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Volume 27, Number 12

May 2017, Pages 1101–1200

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yy American Family Physician yy Cardiology yy Internal Medicine yy Neurology yy Obstetrics and Gynecology yy Expert’s View

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Fademy of F n ica Aca

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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

Dr KK Aggarwal Group Editor-in-Chief IJCP Group, eMedinewS and eMediNexus 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, Dr Vijay Viswanathan, Dr V Mohan, Dr V Seshiah, Dr Vijayakumar ENT Dr Jasveer Singh, Dr Chanchal Pal Dentistry Dr KMK Masthan, Dr Rajesh Chandna Gastroenterology Dr Ajay Kumar, Dr Rajiv Khosla, Dr JS Rajkumar Dermatology Dr Hasmukh J Shroff, Dr Pasricha, Dr Koushik Lahiri, Dr Jayakar Thomas Nephrology Dr Georgi Abraham Neurology Dr V Nagarajan, Dr Vineet Suri, Dr AV Srinivasan Oncology Dr V Shanta Orthopedics Dr J Maheshwari

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

Volume 27, Number 12, May 2017 FROM THE DESK OF THE GROUP EDITOR-IN-CHIEF

1105 The Mosquito Menace is Likely to be Back

KK Aggarwal

AMERICAN FAMILY PHYSICIAN

1108 Acute Monoarthritis: Diagnosis in Adults

Jonathan A. Becker, Jennifer P. Daily, Katherine M. Pohlgeers

1115 Practice Guidelines 1117 Photo Quiz CARDIOLOGY

1120 A Study of Novel Risk Factors, Clinical and Angiographic Profile of Acute Myocardial Infarction in Young Patients Below 35 Years

Dharmendra Jain, Geetha Subramanian, Rajpal Prajapati

1125 A Prospective, Comparative Evaluation of Efficacy and Safety of Olmesartan versus Telmisartan in Stage 1 Hypertensive Patients

Varun Gupta, Shalini Chandra, AK Kapoor, Nitin Agarwal

1134 Gender Differences in Prognosis of Systolic Heart Failure in Patients Undergoing Bypass Surgery

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

INTERNAL MEDICINE

1143 Symmetrical Peripheral Gangrene - A Rare Clinical Manifestation of Hodgkin’s Lymphoma: A Case Report

Praveen Kumar, Kalpana Chandra

NEUROLOGY

1146 Hereditary Spastic Paraplegia with Thin Corpus Callosum and Dementia: A Rare Presentation

Chandramohan Sharma, Banshi Lal Kumawat, Tarachand Saini, Mohit Shah

OBSTETRICS AND GYNECOLOGY

1153 Timing of Elective Repeat Cesarean Section at Term and Neonatal Outcomes in a Peripheral Tertiary Hospital in West Bengal

Tamal Kumar Mandal, Pratima Garain, Sankar Murmu, Sib Sankar Murmu, Debjani Deb

1158 Analysis of Cesarean Deliveries According to Robson’s Ten Group Classification at a Tertiary Care Hospital in Jaipur

Meeta Gupta, Shailesh Jain, RP Khuteta

OBSTETRICS AND GYNECOLOGY

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

1162 Hypertensive Disorders in Pregnancy: An Obstetric Catastrophe

Surya Malik, Khushpreet Kaur, Parneet Kaur

1166 A Prospective Study on Acceptability and Safety of IUCD Among Postpartum Mothers

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

Sushma Sinha, Surya Malik

1170 Anovulation and Infertility: Focus on Clomiphene Citrate and N-acetylcysteine for Ovulation Induction

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.

Anita Kant

1175 A Rare Case of Torsion Ovarian Fibroma

Pradeep Musale Ramamchandra, Lalitha Shivanna, Mamatha Siddappaji

EXPERTâ&#x20AC;&#x2122;S VIEW

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

1179 Which Antihypertensive Drugs can be Safely Taken During Pregnancy?

SP Kalantri

CONFERENCE PROCEEDINGS

1181 7th World Congress of Diabetes (DiabetesIndia 2017) 1185 54th Annual Conference of Indian Academy of Pediatrics (PEDICON 2017) MEDILAW

1189 A Medical Practitioner is not Expected to Achieve Success in Every Case that he Treats AROUND THE GLOBE

1192 News and Views

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.

LIGHTER READING

1196 Lighter Side of Medicine

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FROM THE DESK OF THE GROUP EDITOR-IN-CHIEF

Dr KK Aggarwal

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

The Mosquito Menace is Likely to be Back

Ask before visiting a place “Is your place free of mosquitoes?”

ases of dengue and Chikungunya have started to appear in the capital of India. Unfortunately, no alert has been issued and in sporadic cases, no surgical strikes have been attempted openly in selected breeding places.

Last year I wrote that we needed a paradigm shift in our thinking. We need to over report and act in time. There is no point acting when the cases have started. But even this year, cases have started without alerts and involvement of private sector.

Napoleon Hill once said, “Most great people have attained their greatest success just one step beyond their greatest failure.” It’s time for all of us to convert our biggest last year’s failure of controlling the mosquito menace into a success.

Are we again waiting to act in monsoon season?

We must all agree that collectively we failed last year in controlling the mosquito menace and consequently Delhi again is showing cases. This is again a collective failure of Municipal Corporation, Delhi Government, Central Government, LG office, Medical Associations, CSR departments, Media, NGOs and Private sector. The mosquito container index (the percentage of waterholding containers infested with larvae or pupae) now in Delhi is over 5% and had crossed 40% last year. Any index above 5% requires a community-integrated cluster approach to reduce mosquito density together with effective anti-larval measures. Last year, 3 lakhs mosquito repellent impregnated mosquito nets were distributed by MCD but what about this year. Last year, these nets were not available to actual patients. Even this year anti-larval measures, Temephos, an organophosphate larvicide and/or mosquito fish or Gambusia, a freshwater fish are not available to a common man.

