioids as painkillers (morphine, buprenorphine) often report vivid dreams especially in the beginning of their use. Nonopioid pain killer, naproxen may also affect dreams.2

Endocrinal Agents The hormones dehydroepiandrosterone (DHEA) and testosterone may cause nightmares if the dose is too large.2

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drugs and devices of dreams especially nightmares and night terrors.

Of foremost importance is the behavioral therapy.

Nightmares and night terrors are usually disturbing to family members; therefore, proper diagnosis and education of family members are important components of management. Dream disorders may respond to medication e.g., fluoxetine for posttraumatic stress disorder, clonazepam for night terrors3 and benzodiazepines for ketamine23 induced dreams but behavioral treatment approaches in the form of reassurance and support have shown excellent results, particularly in patients with post-traumatic stress disorder and recurrent nightmares. This therapy reduces the incidence of nightmares in about 70% of patients. If the patient is still not relieved, changing the suspect agent with a suitable alternative or withdrawal of the drug may help. Inspite of all the above mentioned treatment strategies, there is still controversy as to what is the best option for the patient and thus research is going on to find the best approach.

Suggested Reading 1. Dream. The American Heritage Dictionary of the English Language, 4th edition. Available at: http:// americanheritage.yourdictionary.com/dream.

2. Haavisto M. How drugs and herbs affect dreams: medications and supplements can cause vivid dreams and nightmares. 2008. Retrieved from http://www.suite101. com/content/how-drugs-and-herbs-affect-dreams-a75945.

3. Pagel JF. Nightmares and disorders of dreaming. Am Fam Physician 2000;61(7):2037-42, 2044.

4. Drugs and dreams. Can Med Assoc J 1970;102(5):524.

5. Foulkes D. Dreaming: A cognitive-psychological analysis.

Lawrence Erlbaum Associates, 1985.

6. Martin GJ. Drugs and dreams, perspective. Exp Med Surg 1969;27(1-2):1-2.

7. Pagel JF, Helfter P. Drug induced nightmares - an etiology based review. Hum Psychopharmacol 2003;18(1):59-67.

8. Thompson DF, Pierce DR. Drug-induced nightmares. Ann Pharmacother 1999;33(1):93-8.

9. Brismar K, Mogensen L, Wetterberg L. Depressed melatonin secretion in patients with nightmares due to beta-adrenoceptor blocking drugs. Acta Med Scand 1987;221(2):155-8.

10. Jouvet M. The Paradox of Sleep - The Story of Dreaming, MIT Press, Cambridge, 1999.

11. Hobson JA, Steriade M. The neuronal basis of behavioral state control: Internal regulatory systems of the brain.

In Handbook of Psychology, Vol. IV(14), Mountcastle V, Series Edition, American Physiological Society, Washington 1986:p.701-823.

12. Gursky JT, Krahn LE. The effects of antidepressants on sleep: a review. Harv Rev Psychiatry 2000;8(6):298-306.

13. Coupland NJ, Bell CJ, Potokar JP. Serotonin reuptake inhibitor withdrawal. J Clin Psychopharmacol 1996;16(5):356-62.

14. Stacy M. Managing late complications of Parkinson’s disease. Med Clin North Am 1999;83(2):469-81, vii.

15. Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981;30(2):239-45.

16. Pagel JF. Pharmacologic alteration of sleep and dreams - a clinical framework for using the electrophysiological and sleep stage effects of psychoactive medications.

Human Psychopharmacology: Clinical and Experimental 1996;11(3):217-23.

17. Oxorn DC, Ferris LE, Harrington E, Orser BA. The effects of midazolam on propofol-induced anesthesia: propofol dose requirements, mood profiles, and perioperative dreams. Anesth Analg 1997;85(3):553-9.

18. Marsch SC, Schaefer HG, Tschan C, Meier B. Dreaming and anaesthesia: total i.v. anaesthesia with propofol versus balanced volatile anaesthesia with enflurane. Eur J Anaesthesiol 1992;9(4):331-3.

19. Cardiac drugs. In: American Hospital Formulary ServiceDrug Information 2002. McEvoy, G.K. (ed.)Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2002.

20. Krueger JM, Fang J. Sleep and host defense. In: Principles and Practice of Sleep Medicine. Kryger M, Roth T, Dement W, (Eds.), WB Saunders Co: Philadelphia 2003:p.255-65.

21. Edward F. Pace-Schott.

Recent findings on the neurobiology of sleep and dreaming. In: Sleep and Dreaming: Scientific Advances and Reconsiderations.

E. Pace-Schott, M. Solms, M. Blagrove, & S. Harnad (Eds.), Cambridge University Press: New York 2003:p.335-50.

22. William SW. Book: The psychology of dreams. Kessinger Publishing, LLC, 2004.

23. Evers AS, Crowder MC, Balser JR. General Anesthetics.

In: Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 11th edition, Brunton LL, Lazo JS, Parker KL (Eds.), McGraw-Hill Professional 2006:p.341-68.

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ENT

Congenital Facial Palsy with Bilateral Anotia Geeta Gathwala*, Jagjit Singh**, Poonam Dalal**

Abstract Congenital facial palsy is generally considered developmental or acquired. Most of the cases are related to birth trauma. Herein we report a case of congenital facial palsy with bilateral anotia and external auditory canal atresia.

Keywords: Congenital facial palsy, anotia

C

ongenital facial palsy (CFP) is generally considered to be either developmental or acquired in origin. Developmental facial paralysis is associated with other anomalies including those of pinna and external auditory canal, ranging from mild defects to severe microtia and atresia.1 Herein we report a rare case of congenital right facial paralysis associated with bilateral anotia and atresia of right external auditory canal.

Case report A 6-month-old male infant was admitted to the pediatric ward with lower respiratory tract infection.

There was history of facial asymmetry and absent ears since birth. There was no history suggestive of intrauterine infection or drug intake during pregnancy.

The baby was full-term normal vaginal delivery.

Physical examination showed bilateral anotia, preauricular tag was present bilaterally and right lower motor neuron type of facial palsy (Figs. 1-3). There was no other cranial nerve palsy and the rest of the examination including neurological examination was normal.

Magnetic resonance imaging (MRI) brain was normal.

High-resolution CT temporal bone done to define the

*Senior Professor and Head **Assistant Professor Dept. of Pediatrics Pt. BD Sharma PGIMS, Rohtak, Haryana Address for correspondence Dr Jagjit Singh Flat No.15, Couple Hostel, Medical Enclave, Pt. BD Sharma PGIMS Rohtak - 124 001, Haryana Email: drjagjitsingh@hotmail.com

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Figure 1. Showing anotia of right side with skin tags. No external auditory meatus seen.

etiology of facial nerve palsy revealed absence of pinna, right auditory canal was not visualized and the middle ear ossicles were reported normal. Brainstem Evoked Response Audiometry (BERA) was normal.

Discussion Congenital facial nerve palsy is an infrequent condition with a reported incidence of 2.1 per 1,000 live births.2 In 78% of cases CFP is related to birth trauma.

No such history was available in the index case. Other causes include, intrauterine posture, intrapartum

ENT the cardiofacial, Moebius, Polandâ&#x20AC;&#x2122;s, and Goldenhaarâ&#x20AC;&#x2122;s syndrome.1,3 Some cases of CFP have been attributed to agenesis of the petrous portion of the temporal bone, with resulting agenesis of the facial and auditory nerves, the external ear and the mastoid region.4 Most commonly, development facial paralysis is associated with other anomalies. The most common site reported is the maxilla, including defects such as cleft palate, hypoplastic maxilla and duplication of the palate. Others have demonstrated a propensity for anomalies of the pinna and external auditory canal, ranging from mild defects to severe microtia and atresia.1 A striking association of grossly abnormal pinna, multiple defects and facial palsy has been reported in 9-15% of patients. The index case had bilateral anotia and right auditory canal atresia with right facial palsy.

Figure 2. Showing anotia of left side and the external auditory meatus.

Aural atresia occurs in approximately one in 20,000 live births. Atresia and microtia are parts of several syndromes with inherited defects or acquired embryopathies owing to intrauterine infections (rubella, syphilis), ischemic injury (hemifacial microsomia) or toxin exposure (thalidomide, isotretinon).

Embryonic insult, severe enough to cause aural atresia would also affect other organ systems. Aberration in the canalization process of external auditory canal can lead to stenosis, canal tortuosity or fibrosis/osseous obliteration. Since middle ear structure develops independently, the tympanic cavity and ossicles may be normal.

Defects in the canalization process may also be associated with faulty formation of pinna.5 In the index case right side CFP was associated with anotia and right sided atresia. No other abnormalities were observed.

Figure 3. Showing lower motor neuron type of facial palsy on the right side with bilateral anotia.

compression, and familial and congenital aplasia of the nucleus; the last being most frequently reported for bilateral cases. There are a number of syndromes which encompass CFP as part of their symptoms, including

Several surgical techniques are employed for treatment of CFP. The ideal time for the intervention is controversial. Some clinicians advocate early (preschool) surgery for the animation of childrenâ&#x20AC;&#x2122;s faces6,7 while others propose surgery not before adolescence.8 Muscle transplantation for facial paralysis has been shown to be effective.7 However, the possibilities of reconstructive surgery are limited. Traumatic facial palsy in neonates is associated with good prognosis.

In contrast facial palsies, as in the index, case carry a poor functional outcome.9,10

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ENT Otorhinolaryngology Head and Neck Surgery. 16th edition, Snow JB, Ballenger JJ (Eds.), Williams & Wilkins: Spain 2003:p.997-9.

REFERENCES 1. Bergstrom L, Baker BB. Syndromes associated with congenital facial paralysis. Otolaryngol Head Neck Surg 1981;89(2):336-42.

2. Falco NA, Eriksson E. Facial nerve palsy in the newborn: incidence and outcome. Plast Reconstr Surg 1990;85(1):14.

3. Jemec B, Grobbelaar AO, Harrison DH. The abnormal nucleus as a cause of congenital facial palsy. Arch Dis Child 2000;83(3):256-8.

4. Smith JD, Crumley RL, Harker LA. Facial paralysis in the newborn. Otolaryngol Head Neck Surg 1981;89(6):1021-4.

5. Parisier SC, Fayad JN, Kimmelman CP. Microtia, canal atresia, and middle ear anomalies. In: Ballenger’s

6. Harrison DH. Treatment of infants with facial palsy. Arch Dis Child 1994;71(3): 277-80.

7. Zuker RM, Goldberg CS, Manktelow RT. Facial animation in children with Möbius syndrome after segmental gracilis muscle transplant. Plast Reconstr Surg 2000;106(1):1-8; discussion 9.

8. May M. Facial paralysis at birth: medicolegal and clinical implications. Am J Otol 1995;16(6):711-2.

9. Laing JH, Harrison DH, Jones BM, Laing GJ. Is permanent congenital facial palsy caused by birth trauma? Arch Dis Child 1996;74(1):56-8.

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Clues that may Suggest a Serious Underlying Cause of Hoarseness Associated with hemoptysis, dysphagia, odynophagia, otalgia or airway compromise Concomitant discovery of a neck mass History of tobacco or alcohol use Neurologic symptoms Possible aspiration of a foreign body Symptoms do not resolve after surgery (intubation or neck surgery) Symptoms in a neonate Symptoms in a person with an immunocompromising condition Symptoms occur after trauma Unexplained weight loss Worsening symptoms Source: Am Fam Physician. 2010;81(10):1292-1296.

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Gastroenterology

A Study of Clinical Profile and Outcome in Acute Viral Hepatitis E TEJAS N MODI*, SHIVANI A PATEL**, KIRAN M MIRANI†, DHARMESH R VAGHASIYA†, GAUTAM S MAKADIA†, JIGNESH USDADIYA‡

Abstract Introduction: Hepatitis E is the most common cause of acute viral hepatitis in the adult population in India. Acute viral hepatitis E (HEV) is generally mild and self-limiting and resolves within six weeks, with no chronic sequelae. Pregnant women are at increased risk with the risk increasing as the pregnancy progresses near term. Methods: We performed a prospective study of 100 patients who presented to Dept. of Medicine, Civil Hospital, Ahmedabad with jaundice (IgM anti-HEV positive) during 2011-2012 and data were analyzed for the clinical profile and outcome of HEV. Results: The most common age group affected was 21-30 years with overall M:F ratio of 3.4:1. Most common presenting symptom was jaundice (100%) followed by nausea/ vomiting (87%). On presentation, serum bilirubin level was elevated in 89% patients with SGPT raised in 86%. PT was prolonged in 39% patients. Anemia (Hb < 7) was seen in 17% while 9% of patients had renal involvement. Hepatic encephalopathy was seen in 15%. In this study, 12 women were pregnant in whom IUD occurred in 66% with maternal mortality in 33%. Overall mortality was 7%. Conclusion: We found that majority of cases were cured with supportive treatment while risk of mortality and morbidity was more in pregnant women.

Keywords: Fulminant hepatic failure, hepatic coagulopathy, maternal mortality

H

epatitis E is an important cause of acute clinical hepatitis in adults throughout Asia.1 Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis in the adult population in India.2 In men and nonpregnant women, the disease is usually self-limited and has a case-fatality rate of <0.1%. However, in pregnant women, particularly from certain geographical areas in India, HEV infection is more severe, often leading to fulminant hepatic failure and death in a significant proportion of patients.3 The disease was first recognized as a distinct clinical entity in the 1980s when sera from persons affected during a large water-borne epidemic of viral hepatitis during 1955-56 in Delhi2 and another epidemic in Kashmir were found to lack serological markers of acute hepatitis A and B.4 It is an enterically transmitted disease that spreads through fecal contamination of drinking water. HEV infection, a common cause of

water-borne epidemics, is endemic and frequently responsible for acute viral hepatitis in developing countries.5 According to the South-East Asia Regional Office of the World Health Organization (WHO), hepatitis E is widespread in developing countries, accounting for upto 60-70% of all sporadic cases of acute viral hepatitis.2,6 HEV causes high mortality in pregnant women, 20-30% as compared to 0.2-1% in general population.7,8 It has been implicated as an important etiological agent for sporadic fulminant hepatic failure (FHF) in developing countries.

Etiology of acute viral hepatitis cannot be differentiated on the basis of mode of presentation; confirmation is done serologically. The present study was conducted to assess the clinical profile, laboratory profile and outcome of acute viral hepatitis E cases at a tertiary care center in Ahmedabad.

Material and Methods

*Assistant Professor **Associate Professor †3rd Year Resident ‡4th Year Resident Dept. of Medicine BJ Medical College, Civil Hospital, Ahmedabad

This study was conducted over a period of one year from 1st May, 2011 to 30th April, 2012 at Civil Hospital, Ahmedabad, India in patients who were positive for serological viral marker (IgM HEV, ELISA, Smart Test Diagnostics, Israel). Informed written consent was taken from each patient. Details comprising of history, physical examination and laboratory findings of each

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Gastroenterology patient were recorded in the proforma. Serum bilirubin, alanine aminotransferase (ALT), prothrombin time international normalized ratio (PT INR) and serum creatinine were the key parameters in our study.

Patients with pre-existing liver disease were excluded.

Complete liver function tests (LFT), renal function tests (RFT), prothrombin time and ultrasound abdomen of each patient was done on admission and investigations were repeated at regular intervals thereafter for two months. Upper normal limit of ALT, alkaline phosphatase, bilirubin, creatinine and PT INR was 40 IU/l, 170 IU/l, 2.0 mg/dl, 1.2 mg/dl and 1.3, respectively. All patients were given supportive treatment, symptomatic treatment for nausea, vomiting and specific treatment for hepatic encephalopathy, coagulopathy and renal failure when required. Patients were followed up at regular intervals for eight weeks for assessment of clinical and biochemical parameters.

RESULTS Demographic profile of patients as shown in Table 1 revealed that males were affected more than females in all age groups with a male-female ratio of 3.4:1. The highest incidence was found in the age group of 21-30 years. Twelve out of 23 female patients were pregnant on admission.

All patients presented with jaundice and other associated symptoms, which were nausea/vomiting (88%), anorexia (85%) and abdominal pain (49%).

Hepatomegaly was found in 30% of cases. Bleeding diathesis, sleep disturbances and altered level of consciousness were present in 16%, 17% and 14% of patients, respectively (Table 2).

On presentation serum bilirubin level was elevated in 100% patients with ALT raised in 86%. We found that 34% of patients presented with bilirubin in range of 2.1-10 mg/dl and 43% with ALT in range of 500-1,000.

Values started decreasing by 2nd week and laboratory profile of all survivors (93) became normal by 8th week (Figs. 1 and 2).

Hepatic coagulopathy was the commonest complication; documented in 39% of patients. Only one out of the eight patients who had fulminant hepatic failure survived. Out of the 12 pregnant women in this study, intrauterine death occurred in 66%. Maternal mortality was 33%. Overall mortality was 7%, which correlated with the occurrence of complications and was strongly associated with FHF (Table 3).