Public awareness and public involvement must start if not started today. We need to act against all the mosquitoes, Aedes, Culex and Anopheles. Action against only the Aedes mosquito will not work. The campaign that Aedes mosquito is a day biter and only breeds in indoor fresh water will not work. Even if it is true, killing Aedes would increase the density of Culex and malaria causing Anopheles mosquitoes. Culex mosquito, which causes filarial and Japanese encephalitis is already rampant in the city. Even Aedes mosquito, which causes Chikungunya, West Nile, Zika and Dengue can spread by the bite of infected female indoor Aedes aegypti or outdoor Aedes albopictus mosquito. It is true that A. aegypti are more dangerous because they can fly up to 200 meters and only feed on human blood, whereas the A. albopictus that thrives outdoors can only fly as far as 80 meters and feed on animal blood other than human blood. The outdoor Aedes mosquito cannot be ignored. The entire campaign up till now has been focused on Aedes as a day biter, wearing long sleeves shirt and pants

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FROM THE DESK OF THE GROUP EDITOR-IN-CHIEF during the day and using night mosquito nets. But precautions need to be taken throughout the day as the mosquitoes only recognize ‘light’ and not whether it is day or night. The fact that the mosquito only breeds in clear water also needs to be relearnt. The Aedes mosquito breeds in stagnant water anywhere inside or outside the house. Rain water is the most important source and can collect in any plastic container inside or outside the house. Even collected garbage in open areas can have left over plastic cups or tiny bottle caps with rain water collections providing an ideal atmosphere for mosquito breeding. It is true that disease spreading mosquitoes do not make noise but the ‘noise-producing’ nuisance mosquitoes unless addressed will not create a public movement. The law says that dengue or Chikungunya cases must be notified, but one can notify them within 7 days of diagnosis. Aedes mosquito takes up to three meals in a day and within 7 days will bite over 21 people in the vicinity. Municipal anti-mosquito and anti-larval actions must occur within hours of its detection. The very purpose of notification is lost if the disease is not notified within hours of even suspecting a diagnosis of Chikungunya. So, all suspected cases must be reported without waiting to confirm the diagnosis. We have failed because the government has been insisting that only ELISA-confirmed cases be notified. An SMS should be sent to all doctors practicing in that PIN code area with a case so that they can become a part of the public health action chain. All public health measure should have started, right when the first case was suspected in Delhi. It has taken over a decade for us doctors to understand that dengue 1 and 3 strains are not dangerous and cause only platelet deficiency with thinning of blood, while dengue 2 and 4 strains are dangerous as they destroy platelets and thicken blood due to capillary leakage and rise in hematocrit. Also, that platelet transfusion is not required in absence of active bleeding and it is the timely fluid resuscitation that is more important and not platelet resuscitation. Dengue becomes serious when the fever is subsiding. Earlier, dengue patients with high fever were hospitalized and there was always an urgency to discharge them when fever was subsiding. Now we

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know that the machine reading of platelet count can be defective. There can be an error of 20%. A platelet count of 10,000 by machine reading can mean it is actually 50,000. Hospital beds should be reserved only for severe dengue and severe Chikungunya cases. Being able to claim reimbursement in Mediclaim or PSU, should not be the factor to decide on hospital admission. If it was US, Medicare by now would have come out with admission guidelines. The message that is being transmitted is that fogging has no answer. But when the container index is high, aerial fogging is also required and not just ground fogging. When Zika threat came up in Brazil they deployed the army to join and make it a public movement. All political parties reach every house during election process, then why can’t each one of them reach every house and make the anti-mosquito and anti-larval measures effective. Breeding checkers are only with Municipal Corporations and they also have regulatory powers to impose fine. We need breeding checkers in the private sector. The Skill development Ministry should start courses so that anyone can hire a breeding checker on weekly basis to check their premises. Community approach involves that 100% of the society talks about dengue. Every premise must write that their premises are mosquito-free. When you are invited to somebody’s place, you should ask “I hope your premises are mosquito-free” and when you invite somebody, write “Welcome to my house and it is mosquito-free”. Even today most hospitals do not provide mosquito nets to dengue or Chikungunya patients. While they may be having anti-larval mesh doors or mesh windows but for secondary prevention of dengue or Chikungunya, we need to ensure that medial establishments are certified mosquito-free. Many of us live in flats and the mosquitoes may be breeding on the roof top belonging to one of the owners of the flats and if he/she is out of station for a holiday, the anti-larval measures may remain deficient. RWAs should use their powers to check all unoccupied or closed premises including hostels, hotels and construction places in that premises. One of the five great vows of Jainism is Non-attachment/ Non-possession or Aparigraha. It talks about not storing unwanted things. But in today’s era, our roofs

FROM THE DESK OF THE GROUP EDITOR-IN-CHIEF and verandahs are littered with left over tires, utensils, plastic utensils, etc. We buy new car tires and keep the old ones on our roof top. We need to change this habit. We have forgotten to plant Tulsi and Peepal in our premises and stopped the daily Yagna, all of which have anti-mosquito properties. The new strategy has to focus on small collections of water such as bottle caps, finding mosquitoes lower in the room under the table or the bed, to look for them in all three parts of the house - roof tops, verandahs and inside the rooms including unused toilets accessories.

The slogan “Check your house once a week” needs a change. One should be alert every day. It should be a part of your routine. You do not clean your premises once a week. Make it a habit to look for the breeding places. War against indoor or outdoor mosquitoes; fresh stagnant or dirty water mosquitoes; small containers like bottle caps or large containers like overhead tankers; made of mud or plastic; throughout the day (early morning fogging when pupa hatch for Aedes, late night for malaria); scrubbing clean the utensils.

Ghar ke andar maro and ghar ke bahar maro … Din me maro, sham me maro and raat me maro … Deewaron ke niche maro or upar maro … Chote or bade pani ke collection me maro … Eggs ko maro, larvae ko maro, pupae ko maro aur mosquitoes ko maro … Chaat me maro, kamre me maro, veranda me maro … Pani ke niche maro, pani ke upar maro … Aedes ko maro, Culex ko maro aur Anopheles ko maro … ■■■■

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AMERICAN FAMILY PHYSICIAN

Acute Monoarthritis: Diagnosis in Adults JONATHAN A. BECKER, JENNIFER P. DAILY, KATHERINE M. POHLGEERS

ABSTRACT Acute monoarthritis can be the initial manifestation of many joint disorders. The most common diagnoses in the primary care setting are osteoarthritis, gout, and trauma. It is important to understand the prevalence of specific etiologies and to use the appropriate diagnostic modalities. A delay in diagnosis and treatment, particularly in septic arthritis, can have catastrophic results including sepsis, bacteremia, joint destruction, or death. The history and physical examination can help guide the use of laboratory and imaging studies. The presence of focal bone pain or recent trauma requires radiography of the affected joint to rule out metabolic bone disease, tumor, or fracture. If there is a joint effusion in the absence of trauma or recent surgery, and signs of infection (e.g., fever, erythema, warmth) are present, subsequent arthrocentesis should be performed. Inflammatory synovial fluid containing monosodium urate crystals indicates a high probability of gout. Noninflammatory synovial fluid suggests osteoarthritis or internal derangement. Pitfalls in the diagnosis and early treatment of acute monoarthritis include failure to perform arthrocentesis, administering antibiotics before aspirating the joint when septic arthritis is suspected (or failing to start antibiotics after aspiration), and starting treatment based solely on laboratory data, such as an elevated uric acid level.

Keywords: Acute monoarthritis, osteoarthritis, gout, trauma, septic arthritis, imaging studies

onoarthritis refers to the clinical presentation of pain or swelling in a single joint.1 The diagnosis can pose a considerable challenge in the primary care setting because the pain may be limited to the joint, or it may represent early manifestation of a systemic disease.2 Understanding the clinical clues associated with potential diagnoses and using an evidence-based, systematic clinical approach are of utmost importance.3 A delay in diagnosis and treatment, particularly with septic arthritis, can have catastrophic results including sepsis, bacteremia, joint destruction, or death.3-5 Pitfalls in the diagnosis and early treatment of acute monoarthritis include failure to perform arthrocentesis, administering antibiotics before aspirating the joint when septic arthritis is suspected (or failing to start antibiotics after aspiration), and starting treatment based solely on laboratory data, such as an elevated uric acid level.3-5

JONATHAN A. BECKER, MD, is an associate professor in the Department of Family and Geriatric Medicine and program director for the Family Medicine Residency at the University of Louisville (Ky.) School of Medicine. JENNIFER P. DAILY, MD, is an assistant professor in the Department of Family and Geriatric Medicine and associate director of the University of Louisville and Kentucky One Health Primary Care Sports Medicine Fellowship at the University of Louisville. KATHERINE M. POHLGEERS, MD, MS, is a primary care sports medicine fellow at the University of Louisville School of Medicine. At the time the article was submitted, Dr. Pohlgeers was a third-year family medicine resident at the University of Louisville School of Medicine. Source: Adapted from Am Fam Physician. 2016;94(10):810-816.

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ETIOLOGY OF ACUTE MONOARTHRITIS Any condition that may cause joint pathology can initially present as monoarthritis, resulting in a broad differential diagnosis1 (Table 16). Because of this, monoarthritis has no unifying etiology. The most common diagnoses in the primary care setting are osteoarthritis, gout, and trauma.3 Symptoms consistent with osteoarthritis include pain that tends to worsen with activity, morning stiffness lasting less than 30 minutes, and asymmetric joint pain.7 The most commonly affected joints are the hands, knees, hips, and spine.7 Although osteoarthritis often follows an insidious course, acute flare-ups are common and can be mistaken for other etiologies. The presence of focal bone pain or recent trauma requires radiography of the affected joint to rule out metabolic bone disease, tumor, or fracture.3,4 Gout is a common disorder with a 3% prevalence worldwide. It accounts for more than 7 million ambulatory visits in the United States annually.8,9 Crystalinduced arthritis presents as a rapidly developing monoarthritis with swelling and erythema, and most commonly involves the first metatarsophalangeal joint.8 Over time, the joint space can be irreversibly damaged with tophi formation.8,10 The presence of monosodium urate crystals indicates gout; these crystals are identified by their needle-like appearance and strong negative

AMERICAN FAMILY PHYSICIAN birefringence3,8 (Figure 16). Calcium pyrophosphate dihydrate crystals are polymorphic, weakly positive under birefringent microscopy, and their presence indicates pseudogout.3 Other crystal-induced arthritis etiologies include calcium oxalate and hydroxyapatite.1 Infection is a common etiology of joint pain. When infection is suspected in the presence of a joint effusion or inflammation, arthrocentesis should be performed, in addition to further laboratory testing as indicated (Figure 26). (A video of arthrocentesis of the knee is available at https://www.youtube.com/ watch?v=fZ2dcZhoGP8.) Gonococcal arthritis is the most common type of nontraumatic acute monoarthritis in young, sexually active persons in the United States.11 Septic arthritis is a key consideration in adults presenting with acute monoarthritis, particularly in the presence of joint pain, erythema, warmth, and immobility.12 The most important risk factors for septic arthritis are a prosthetic joint, skin infection, joint surgery, rheumatoid arthritis, age older than 80 years, diabetes mellitus, and renal disease.11 One study found that among persons presenting with acute joint pain and a predisposing condition, 10% had septic arthritis.4 When septic arthritis is suspected, it is important to begin empiric antibiotics immediately following arthrocentesis, because failure to initiate prompt antibiotic therapy can lead to subchondral bone loss and permanent joint dysfunction.5,11,12 The most common route of entry into the joint is hematogenous spread during bacteremia4,12-16; therefore, isolation of the causative agent through synovial fluid culture is essential for the diagnosis and guidance of antibiotic therapy.12 Less common causes of monoarthritis include systemic diseases such as spondyloarthropathies (e.g., psoriatic arthritis, reactive arthritis, ankylosing spondylitis), sarcoidosis, Behรงet syndrome, systemic lupus erythematosus, and rheumatoid arthritis.1 Rheumatic diseases and corticosteroid use can cause avascular necrosis of the bone.1 DIAGNOSING ACUTE MONOARTHRITIS The diagnosis of acute monoarthritis begins with a comprehensive history and physical examination to reveal potential diagnostic clues3,6,17 (Table 21,3,6,12,18,19). Key elements of the patient history include a review of systems, age, previous joint disease, recent trauma, medication use, family history of gout, concurrent illness, sexual history, diet, travel history, tick bites, alcohol use, intravenous drug use, and an occupational assessment.3,6,17