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Table 1. Demographic Profile Age <20 21-30 31-40 41-50 >50 Total

Male 09 23 19 11 15 77

Female 02 08 05 04 04 23

Table 2. Clinical Profile

Symptoms and signs Jaundice Nausea/Vomiting Anorexia Abdominal pain Hepatomegaly Sleep disturbances Bleeding Altered level of consciousness 100 90 80 70 60 50 40 30 20 10 0

Total 11 31 24 15 19 100

Total 100 88 85 49 30 17 16 14

â&#x2030;¤1.2 1.3-4.9 5-9.9 10-14.9 â&#x2030;Ľ15

Day 1

1st week

2nd week

4th week

6th week

8th week

Figure 1. Bilirubin level of patients (n = 100) at Day 1 of study and at regular intervals. Colors shown in the figure demonstrate range of bilirubin and the horizontal lines show the number of persons lying within that range.

100 90 80 70 60 50 40 30 20 10 0

<40 40-500 500-1,000 >1,000

Day 1

1st week

2nd week

4th week

6th week

8th week

Figure 2. Level of ALT of 100 patients at various interval.

Colors shown in the figure demonstrate range of ALT and the horizontal lines show the number of persons lying within that range.

Gastroenterology acute viral hepatitis E has a higher morbidity and mortality in pregnant women than in the general population.

Table 3. Complications Complications

Total (n)

Hepatic coagulopathy

39

Hepatic encephalopathy

17

Acknowledgment

Fulminant hepatic failure

08

Renal failure

09

Intrauterine death

08

Maternal mortality rate

04

Dr MM Prabhakar, Hospital Superintendent, CHA; HOD, Dept. of Medicine, BJMC and CHA; HOD, Dept. of Microbiology, BJMC and CHA; HOD, Dept. of Biochemistry, BJMC and CHA.

Overall mortality

07

References 1. Purcell RH, Emerson SU. Hepatitis E: an emerging awareness of an old disease. J Hepatol 2008;48(3):494-503.

DISCUSSION Hepatitis E virus infection is responsible for 30-70% cases of acute sporadic hepatitis.2 The classic epidemiological studies by Viswanathan4 and recent serological studies by Wong et al,9 Khuroo et al,2 have convincingly demonstrated that HEV is an important cause of non-A non-B viral hepatitis. Our data correspond with the existing epidemiological features of HEV. Male preponderance was noted. In our study, the youngest patient was a child of 12 years age and the oldest patient was a 67-year-old male.

Thus, we found that all age groups were susceptible to hepatitis E infection, which was comparable to Khuroo et al.2 Analysis of clinical profile showed that uncomplicated acute hepatitis accounted for majority (61%) of cases. Resolution occurred in all survivors (93) by eight weeks. In pregnant women with HEV, the disease ran a virulent course with maternal mortality of 33% and fetal wastage of 66%. Similar findings have been reported by Patra et al7 and Tandon et al.10

2. Khuroo MS, Rustgi VK, Dawson GJ, Mushahwar IK, Yattoo GN, Kamili S, et al. Spectrum of hepatitis E virus infection in India. J Med Virol 1994;43(3):281-6.

CONCLUSION

9. Wong DC, Purcell RH, Sreenivasan MA, Prasad SR, Pavri KM. Epidemic and endemic hepatitis in India: evidence for a non-A, non-B hepatitis virus aetiology. Lancet 1980;2(8200):876-9.

We concluded that acute viral hepatitis E is a selflimiting illness with the time to resolution directly correlating with initial severity at presentation and occurrence of complications. We also concluded that

3. Navaneethan U, Al Mohajer M, Shata MT. Hepatitis E and pregnancy: understanding the pathogenesis. Liver Int 2008;28(9):1190-9.

4. Viswanathan R. Infectious hepatitis in Delhi (1955-56): A critical study: Epidemiology. Indian J Med Res 1957;45: 1-30.

5. Goumba CM, Yandoko-Nakouné ER, Komas NP. A fatal case of acute hepatitis E among pregnant women, Central African Republic. BMC Res Notes 2010;3:103.

6. Chandra NS, Sharma A, Rai RR, Malhotra B. Contribution of hepatitis E virus in acute sporadic hepatitis in north western India. Indian J Med Res 2012;136(3):477-82.

7. Patra S, Kumar A, Trivedi SS, Puri M, Sarin SK. Maternal and fetal outcomes in pregnant women with acute hepatitis E virus infection. Ann Intern Med 2007;147(1): 28-33.

8. Aggarwal R, Krawczynski K. Hepatitis E: an overview and recent advances in clinical and laboratory research.

J Gastroenterol Hepatol 2000;15(1):9-20.

10. Tandon BN. Viral hepatitis in tropics and its management.

JAMA India - The physicians’ Update 2001;4:102-6.

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Interferon may be Harmful in Retreatment of Hepatitis C When patients with hepatitis C and chronic liver disease suffer relapses or fail to respond to initial treatment, monotherapy with interferon may not be a good idea, according to results from a recent meta-analysis. In fact, employing that approach may raise the risks for death and adverse effects. (Source: Medscape)

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637

Neurology

Giant Asymptomatic Cystic Dilatation in Dandy-Walker Malformation Amit Agarwal

Abstract Dandy-Walker malformation (DWM) is a rare congenital abnormality that involes the cerebellum and the fourth ventricle.

It is characterized by cystic dilatation of the fourth ventricle, hypoplasia of the vermis cerebelli, separation of the cerebellar hernispheres, dilatation of the aqueductus mesencephali and absence of the lateral and median apertures of the fourth ventricle, an enlarged or normal-sized posterior cranial fossa and in some patients there may be hydrocephalus.

We report a case of a 9-year-old male child with DWM who underwent right ventriculoperitoneal shunt at the age of three months. He is doing well since then except he is mentally retarded.

Keywords: Dandy-Walker malformation, right ventriculoperitoneal shunt, CT scan

D

andy-Walker is a congenital abnormality characterized by a hindbrain abnormality associated with cystic dilatation of the fourth ventricle, hypoplasia of the vermis cerebelli, separation of the cerebellar hernispheres, dilatation of the aqueductus mesencephali and absence of the lateral and median apertures of the fourth ventricle, an enlarged or normal-sized posterior cranial fossa and in some patients there may be hydrocephalus.1,2

Case report A 9-year-old male child with Dandy-Walker malformation (DWM) who underwent right ventriculoperitoneal shunt at the age of three months.

He is doing well since then except he is mentally retarded (chronological age three years). There were no features of raised intracranial pressure. Recently parents investigated the child with a CT scan to know the functioning of the shunt and it showed massive posterior fossa cyst and other features of DWM and well-functioning shunt (Fig. 1).

Figure 1. Typical features of DWM on CT scan with associated giant cyst in the posterior fossa, note the well-functioning shunt.

Associate Professor Dept. of Surgery, Datta Meghe Institute of Medical Sciences Sawangi (Meghe), Wardha, Maharashtra Address for correspondence Dr Amit Agrawal Associate Professor (Neurosurgery) Clinical and Administrative Head, Division of Neurosurgery Datta Meghe Institute of Medical Sciences Sawangi (Meghe), Wardha - 442 004, Maharashtra E-mail: dramitagrawal@gmail.com

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Classically DWM is diagnosed when a cyst fills an enlarged posterior cranial fossa and separates rudimentary cerebellar hemispheres and can be associated with live-born mortality rates as high as 70%.3 The prognosis in patients with DWM is guarded and in survivors many children demonstrate significant disabilities or problems.4

Neurology In patients where Dandy-Walker syndrome is not complicated by hydrocephalus and consists of a large cyst communicating to the fourth ventricle early cystoperitoneal shunt surgery is recommended.5 In present case, the patient is doing well after nine years of surgery and is not symptomatic for the malformation except mental retardation that is persisting. Conservative management and regular follow-up was advised for this child.

References 1. D andy WE, Blackfan KD. Internal hydrocephalus: an experimental, clinical and pathological study. Am J Dis Child 1914;8:406-82.

2. Kollias SS, Ball WS, Prenger EC. Cystic malformations

of the posterior fossa: differential diagnosis clarified through embryologic analysis. Radiographics 1993;13(6): 1211-31.

3. Nyberg DA, Mahony BS, Hegge FN, Hickok D, Luthy DA, Kapur R. Enlarged cisterna magna and the Dandy-Walker malformalion: factors associated with chromosome abnormalities. Obstet Gynecol 1991;77(3): 436-42.

4. Chang MC, Russell SA, Callen PW, Filly RA, Goldstein RB. Sonographic detection of inferior vermian agenesis in Dandy-Walker malformations: prognostic implications.

Radiology 1994;193(3):765-70.

5. Miyamori T, Okabe T, Hasegawa T, Takinami K, Matsumoto T. Dandy-Walker syndrome successfully treated with cystoperitoneal shunting - case report.

Neurol Med Chir (Tokyo) 1999;39(11):766-8.

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PET Scan Spots Brain Trauma in Ex-athletes while Alive A new imaging technique has allowed detection of tau protein abnormalities in the concussed brains of living retired football players that are identical to the autopsy findings of chronic traumatic encephalopathy (CTE) in deceased athletes, researchers reported. (Source: Medpage Today)

‘Sticker Shock’ is Nonissue when Ordering Tests Providing clinicians with information about the cost of the imaging tests they order failed to cut down on test utilization, a randomized study found. (Source: Medpage Today)

Shared Genetic Link Found in Epilepsy, Migraine with Aura For the first time, researchers have demonstrated a shared genetic susceptibility to epilepsy and migraine with aura in a large cohort of patients with generalized epilepsy (GE) or nonacquired focal epilepsy (NAFE). (Source: Medscape)

Little Evidence for Nondrug Tx for ADHD Nondrug treatments for attention deficit/hyperactivity disorder have limited evidence of efficacy and their use for core symptoms is not supported, an European Guideline Committee concluded. (Source: Medpage Today)

New AHA/ASA Guidelines for Acute Stroke Treatment The American Heart Association/American Stroke Association (AHA/ASA) has released new guidelines on the early management of acute ischemic stroke. The document is published online January 31 and will appear in the March issue of Stroke. The American Academy of Neurology “affirms the value of this guideline as an educational tool for neurologists,” and it is further endorsed by the American Association of Neurological Surgeons and the Congress of Neurological Surgeons. (Source: Medscape)

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639

Obstetrics and Gynecology

Labetalol - An Emerging First-line Drug for Pregnancy-induced Hypertension Sushrut D*, Girija**

Abstract Research questions: To study labetalol as a first-line drug for hypertension in pregnancy and endorse its superiority over alpha-methyldopa. Settings: Dept. of Obstetrics and Gynecology, Bharati Vidyapeeth Medical College and Hospital, Pune.

Study design and methodology: Patients with diastolic blood pressure recorded above 100 mmHg have been admitted and administered labetalol 100 mg twice-daily orally, the dose escalating to 1.2 g/day. The control of pressures and side effects have been noted. Results: Labetalol is instrumental in causing a sustained and smooth fall in blood pressure and is free of the side effects of alpha-methyldopa. Conclusion: Thus, labetalol supercedes alpha-methyldopa as a first-line drug for hypertension in pregnancy.

Keywords: Labetalol, alpha-methyldopa, pre-eclampsia, fetal surveillance

H

ypertensive disorders are the most common medical disorders in pregnancy contributing significantly to maternal and perinatal mortality and morbidity worldwide. The incidence is around 3-10% of all pregnancies.

According to the National High Blood Pressure Working Group,1 hypertensive disorders in pregnancy are classified as: ÂÂ

Gestational hypertension

ÂÂ

Pre-eclampsia and eclampsia syndromes

ÂÂ

Pre-eclampsia hypertension

ÂÂ

Chronic hypertension

superimposed

on

chronic

The commonly used antihypertensive drugs in pregnancy with proven safety are: ÂÂ

Alpha-methyldopa

ÂÂ

Nifedipine (calcium channel blocker)

ÂÂ

Labetalol

*Fellow in Perinatology **Professor and Head Dept. of Obstetrics and Gynecology Bharati Vidyapeeth Medical College and Hospital, Dhankawadi, Pune Address for correspondence Dr Ghaisas Sushrut Dilip Ashwini, 13/59, Nav Sahyadri Soc., Karvenagar , Opp. Sahyadri Park Pune - 411 052 E-mail: sdghaisas @rediffmail.com

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Labetalol is an a-blocker with nonselective b-blocking properties. It is available in oral as well as injectable forms. Its safety in the first trimester of pregnancy has been documented.

The aim of antihypertensives is to reduce and stabilize the blood pressure, in an attempt to minimize the risks such as placental abruption, maternal cardiac failure, cerebral hemorrhage; at the same time they should not have any adverse effects on the uteroplacental circulation and the fetus.

TRIAL We conducted a trial at the Dept. of Obstetrics and Gynecology, Bharati Vidyapeeth University Medical College and Hospital, Pune about the usage of labetalol as a primary drug for hypertensive disorders in pregnancy.

AIM The purpose of the trial was to study the role of labetalol (oral) as a first-line drug for hypertensive disorders in pregnancy in an open prospective trial, the primary efficacy parameter being control of blood pressure (BP) and secondarily studying tolerability and effects on labor and fetus.

METHODS Labetalol was introduced in pregnant women with recorded diastolic blood pressures above 100 mmHg. The drug was started as 100 mg twice-daily with escalating doses at weekly intervals if uncontrolled, reaching a maximum of 1.2 g in 24 hours.

Obstetrics and Gynecology Inclusion Criteria Patients included in the trial had no concurrent antihypertensive therapy administered and were not suffering from any other medical diseases.

Exclusion Criteria Patients suffering from bronchial asthma, any preexisting cardiovascular disorder, diabetes were excluded from the trial.

OBSERVATIONS Fall in BP upto 100 mmHg or below was recorded from within an hour of administration of the drug. There was no precipitous fall in BP and the fall in pressures was consistent. Tachycardia or any other maternal side effect was not observed. There was no fetal growth restriction or any other effect on the fetus. Also no improvement in proteinuria was observed.

CONSIDERATION Alpha-methyldopa has been traditionally considered as the first-line drug for pregnancy-induced hypertension (PIH) in India, owing to its safety, efficacy and low cost. However, labetalol could replace it as the first choice.

WHY NOT ALPHA-METHYLDOPA? Upon introduction, alpha-methyldopa takes 24 hours for complete action, and upon starting with a 250 mg dose, it needs to be taken three times daily. Patients commonly suffer from postural hypotension due to a-receptor blockade. The common side effects are constipation, galactorrhea, postpartum depression and altered sleep pattern. Although minor, they could be distressing to some. It also causes headache, which can be confused with impending eclampsia.

The hematological manifestations include hemolysis and thrombocytopenia on blood smear, and false positive Coombâ&#x20AC;&#x2122;s test in 10% cases. As regards antepatum fetal surveillance, it causes falsely nonassuring fetal heart patterns on electronic fetal monitoring. Alpha-methyldopa accumulates in renal failure, which can sometimes complicate pre-eclampsia.

WHY LABETALOL? Labetalol can boast of some characteristic merits over alpha-methyldopa. It is free of the above mentioned side effects. It results in good and sustained control of BP. There is no tachycardia and BP is stabilized.

Labetalol has no effect on uteroplacental blood flow.

Also, an injectable form is available for hypertensive crisis.

The National Guideline Clearinghouse,2 regarding treatment of hypertensive disorders of pregnancy has recommended that the initial antihypertensive therapy should be started with labetalol (IA evidence) or nifedipine, to bring down the target BP to 160 systolic and 110 diastolic. For women with preexisting hypertension, pre-conceptional counseling is recommended. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB) are to be discontinued, and replaced with safer drugs labetalol, nifedipine and alpha-methyldopa.

In a Kuwaiti trial3 involving 104 primigravidas with mild-moderate PIH, the investigators compared alpha-dopa with labetalol for antihypertensive management, and concluded that labetalol is quicker, more efficient and better tolerated. Although it crosses placenta, there is no evidence of intrauterine growth retardation (IUGR), perinatal death and neonatal hypoglycemia. It may ripen the cervix, and reduce the latency of labor in term patients.

A double-blinded controlled trial4 involving 152 patients of moderate hypertension involving labetalol versus placebo reported that labetalol reduced the incidences of preterm delivery, neonatal jaundice and RDS. Thus, there are possible advantages with no apparent disadvantages for the fetus.

Thus, we foresee labetalol being considered over the traditionally used alpha-dopa as a first-line drug4 for hypertensive disorders in pregnancy, irrespective of gestational age.

References 1. Iffy L, Ganesh V; National High Blood Pressure Education Program Working Group. High blood pressure in pregnancy. Am J Obstet Gynecol 1991;165(1):236-7.

2. Magee LA, Helewa M, Moutquin JM, von Dadelszen P. Diagnosis, evaluation, and management of the hypertensive disorders of pregnancy. J Obstet Gynecol Can 2008;30(3 Suppl 1):S9-15.

3. el-Qarmalawi AM, Morsy AH, al-Fadly A, Obeid A, Hashem M. Labetalol vs methyldopa in the treatment of pregnancy-induced hypertension. Int J Gynecol Obstet 1998;49(2):125-30.

4. Pickles CJ, Symonds EM, Broughton Pipkin F. The fetal outcome in a randomized double-blind controlled trial of labetalol versus placebo in pregnancy-induced hypertension. Br J Obstet Gynecol 1989;96(1):38-43.

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Obstetrics and Gynecology

Ulipristal Acetate: The Latest in Emergency Contraception Monica Soni*, Prasoon Soni**

Abstract Unintended pregnancy is a global reproductive health problem. Emergency contraception (EC) provides women with a safe means of preventing unwanted pregnancies following unprotected intercourse. Current gold standard emergency contraceptive is levonorgestrel (LNG) given within 72 hours of unprotected intercourse. Ulipristal acetate is a selective progesterone receptor modulator (SPRM) recently approved by US FDA for emergency contraception. It can be used upto five days (120 hours) after an unprotected intercourse and a single dose of 30 mg is effective.

Keywords: Ulipristal acetate, ella, emergency contraception

U

nintended pregnancy is a global reproductive health problem.1 Emergency contraception (EC) provides women with a safe means of preventing unwanted pregnancies following an unprotected intercourse or a known or suspected contraceptive failure.1,2 It is not intended for routine use as a contraceptive. Current methods of EC include combined oral contraceptives, progestin only products, copper-containing intrauterine devices (IUD) and mifepristone.3

Current gold standard emergency contraceptive is levonorgestrel (LNG) given within 72 hours of unprotected intercourse.1 Ulipristal (UPA) is a selective progesterone receptor modulator (SPRM) recently approved by US Food and Drug Administration (US FDA) for EC within 120 hours (5 days) after an unprotected intercourse or contraceptive failure.2,4,5 Single dose of 30 mg UPA provides an effective alternative for EC.1,6

HISTORY UPA was approved in May 2009 by the European Commission for marketing as an emergency contraceptive within 120 hours (5 days) of unprotected sexual intercourse or contraceptive failure. The product was launched in October 2009 by 2010, it was marketed in 22 countries in Europe.3,5 The US FDA approved the drug for use in US on August 13, 2010.7 The 11-member committee voted unanimously that sufficient information was available about the efficacy of ulipristal. They also agreed that the safety profile appeared to be acceptable for the proposed indication.5 It became available to US women only by prescription on December 1, 2010.7 The drug is marketed by trade name EllaOne in European Union and Ella in US. Clinical Results2 FDA approval was based on two studies: An open label study and a single-blind comparative study.

Open Label Study

*Assistant Professor Dept. of Obstetrics and Gynecology **Senior Resident Dept. of Dermatology SP Medical College and PBM Groups of Hospitals Bikaner, Rajasthan Address for correspondence Dr Monica Soni C/o: Dr KP Soni, IV E 477-78 JN Vyas Colony Bikaner - 334 003, Rajasthan E-mail: drmonikasoni3008@gmail.com

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Indian Journal of Clinical Practice, Vol. 23, No. 10 March 2013

This trial enrolled 1,242 healthy female subjects with a mean age of 24 years who requested emergency contraception 48-120 hours after unprotected intercourse. The subjects received 30 mg of Ella. Ella statistically significantly reduced pregnancy rate from an expected rate of 5.5% to an observed rate of 2.2% (27 pregnancies).

Single Blind Study This multicenter, single-blind, randomized trial was designed to compare the efficacy and safety of 30 mg

Obstetrics and Gynecology Ella to LNG. The trial enrolled 844 female subjects.

Ella statistically significantly reduced the pregnancy rate from an expected 5.6% to an observed 1.4%, when taken within 72 hours after unprotected intercourse.

There were no pregnancies in the woman who were administered Ella >72 hours after unprotected intercourse (10% of women who received Ella).

Pooled Analysis Data from the two studies were pooled to provide total efficacy in woman treated with UPA upto 120 hours after unprotected intercourse. Time-Trend analysis for the five 24-hour intervals from 0 to 120 hours between unprotected intercourse and treatment was conducted.

There were no significant differences in the observed pregnancy rates across the five time intervals.

MECHANISM OF ACTION UPA is an orally active, synthetic, progesterone receptor modulator (agonist/antagonist).2 It reversibly blocks the progesterone receptor in its target tissues (uterus, cervix, ovaries, hypothalamus) and acts as a potent anti-progestational agent.2,8 It also binds to the glucocorticoid receptor.8 There is no relevant affinity to estrogen, androgen and mineralocorticoid receptors.8 The main mechanism of action of both LNG and UPA is delaying or inhibiting ovulation; however alterations to the endometrium that may affect implantation may also contribute to efficacy.1,2,9 The window of effect for LNG EC seems to be rather narrow, beginning after selection of the dominant follicle and ending when luteinizing hormone peak begins to rise, whereas, UPA appears to have a direct inhibitory effect on follicular rupture, which allows it to be also effective even when administered shortly before ovulation, a time period when use of LNG is no longer effective.

PHARMACOLOGY The Ella tablet for oral use contains 30 mg of a single active steroid ingredient ulipristal acetate, a synthetic progesterone agonist/antagonist.9 Chemical formula9 is C30H37NO4. The inactive ingredients are lactose monohydrate, povidone K-30, croscarmellose sodium and magnesium stearate.9 Pharmacodynamics The pharmacodynamics of UPA depends on the timing of administration in the menstrual cycle.9

Administration in the mid-follicular phase causes inhibition of folliculogenesis and reduction of estradiol concentration.9 Administration at the time of the luteinizing hormone peak delays follicular rupture by 5-9 days.9 Dosing in the early luteal phase does not significantly delay endometrial maturation but decreases endometrial thickness by 0.6 ± 2.2 mm (mean ± SD).9 Pharmacokinetics The route of administration is oral. Absorption is almost complete and peak plasma concentrations of UPA and the active metabolite, monodemethyl-UPA are reached at around one hour.9 Food delays absorption but the difference is not to a significant extent; therefore, Ella can be taken with or without food.9 UPA is highly bound (>94%) to plasma proteins.9 Metabolism occurs in the liver. UPA is metabolized to mono-demethylated and de-demethylated metabolites predominantly mediated

by CYP3A4. The mono-demethylated metabolite is pharmacologically active.9 The active terminal half-life after 30 mg single dose is estimated to be 32.4 ± 6.3 hours.9 Ninety percent of the excretion is with feces.

DOSAGE and ADMINISTRATION Instruct patient to take one tablet orally as soon as possible within 120 hours (5 days) after unprotected intercourse or a known or suspected contraceptive failure. The tablet can be taken with or without food.

If vomiting occurs within three hours of Ella intake, consideration should be given to repeating the dose. Ella can be taken at any time during the menstrual cycle.10 OVERDOSAGE Experience is limited. In a clinical study, single doses equivalent to upto four times were administered to a limited number of subjects without any adverse reactions.11 DRUG INTERACTIONS No drug interaction studies have been conducted for UPA in vivo. However, in vitro data indicate that Ella is predominantly metabolized by CYP3A4. Drugs or herbal products that induce enzymes, including CYP3A4, may decrease the plasma concentrations of UPA and may decrease its effectiveness. These include barbiturates, carbamazepine, griseofulvin, phenytoin and rifampin. CYP3A4 inhibitors such as itraconazole and ketaconazole may increase plasma concentrations of Ella.11

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Obstetrics and Gynecology emergency contraception: a randomized controlled trial.

Obstet Gynecol 2006;108(5):1089-97.

CONTRAINDICATIONS ÂÂ

Severe liver disease, owing to metabolism in liver.

ÂÂ

It is recommended to avoid breastfeeding within 36 hours of taking the drug because amount excreted in breast milk has not been studied.

ÂÂ

Known or suspected pregnancy.11

ADVERSE EFFECTS The side effects are similar to those experienced by women who use progestin-only emergency contraception.12 Headache, nausea and abdominal pain have been reported.12 Fewer women reported dizziness, fatigue or menstrual pain or discomfort at their next period.2,12 OTHER USES At a much lower daily dose, UPA is currently undergoing late stage clinical trials as a treatment for uterine fibroids.13 REFERENCES 1. G

emzell-Danielsson K, Meng CX. Emergency contraception: potential role of ulipristal acetate. Int J Womens Health 2010;2:53-61.

2. E lla (Ulipristal acetate) – Drug information. Available from: http://www.medilexicon.com/drugs/ella.php.

3. C unningham F, Leveno K, Bloom S, Hauth J, Rouse D, Spong C. Williams Obstetrics. 23rd edition, 2010: p.692-4.

4. C reinin MD, Schlaff W, Archer DF, Wan L, Frezieres R, Thomas M, et al. Progesterone receptor modulator for

5. Emma Hit. FDA Panel Gives Ulipristal Acetate Unanimous Positive Vote for Emergency Contraception Indication. Medscape Medical News 2010. Available from: http://www.medscape.com/viewarticle/723822.

6. Glasier AF, Cameron ST, Fine PM, Logan SJ, Casale W, Van Horn J, et al. Ulipristal acetate versus levonorgestrel for emergency contraception: a randomised non-inferiority trial and meta-analysis. Lancet 2010;375(9714):555-62.

7. Background on Ulipristal Acetate (Ella): A new emergency contraception pill. Available from: http://www.planned parenthood.org/files 8. Attardi BJ, Burgenson J, Hild SA, Reel JR. In vitro antiprogestational/antiglucocorticoid activity and progestin and glucocorticoid receptor binding of the putative metabolites and synthetic derivatives of CDB2914, CDB-4124, and mifepristone. J Steroid Biochem Mol Biol 2004;88(3):277-88.

9. Ella (Ulipristal Acetate)-Description and Clinical Pharmacology. Available from: http://www.druglib.com/ druginfo/ella/description_pharmacology/-Cached.

10. Ella Drugs.com.Drug Information Online.

11. Ella (Ulipristal Acetate)-Drug Interactions, Contraindications, Overdosage, etc. Available from: www. druglib.com/druginfo/ella/interactions_overdosage_ contraindic.

12. Fine P, Mathé H, Ginde S, Cullins V, Morfesis J, Gainer E. Ulipristal acetate taken 48-120 hours after intercourse for emergency contraception. Obstet Gynecol 2010;115(2 Pt 1):257-63.

13. RHTP - Reproductive Health Technologies Project. (2010).

A New Option for Emergency Contraception: The Facts on Ulipristal Acetate. [Online]. www.rhtp.org/documents/ EllaECFactSheet-UPDATES.21.10.pdf accessed June 4, 2010.

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FDA Panel to Address Two Menopause Drugs Two drugs under review by the FDA to treat symptoms associated with menopause reduced the frequency and severity of hot flashes, the agency said in advance of an advisory committee review of the products. (Source: Medpage Today)

Six Factors Best Predict Afib Risk in Women Researchers have devised a simple method for determining 10-year atrial fibrillation (Afib) risk in women, and the method gained very little when combined with genetic risk markers. (Source: Medpage Today)

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Obstetrics and Gynecology

Effect of Raised Mid-trimester Serum hCG and a-fetoprotein on Pregnancy Outcome Preeti Dubey*, Kiran Pandey*, Shaily Agarwal**, Sunita Jain*, Neetu Singh†, Shilpi Gupta‡

Abstract Objective: To study the effect of elevated maternal serum human choriogonadotrophin (MShCG) levels and maternal serum a-fetoprotein (MSAFP) levels measured at 14-24 weeks gestation on pregnancy outcome. Material and methods: A prospective study was conducted in 400 antenatal women with gestational age 14-24 weeks attending OPD and Indoor in Dept. of Obstetrics and Gynecology over a period of 12 months. Maternal serum b-hCG and a-fetoprotein levels were measured by fully automated chemiluminesence method. Result: Elevated mid-trimester MShCG levels and MSAFP level were associated with development of pre-eclampsia. Conclusion: Elevated mid-trimester MShCG and MSAFP level may help in the prediction of pre-eclampsia and hence they can be used as screening tools for prediction of pre-eclampsia.

Keywords: Human choriogonadotrophin, maternal serum a-fetoprotein, pre-eclampsia

P

re-eclampsia is associated with adverse pregnancy outcome and is a major cause of maternal and perinatal morbidity and mortality worldwide.

In developing countries, they rank second only to anemia with approximately 7-10% of all pregnancies being complicated by some form of hypertensive disease.

Several studies have demonstrated an association between unexplained increase of maternal second trimester serum human choriogonadotrophin (MShCG) levels and development of pre-eclampsia. This may be due to abnormal placental invasion or placental immaturity. Production of hCG may also be linked to trophoblast response to hypoxia with the development of hypersecretory state.

Raised a-fetoprotein (AFP) levels are associated with neural tube defect. Abnormal placentation may be associated with increased transfer of AFP across

*Professor **Lecturer (Assistant Professor) †Assistant Professor ‡Resident Dept. of Obstetrics and Gynecology GSVM Medical College, Kanpur Address for correspondence Dr Preeti Dubey Professor 106/107, Gandhi Nagar, Kanpur E-mail: drpreetidubey@gmail.com

the placenta, so, it may help to predict severity of pre-eclampsia. This study was conducted to assess the effect of elevated mid-trimester levels of MShCG and AFP on pregnancy outcome.

Material and Methods This study was conducted in 300 pregnant women attending OPD and Indoor in Dept. of Obstetrics and Gynecology, GSVM Medical College, Kanpur, over a period of 12 months during the year 2009-2010. This was a blind prospective study. The cases were randomly allocated.

Antenatal women with gestational age between 14-24 weeks with singleton pregnancy were included in the study. Dating was based on the last menstrual period or an early sonogram. Patients with chronic hypertension, twin pregnancy, molar pregnancy, chromosomally abnormal fetus, diabetes, chronic renal disease, autoimmune disorders, thrombophelias, family history of diabetes mellitus, hypertension, cardiovascular diseases and history of pre-eclampsia or eclampsia were excluded from the study.

After taking detailed history, general and obstetrical examination was done. Routine investigations, liver function tests, kidney function tests and determination of serum hCG and AFP levels in maternal serum (by fully automated chemiluminescence method) were done. b-hCG levels >50,000 mIU/ml and AFP levels >100 ng/ml were considered as elevated levels.

All these patients were followed till delivery and the fetal outcome was reported in terms of livebirth,

Indian Journal of Clinical Practice, Vol. 23, No. 10 March 2013

645

Obstetrics and Gynecology severe pre-eclampsia (Table 1). Out of 27 hypertensive patients 44.45% patient had mild pre-eclampsia and among them 50% had AFP levels between 100-120 ng/ml and 80% patient of severe pre-eclampsia had AFP levels 120-160 ng/ml. As the level of BP raises, AFP value increases significantly and two patients having AFP value between 140-160 ng/ml later developed eclampsia (Table 2).

stillbirth, neonatal death, mode of delivery, Apgar score and fetal birth weight.

Statistical analyses were performed with SPSS for windows 10.0. The differences of pregnancy outcomes among the control, mild pre-eclampsia, severe preeclampsia groups were carried out with ANOVA, Studentâ&#x20AC;&#x2122;s t-test. P value <0.05 was considered statistically significant.

Serum b-hCG and AFP levels were significantly high in hypertensive group as compared with normotensive group (p < 0.0001) (Table 3).

Observations Out of 300 patients, 24 patients had nonviable pregnancies hence they were excluded from the study.

Sixty-six patients were lost during follow-up. Only 210 patients could be followed-up to delivery. Out of these 210 patients, 27 patients were hypertensive and rest 183 were normotensive.

Table 4 shows that maximum no. of normotensive patients i.e., 108 (59.01%) had spontaneous vaginal delivery while only 22.2% hypertensive patients had spontaneous vaginal delivery (p < 0.05). Pregnancy outcomes are also summarized in Table 5. There were significant differences seen for baby birth weight, gestational age and one minute and 5 minutes Apgar scores (all p values <0.001).

Maximum number of hypertensive patients had b-hCG 50,000-70,000 mIU/l (66.6%) among this group 50% patient had mild pre-eclampsia and 50% had

Table 1. Relation of Level of b-hcg and Severity of Pre-elcampsia b-hCG levels (mIU/ml)

Total no. of patients

Mild PET

Severe PET

No.

%

No.

%

No.

%

50-60,000

9

33.3

3

25

6

40

60-70,000

9

33.3

6

50

3

20

70-80,000

9

11.1

-

-

3

20

80-90,000

6

22.2

3

25

3

20

Total

27

12

15

Discussion

Table 2. Relation of Afp Levels and Severity of Pre-eclampsia AFP levels (ng/ml)

Total no. of patients

Mild PET

Severe PET

No.

%

No.

%

No

%

100-120

9

33.3

6

50

3

20

120-140

9

33.3

3

25

6

40

140-160

9

33.3

3

25

6

40

Total

27

12

15

Table 3. Comparison of b-hcg and Afp Levels between Hypertensive and Normotensive Cases Hypertensive

Normotensive

p value

b-hCG (mIU/ml)

71,222.22 + 14,847

25,365 + 11,193

<0.0001

AFP (ng/ml)

136.7666 + 17.148

36.339002 + 13.050

<0.0001

Mean Âą SD

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Indian Journal of Clinical Practice, Vol. 23, No. 10 March 2013

There is an association between serum hCG and the subsequent development of pre-eclampsia. Our data also support a significant association between elevated second trimester MShCG and severity of pre-eclampsia. In recent years, many studies have been conducted to determinate the association between MShCG levels in the mid-trimester and subsequent development of pre-eclampsia.