Symptoms that worsen with activity and improve with rest suggest a mechanical process, whereas symptoms with an inflammatory process often worsen with rest and present with morning stiffness.1 Osteoarthritis often starts as mild joint inflammation that may initially arouse suspicion for new-onset inflammatory diseases, such as rheumatoid arthritis.20 Morning stiffness and its duration in the affected joint, pain with activity or rest, recent history of trauma, history of previous joint symptoms, and family history of joint inflammation are all important factors that can help differentiate etiologies.12 Osteoarthritis typically worsens with activity, particularly after a period of rest (gelling phenomenon).18 Morning stiffness from osteoarthritis usually lasts for a shorter duration than that of rheumatoid arthritis, which typically lasts 45 minutes or more.7 A gout attack typically begins at night and peaks within 24 hours, causing pain, swelling, and erythema.20 Common clues from the patient history include obesity, a high-calorie diet, alcohol intake, and the use of loop and thiazide diuretics.8 Trauma may also precipitate an acute gout flare-up,8,21 and the presentation can closely resemble septic arthritis.20 Determining whether a condition is truly monoarticular can prove beneficial, because prodromal arthralgias can suggest infection.1 Gonococcal arthritis is often preceded by migratory arthritis and tenosynovitis before settling in a primary joint.1 Conducting a sexual history is imperative, as is documenting any urinary problems, purulent discharge from the urethra, or other signs of infection, such as pharyngitis.11,12 Risk factors such as intravenous drug use, tick bites, and travel history can lead to a diagnosis of infectious or reactive arthritis.1 Axial skeleton inflammatory arthritis (e.g., sacroiliitis) in addition to symptoms in a single peripheral joint suggest a spondyloarthropathy.1 Spondyloarthropathies can often present as monoarthritis and progress from joint to joint in a migratory or additive pattern.20 It is important to ask patients about other symptoms, such as enthesopathy (tenderness at the muscle or fascia attachment sites) and dactylitis (sausage-like swelling of fingers or toes), because these are common.20 Some patients also present with ocular inflammation (uveitis) and urethritis (Reiter syndrome).20 A history of skin conditions and a positive family history of inflammatory arthritis suggest psoriatic arthritis, which can present as monoarthritis in the early stages.20

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AMERICAN FAMILY PHYSICIAN PHYSICAL EXAMINATION The physical examination should focus on the involved and contralateral joints, the surrounding area, possible systemic manifestations, or polyarticular involvement.3,6,17 The first step is to confirm that the joint pain is truly localized and not a periarticular process, such as tendinitis, bursitis, or cellulitis.1 The presence of a joint effusion signifies intra-articular pathology, with patients typically reporting painful limitation of active and passive joint motion.1 A diagnosis of osteoarthritis can often be based on the history and physical examination.3 The characteristic presentation includes painful and limited range of motion, crepitus, effusions, instability, or deformities.18 Heberden and Bouchard nodes are pathognomonic for osteoarthritis. They result from hard, bony thickening that gradually forms around the distal and proximal interphalangeal joints of the fingers, respectively.20 The first carpometacarpal joint is one of the most common sites of osteoarthritis.20 Inflammatory arthritis elicits painful range of motion and erythema that is typically confined to the affected joint. Gout can present with intense erythema of the skin. It is often confused with cellulitis because this finding may extend past the joint margin.1,8 There are many superficial examination findings that can suggest specific diagnoses. Subcutaneous nodules (tophi) and podagra (gouty arthritis of the first metatarsophalangeal joint) are highly specific for gout.20 Erythema nodosum may be a manifestation of sarcoidosis or inflammatory bowel disease; psoriatic skin plaques are associated with psoriatic arthritis; and oral ulcers can indicate reactive arthritis or BehĂ§et syndrome.1 Septic arthritis is most likely to seed within a larger joint,1,22 and to be accompanied by erythema, warmth, and immobility.12 Although clinical manifestations have low sensitivity,12 acute monoarthritis with fever should be considered to have a bacterial etiology until proven otherwise because of the potential consequences of inadequate treatment.20 For example, morbidity associated with septic arthritis includes functional deterioration, arthrodesis, and amputation11,12; the mortality rate is 10% to 20%.12 DIAGNOSTIC TESTS Because the causes of acute monoarthritis vary widely, a stepwise approach to diagnosis can aid decision making (Figure 26). In the setting of trauma,

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radiography of the affected joint is required to rule out dislocation or fracture before performing active physical examination maneuvers.1 Radiography can also show signs of osteoarthritis, such as joint space narrowing, osteophytes, and subchondral sclerosis.1 If a joint effusion is present in the absence of traumatic injury, arthrocentesis should be performed, particularly when other inflammatory signs are present and there is a reasonable concern for infection (e.g., fever, erythema, warmth).1 Analysis of synovial fluid distinguishes infectious and inflammatory causes of acute monoarthritis (e.g., rheumatoid, septic, and crystal-induced arthritis) from noninflammatory causes (e.g., trauma, osteoarthritis).3,4,11,14 Analysis should include cell count and differential, white blood cell count, Gram stain, cultures, and crystal evaluation.1,4 Many cases of acute gouty arthritis are diagnosed without synovial fluid analysis.23 To improve the predictive value of clinical diagnosis, a gout calculator has been developed24,25 (Table 324). Seven predictive variables are included in this rule, and a scoring system has been developed to guide the decision to treat the patient for gout, pursue synovial fluid analysis, or search for other causes.24,25 A complete blood count and uric acid level can also aid in the diagnosis, especially if synovial fluid cannot be successfully obtained.3,19 A synovial fluid white blood cell count greater than 50,000 per mm3 (50.0 Ă&#x2014; 109 per L) with at least 90% neutrophils is the most useful laboratory finding for making an early diagnosis of septic arthritis.3 This traditional cutoff lacks sensitivity because there can be wide overlap with inflammatory conditions, but higher white blood cell counts in the synovial fluid have a greater association with septic arthritis.1,26 Staphylococci and streptococci are the most common bacterial causes at 40% and 28%, respectively, and their presence may suggest drug abuse. These organisms are also associated with cellulitis, endocarditis, and chronic osteomyelitis.12,27,28 Gram-stain results should guide initial antibiotic choice. Gram-negative organisms account for 10% to 21% of cases of septic arthritis.1,12,29 Mycobacterial and fungal arthritis typically present in immunocompromised patients, and Lyme arthritis often presents as a late manifestation of Lyme disease.1,12,30 Special consideration should be given to patients with prosthetic joint infection because the cutoff values for infection may be as low as 1,100 white blood cells per mm3

AMERICAN FAMILY PHYSICIAN (1.1 × 109 per L), with a neutrophil differentiation greater than 65%.3 Gonococci are cultured from joints in fewer than 50% of cases of gonococcal arthritis1,31,32; therefore, it is often necessary to obtain cultures from appropriate mucosal sites of infection.1,31,32 Noninflammatory synovial fluid (less than 2,000 cells per mm3 [2.0 × 109 per L]) is suggestive of osteoarthritis or internal derangement.1 Inflammatory synovial fluid containing monosodium urate crystals is highly suggestive of gout, particularly in the presence of podagra; however, the absence of crystals does not exclude crystal-induced arthritis, such as pseudogout.23,24 Erythrocyte sedimentation rate and C-reactive protein level are often elevated in inflammatory conditions.19,33 Literature comparing these two values is limited; however, it has been determined that these tests are more useful for following a disease course than discriminating the presence or absence of the disease.19,33 Note: For complete article visit: www.aafp.org/afp. REFERENCES 1. Gorn AH, Brahn E. Monoarticular arthritis (diagnostic approach). Essential Evidence Plus; 2015. http://www. essentialevidenceplus.com/content/eee/702[login required]. Accessed July 11, 2016. 2. Jeong H, Kim AY, Yoon HJ, et al. Clinical courses and predictors of outcomes in patients with monoarthritis: a retrospective study of 171 cases. Int J Rheum Dis. 2014;17(5):502-510. 3. Ma L, Cranney A, Holroyd-Leduc JM. Acute monoarthritis: what is the cause of my patient’s painful swollen joint? CMAJ. 2009;180(1):59-65. 4. Margaretten ME, Kohlwes J, Moore D, Bent S. Does this adult patient have septic arthritis? JAMA. 2007;297(13):1478-1488. 5. Mathews CJ, Weston VC, Jones A, Field M, Coakley G. Bacterial septic arthritis in adults. Lancet. 2010;375(9717):846-855. 6. Siva C, Velazquez C, Mody A, Brasington R. Diagnosing acute monoarthritis in adults: a practical approach for the family physician. Am Fam Physician. 2003;68(1):83-90. 7. Manek NJ, Lane NE. Osteoarthritis: current concepts in diagnosis and management. Am Fam Physician. 2000;61(6):1795-1804. 8. Hainer BL, Matheson E, Wilkes RT. Diagnosis, treatment, and prevention of gout. Am Fam Physician. 2014;90(12):831-836. 9. Smith E, Hoy D, Cross M, et al. The global burden of gout: estimates from the Global Burden of Disease 2010 study. Ann Rheum Dis. 2014;73(8):1470-1476.

10. Schlesinger N, Thiele RG. The pathogenesis of bone erosions in gouty arthritis. Ann Rheum Dis. 2010;69(11):1907-1912. 11. Goldenberg DL. Septic arthritis. Lancet. 1998;351(9097): 197-202. 12. Horowitz DL, Katzap E, Horowitz S, Barilla-LaBarca ML. Approach to septic arthritis. Am Fam Physician. 2011;84(6):653-660. 13. Cooper C, Cawley MI. Bacterial arthritis in an English health district: a 10 year review. Ann Rheum Dis. 1986;45(6):458-463. 14. McCarthy DJ. Joint sepsis: a chance for cure. JAMA. 1982;247(6):835. 15. Ross JJ, Saltzman CL, Carling P, Shapiro DS. Pneumococcal septic arthritis: review of 190 cases. Clin Infect Dis. 2003;36(3):319-327. 16. Smith JW, Piercy EA. Infectious arthritis. Clin Infect Dis. 1995;20(2):225-230. 17. Baker DG, Schumacher HR Jr. Acute monoarthritis. N Engl J Med. 1993;329(14):1013-1020. 18. Sinusas K. Osteoarthritis: diagnosis and treatment [published correction appears in Am Fam Physician. 2012;86(10):893]. Am Fam Physician. 2012;85(1):49-56. 19. Waits JB. Rational use of laboratory testing in the initial evaluation of soft tissue and joint complaints. Prim Care. 2010;37(4):673-689, v. 20. Luosujärvi R. Disease-specific signs and symptoms in patients with inflammatory joint diseases. Essential Evidence Plus; 2013. http://www.essentialevidenceplus. com/content/ebmg_ebm/440 [login required]. Accessed July 11, 2016. 21. Pittman JR, Bross MH. Diagnosis and management of gout. Am Fam Physician. 1999;59(7):1799-1806, 1810. 22. Morgan DS, Fisher D, Merianos A, Currie BJ. An 18 year clinical review of septic arthritis from tropical Australia. Epidemiol Infect. 1996;117(3):423-428. 23. Janssens HJ, Fransen J, van de Lisdonk EH, van Riel PL, van Weel C, Janssen M. A diagnostic rule for acute gouty arthritis in primary care without joint fluid analysis. Arch Intern Med. 2010;170(13):1120-1126. 24. Kienhorst LB, Janssens HJ, Fransen J, Janssen M; British Society for Rheumatology. The validation of a diagnostic rule for gout without joint fluid analysis: a prospective study. Rheumatology (Oxford). 2015;54(4):609-614. 25. Krishnan E, Svendsen K, Neaton JD, Grandits G, Kuller LH; MRFIT Research Group. Long-term cardiovascular mortality among middle-aged men with gout. Arch Intern Med. 2008;168(10):1104-1110. 26. Li SF, Henderson J, Dickman E, Darzynkiewicz R. Laboratory tests in adults with monoarticular arthritis: can they rule out a septic joint? Acad Emerg Med. 2004;11(3):276-280.