Most researchers indicated that an unexplained elevation of serum hCG significantly correlated with the occurrence of pre-eclampsia.1-3 By contrast Pouta et al4 and Aquilina et al5 demonstrated no relation between

Obstetrics and Gynecology Table 4. Distribution of Cases According to Mode of Delivery Mode of delivery

Hypertensive (n = 27)

Normotensive (n = 183)

p value

No.

%

No.

%

Spontaneous vaginal delivery

6

22.2

108

59.01

< 0.05

Induction Ventouse Cesarean section

9 3 9

33.3 11.1 33.3

42 9 24

22.9 4.9 13.1

> 0.05 > 0.05 < 0.05

Table 5. Pregnancy Outcome Pregnancy outcome Baby birth weight 1 min Apgar 5 min Apgar Gestational age (w) Data - mean ± SD

Severe PET (n = 15) 1,751.56 ± 794.05 6.00 ± 2.14 7.38 ± 2.24 33.78 ± 3.27

Mild PET (n = 15) 3,192.66 ± 671.74 7.66 ± 0.55 8.84 ± 0.37 38.09 ± 1.87

levels of serum hCG and severity of pre-eclampsia.

Stamilio et al,6 also found no association between severe pre-eclampsia and elevated second trimester hCG levels evaluated at multiple cut-off points (1.5, 2.0, 2.5 and 3.0).

We found significant association between high MSAFP and severe pre-eclampsia (p < 0.05). In many studies unusually high AFP values have been associated with pre-eclampsia and or gestational hypertension.7 Räty et al8 also found the AFP values in the severe pre-eclampsia group differed significantly from all other groups.

Conclusion

2.

3.

4.

5.

Pre-eclampsia remains a major cause of perinatal morbidity worldwide. Exact etiology is still not defined. In spite of the reduction of morbidity and mortality of pre-eclampsia by improvement of maternal obstetrics care, no significant changes have occurred in prediction of pre-eclampsia. Hence, our study is an effort to identify a screening trial, which can identify women at risk for developing preeclampsia in pregnancy before the disease manifests and hence the study is significant.

6.

7.

8.

References 1. Luckas M, Hawe J, Meekins J, Neilson J, Walkinshaw S. Second trimester serum free beta human chorionic

Normotensive (n = 15) 3,404.95 ± 467.83 7.88 ± 0.55 8.90 ± 0.42 40.18 ± 1.29

p value < 0.001 < 0.001 < 0.001 < 0.001

gonadotrophin levels as a predictor of pre-eclampsia.

Acta Obstet Gynecol Scand 1998;77(4):381-4.

Benn PA, Horne D, Briganti S, Rodis JF, Clive JM. Elevated second-trimester maternal serum hCG alone or in combination with elevated alpha-fetoprotein. Obstet Gynecol 1996;87(2):217-22.

Ashour AM, Lieberman ES, Haug LE, Repke JT. The value of elevated second-trimester beta-human chorionic gonadotropin in predicting development of preeclampsia. Am J Obstet Gynecol 1997;176(2):438-42.

Pouta AM, Hartikainen AL, Vuolteenaho OJ, Ruokonen AO, Laatikainen TJ. Midtrimester N-terminal proatrial natriuretic peptide, free beta hCG, and alpha-fetoprotein in predicting pre-eclampsia. Obstet Gynecol 1998;91(6): 940-4.

Aquilina J, Maplethorpe R, Ellis P, Harrington K. Correlation between second trimester maternal serum inhibin-A and human chorionic gonadotrophin for the prediction of pre-eclampsia. Placenta 2000;21(5-6): 487-92.

Stamilio DM, Sehdev HM, Morgan MA, Propert K, Macones GA. Can antenatal clinical and biochemical markers predict the development of severe preeclampsia? Am J Obstet Gynecol 2000;182(3):589-94.

Wenstrom KD, Owen J, Davis RO, Brumfield CG. Prognostic significance of unexplained elevated amniotic fluid alpha-fetoprotein. Obstet Gynecol 1996;87(2):213-6.

Räty R, Koskinen P, Alanen A, Irjala K, Matinlauri I, Ekblad U. Prediction of pre-eclampsia with maternal mid-trimester total renin, inhibin A, AFP and free betahCG levels. Prenat Diagn 1999;19(2):122-7.

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Indian Journal of Clinical Practice, Vol. 23, No. 10 March 2013

647

Obstetrics and Gynecology

Pregnancy Following Laparotomy for Ruptured Interstitial Pregnancy Parneet Kaur*, Bajwa Surjit Kaur**, Harjinder Kaur†, Balwinder Kaur‡, Satinder Kaur#

Abstract An interstitial pregnancy is an uncommon type of ectopic pregnancy, accounting for 2-4% of all ectopic pregnancies. We present a patient with history of ruptured interstitial pregnancy who had been managed successfully at our hospital. The patient had refused tubectomy and conceived against medical advice within six months after laparotomy. She was counseled for risk of rupture of uterus and admitted to the hospital at the beginning of 9th month. She underwent an elective cesarean section and a male baby was delivered. Palpation of the uterine scar revealed that it was papery thin. Had there been any delay, the uterus would have ruptured with resultant maternal and fetal morbidity and mortality.

Keywords: Interstitial pregnancy, ruptured ectopic pregnancy

B

abita, G2P1A0 a 24 years female, reported in labor room of Government Medical College, Rajindra Hospital, Patiala on 8-9-06 at 6.30 p.m. with c/c of amenorrhea since three months and fainting attack at 11.30 a.m., which was preceded by vomiting.

She belonged to Mandi, Gobindgarh, which is 40 km from Patiala. She was refused admission there and referred to our institution.

At time of admission, her pulse rate (PR) was 140/ minute, systolic blood pressure was 80 mmHg and pallor was +++. Her urine for pregnancy test came out to be positive and on paracentesis there was frank blood. Diagnosis of ruptured ectopic pregnancy was made and laparotomy was immediately undertaken under general anesthesia along with all resuscitative antishock measures. Her hemoglobin (Hb) was 5.0 g/dl, BT 1’30”, CT 4’35” and urine C/E showed no abnormality.

uterus including right interstitial portion and right cornua ÂÂ

The fetus protruded out ensac (Figs. 1 and 2)

ÂÂ

The gestation of fetus was around 14 weeks

ÂÂ

Placenta was still inside uterus.

Upon opening the sac, a male fetus was identified.

Fragments of myometrium showing an implantation site with chorionic villi were seen. The findings were interpreted as an ectopic pregnancy, interstitial in

Findings at laparotomy were: ÂÂ

Massive hemoperitoneum (about 2.5 liters)

ÂÂ

There was rupture of along right lateral wall of

*Associate Professor **Ex-Professor and Head †Ex-Professor ‡Medical Officer Dept. of Obstetrics and Gynecology Government Medical College Rajindra Hospital, Patiala, Punjab Address for correspondence Dr Parneet Kaur Associate Professor H. No. 151, Punjabi Bagh Patiala - 147 001, Punjab E-mail: parneetkd@yahoo.co.in

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Indian Journal of Clinical Practice, Vol. 23, No. 10 March 2013

Figure 1. Showing fetus protruding ensac at time of laparotomy on 8-9-06.

Obstetrics and Gynecology location, with placental implantation involving the uterine cornu.

After removing the fetus and placenta about two inches rent along right lateral border of uterus was repaired. Right tube removed along with. As she had only one living female of one year, her husband refused tubectomy. Five units of blood were transfused. Her postoperative period remained uneventful.

She was discharged on 10th postoperative day with advice for abstinence. She was put on oral pills on her next visit. Patient did not comply with advice and

conceived in Marchâ&#x20AC;&#x2122;07 (her last menstrual period [LMP] 19-3-07). She came for abortion, which was refused and she was counseled thoroughly about regular antenatal check-ups.

Inspite of our best efforts, she came for antenatal check-up once each in first and second trimesters.

Again a thorough counseling was done along with her husband and all sorts of risks explained; thereafter her visits became regular in third trimester.

She was admitted at the beginning of 9th month on 25-11-07 for elective lower segment cesarean section (LSCS) (planned date 4-12-07). Her Hb was 8.0 g/dl, so two blood transfusions were given. On 3-12-07 (8 months and 14 days) at 9.30 a.m. patient c/o pain on right side of abdomen. On examination, PR was 100/ minute, BP 120/80 mmHg and on local examination, there was tenderness over right upper part of uterus and uterine contractions were present. Fetal heart sounds (FHS) were regular (140/min). Patient was immediately taken up for LSCS. An alive male baby was delivered on 3-12-07 at 11.38 a.m. Apgar score of baby was 8 at one minute and 9 at five minute. Birth weight was 2.2 kg.

On inspecting the uterus, the previous scar area looked bluish and hyperemic ~5 Ă&#x2014; 2 cm (Figs. 3 and 4).

On palpation from inside, the area was papery thin.

Figure 2. Showing fetus protruding from ruptured right cornua.

Figure 3. Showing previous repair site at time of LSCS on 3-12-07.

Figure 4. The instrument pointing at the previous repair site (3-12-07).

Indian Journal of Clinical Practice, Vol. 23, No. 10 March 2013

649

Obstetrics and Gynecology Had there been any delay, the uterus would have ruptured with result and maternal and fetal morbidity and mortality. As right tube was already removed so tubectomy was done on left side. Postoperative period remained uneventful.

Discussion An interstitial pregnancy is an uncommon type of ectopic pregnancy, accounting for 2-4% of all ectopic pregnancies and has mortality rate in range of 2.0-2.5%.1 Interstitial pregnancies occur when the gestational sac implants in the interstitial portion of the fallopian tube.1 The interstitial portion of the fallopian tube is a highly vascularized, muscular site that offers more support and distensibility to the embryo than any other portion of the fallopian tube. These anatomic features allow the gestation to advance much further into its development than when the embryo implants in other portions of the tube.2 Because, it is difficult, to confirm interstitial pregnancy in early stages even by transvaginal ultrasound, the patients usually present with life-threatening hypovolemic shock.3,4 Normally, it’s advisable to go for tubectomy after ruptured cornual pregnancy because rupture occurs late and rent is big but in this case we did not go for sterilization as patient’s husband did not give consent. Actual risk of uterine rupture in subsequent pregnancies is unknown but a potential threat.5

The possible mechanism is through defective area in the uterine wall.1 Again, she did not follow the advice and conceived within six months of laparotomy but after initial carelessness we could convince them for regular follow-up by a thorough counseling and all of us got the results.

These days, because of early diagnosis of interstitial pregnancy by three dimensional ultrasonography6 and conservative management by methotrexate1 and selective uterine artery embolization,5 such occurrences are rare.

References 1. Faraj R, Steel M. Management of corneal (interstitial) pregnancy. Obstet Gynaecol 2007;9(4):249-55.

2. Rajab KE, Issa A, Sanbhu AK. Interstitial pregnancy.

Bahrain Med Bull 2006;28(2):95-7.

3. Kim SW, Ha YR, Chung SP, Kwon OY. Ruptured interstitial pregnancy presenting with negative beta-hCG and hypovolemic shock. Am J Emerg Med 2003;21(6):511.

4. Sahu L, Induvadhani M. A case report of ruptured interstitial tubal pregnancy. J Obstet Gynecol India 2002;52:81.

5. Deruelle P, Lucot JP, Lions C, Robert Y. Management of interstitial pregnancy using selective uterine artery embolization. Obstet Gynecol 2005;106(5 Pt 2):1165-7.

6. Rastogi R, Gl M, Rastogi N, Rastogi V. Interstitial ectopic pregnancy: a rare and difficult clinicosonographic diagnosis. J Hum Reprod Sci 2008;1(2):81-2.

■■■■

FDA OKs Drug for Postmenopausal Dyspareunia The US Food and Drug Administration (FDA) has approved ospemifene (Osphena, Shionogi, Inc) for treating moderate to severe dyspareunia in postmenopausal women, the agency announced today. (Source: Medscape)

Advanced Breast Cancer Now more Common in Younger Women The number of young women presenting with metastatic breast cancer has been slowly but steadily rising over the past 3 decades, a national study found. (Source: Medpage Today)

New Form of Misoprostol Speeds up Labor A novel form of misoprostol (Cytotec) designed for induction of labor works faster than a similar vaginal insert of dinoprostone (Cervidil), a clinical trial showed. (Source: Medpage Today)

Pine Bark Extract Improves Several Perimenopausal Symptoms Low-dose treatment with French maritime pine bark extract (Pycnogenol, Horphag Research Ltd.) appears to alleviate several of the symptoms associated with perimenopause in women but has no effect on many other symptoms, according to the findings of a randomized, double-blind, placebo-controlled trial. (Source: Medscape)

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Indian Journal of Clinical Practice, Vol. 23, No. 10 March 2013

Orthopedics and Rheumatology

An Unusual Swelling at Ankle: An Osteochondroma in Adult?

Vivek AN

Abstract Osteochondroma is the most common benign tumor of bone commonly seen in children and young adults, arising in the metaphyseal region of a long bone, though it is occasionally seen affecting flat bones. It affects the small bones, of the hand and feet in approximately 10% of cases and the growth of the lesion usually ceases with fusion of the adjacent growth plate. We present a rare case of osteochondroma in a 60-year-old patient who had a swelling arising from the talus, which was treated by excisional biopsy and histologically confirmed to be osteochondroma.

Keywords: Osteochondroma, benign tumor, talus

O

steochondroma is the most common benign tumor of bone commonly seen in children and young adults. In most cases, the osteochondroma ceases to grow at skeletal maturity.

To our knowledge, a case developing such lesions after 30 years of age has not been reported in the literature.

We report a 60-year-old patient presenting with swelling arising from the talus, which was treated by excisional biopsy and histologically confirmed to be osteochondroma.

Case Report A 60-year-old male presented with a hard swelling at the right ankle of 8-month duration. He gave a history of trauma to the ankle due to fall and development of swelling and pain, which subsided without any specific treatment. He noticed a small painless swelling developing at the same area after a month, which was not associated with pain.

When the patient presented to us, the swelling was 8 Ă&#x2014; 6 cm anterior to the ankle. The swelling was nontender, bony hard and was immobile. Ankle movements were restricted with 100 and 200 of dorsiflexion and plantar flexion, respectively. An excisional biopsy was performed by anterior approach

Consultant Orthopedic and Arthroscopic Surgeon Lifeline Hospitals Perugudi, Chennai

and the swelling was excised in toto. Peroperatively the swelling was attached to the neck of talus by a narrow stalk, which was osteotomized along with a flake of normal bone.

Grossly, the tumor was glistening white and was entirely covered by cartilage except at its attachment to talus. On sectioning, the tumor was bony hard and revealed a uniformly thick cartilage cap. Histologically, there was normal trabecular pattern of mature bone tissue with uniform layer of cartilage cap. There were areas of marrow fat within the tumor. There were no features suggesting malignancy.

Multiple sections were made at regular intervals along the length of the tumor to rule out malignancy and other likely lesions.

Figure 1. Preoperative radiograph.

Figure 2. Postoperative radiograph.

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Orthopedics and Rheumatology

Figure 3. Photograph of the excised specimen.

Figure 4. Histopathological picture.

Discussion

woven bone, cartilage or a mix of chondroid, osteoid and myxoid elements. There may be zonal maturation of the tissues as is seen in myositis ossificans.

Differential diagnosis of a bony swelling which clinically and radiologically appears benign arising from an atypical location in an elderly patient includes heterotrophic ossification, florid reactive periostitis, Nora’s lesion, turret exostoses and osteochondroma.1-3 Heterotrophic ossification or post-traumatic ossification is a rare cause of joint stiffness. It occurs in cases of severe injury to a joint, and especially when the capsule and periosteum have been stripped from the bone. In general, the degree of ossification is inversely proportional to the age of the subject, so that the most exuberant ossifications are observed in children and young adults.

Florid reactive periostitis was first described

by Spjut and Dorfman in 1981.4 It is a rare benign bone lesion that affects the fingers or toes of adolescents and young adults (range 5-70 years). The lesion appears to be a reactive process rather than a true neoplasm.

The cause is unknown, but about one-half of patients with this lesion give a history of trauma to the area.

Clinically, there is a history of gradually progressive swelling, erythema and pain or a painful mass in the affected part. Approximately 50% of patients have a history of trauma. Plain radiographs show the tumor is adjacent to the bone rather than arising from it. Soft tissue swelling is accompanied by marked periosteal reaction. There may be new bone formation in the soft tissues and subtle cortical thinning. While the lesion is benign, the findings overlap with that of osteosarcoma, infection and other aggressive lesions. Histologically, the predominant cells are large spindle shaped fibroblasts with prominent nuclei. There is no pleomorphism.

Mitoses are present, which may be frequent but not abnormal. Multinucleated giant cells are frequently seen. There is mature and immature osteoid and

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Indian Journal of Clinical Practice, Vol. 23, No. 10 March 2013

Bizarre parosteal osteochondromatous proliferation (BPOP) or Nora’s lesion was described by Nora et al in 1983.5 It is a rare lesion commonly affecting the hands and feet of young adults in their 20s and 30s. Males and females are equally affected. It most commonly occurs in the proximal and middle phalanges, metacarpal and metatarsal bones.3 BPOP typically presents with a painless or mildly painful mass that grows over a period of weeks to months.5 In contrast to malignant lesions, BPOP exhibits no periosteal reaction and has normal underlying bone and adjacent soft tissue radiologically. On gross examination, BPOP appears as a lesion with a nodular surface covered by glistening cartilage and a distinct blue tint of the bone within.3 It contains disorganized and irregular cartilage with patchy ossification. The periphery of the lesion contains lobulated hypercellular cartilage and fibrous tissue with occasional large chondrocytes. There are uniform osteoblasts on the bony trabeculae. Chondrocytes may be binucleated5 and proliferation of bizarre (even spindle-shaped) fibroblast in the intertrabecular spaces of disorganized bone has been reported.6 Typically, the cartilage lobules show mild atypia and moderate mitotic activity is seen in the spindle cells. This often confuses the diagnosis and the lesion needs to be distinguished from conventional osteosarcoma, low-grade parosteal osteosarcoma and chondrosarcoma. Osteochondromas on the other hand, contains a few-millimeters thick chondral cap resembling normal cartilage, beneath which is cancellous bone that is in direct continuity with the underlying bone.7 The cap however, may be entirely absent in adults, and binucleated chondrocytes may be found in young patients.7 In contrast to BPOP, osteochondromas have normal ‘columnation’ of the cartilage.5

Orthopedics and Rheumatology Turret exostosis or acquired osteochondroma is an uncommon lesion that mainly affects phalanges of the upper extremity and rarely phalanges of the foot.

Turret exostosis was proposed by Wissinger et al in 1966.2 Radiologically, there is a well-defined osseous mass fused to the underling bony cortex without communication to the medullary canal, which is typical of osteochondromas. The lesion is covered by a thin cartilage shell, which demonstrates less cytologic atypia. Subungual exostosis is a clinical entity similar to turret exostosis. This type of exostosis more often affects the distal phalanx of the big toe.

References

The osteochondroma or osteocartilaginous exostosis is the most common tumor of bone. Seventy to 80% of solitary osteochondromas occur in children or adolescents younger than 20 years of age, arising in the metaphyseal region of a long bone, though it is occasionally seen affecting flat bones (pelvis and scapula). It affects the small bones of the hand and feet in approximately 10% of cases and the growth of the lesion usually ceases with fusion of the adjacent growth plate.7 Since, these tumors are active during the period of normal skeletal growth and cease to grow at the time of skeletal maturation, it may be argued that they are not true tumors but simply aberrations of bone growth.

Essentially, they are cylinders or pedicles of adult bone capped by an epiphyseal disk of cartilage.

4. Spjut HJ, Dorfman HD. Florid reactive periostitis of the tubular bones of the hands and feet. A benign lesion which may simulate osteosarcoma. Am J Surg Pathol 1981;5(5):423-33.

1. Abramovici L, Steiner GC. Bizarre parosteal osteochondromatous proliferation (Nora’s lesion): a retrospective study of 12 cases, 2 arising in long bones.

Hum Pathol 2002;33(12):1205-10.

2. Wissinger HA, McClain EJ, Boyes JH. Turret exostosis.

Ossifying hematoma of the phalanges. J Bone Joint Surg Am 1966;48(1):105-10.

3. Meneses MF, Unni KK, Swee RG. Bizarre parosteal osteochondromatous proliferation of bone (Nora’s lesion).

Am J Surg Pathol 1993;17(7):691-7.

5. Nora FE, Dahlin DC, Beabout JW. Bizarre parosteal osteochondromatous proliferation of the hands and feet.

Am J Surg Pathol 1983;7(3):245-50.

6. Smith NC, Ellis AM, McCarthy S, et al. Bizarre parosteal osteochondromatous proliferation: a review of seven cases. Aust NZ J Surg 1996;66(10):694-7.

7. Resnick D, Kyriakos M, Greenway GD. Tumors and tumorlike lesions of bone: imaging and pathology of specific lesions. In: Diagnosis of Bone and Joint Disorders. 3rd edition, Resnick D (Eds.), WB Saunders, Co.:Philadelphia 1995;p.3725-66, 3978-9.

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Adolescents with Joint Hypermobility at Increased Risk for Joint Pain A prospective study by UK researchers found that adolescents who are double-jointed - medically termed joint hypermobility - are at greater risk for developing musculoskeletal pain as they get older, particularly in the shoulders, knees, ankles and feet. Findings published in Arthritis & Rheumatism, a journal of the American College of Rheumatology (ACR), indicate that children with joint hypermobility are approximately twice as likely to develop pain at these joints.

Vitamin D and Calcium may not Prevent Fractures Vitamin D and calcium supplements do not prevent fractures in adult men or women, according to a report published in the journal Annals of Internal Medicine.

After discovering that there was not sufficient scientific proof to demonstrate that vitamin D and calcium supplements help protect bones from breaking in men or the majority of postmenopausal women, the US Preventive Services Task Force (Task Force) made their final recommendation.

Indian Journal of Clinical Practice, Vol. 23, No. 10 March 2013

653

Pediatrics

The Role of Clinical Signs in the Diagnosis of Late-onset Neonatal Sepsis and Formulation of Clinical Score Subhranshu Sekhar Kar*, Rajani Dube**, Samarendra Mahapatro*, Sitanshu Sekhar Karâ&#x20AC;

Abstract Neonatal sepsis is the most important cause of morbidity and mortality in developing countries. The low birth weight and preterm babies are more vulnerable to it. It is diagnosed when generalized systemic features are associated with pure growth of bacteria from one or more sites. However, the signs of sepsis are nonspecific and the outcome of a neonate with sepsis depends on its early identification. So, this study is done to evaluate the role of various clinical signs in diagnosing late-onset sepsis, their statistical analysis and to develop a scoring system-based purely on clinical signs for early diagnosis and prompt institution of treatment.

Keywords: Sepsis, late-onset, clinical score

I

nfection, as either prime pathology or a complication of other illness, is a major cause of neonatal mortality and morbidity throughout the world.1,2 In developing countries, sepsis accounts for 30-50% of five million total deaths each year.3,4 It is estimated that almost 20% of all neonates develop infection and approximately 1% die of the serious systematic infection.4 The incidence of neonatal sepsis according to the data from National Neonatal Perinatal Database (NNPD, 2002-03) is 30 per 1,000 live births.5 The microorganisms most commonly associated with sepsis include Group B Streptococcus (GBS), Escherichia coli, coagulase-negative Staphylococcus (CoNS), Haemophilus influenzae and Listeria monocytogenes.6,7 As the clinical signs of sepsis are mostly nonspecific, hence the outcome of a neonate with sepsis depends on its early identification.8

Through there are various scoring systems on perinatal risk factors and hematological parameters, there is paucity of data regarding the scoring purely based on clinical signs for the prediction of neonatal sepsis (late-onset) and hence the intention of the study is to develop a scoring system for risk predictability and early management.

Aims and Objectives To evaluate the role of various clinical signs in the diagnosis of late-onset neonatal sepsis, their statistical analysis and formulation of clinical score.

Material and Methods The present prospective study was undertaken in the neonatal intensive care unit (NICU) and special care neonatal unit (SCNU), Hi-Tech Medical College, Bhubaneswar during the year 2007-2010.

Selection of Cases *Associate Professor Dept. of Pediatrics **Associate Professor Dept. of Obstetrics and Gynecology Hi-Tech Medical College, Bhubaneswar â&#x20AC; Assistant Professor Dept. of Community Medicine, JIPMER, Puducherry Address for correspondence Dr Subhranshu Sekhar Kar Associate Professor, Dept. of Pediatrics Plot No.: 1, Lane-12, Aryabarta Colony Jagannathnagar, Rasulgarh, Bhubaneswar - 751 010, Odisha E-mail: drsskar@gmail.com

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Indian Journal of Clinical Practice, Vol. 23, No. 10 March 2013

The newborns having clinical signs of sepsis after three days of life were included in this study. Those having major congenital malformations were excluded.

Data Collection In all cases detail maternal and neonatal history with respect to symptoms, signs, complications and other relevant data were recorded in a pre-prepared proforma. All admitted neonates were monitored for

Pediatrics clinical signs till 28 days of life or till discharge from hospital whichever is earlier. Babies showing any of the clinical signs were evaluated for sepsis. Repeat sepsis screen and cultures were done only if there was a fresh clinical sign after 72 hours of first blood culture.

ÂÂ

Categories

l

Sick looking

l Apnea

The neonates were grouped into three categories:

l

Refusal to feed

l

Increased prefeed aspirate

l Lethargy

l

Chest retraction

l Seizure

l Grunting

l Sclerema

l

ÂÂ

ÂÂ

Definite sepsis:

Presence of clinical signs

Isolation of bacterial infective agent from either blood or cerebrospinal fluid (CSF).

Probable sepsis:

Presence of clinical signs

Two screening parameters positive

Blood/CSF culture sterile

No sepsis:

Presence of clinical signs

Sepsis screen and cultures - negative

Clinical signs studied:

Abdominal distension increase abdominal girth by 2 cm

l

Central cyanosis l Increased respiratory rate >60/min

l

Hypothermia (axillary temperature <360 C).

Table 1. Day of Occurrence of Symptomatic Events (n = 210)

l

Fever (axillary temperature >37.50 C)

l

Bradycardia - Heart rate <100/min

Onset (days)

l

Tachycardia - Heart rate >160/min

Frequency of occurrence (events)

Percentage (%)

4-7

90

42.8

8-14

66

31.4

15-21

30

14.3

22-28

24

11.5

Total

210

100%

The mean of onset (days) = 10.7 ± 6.8

Sepsis screening parameters ● CRP ● ANC

● ●

mESR Band cell count

● TLC

● I/T (Immature to total neutrophil) ratio ● Platelets

Table 2. Presenting Clinical Signs Presenting feature

Frequency of occurrence (Events) (n = 210)

Percentage (%)

Sepsis

No sepsis

Sick looking

38

18.1

20

18

Refusal to feed

24

11.4

6

18

Lethargy

76

36.1

40

36

Apnea

102

48.6

46

56

Increased prefeed aspirates

24

11.4

10

14

Chest retraction

12

5.7

6

6

Grunting

8

3.8

6

2

Abdominal distension

28

13.3

16

12

Increased respiratory rate

34

16.2

16

18

Bradycardia

0

0

0

0

Tachycardia

46

22

20

26

Hypothermia

8

3.8

4

4

Fever

36

17.1

20

16

Seizure

0

0

0

0

Sclerema

0

0

0

0

Central cyanosis

0

0

0

0

Indian Journal of Clinical Practice, Vol. 23, No. 10 March 2013

655

Pediatrics Table 3. Relationship of Sepsis with Occurrence of Events Events (n = 210)

Table 4. Bacteriological Profile in Definite Sepsis Bacteria

Sepsis

No. of events (n = 60)

Percentage (%)

Definite

Probable

Gram-positive bacteria

26

43.3

8 (40%)

12 (60%)

Staphylococcus aureus

18

30

Refusal to feed (n = 6)

2 (33.3%)

4 (66.7%)

Enterococcus faecalis

6

10

Lethargy (n = 40)

24 (60%)

16 (40%)

3.3

18 (39.2%)

Coagulase-negative staphylococcus (CoNS)

2

28 (60.8%) 8 (80%)

2 (20%)

Gram-negative bacteria

34

56.7

Klebsiella pneumoniae

12

20

Alkaligenes faecalis

8

13.3

Escherichia coli

6

10

Enterobacter spp.

4

6.7

Acinetobacter

4

6.7

Sick looking (n = 20)

Apnea (n = 46) Increased prefeed aspirates (n = 10) Chest retraction (n = 6)

4 (66.7%)

2 (33.3%)

Grunting (n = 6)

4 (66.7%)

2 (33.3%)

Abdominal distension (n = 16)

12 (75%)

4 (25%)

Increased respiratory rate (n = 16)

12 (75%)

4 (25%)

Bradycardia (n = 0)

0

0

Tachycardia (n = 20)

18 (90%)

2 (10%)

Hypothermia (n = 4)

2 (50%)

2 (50%)

Fever (n = 20)

12 (60%)

8 (90%)

Seizure (n = 0)

0

0

Sclerema (n = 0)

0

0

Central cyanosis (n = 0)

0

0

OBSERVATIONS The study cohort included 160 neonates with 210 symptomatic events (i.e., the occurrence of one or more clinical signs in each event).

Out of 160 cases - male to female ratio is - male (118): Female (42) = 2.8:1 and majority 91% (=146) babies were preterms with mean gestational age Âą SD = 31.4 Âą 3.4 weeks. 150 (93%) were low birth weight (LBW) babies

Table 5. Statistical Analysis of Clinical Signs in Definite Sepsis Signs

Sensitivity (%)

Specificity (%)

PPV (%)

NPV (%)

LR+

LR-

Apnea (n = 102)

47

51

28

70

0.95

1.08

Lethargy (n = 76)

40

65

32

73

1.14

0.92

Tachycardia (n = 46)

30

81

39

74

1.57

0.86

Sick looking (n = 38)

13

80

21

70

0.65

1.08

Fever (n = 36)

20

84

33

73

1.25

0.95

Increased respiratory rate (n = 34)

10

81

18

69

0.5

1.1

Abdominal distension (n = 28)

20

89

43

74

1.8

0.89

Refusal to feed (n= 24)

3

85

83

69

0.22

1.13

Increased prefeed aspirate (n = 24)

17

91

41

73

1.6

0.93

Chest retraction (n = 12)

7

95

33

72

1.22

0.99

Grunting (n = 8)

7

97

50

72

2.33

0.96

Hypothermia (n = 8)

3

96

25

71

0.07

0.95

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Indian Journal of Clinical Practice, Vol. 23, No. 10 March 2013

Pediatrics Table 6. Clinical Score Clinical sign

Score

Lethargy

1

Tachycardia

1

Fever

1

Abdominal distension

1

Increased prefeed aspirate

1

Chest retraction

1

Grunting

2

The clinical signs showing LR+ >1 were considered for clinical score, score-1 was given for signs with LR+ between 1 & 2 and score 2 for signs with LR+ >2.

Table 7. Statistical Analysis of Clinical Score Score Sensitivity (%)

Specificity (%)

PPV (%)

NPV (%)

LR+

2

47

77

45

78

2

3

13

92

40

73

1.6

4

3

99

100

72

3

and 10 (6.2%) weighed >2.5 kg at birth with mean birth weight (mean ± SD) = 1,378 ± 507 g.

The frequency of occurrence of apnea is maximum followed by lethargy and tachycardia. However, tachycardia, increased prefeed aspirates, increased respiratory rate and abdominal distension were more common in definite sepsis, whereas, refusal to feed, sick looking and hypothermia were more common in probable sepsis. But in no sepsis group, refusal to feed, increased prefeed aspirate and tachycardia predominated. In this study, central cyanosis, sclerema, seizures and bradycardia were not present in any group (Tables 2 and 3).

It is found that, with respect to the symptomatic events (n = 210), two clinical signs were present in 94 events (44.8%), followed by one sign in 62 events (29.5%), three clinical signs in 34 events (16.2%) and ≥4 signs in 20 (9.5%) events, respectively. And out of 210 symptomatic events; in 60 (28.5%) events, blood culture was positive (definite Sepsis), in 34 (16%) events, sepsis screen was positive only (probable sepsis) and in 116 (55.5%) events, no sepsis was found.

The sensitivity of clinical signs varied from 3 to 47% and specificity from 51 to 97%. The positive predictive value (PPV) ranges from 8.3 to 50%. Grunting is the only sign

having LR+ of >2. It showed that the combined clinical score of 2 and 3 had PPV of 45 and 40%, respectively.

However, a clinical score of 4 gave a maximum PPV of 100% and LR+ of 3. So, this predictive ability is significantly more than any of the clinical signs in isolation.

DISCUSSION Infections are the single largest cause of neonatal deaths globally. Klebsiella pneumoniae and Staphylococcus aureus were the two most common organisms isolated. Based on the onset, neonatal sepsis is classified into two major categories: Early-onset sepsis, which usually presents with respiratory distress and pneumonia within 72 hours of age and late-onset sepsis that usually presents with septicemia and pneumonia after 72 hours of age.

Clinical features of sepsis are nonspecific in neonates and a high index of suspicion is required for timely diagnosis. Although blood culture is the gold standard for the diagnosis of sepsis, culture reports would be available only after 48-72 hours. In our study, there is male preponderance, which is due to the prevalent custom of taking male babies preferentially to healthcare institutions and also because female babies are immunologically more competent.9,10 Gerdes et al11 reported that male infants are four times vulnerable to sepsis than females. Also majority of this study group are preterms, which may be attributed to the occurrence of more number of premature deliveries in our institution hence they are more prone for sepsis.2 It is found that the mean age of onset of symptomatic events is 10.7 ± 6.8 days. Majority occurred between 4-7 days of life. This is in accordance with other studies.13 Also apnea, lethargy and tachycardia were the common clinical signs present in babies at enrollment for evaluation of sepsis which is similar to the study by Fanaroff et al.14 Any illness in neonates is bound to present with a constellation of clinical signs, hence, majority of symptomatic events presented with two clinical signs per event. Sixty (28.5%) events belong to the culture-positive group hence classified under definite sepsis category, which correlates with the report by Singh et al.15 Gram-negative sepsis predominates in our study (Table 4) with Klebsiella being the most frequent gramnegative isolate and S. aureus the gram-positive one.