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AMERICAN FAMILY PHYSICIAN 27. Ryan MJ, Kavanagh R, Wall PG, Hazleman BL. Bacterial joint infections in England and Wales: analysis of bacterial isolates over a four year period. Br J Rheumatol. 1997;36(3):370-373. 28. Deesomchok U, Tumrasvin T. Clinical study of cultureproven cases of non-gonococcal arthritis. J Med Assoc Thai. 1990;73(11):615-623.

30. Steere AC, Schoen RT, Taylor E. The clinical evolution of Lyme arthritis. Ann Intern Med. 1987;107(5):725-731. 31. Wise CM, Morris CR, Wasilauskas BL, Salzer WL. Gonococcal arthritis in an era of increasing penicillin resistance. Presentations and outcomes in 41 recent cases (1985-1991). Arch Intern Med. 1994;154(23):2690-2695.

32. 29. Dubost JJ, Soubrier M, De Champs C, Ristori JM, Bussiére JL, Sauvezie B. No changes in the distribution 33. of organisms responsible for septic arthritis over a 20 year period. Ann Rheum Dis. 2002;61(3): 267-269. ■■■■

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Bardin T. Gonococcal arthritis. Best Pract Res Clin Rheumatol. 2003;17(2):201-208. Guidelines for the initial evaluation of the adult patient with acute musculoskeletal symptoms. American College of Rheumatology Ad Hoc Committee on Clinical Guidelines. Arthritis Rheum. 1996;39(1):1-8.

AMERICAN FAMILY PHYSICIAN

Practice Guidelines SOCIETY FOR VASCULAR SURGERY RELEASES GUIDELINE ON MANAGING THE DIABETIC FOOT The diabetic foot is a key area of morbidity associated with diabetes mellitus. The Society for Vascular Surgery collaborated with the American Podiatric Medical Association and the Society for Vascular Medicine to create evidence-based guidelines to improve the care of patients with a diabetic foot. Although there is limited high-quality evidence, the guidelines use the best available evidence and consider patient preference and clinical context. The authors used the Grades of Recommendation Assessment, Development, and Evaluation system to rate the evidence, which identified stronger recommendations for which the benefits outweigh the risks and weaker recommendations for which the ratio of benefits to risks is dependent on the clinical scenario.

Prevention of Diabetic Foot Ulcers Stronger Recommendations Patients with diabetes should have an annual foot evaluation performed by a physician or clinician with training in foot care. The evaluation should include the Semmes-Weinstein monofilament test to assess for peripheral neuropathy. Patients and families should be educated about preventative foot care. Custom therapeutic footwear is recommended for high-risk patients, such as those with significant neuropathy, foot deformities, or previous amputations. Prophylactic arterial revascularization is not recommended for preventing diabetic foot ulcers. Weaker Recommendations Custom therapeutic footwear is not recommended for average-risk patients. To lower the risk of diabetic foot ulcers, glycemic control should be maintained (A1C level of less than 7%), with strategies to minimize hypoglycemia.

Offloading for Patients with Diabetic Foot Ulcers Stronger Recommendations A total contact cast or irremovable fixed ankle walking boot should be used for offloading in patients with Source: Adapted from Am Fam Physician. 2016;94(10):834-835.

plantar diabetic foot ulcers. In patients with nonplantar wounds, any modality that relieves pressure at the ulcer site can be used, such as a surgical sandal or heel relief shoe. To prevent recurrence after a healed diabetic foot ulcer in high-risk patients, those with a history of diabetic foot ulcer, partial foot amputation, or Charcot foot, therapeutic footwear with pressurerelieving insoles is recommended. Weaker Recommendations If frequent dressing changes are required, a removable cast walker can be used. Postoperative shoes and standard or customary footwear should not be used for offloading plantar ulcers.

Diagnosis of Diabetic Foot Osteomyelitis Stronger Recommendations If more sensitive or specific imaging is needed, particularly if soft tissue abscess is suspected or the diagnosis of osteomyelitis is uncertain after standard imaging, magnetic resonance imaging is recommended. In patients at high risk of diabetic foot osteomyelitis, the diagnosis should be confirmed using bone culture and histology findings; a sample can be taken when the bone is debrided. Weaker Recommendations In patients with an open-wound diabetic foot infection, a probe-to-bone test should be performed to aid in the diagnosis. In all patients with a new infection, serial plain radiography should be used to identify bone abnormalities, soft tissue gas, and foreign bodies. If additional imaging is needed in a patient with suspected diabetic foot osteomyelitis and magnetic resonance imaging cannot be used, the best alternative is a leukocyte or antigranulocyte scan, ideally in conjunction with a bone scan. If debridement is not performed, diagnostic bone biopsy should be considered if there is diagnostic uncertainty or inadequate culture information, or if empiric treatment is ineffective.

Wound Care for Diabetic Foot Ulcers Stronger Recommendations Diabetic foot ulcers should be evaluated every one to four weeks, with measurement of wound size

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AMERICAN FAMILY PHYSICIAN to assess healing progress. The patient should be evaluated for infection at presentation, with sharp debridement of devitalized tissue and surrounding callus material (initially and at one- to four-week intervals). Additionally, urgent surgical intervention for infections involving abscess, gas, or necrotizing fasciitis should be pursued. Dressing products should be used that maintain a moist wound bed, control exudate, and avoid maceration of intact skin. Treatment should follow current Infectious Diseases Society of America guidelines. If there is inadequate improvement (less than a 50% reduction in the wound area) after four weeks of standard care, then vascular status, infection control, and offloading should be reevaluated, and adjunctive therapy considered. Choice of therapy should be based on clinical findings, availability, and cost-effectiveness. Options include negative pressure therapy, biologics (e.g., platelet-derived growth factor, living cellular therapy, extracellular matrix products, amniotic membrane products), and hyperbaric oxygen therapy. Weaker Recommendations Because evidence is lacking regarding the superiority of debridement techniques, sharp debridement is the recommended method with subsequent choices made based on clinical context, availability, patient tolerance and preference, and cost-effectiveness. Negative pressure wound therapy is recommended for chronic wounds that do not heal adequately after four to

eight weeks of using standard or advanced dressings. The following therapies should be considered for recalcitrant wounds: platelet-derived growth factor (becaplermin), living cellular therapy, and extracellular matrix products. Hyperbaric oxygen therapy is recommended for recalcitrant wounds in patients with adequate perfusion.