Kuruvilla et al16 reported similar isolates in his study in 1998. However, the incidence of CoNS is low in our set up. It is seen from Table 4 that the sensitivity of

Indian Journal of Clinical Practice, Vol. 23, No. 10 March 2013

659

Pediatrics clinical signs is low (3-47%). It is because of the variable presentation of clinical signs at one time or other. Also, the PPV is low as these signs may be present in multiple other causes apart from sepsis.14

of sepsis on neonatal mortality: field trial in rural India.

Lancet 1999;354(9194):1955-61.

4. Stoll BJ. The global impact of neonatal infection. Clin Perinatol 1997;24(1):1-21.

This study tries to find out a scoring system based on individual clinical signs, hence signs with LR+ >1 are included in the score (Table 6). The diagnostic value of combined clinical score was depicted in Table 7.

A clinical score of 4 and maximum PPV of 100% with a positive LR of three meaning, when the clinical score is 4 then there is 3 times higher chance that the clinical signs are due to sepsis and there is 100% probability of presence of disease among test positives.

5. Report of the National Neonatal Perinatal Database (National Neonatology Forum), 2002-2003.

Scores for diagnosis of early-onset sepsis basing on clinical, laboratory and perinatal risk factors have been developed by many workers.17,18 But in India, where ready access to laboratory tests is meagre, the score based on clinical signs can significantly contribute to the diagnosis of late-onset septicemia and its early management.

8. Gotoff SP, Behrman RE. Neonatal septicemia. J Pediatr 1970;76(1):142-53.

KEY MESSAGE ÂÂ

The early diagnosis and timely treatment of neonatal sepsis is rather difficult due to the nonspecific clinical presenting signs.

ÂÂ

Also, in India ready access to laboratory tests is meager and cost-prohibitive.

ÂÂ

So, on the basis of the clinical score, i.e., a score ≥4, which has 100% positive predictive value, early diagnosis and prompt institution of therapy can be started without waiting for other laboratory parameters. The clinical score may be very useful in resource-poor settings.

References 1. Rennie Janet M, Roberton NRC. TB of Neonatology. 3rd edition, 1999:p.1109.

2. Khatua SP, Das AK, Chatterjee BD, Khatua S, Ghose B, Saha A. Neonatal septicemia. Indian J Pediatr 1986; 53(4):509-14.

3. Bang AT, Bang RA, Baitule SB, Reddy MH, Deshmukh MD. Effect of home-based neonatal care and management

6. Klinger G, Levy I, Sirota L, Boyko V, Reichman B, LernerGeva L; Israel Neonatal Network. Epidemiology and risk factors for early onset sepsis among very-low-birth weight infants. Am J Obstet Gynecol 2009;201(1):38.e1-6.

7. van den Hoogen A, Gerards LJ, Verboon-Maciolek MA, Fleer A, Krediet TG. Long-term trends in the epidemiology of neonatal sepsis and antibiotic susceptibility of causative agents. Neonatology 2010;97(1):22-8.

9. Singh M. Care of Newborn. 5th edition, 1999:p.211.

10. Klein JO, Marey SM. Bacterial Sepsis and Meningitis - Infectious D. of the Fetus & Newborn, 3rd edition, 1990:p.601-50.

11. Gerdes JS, Polin RA. Sepsis screen in neonates with evaluation of plasma fibronectin. Pediatr Infect Dis J 1987;6(5):443-6.

12. Gotoff SP. Nelson TB of Pediatrics. 16th edition, WB Saunders: Philadelphia 2000:p.541.

13. Sepsis and Septic Shock. Drug Ther Perspect 2001;17(6): 8-13.

14. Fanaroff AA, Korones SB, Wright LL, Verter J, Poland RL, Bauer CR, et al. Incidence, presenting features, risk factors and significance of late onset septicemia in very low birth weight infants. The National Institute of Child Health and Human Development Neonatal Research Network.

Pediatr Infect Dis J 1998;17(7):593-8.

15. Singh M, Narang A, Bhakoo ON. Evaluation of a sepsis screen in the diagnosis of neonatal sepsis. Indian Pediatr 1987;24(1):39-43.

16. Kuruvilla KA, Pillai S, Jesudason M, Jana AK. Bacterial profile of sepsis in a neonatal unit in south India. Indian Pediatr 1998;35(9):851-8.

17. Takkar VP, Bhakoo ON, Narang A. Scoring system for the prediction of early neonatal infections. Indian Pediatr 1974;11(9):597-600.

18. Bergqvist G, Eriksson M, Zetterström R. Neonatal septicemia and perinatal risk factors. Acta Paediatr Scand 1979;68(3):337-9.

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Renal

Intrarenal Abscess: When to Suspect?

SL Margekar*, N Singh*, OP Jatav**, P Kori†

Abstract Renal abscess is not so common therefore hardly suspected and often missed. Situation worsens when there is comorbid illness like malaria, which repeatedly tests positive further misleading the clinician leading to prolonged or recurrent fever or abdominal emergencies. When to suspect renal abscess is crucial, hence this report.

Keywords: Abdominal emergencies, fever, renal abscess

R

enal abscess is rather an uncommon lesion caused by urogenic infections (Staphylococcus aureus, members of Enterobacteriaceae family and Pseudomonas aeruginosa).1

Diabetics are particularly prone to renal inflammatory disease, which range from renal cortical abscess, perinephritis and perinephric abscess. Other predisposing factors include renal calculi, urethral obstruction, vesicourethral reflux, longer duration of symptom of urinary tract infection and renal failure.

Immunocompromised status, chronic debilitating disease and intravenous (IV) drug abuse are other less common causes.1-3 The purpose of this report is to identify the initial clinical characteristics that can lead to early diagnosis of renal abscess as perinephric and intranephric abscess are associated with considerable mortality and are often difficult to diagnose.2 USG abdomen and computerized tomography abdomen facilitate determination of the diagnosis. Treatment of renal abscess includes at least four weeks of antibiotics depending upon the organism isolated.4

*Assistant Professor **Professor and Head †PG Student, Final Year Dept. of Medicine GR Medical College, Gwalior, MP Address for correspondence Dr Neelima Singh Kamla Bhawan, Dal Bazar Tiraha, Lashkar, Gwalior - 474 009, MP E-mail: neelimajadon@yahoo.com

CASE REPORTS

Case 1 A 30-year-old diabetic female was admitted with a history of fever with chills and rigor since seven days, hematuria, pain abdomen and vomiting since three days. On examination, the patient was febrile but hemodynamically stable. Systemic examination was unrevealing except for epigastric tenderness.

The investigations revealed hemoglobin of 8.5 g/dl, total leukocyte count (TLC) - 7,400/mm3 with 90% neutrophils, erythrocyte sedimentation rate (ESR) was 75 mm and MP by FM was positive for Plasmodium vivax. Her random blood sugar was 240 mg/dl.

The urine routine and microscopic examination revealed presence of albumin, 10-12 pus cell/hpf and red blood cell 6-8/hpf. No cast or crystals were found.

Renal function test were within the normal range. This prompted us to go for USG abdomen, which revealed finding suggestive of bilateral renal abscess (2 in left kidney of size 4.1 × 2.9 and 2.3 × 2.1 cm and 1 in right kidney of size 1.9 × 1.3 cm) with splenomegaly (Fig. 1). Escherichia coli was grown on urine culture. In view of persistent fever and raised ESR, enzyme-linked immunosorbent assay (ELISA) for tuberculosis was performed, which was negative for IgA, IgG, IgM. She responded well to antibiotics, antimalarials and insulin and was discharged on 20th day with an advise to continue antibiotics and come for follow-up after one week. There was a history of previous hospitalization one month ago for diabetic ketoacidosis, vivax positive malaria with urinary tract infection. Reports of previous hospitalization were suggestive of glycosylated hemoglobin (HbA1C) –12.46%, normal renal function test, P. vivax positive malaria and presence of albumin, 3-4 pus cell/hpf, with no cast or crystal in urine routine microscopy.

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Renal were present. Twenty-four hours total urinary protein was 1 g/l. USG abdomen was suggestive of multiple renal abscess (multiple lesion of 1-1.5 cm diameter with the largest measuring 4.4 Ă&#x2014; 2.6 cm throughout renal parenchyma in the right kidney, and multiple lesions measuring 1-1.5 cm diameter in the left kidney), with cystitis and splenomegaly (Fig. 2). E. coli was grown in urine culture. Patient was treated with antibiotics, insulin and supportive measures and discharged on 18th day with an advise to continue antibiotics and come for follow-up after one week.

Case 3 Figure 1. USG abdomen showing round hyoechoic lesion suggestive of renal abscess.

Figure 2. USG abdomen showing round hyoechoic lesion suggestive of renal abscess.

Case 2 A 52-year-old male was admitted with the complaints of pain and distension of abdomen, decreased passage of feces and flatus, swelling of both lower limbs and reduced urine output since five days. He was not a known diabetic or hypertensive. On admission, he was hypotensive with a blood pressure of 90/60 mmHg and pulse was 104/min.

Blood sent for investigations revealed hemoglobin of 10.2 g/dl and TLC of 7,100/mm3.His blood sugar was 368 mg/dl, blood urea 174 mg/dl and serum creatinine was 5.62 mg/dl. Liver function test was near normal except for hypoalbuminemia and elevated alkaline phosphatase, which rose from 512 IU/l to 1,239 IU/l and urine routine and microscopy showed trace albumin with 1-2 RBC/hpf and innumerable pus cells. No cast was found although ammonium phosphate crystals

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A 24-year-old postnatal female who underwent cesarean section one month ago presented with fever, vomiting and pain in abdomen since 10 days. She was Plasmodium falciparum positive for which, she had received antimalarials including mefloquine prior to admission. On admission, her BP was 90/60 mmHg for which IV fluids, IV antibiotics and supportives were administered. Blood and urine sample sent for investigations revealed Hb% - 6.0 gm%, TLC - 2,000/ mm3. Urine examination showed pus cells 40-50/ hpf and albumin in traces. Other blood parameters including blood sugar were normal. USG abdomen was suggestive of abscess in left kidney measuring 2.2 Ă&#x2014; 2.7 cm. Patient improved with antibiotics and was discharged on 16th day with an advise to continue antibiotics and report for follow-up after one week.

DISCUSSION All three cases presented with fever, pain in abdomen and active urinary sediments. First case was a known diabetic patient who was P. vivax positive on two occasions over a span of one month. This could have mislead us, had we not gone for USG abdomen for acute pain in abdomen with which the patient presented.

Third case presented similarly with P. falciparum malaria. She was a nondiabetic but a postnatal, postoperative female with anemia. In the second case, USG abdomen was advised as the patient presented with subacute intestinal obstruction. He was diagnosed as diabetic during hospitalization. All the three cases were immunosuppressed, two were diabetic and third was a postnatal postoperative case. They were discharged on 20th, 18th and 16th day, respectively. This probably suggests that immunosuppressed patients are prone to renal abscess and require prolonged treatment for at least three weeks.4

Renal Diabetic ketoacidosis per se may present with acute abdomen but all abdominal emergencies in diabetics should be screened with USG abdomen to rule out renal abscess as the symptoms and signs that accompany renal abscess vary greatly and are nonspecific.

Predisposing factors for intrarenal abscess among diabetics may include diabetic nephropathy and diabetic cystopathy as in the second case. Renal abscess are infrequent renal pathology and if timely diagnosed can be treated successfully.4 CONCLUSION All diabetics and immunosuppressed patients presenting with acute abdomen should be subjected to ultrasound abdomen as a few may have renal

abscess, which requires prolonged treatment failing which there may be increased morbidity and recurrent hospitalization.

REFERENCES 1. Baradkar VP, Mathur M, Kumar S. Renal and perinephric abscess due to Staphylococcus aureus. Indian J Pathol Microbiol 2009;52(3):440-1.

2. Saiki J , Vaziri ND, Barton C. Perinephric and intranephric abscesses: a review of the literature. West J Med 1982;136(2):95-102.

3. Yen DH, Hu SC, Tsai J, Kao WF, Chern CH, Wang LM, et al. Renal abscess: early diagnosis and treatment. Am J Emerg Med 1999;17(2):192-7.

4. Jaik NP, Sujuitha K, Mathew M, Sekar U, Kuruvilla S, Abraham G, et al. Renal abscess. J Assoc Physicians India 2006;54:241-3.

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Gestational HTN, other high-BP States in Pregnancy Raise Later CV, Renal Risks A range of different high blood pressure conditions of pregnancy predicted onset of cardiovascular events, chronic kidney disease (CKD), and diabetes over the subsequent decades, to varying degrees, over an average of about 40 years in the Northern Finland Birth Cohort 1966. (Source: Medscape)

Hype or Hope? Renal Denervation Hits the Headlines Renal sympathetic denervation for the treatment of resistant hypertension has been the subject of much media coverage this week, with the publication of one-year results from the Symplicity HTN-2 trial in the December 18, 2012 issue of Circulation by Dr Murray Esler (Baker IDI Heart and Diabetes Institute, Melbourne, Australia) and colleagues, showing 10- to 20-mmHg drops in blood pressure with the procedure. (Source: Medscape)

Wider Fibrate use Urged in Mild-to-moderate CKD A new meta-analysis shows that fibrate therapy improves lipid profiles and prevents cardiovascular events in people with chronic kidney disease (CKD), cutting CV deaths by 40%. The findings also show that despite increasing serum creatinine–a long-known side effect of fibrates–the drug class caused no harm to the kidneys in the long run and may even provide some renal benefits, say Dr Min Jun (George Institute for Global Health, Sydney, Australia) and colleagues in their paper published online October 17, 2012 in the Journal of the American College of Cardiology. (Source: Medscape)

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Medifinance

Financial Advisory Team

W

hen most people think of a successful careerist like a medical professional, they think of someone who can afford a lavish lifestyle and its entrapments—a home in a gated highrise community, a swanky car or two, and the best educational institutions for their children.

The correlation between a high-income occupation and net worth is not inherently a positive one. The concepts of finance and accounting are alien for many doctors, since they go to medical school to learn medicine and not business. If these successful careerists are queried on their savings, generally they have purchased a few insurance policies and perhaps some stocks and mutual fund policies, mostly to oblige a friend or relative or based on the advice of a colleague or friend. However, if you look in greater detail at the investments these careerists have made, you may find that their life insurance is woefully inadequate, health insurance has not even been considered, and the investments are not customized to the needs of the individual.

No matter how well-educated or financially sophisticated, medical professionals are busy people who don’t have the time or inclination to effectively manage their own financial affairs. Attending a seminar, reading books on personal finance, casual discussion of money management or using computer software can help measure the dimension of their concern about these issues. They can also help doctors focus on the areas that need the immediate attention, such as education funding or liability protection. However, these steps cannot help doctors determine:

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How to reorganize their present investments in order to increase their net after-tax investment return

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How to structure the investments held by them and their family in order to maximize the potential financial aid for education funding or long-term care

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How to select and purchase the best mix of investments and insurance to pre-fund education, survivor needs and retirement income expenses

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What changes should be made in their estate plan and retirement plan as result of a thorough needs analysis and goal setting.

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Achieving one’s financial goals requires a coordinated, integrated approach. Peace of mind is achieved from knowing that they have planned well. To prepare a financial plan with the same attention to detail as that of a professional advisory team would just take too much time away from their personal life, occupation, business or civic responsibilities.

If a doctor’s financial situation is being monitored by a financial advisory team, he can be assured that his ‘financial house’ is in order. His time and attention can be focused on effective management of his business and pursuing his personal interests.

An ideal financial advisory team would consist of people with a wide range of skills like accountants, psychologists, solicitors, training consultants, management consultants, financial planners, real estate agents and property consultants. Working with an advisory team before making a purchase is more likely to make a doctor feel informed and confident about a product without the pressure to buy because they can separate the advice stage from the actual purchase.

Integrating the accounting processes with the financial planning processes is the most cost-efficient way of advising a doctor. The aim is to manage the financial affairs and work hard to make sure that doctors grow their practice and investments as fast, as efficiently and as safely as possible.

Reasons for Financial Planning

Confirming that Financial Objectives are being Met By evaluating a doctor’s total financial situation, they can coordinate strategies that do not interfere with any of the stated goals and objectives. By focusing on the whole, rather than on a part, recommendations can be made that are consistent with the long-term financial strategy.

Monitoring Implementation A financial plan that is not implemented becomes merely an educational experience. The stated goals and objectives can never be met without putting the plan into action. Follow-through is crucial.