Diabetic Foot Ulcer and Peripheral Arterial Disease Stronger Recommendations In patients with diabetic foot ulcers, pedal perfusion should be assessed annually using ankle-brachial index measurement, ankle and pedal Doppler arterial waveforms, and toe systolic pressure or transcutaneous oxygen pressure. In concomitant peripheral arterial disease, revascularization with surgical bypass or endovascular therapy should be performed. Weaker Recommendations In patients with diabetes, ankle-brachial index measurements should begin at 50 years of age. An annual vascular examination of the lower extremities and feet, including ankle-brachial index and toe pressure measurements, is recommended in patients with diabetes and a history of diabetic foot ulcers, abnormal vascular examination, intervention for peripheral vascular disease, or known atherosclerotic cardiovascular disease.

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AMERICAN FAMILY PHYSICIAN

Photo Quiz SWELLING AND ERYTHEMA OF THE SCALP ON A TEENAGER A 16-year-old boy presented with swelling and erythema on the scalp that had worsened over the previous four weeks. Three to four months prior to the development of the swelling, he noted a red circular rash on the same area of his scalp. The rash resolved with application of an over-the-counter antifungal cream. After resolution of the rash, the swelling and erythema began, and the area became painful. He did not have a fever or chills, and there was no discharge from the site. The patient was otherwise healthy and active, and was a member of his school’s wrestling team. Examination of the scalp revealed an area of erythema and induration (Figure 1). The scalp was tender to palpation but not fluctuant. There was no cervical or occipital lymphadenopathy. Ultrasonography showed no fluid collection in the lesion.

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

Figure 1.

A. Id reaction. B. Kerion. C. Pustular psoriasis. D. Staphylococcal abscess.

SEE THE FOLLOWING PAGE FOR DISCUSSION.

Source: Adapted from Am Fam Physician. 2016;94(10):836-842.

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AMERICAN FAMILY PHYSICIAN Discussion

Summary Table

The answer is B: kerion. Kerions are the result of an inflammatory response to an invasive fungal infection of the hair follicles and scalp. The fungus is usually a dermatophyte such as Trichophyton verrucosum or Trichophyton mentagrophytes.1 Presentation ranges from a raised, spongy lesion to an extremely painful indurated lesion.1 Kerions are commonly mistaken for a staphylococcal abscess, but the absence of fever and fluctuance can help to distinguish them from a bacterial infection. The initial rash is red and circular, which is typical of tinea capitis, a Trichophyton infection that often occurs in wrestlers.

Condition

Characteristics

Id reaction

Intensely pruritic, symmetric, maculopapular or papulovesicular rash; can have widespread follicular pustules

Kerion

Raised, spongy lesion that is painful and sometimes indurated; typically associated with tinea capitis

Pustular psoriasis

White pustules surrounded by erythematous skin; autoimmune etiology

Staphylococcal abscess

Area of redness and induration with painful fluctuance; associated with fever and other systemic symptoms

If the fungal infection is untreated, alopecia and scarring may develop. The first-line therapy is oral griseofulvin.2 Topical treatment is not effective because of the depth of the fungal infection. Although bacterial infections can occur with kerions, they are uncommon. Fever, chills, and malaise are common signs of a superimposed bacterial infection, and the lesion is typically fluctuant.3 When there is concern for bacterial superinfection, an antibiotic that covers Staphylococcus and Streptococcus should be used in addition to griseofulvin. An id reaction, also known as disseminated eczema or autoeczematization, is a generalized acute eczematous reaction that can be triggered by a variety of stimuli, including infection or inflammation. It typically presents as an intensely pruritic, symmetric, maculopapular or papulovesicular rash. Widespread follicular pustules are possible. A focal circular lesion without scaling or lichenification would be an unlikely presentation. An id reaction responds to treatment of the underlying cause.4 Pustular psoriasis is a rare form of the autoimmune disease psoriasis, characterized by white pustules surrounded by erythematous skin. It can be generalized or focal, and has a cyclic nature with reddening of the skin followed by pustule eruption.5

fluctuance. Ultrasonography is helpful to identify fluid collection. An abscess is typically associated with fever and other systemic symptoms.3,6 REFERENCES 1. Fuller LC, Child FJ, Midgley G, Higgins EM. Diagnosis and management of scalp ringworm. BMJ. 2003;326(7388): 539-541. 2. Trovato MJ, Schwartz RA, Janniger CK. Tinea capitis: current concepts in clinical practice. Cutis. 2006;77(2): 93-99. 3. Cheng AG, DeDent AC, Schneewind O, Missiakas D. A play in four acts: Staphylococcus aureus abscess formation. Trends Microbiol. 2011;19(5):225-232. 4. Evans MP. Id reaction (autoeczematization). Updated August 5, 2016. Medscape. http://www.emedicine. medscape.com/article/1049760-overview. Accessed September 8, 2016. 5. Borges-Costa J, Silva R, Gonçalves L, Filipe P, Soares de Almeida L, Marques Gomes M. Clinical and laboratory features in acute generalized pustular psoriasis: a retrospective study of 34 patients. Am J Clin Dermatol. 2011;12(4):271-276.