A financial advisory team will ensure that all phases of your plan are properly implemented by selected

Medifinance agents, not only in terms of the types and categories of investments, but with respect to estate, tax and retirement planning. All areas of risk assessment are important. Any area if overlooked could wipe out the rewards of years of work and saving.

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Liabilities: Present and anticipated debt obligations.

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Income tax analysis: Projections for 10 years, with review of personal tax returns for last two years.

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Cash flow management: Projections for 10 years, determine effective use of anticipated surplus, managing deficits.

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Investment review: Analysis and recommendations.

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Insurance review: Analysis and recommendations.

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Employee benefits: Review and recommendations; coordinate with personal assets and spousal plans.

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Disability income: Analysis and recommendations; 10-year projections of taxes, cash flow and net worth.

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Estate distribution: Costs and taxation analysis methods of reducing probate costs and estate duties.

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Capital needs and survivor income analysis: Analysis and recommendations.

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Retirement income: Analysis and recommendations inflation, qualified plans and increasing net cash flow.

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Financial organizer file: For all documents, policy records.

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Income tax organizer file: Used each year to accumulate and store vital records to support tax returns.

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Master implementation checklist: To monitor your financial progress and be aware of advisor performance.

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Periodic review sessions: Verify progress evaluation of investments, benefit plans and document completion.

Frequent Reviewing to Remain on Schedule Financial planning is a dynamic process and should be reviewed on a continuing basis to verify that the goals are being met and that they are remaining on your financial schedule. Since “nothing is as constant as change itself” the goals, attitudes toward financial risks and family circumstances will change. Even if, we as individuals were to remain the same, the financial world around us changes so frequently that constant monitoring is a necessary part of the planning process.

The political, tax, legislative and economic changes increase in frequency. Reviews also ensure that any necessary adjustments are made before it is too late.

Providing Peace of Mind Dealing with a financial advisory team gives the doctor the peace of mind knowing that his financial situations are being handled by full-time professionals who are dedicated to his financial needs and who are in constant pursuit of his goals.

Planning Process Components ÂÂ

Review of your objectives and risk/reward attitudes: Short-term, medium range and longterm goals as well as perceptions of risks and expected rewards.

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Asset structure: Review of current holdings, present value, cost basis, growth and expected purchases.

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Cash flow management is a mechanism, not a budget. It allows the doctor to assess his financial situation from a long-term, systematic perspective.

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Time is a doctor’s greatest ally. The more time one has, then less money one will need to save and invest.

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Most people lose control over cash flow because they have no system to handle periodic known expenses of a substantial nature.

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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.

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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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Medilaw

What are the Pros and Cons of Death Penalty?

Which Method of Execution is Best?

MC Gupta

1. The simple answer is that courts award death sentence because they are obliged to do so by law.

Courts have to follow law.

2. As per criminology, there are supposed to be three main reasons for awarding death sentence:

Mainly, the death sentence is awarded as retribution for a heinous crime, usually involving killing somebody. This concept is clearly reflected in the “eye for an eye” concept of the medieval days. Gandhi had this to say about it - “If we follow the axiom an eye for an eye, we would all be blind”.

Another reason is that the person is considered to be so dangerous to society that the society will not be safe if he is allowed to live.

A third reason is that death sentence given to criminals will act as a deterrent for others in the society.

3. Arguments against death penalty are as follows:

Moral argument - There is a reasoned view that when man cannot give life, he has no right to take away life. Man should not interfere in god’s domain.

There are often no clear cut guidelines regarding whom to award death sentence.

As per Indian law, it has to be given in rarest of rare cases. In practice, it is not defined what is “rarest of the rare”. Courts act rather arbitrarily in arriving at such decision.

Court verdicts are not fool-proof. Innocents may be given death penalty by the courts.

Death sentence given by a lower court may be dispended with by a higher court.

However, innocence may be discovered after a long time. If the person has already been hanged, he can’t be brought back to life even if proved innocent. There are several examples of this happening. A well-known example is that of Dr Hawley Crippen who was hanged in 1910, after an Old Bailey jury Advocate and Medicolegal Consultant, New Delhi

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took just 27 minutes to find him guilty of murdering his wife, Cora, who had vanished earlier that year. A hundred years later, DNA studies revealed that the corpse found in his cellar could not have been that of Cora.

Dr Crippen maintained till the end that he was innocent.

http://www.guardian.co.uk/uk/2007/oct/17/ ukcrime.science

The legal defense available to the accused/ defendant, especially when he is from a low socioeconomic background, is often of poor quality and hence acts against him. It has been said that the competence of the defense attorney “is a better predictor of whether or not someone will be sentenced to death than the facts of the crime themselves”. It is well-proven by data that the proportion of adult US population in jails, including those condemned to death, is much higher in case of blacks and Hispanics.

The individual who is executed may not be himself responsible for his deed. The real culprits are the society and the social circumstances that made a criminal out of him. There might even be genetic factors at work.

With increased use of laboratory investigative techniques, punishment is often awarded on the basis of laboratory reports. Such reports may be faulty. Examples are as follows: zz

In West Virginia, a serologist falsified test results in hundreds of cases over a 10-year period, sentencing hundreds of defendants to lengthy prison terms.

zz

In Texas, a pathologist faked autopsy results, resulting in as many as 20 death penalty verdicts.

zz

A police chemist elsewhere falsified reports and sent hundreds of innocent people away to jail on rape charges.

zz

According to one report, 123 people were

Medilaw released from death row between 1973 and 2005 in 25 states of USA when new evidence of their innocence emerged.

before they commit a crime, the general opinion is that most homicides are spurof-the-moment, spontaneous, emotionally impulsive acts and, in this type of setting, murderers do not weigh their options very carefully. It is very doubtful that killers give much thought to punishment before they kill. On the other hand, the terrorists who kill are already prepared mentally to die (“martyr to the cause”) in the course of committing their heinous deeds. In such a situation, death penalty is unlikely to have any deterrent effect on them.

The above aspect has been discussed in— http://www.apsu.edu/oconnort/3210/ 3210lect01a.htm

It may be mentioned that the maximum misuse of scientific evidence is proprosecution.

Laws differ from country to country. They are unreasonably stringent in some countries.

The result is that the same person would be given death punishment in one country and not in another even when death penalty is permissible in both.

Amnesty International has given the example of Singapore whose “Misuse of Drugs Act” contains a series of presumptions, which shift the burden of proof from the prosecution to the accused. This is in conflict with the general legal principle that accused should be “presumed innocent until proven guilty”.

Some countries still retain death penalty.

Death penalty is allowed in some states of USA and not in others. A study of crime rates in relation to death penalty does not reveal an association. Crime rates have not increased after abolition of death penalty.

Crime rates continue to increase in countries where death penalty is given.

Death penalty does not act as deterrent for serious crime as per the following evidence: zz

John J. Donohue III, a law professor at Yale with a doctorate in economics, and Justin Wolfers, an economist at the University of Pennsylvania, published an article in 2005 in the Stanford Law Review regarding the deterrent effect of death penalty. They observed that death penalty is applied so rarely that the number of homicides it can plausibly have caused or deterred cannot reliably be disentangled from the large year-to-year changes in the homicide rates caused by other factors. They concluded that the evidence for death penalty having a deterrent effect was surprisingly fragile.

zz

As per the opinion of psychologists regarding whether murderers think about the consequences of their actions

zz

The rate of homicide rate per 1,00,000 population in Canada was 3.09 in 1975.

Capital punishment was abolished in 1976 and the homicide rate dropped to 1.8 by 2000. The reasons for the fall were attributed to better policing and social factors.

zz

On the other hand, capital punishment for nonhomicidal crimes like rape may actually provide an incentive to the rapist to murder the victim in order to avoid identification.

Award of death penalty by law conflicts with the law/ethics related to the working of a physician. In India, the death penalty implies hanging; some jail manuals specify for half an hour after which a doctor must certify death. In 1995, disposing of a petition, the Supreme Court agreed that keeping the body hanging for half an hour was barbarous and ruled that “a convict shall remain hanging only till he is declared dead by a medical officer”. This assumes an examination by a doctor every minute or so in the hanging position, and if found alive, advise the jail authorities to continue the hanging. No resuscitation or attempts to provide relief to the victim are permitted. This strikes at the very core of the Hippocratic Oath by which a doctor is committed to preserving life. The process of death is often so gory that it crosses all limits of medical ethics, and violates the precepts of beneficence and nonmalfeasance. It contradicts the Supreme Courts’ own ruling in “Deena vs Union of India” 1983, that the death should be “quick,

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Medilaw simple, decent and without mutilation, causing immediate unconsciousness passing to death”.

4. Arguments in favor of death penalty are as follows:

The society wants it. Law reflects public opinion. Death penalty has been abolished in most countries of the world but continues in the most populous countries like China, India, USA and Pakistan. It is banned in the whole of the European Union.

Death penalty has been challenged in courts but held to be legal by the SC. In democracies, we need to accept a situation whereby peoples’ representatives make differential laws for the people for their benefit.

The cost of maintaining a prisoner in a high security prison with facilities compatible with human rights requirements for the whole of life can be very high. The society may legitimately think, especially in countries with high poverty rates, that proper allocation of resources necessitates death penalty so that innocent children and others do not die of starvation while the dreaded criminals are looked after and fed properly.

5. The number of executions per year is much more in USA than the number of people executed in India since independence. In spite of this, the following is quite revealing as regards the effect of death penalty as a deterrent in the perception of US police. In a 1995 poll of randomly selected police chiefs from across the US, the officers were asked to rank the efficacy of death penalty in deterring or preventing violent crimes in comparison to other approaches, such as: Reduction in use/abuse of drugs; lowering technical barriers to prosecution; Putting more officers on the streets; and, making prison sentences longer. They responded that a better economy with more jobs would lessen crime rates more than the death penalty. In fact, only one percent of the police chiefs surveyed thought that the death penalty should be the primary focus for reducing crime.

6. Section 354(5) of the Code of Criminal Procedure, 1973, provides that a person condemned to death shall be hanged by the neck till he is dead.

7. Supreme Court has looked into the constitutionality of Section 354(5). While doing so, it referred to the findings of the British Royal Commission’s report on various methods of capital punishment

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and approved the method in vogue in India, i.e., hanging till dead.

8. The Royal Commission on Capital Punishment (1949-1953) had the following terms of reference: “To consider and report whether liability under the criminal law in Great Britain to suffer capital punishment for murder should be limited or modified, and if so, to what extent and by what means, for how long and under what conditions persons who would otherwise have been liable to suffer capital punishment should be detained, and what changes in the existing law and the prison system would be required; and to inquire into and take account of the position in those countries whose experience and practice may throw light on these questions.”

It should be noted the Commission was not asked to decide whether the death penalty should be abolished The Commission, comprising 10 men and two women had 63 meetings over the next four years at Carlton House Terrace in London and took evidence from a wide range of people with expertise in the field, including judges, prison governors and chaplains, medical officers and staff and also hangman, Albert Pierrepoint. It also visited ten British prisons, plus Broadmoor and prisons in various European countries and the USA to examine their practices.

Their 506 page report (often referred to as the Gowers report) was published in September 1953. http://www.capitalpunishmentuk.org/gowers.html The Commission examined the various methods of execution as an alternative to hanging, including the guillotine, shooting, electrocution, gassing and lethal injection. The last was opposed by the British Medical Association on the grounds that its members would have to be involved in carrying out executions, rather than in just certifying death and was considered as impractical and not necessarily humane by the Commission. Shooting was rejected it on the grounds that “it does not possess even the first requisite of an efficient method, the certainty of causing immediate death.” This was interesting in the light of the then recent firing squad execution of Josef Jakobs in 1941.

The guillotine was dismissed on the grounds of the unacceptable mutilation of the criminal’s body.

The Commission visited prisons in the USA and examined electrocution and lethal gas in depth but did not conclude that these methods offered any significant advantage over hanging.

It looked into the following 5 methods of capital punishment in various countries:

Medilaw

Electrocution: In 23 states of USA Guillotine: In France and Belgium Hanging: In England, Scotland, Commonwealth countries and 10 states of USA Lethal gas: In 8 states of USA Shooting: In the state of Utah in US and in almost all countries when ordained by Court Martial.

It also studied the practice of lethal injection.

It may be noted that this practice has been criticized because it compels a doctor to act in violation of Hippocratic Oath.

9. Hanging is supposed to precipitate immediate death by causing a specific type of fracture of the

second cervical vertebra known as the “hangmans’ fracture”. However, this occurs in only a small proportion of cases. In one study only six out of 34 cases had neck fractures, and of these only three had the classical hangmans’ fracture.

10. More commonly, death occurs by strangulation.

It is relatively painful, prolonged and gruesome, with the victim thrashing about for 20 minutes or so. The tongue swells and protrudes from the mouth, the eyes pop out of the head, with severe congestion of the head and neck veins. There is bowel and bladder incontinence, sometimes terminal ejaculation. The skin of the neck is often ripped off by the rope; sometimes causing decapitation.

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Forthcoming Events 2nd International Conference on Psychology and Allied Sciences

CME ON “STATE OF THE ART ANTENATAL CAREBASICS IN FETAL MEDICINE”

Theme of the Conference: Psychology in Everyday Life

Date: 28 April, 2013

Date: 21-22 March, 2013 Venue: Center for Behavioral Research and Intervention, Guru Jambheshwar University of Science and Technology, Hisar, Haryana

Venue: Room No. 3073, 3rd floor, Teaching Block, Conference Hall, AIIMS, New Delhi E-mail: kaparnasharma@gmail.com

Website: http://iahrw.com/index.php/conference/

WORKSHOP on FETAL MEDICINE

21st Annual Conference of Indian National Association for Study of The Liver

Date: 29 April to 2 May, 2013

Date: 22-24 March, 2013

Venue: Fetal Medicine OT, Dept. of Obstetrics and Gynecology, AIIMS, New Delhi

Venue: Hyderabad Interventional Convention Centre Hyderabad

E-mail: kaparnasharma@gmail.com

Website: http://www.inasl2013.org Annual Conference of Indian Society of Electrocardiology (ISECON 2013) Date: 6-7 April, 2013

Comprehensive course in pediatric Gastroenterology, Hepatology, Nutrition and Liver Transplantation Date: 28 August to 1 September 2013

Venue: Hotel Intercontinental, Eros, Nehru Place, New Delhi

Venue: Auditorium, Indraprastha Apollo Hospitals, Sarita Vihar, Delhi Mathura Road, New Delhi

Website: http://www.iseindia.org/

E-mail: profanupamsibal@gmail.com

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eMedinewS Inspiration

A Promise is a Promise GM Singh

A

man’s wife called him, “How long will you be poring over that newspaper? Will you come here and make your darling daughter eat her food?” he tossed the paper away and rushed to the scene.

His only daughter Sindu, looked frightened, tears were welling up in her eyes, in front of her was a bowl filled to its brim with Curd Rice, which she particularly detested.

His mother and his wife are orthodox and believe firmly in the ‘cooling effects’ of Curd Rice! He cleared his throat, and picked up the bowl. “Sindu, darling, why don’t you take a few mouthfuls of this Curd Rice?

Just for Dad’s sake, dear? And, if you don’t, your Mom will shout at me.” Sindu softened a bit, and wiped her tears with the back of her hands.

“OK, Dad. I will eat – not just a few mouthfuls, but the whole lot of this. But, you should…” Sindu hesitated, “Dad, if I eat this entire curd Rice, will you give me whatever I ask for?”

“Oh sure, darling”. “Promise?” “Promise.”

“Ask Mom also to give a similar promise”, his daughter insisted, his wife slapped her hand on Sindu’s, muttering, “Promise”, without any emotion.

Now he became a bit anxious. “Sindu dear, you shouldn’t insist on getting a computer or any such expensive items, Dad does not have that kind of money right now. OK?” “No, Dad. I do not want anything expensive.”

Slowly and painfully, she finished eating the whole quantity. After the ordeal was through, Sindu came to him with her eyes wide with expectation, all our attention was on her.

“Dad, I want to have my hair shaved off, this Sunday!’ was her demand.

“No, Dad. I do not want anything else”, Sindu said with finality.

“Please, Sindu, why don’t you try to understand our feelings?” he tried to plead with her.

“Dad, you saw how difficult it was for me to eat that Curd Rice.” Sindu was in tears. “And you promised to grant me whatever I ask for, now, you are going back on your words.

Was it not you who told me the story of King Harishchandra, and its moral that we should honor our promises no matter what?”

It was time for him to call the shots. “Our promise must be kept.”

“Are you out your mind?” chorused his mother and wife.

“No. If we go back on our promises, she will never learn to honor her own, Sindu, your wish will be fulfilled.”

With her head clean-shaven, Sindu had a round-face, and her eyes looked big and beautiful. On Monday morning, he dropped her at her school. It was a sight to watch his hairless Sindu walking towards her classroom. She turned around and waved, he waved back with a smile.

Just then, a boy alighted from a car, and shouted, “Sinduja, please wait for me!”

What struck me was the hairless head of that boy.

Maybe, that is the in-stuff, he thought.

“Sir, your daughter Sinduja is great indeed!”

“That boy who is walking along with your daughter is my son Harish. He is suffering from leukemia.” She paused to muffle her sobs. “Harish could not attend school for the whole of the last month. He lost all his hair due to the side effects of the chemotherapy.

“Atrocious!” shouted her wife, “A girl child having her hair shaved off? Impossible!”

He refused to come back to school fearing the unintentional but cruel teasing of the schoolmates.

Sinduja visited him last week and promised him that she would take care of the teasing issue.

“Never in our family!” her mother rasped. “She has been watching too much television, our culture is getting totally spoiled with these TV programs!”

But, I never imagined she would sacrifice her lovely hair for the sake of my son! Sir, you and your wife are blessed to have such a noble soul as your daughter.”

“Sindu darling, why don’t you ask for something else?

We will be sad seeing you with a clean-shaven head.”

He stood transfixed and then, wept. He said “My little Angel, you are teaching me how selfless real love is!”

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Confederation of Medical Associations in Asia and Oceania

Be Human Stop Child Abuse Sexual Harassment and Punishment Therefore A person is said to commit sexual harassment upon a child, when such person with sexual intent: ÂÂ

ÂÂ

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Utters any word or makes any sound, or makes any gesture or exhibits any object or part of body with the intention that such word or sound shall be heard, or such gesture or object or part of body shall be seen by the child; or Makes a child exhibit his body or any part of his body so as it is seen by such person or any other person; or Shows any object to a child in any form or media for pornographic purposes; or

ÂÂ

Repeatedly or constantly follows or watches or contacts a child either directly or through any means; or

ÂÂ

Threatens to use, in any form of media, a real or fabricated depiction through electronic, film or digital or any other mode, of any part of the body of the child or the involvement of the child in a sexual act.

Explanation: Whoever commits sexual harassment upon a child shall be punished with imprisonment of either description for a term, which may extend to three years and shall also be liable to fine.

Do’s and Don’ts for the Medical Officer

Do’s ÂÂ

Document the findings chronologically and with consistency.

ÂÂ

Maintain objectivity and avoid subjectivity.

ÂÂ

Authenticity of information should be ensured.

ÂÂ

Conduct the age determination test, whether requested or not by the investigating agency.

ÂÂ

Provide a comfortable and relaxed atmosphere to the victim to seek his/her cooperation for the medical examination.

ÂÂ

Build “trust and confidence” with the victim.

ÂÂ

Make sure that even minute detail of the examination is recorded in the Medicolegal Reports.

ÂÂ

Currently there is no prescribed format for interviewing the victim or for writing the Medicolegal Reports. It is advisable to follow a ready format. A recommended format is included in Annexure 3.

Don’ts ÂÂ

Don’t ally with any individual involved in investigation.

ÂÂ

Do not concur with traffickers, who may pressurize you to give false age determination report.

ÂÂ

Do not get emotionally influenced by allegations.

ÂÂ

Trial of the case has to be done by Court not by you.

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Write the report clearly and precisely.

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American Academy of Pediatrics recommends that physicians respect parental religious beliefs and the role of parents in rearing their children, and seek to make collaborative decisions with families whenever possible.

Do not use ambiguous words, those that have more than one meaning, or which can be interpreted wrongly by either side.

ÂÂ

Do not disclose the identity of the victim and findings to any unauthorized persons.

But, if the physician believes that parental religious convictions interfere with appropriate medical care that is likely to prevent substantial harm, suffering or death, the doctor should request court authorization to override parental authority.

ÂÂ

Do not try to become an investigator. Remain a person of science.

ÂÂ

Do not write a very lengthy and irrational history in the report.

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Do not venture a premature opinion.

Medical neglect in a child In addition to refusal to seek or delay in seeking medical care, medical neglect also includes lack of adherence to healthcare recommendations.

Lack of adherence can be due to lack of education, motivation, resources or understanding.

Indian Journal of Clinical Practice, Vol. 23, No. 10 March 2013

671

Around the Globe

News and Views Handwashing is the answer for most of the communicable diseases in India – IMA

No FDA approval yet for extended-release PD treatment

In the recent International Conference held in China on the subject “Infection challenges in South Asian countries”, Dr Narendra Saini, Secretary General, India Medical Association who represented IMA in the conference said that major issues concerning the country are antibiotic resistance re-emergence of chikungunya and diseases like typhoid, drug-resistant tuberculosis, malaria, japanese encephalits, etc. In all Asian countries, water sanitation and hygiene is a major concern. Hand washing is one of the answers to reduce the burden of infections in the society.

The US Food and Drug Administration (FDA) has issued a complete response letter on a New Drug Application (NDA) from Impax Pharmaceuticals for an extended-release capsule formulation of carbidopalevodopa known as Rytary (IPX066) for the treatment of idiopathic Parkinson’s disease (PD). (Source: Medscape)

IMA is presently running a project under which it is training students, school children, residential welfare associations members and healthcare workers in the correct hand washing technique. The correct hand washing involves six steps in which we wash our hands - palm to palm, palm to back, palm to palm with finger interlaced, back of fingers to palm, thumb to palm and fingertips to palm.

Cholesterol trial shut down An increase in adverse events, in particular myopathy led to the shut down a pivotal trial of Tredaptive, the agent that many hoped would improve niacin tolerance.

At 3.9 years of follow-up, one-quarter of the patients randomized to Tredaptive, a combination of extendedrelease niacin and the antiflushing agent laropiprant, had discontinued treatment because of side effects compared with 16.6% of patients in the control arm, according to Jane Armitage, FFPH, FRCP, from the University of Oxford, and colleagues. The finding comes from a substudy of HPS2-THRIVE published online in the European Heart Journal.

H1N1 Swine Flu Vaccine Tied to Sleep Disorder in British Children A British study in Feb. BMJ finds that children and teens who were vaccinated during the 2009 swine flu outbreak are at increased risk for narcolepsy, a disorder that causes people to fall asleep during the day. One in 52,000-57,500 doses of the vaccine are associated with narcolepsy.

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Indian Journal of Clinical Practice, Vol. 23, No. 10 March 2013

ARDS numbers after trauma may be on the wane The incidence of post-trauma acute respiratory distress syndrome (ARDS) declined over the course of a decade, researchers reported at the Society of Critical Care Medicine meeting. (Source: Medpage Today) Folic acid supplementation not linked to cancer Folic acid supplementation does not appear to increase or decrease the risk for site-specific or overall cancer in the first 5 years of treatment, according to the findings of a meta-analysis. Stein Emil Vollset, MD, from the University of Bergen in Norway, and colleagues published their findings online January 25 in the Lancet.

(Source: Medscape) Shorter wean time seen with tracheostomy Using a tracheostomy collar enables earlier weaning from mechanical ventilation than pressure support in patients who need prolonged mechanical ventilation, researchers reported at the Society of Critical Care Medicine meeting. (Source: Medpage Today) FDA approves new use for Exjade The iron chelator drug deferasirox (Exjade) may be used to reduce iron overload in thalassemia patients 10 and older who do not require regular transfusions, the FDA has announced. Deferasirox was previously approved to treat the condition in transfusion-dependent thalassemia patients. The expanded indication covers nontransfusion-dependent patients with liver iron concentrations of at least 5 mg/g of dry liver tissue.

(Source: Medpage Today)

eMedi Quiz

Quiz Time Q1. If a client has severe bums on the upper torso, which item would be a primary concern?

A. Debriding and covering the wounds B. Administering antibiotics C. Frequently observing for hoarseness, stridor and dyspnea D. Establishing a patent IV line for fluid replacement Q2. After Billroth II Surgery, the client developed dumping syndrome. Which of the following should the nurse exclude in the plan of care?

A. Sit upright for at least 30 minutes after meals B. Take only sips of H2O between bites of solid food C. Eat small meals every 2-3 hours D. Reduce the amount of simple carbohydrate in the diet Q3. A patient received spinal anesthesia 4 hours ago during surgery. The patient has been on the unit for ½ hours and now reports severe incisional pain.

The patient’s blood pressure is 170/90 mmHg, pulse is 108 beats/min, temperature is 99°F (37.2°C), and respirations are 30 breaths/min. The patient’s skin is pale and the dressing is dry and intact. The most appropriate nursing intervention is to: A. Call the physician and report the findings B. Medicate the patient for pain C. Place the patient in a high Fowler position and administer oxygen

D. Place the patient in a reverse Trendelenburg position and open the IV line.

Q4. An adult is receiving total parenteral nutrition (TPN). Which of the following assessment is essential?

A. Evaluation of the peripheral IV site B. Confirmation that the tube is in the stomach C. Assess the bowel sound D. Fluid and electrolyte monitoring Q5. Patients taking furosemide (Lasix) are instructed to notify their healthcare practitioner if they develop: A. A change in appetite B. A disruption in sleep patterns C. Increased urinary frequency D. Leg cramps Q6. A patient suffered a head injury 24 hours ago.

During a routine hourly neurologic check, the nurse notes that the patient’s speech has become slurred and that the patient now is disoriented to time and place. The nurse’s first action is to: A. Continue the hourly neurologic checks B. Inform the neurosurgeon of the patient’s status C. Prepare the patient for emergency surgery D. Recheck the patient’s neurologic status in 15 minutes

Answers to eMedi Quiz Published in February 2013 Issue Q1. (B) Avoid taking blood pressure measurements or blood samples from the affected arm. Q2. (C) Right lower quadrant. Q3. (A) Telling him to avoid heavy lifting for 4-6 weeks. Q4. (A) Inhibit bacterial growth.

Q5. (C) Relieve pain and promote rapid epithelialization Photo Quiz 1. Pneumothorax with pneumopericardium with pneumomediastinum. 2. Cutis Laxa. 3. Jeune asphyxiating thoracic dystrophy.

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.

Indian Journal of Clinical Practice, Vol. 23, No. 10 March 2013

673

Humor

Laugh-A-While

“Doctor, please hurry.

My son swallowed a razor-blade.”

“Don’t panic, I’m coming immediately.

Have you done anything yet?”

“Yea, I shaved with the electric razor.”

What’s the difference between a general practitioner and a specialist?

One treats what you have, the other thinks you have what he treats.

Patient to the eye doctor:

674

“Whenever I drink coffee, I have

The difference between a

this sharp, excruciating pain.”

neurotic and a psychotic is that,

Doctor: “Try to remember

while a psychotic thinks that

to remove the spoon from

2 + 2 = 5, a neurotic knows the

the cup before drinking.”

answer is 4, but it worries him.

Indian Journal of Clinical Practice, Vol. 23, No. 10 March 2013

lighter reading

Lighter Side of Medicine Quote

Make Sure

During Medical Practice A patient developed fainting attack after sublingual nitrate.

Oh my God! Why was the systolic murmur missed on auscultation?

“Insan Kehta Hai Agar Paisa Ho To Mai Kuch Kar Ke Dikhau aur Paisa Kehta He Tu Kuch Kar Ke Dikha To Mai Aau .... Create Success....” −Dr GM Singh

Mind Trivia 1. What is special about the following number sequence?

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

2. Stands

©IJCP Academy

-----------

1. It’s the numbers 0 through 10 in alphabetical order. 2. No one understands 3. 5 4 5 + 5 = 550

Dr. Good & Dr. Bad Situation: A type 1 diabetic came with A1C of 7.2%.

ILLUSION

©IJCP Academy

You need better control

retinopathy, nephropathy and neuropathy in both type 1 and type 2 diabetes, and cardiovascular disease in type 1 diabetes.

Dr KK Aggarwal

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Indian Journal of Clinical Practice, Vol. 23, No. 10 March 2013

5 + 5 + 5 = 550

4. Add a diagonal line on the top left of the first plus sign to convert + into a 4.

KK Aggarwal

Lesson: Blood sugar control can minimize risks for

3. How can you alter the following equation by a single stroke to make it correct?

Make sure that patient with left ventricular outflow tract (LVOT) obstruction are not given sublingual nitrates.

Its ok

0_2345

Information for Authors Manuscripts should be prepared in accordance with the ‘Uniform requirements for manuscripts submitted to biomedical journals’ compiled by the International Committee of Medical Journal Editors (Ann. Intern. Med. 1992;96: 766-767).

Indian Journal of Clinical Practice strongly disapproves of the submission of the same articles simultaneously to different journals for consideration as well as duplicate publication and will decline to accept fresh manuscripts submitted by authors who have done so.

The boxed checklist will help authors in preparing their manuscript according to our requirements. Improperly prepared manuscripts may be returned to the author without review. The checklist should accompany each manuscript.

Authors may provide on the checklist, the names and addresses of experts from Asia and from other parts of the World who, in the authors’ opinion, are best qualified to review the paper.

Covering letter –

– –

The covering letter should explain if there is any deviation from the standard IMRAD format (Introduction, Methods, Results and Discussion) and should outline the importance of the paper.

Principal/Senior author must sign the covering letter indicating full responsibility for the paper submitted, preferably with signatures of all the authors.

Articles must be accompanied by a declaration by all authors stating that the article has not been published in any other Journal/Book. Authors should mentioned complete designation and departments, etc. on the manuscript.

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

–

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

–

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

Note: Please keep a copy of your manuscript as we are not responsible for its loss in the mail. Manuscripts will not be returned to authors.

Title page Should contain the title, short title, names of all the authors (without degrees or diplomas), names and full location of the departments and institutions where the work was performed,

name of the corresponding authors, acknowledgment of financial support and abbreviations used.

– The title should be of no more than 80 characters and should represent the major theme of the manuscript.

A subtitle can be added if necessary.

– A short title of not more than 50 characters (including inter-word spaces) for use as a running head should be included.

– The name, telephone and fax numbers, e-mail and postal addresses of the author to whom communications are to be sent should be typed in the lower right corner of the title page.

– A list of abbreviations used in the paper should be included. In general, the use of abbreviations is discouraged unless they are essential for improving the readability of the text.

Summary – The summary of not more than 200 words. It must convey the essential features of the paper.

– It should not contain abbreviations, footnotes or references.

Introduction – The introduction should state why the study was carried out and what were its specific aims/objectives.

Methods – These should be described in sufficient detail to permit evaluation and duplication of the work by others.

– Ethical guidelines followed by the investigations should be described.

Statistics The following information should be given: – The statistical universe i.e., the population from which the sample for the study is selected.

– Method of selecting the sample (cases, subjects, etc. from the statistical universe).

– Method of allocating the subjects into different groups.

– Statistical methods used for presentation and analysis of data i.e., in terms of mean and standard deviation values or percentages and statistical tests such as Student’s ‘t’ test, Chi-square test and analysis of variance or non-parametric tests and multivariate techniques.

–

Confidence intervals for the measurements should be provided wherever appropriate.

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

Indian Journal of Clinical Practice, Vol. 23, No. 10 March 2013

677

Discussion –

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

References These should conform to the Vancouver style. References should be numbered in the order in which they appear in the texts and these numbers should be inserted above the lines on each occasion the author is cited (Sinha12 confirmed other reports13,14...). References cited only in tables or in legends to figures should be numbered in the text of the particular table or illustration. Include among the references papers accepted but not yet published; designate the journal and add ‘in press’ (in parentheses). Information from manuscripts submitted but not yet accepted should be cited in the text as ‘unpublished observations’ (in parentheses).

At the end of the article the full list of references should include the names of all authors if there are fewer than seven or if there are more, the first six followed by et al., the full title of the journal article or book chapters; the title of journals abbreviated according to the style of the Index Medicus and the first and final page numbers of the article or chapter. The authors should check that the references are accurate. If they are not this may result in the rejection of an otherwise adequate contribution.

Examples of common forms of references are: Articles Paintal AS. Impulses in vagal afferent fibres from specific pulmonary deflation receptors. The response of those receptors to phenylguanide, potato S-hydroxytryptamine and their role in respiratory and cardiovascular reflexes.

Q. J. Expt. Physiol. 1955;40:89-111.

Figures – Two complete sets of glossy prints of high quality should be submitted. The labelling must be clear and neat.

– All photomicrographs should indicate the magnification of the print.

– Special features should be indicated by arrows or letters which contrast with the background.

– The back of each illustration should bear the first author’s last name, figure number and an arrow indicating the top. This should be written lightly in pencil only. Please do not use a hard pencil, ball point or felt pen.

– Color illustrations will be accepted if they make a contribution to the understanding of the article.

–

Do not use clips/staples on photographs and artwork.

–

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

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

Books

5. Special requests _____________________________

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

6. Suggestions for reviewers (name and postal address)

Articles in Books

2.____________ 2.________________

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

3.____________ 3.________________

4.____________ 4.________________

Tables –

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

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

–

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

Indian Journal of Clinical Practice, Vol. 23, No. 10 March 2013

Indian 1.____________Foreign 1.________________

7. All authors’ signatures________________________ 8.

Corresponding author’s name, current postal and e-mail address and telephone and fax numbers __________________________________________

Online Submission Also e- Issue @ www.ijcpgroup.com For Editorial Correspondence

Dr KK Aggarwal

Group Editor-in-Chief Indian Journal of Clinical Practice E-219, Greater Kailash, Part-1 New Delhi - 110 048. Tel: 40587513 E-mail: editorial@ijcp.com Website: www.ijcpgroup.com

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

Padma Shri & Dr BC Roy National Awardee

Dr SM Rajendran