6. Kemper AR, Dolor RJ, Fowler VG Jr. Management of skin abscesses by primary care pediatricians. Clin Pediatr (Phila). 2011;50(6):525-528. ■■■■

A staphylococcal abscess can present on the scalp with redness and induration but would likely have painful

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CARDIOLOGY

A Study of Novel Risk Factors, Clinical and Angiographic Profile of Acute Myocardial Infarction in Young Patients Below 35 Years DHARMENDRA JAIN*, GEETHA SUBRAMANIAN†, RAJPAL PRAJAPATI‡

ABSTRACT Objective: Acute coronary syndrome below 35 years of age is rare and constitutes a specific subset of population having different risk factors and clinical features as compared to older patients. Pattern of coronary artery involvement and clinical outcome also varies suggesting different underlying pathophysiology. Better understanding of this specific problem will lead to further improvement in management. Methods: Over a period of 1 year, 40 consecutive patients diagnosed to have acute myocardial infarction and who were below 35 years of age were enrolled in the study. Clinical parameters, risk factors, angiographic patterns were analyzed. Results: Out of total patients studied, 80% were males and 20% females, 75% were smokers, 65% were dyslipidemic, hyperhomocysteinemia was present in 42.5%, hypertension in 30% and diabetes in 15%. There was history of recreational drug abuse in 2.5% of patients. Anterior wall myocardial infarction was presentation in 75%, inferior wall in 20% and anterior plus inferior in 5% patients. Single vessel disease (65%) was the most common finding in coronary angiography and 20% patients had normal or nonobstructive coronary lesions. Conclusions: In young acute myocardial infarction patients, smoking is the single most important modifiable risk factor. Other conventional risk factors are less strongly associated than older patients. Young patients tend to have less extensive coronary artery lesions. In few patients, presence of normal or nonobstructive coronary lesions would suggest possibility of different mechanism of myocardial necrosis. Overall, these patients had favorable outcome and better prognosis.

Keywords: Acute coronary syndrome, acute myocardial infarction, risk factors

t is predicted that more than half the worldwide cardiovascular disease (CVD) risk burden will be borne by Indian subcontinent in the next decade, according to a recent epidemiological study.1 Coronary artery disease (CAD) in the Indian subcontinent has been reported to manifest almost a decade earlier than in the West.2 Moreover, deaths related to CAD occur 5-10 years earlier in the Indian subcontinent than in Western countries.3 The incidence of CAD in the young has been reported to be 12-16% in Indians.4,5 The association of

*Assistant Professor †Professor and Head ‡Senior Resident Dept. of Cardiology Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh Address for correspondence Dr Dharmendra Jain C-2, New Medical Enclave, Near Naria Gate Banaras Hindu University, Varanasi - 221 005, Uttar Pradesh E-mail: djaincard@gmail.com

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smoking, dyslipidemia, hypertension, diabetes, central obesity and a positive family history with CAD are wellestablished risk factors with premature CAD.6,7 Newer risk factor like higher levels of lipoprotein(a) or Lp(a), homocysteine and high-sensitivity C-reactive protein (hsCRP) are associated with premature CAD with weak supportive evidence.8,9 Small studies comparing younger and older patients with myocardial infarction (MI) show that young patients are discharged with higher ejection fractions (EF), have fewer comorbidities and are more likely to return to work. Also, short-term mortality studies indicate that these patients have a more favorable outcome.10,11 METHODS

Study Area The study was carried out on patients admitted with acute MI (AMI) in the Dept. of Cardiology at SS Hospital, Institute of Medical Sciences (IMS), Banaras Hindu University (BHU), Varanasi.

CARDIOLOGY Study Population

Table 1. Baseline Characteristics

This is a hospital-based study done on patients, 35 years or younger, admitted to hospital with AMI. A detailed clinical history, physical examination, electrocardiography (ECG), biochemical and echocardiographic evaluation was done using a pretest proforma.

Parameters

Observations (n = 40)

Age (mean)

Male - 33.12 years (n = 32),

Inclusion Criteria All patients aged 35 years or younger admitted to the Dept. of Cardiology at SS Hospital, IMS, BHU, Varanasi diagnosed with AMI. The final diagnosis of AMI was based on the following criteria: ÂÂ

Ischemic chest pain lasting 20 minutes or more

ÂÂ

ECG evidence of myocardial injuryzz

ÂÂ

≥0.1 mv ST elevation in two contiguous leads other than V2-V3 where the cut-off point of ≥0.2 mv in men ≥40 years; ≥0.25 mv in men <40 years or ≥0.15 mv in women New horizontal or down sloping ST depression ≥0.05 mv in two contiguous leads and/or T wave inversion ≥0.1 mv in two contiguous leads with prominent R wave or R/S ratio >1.

Females - 32.12 years (n = 8) Hypertension

30% (n = 12)

Diabetes mellitus

15% (n = 6)

Smoking

70% (n = 28)

Family history

12.5% (n = 5)

Dyslipidemia

65% (n = 26)

Homocysteine (>15 µmol/L)

42.5% (n = 17)

Lp(a) (>30 mg/dL)

27.5% (n = 11)

CRP (positive)

47.5% (n = 19)

Type of MI on ECG

Anterior - 75% (n = 30) Inferior - 20% (n = 8) Ant + Lateral - 5% (n = 2)

LVEF

>40% = 45% (n = 18) Angiography pattern

As depicted in (Table 1) total of 40 patients included in this study with age ≤35 years. The mean age at presentation was 33.12 years for men and 32.12 years for women, 82% patients belonged to 31-35 years group, 5% patients belonged to age <25 years. Out of this, 80% patients were male and 20% patients were female. The most common symptom in young patients with AMI was chest pain, which was present in 95% of the patients, followed by sweating (20%) and breathlessness (7.5%). Smoking was the most common risk factor for AMI (70%), while hyperlipidemia was the second common risk factor for AMI (65%). Thirty percent of patients had body mass index (BMI) of >25 kg/m-2. Fifteen percent of the patients were diabetic, of which 10% were newly detected. Hypertension was present in 30%, while family history of premature CAD was present in 12.5%. Sixty percent of the patients had multiple risk factors for AMI, 26% had a single risk factor, while 4% had none of the risk factors. Substance abuse (cocaine) was present in 2.5%. Lp(a) levels were high (>30 mg/dL) in 27.5% of the patients. The mean Lp(a) was 25.63 mg/dL. Homocysteine level was above normal (>15 µmol/L) in 42.5% patients

Normal coronary - 20% (n = 8) Single vessel - 65% (n = 26) Double vessel - 12.5% (n = 5)

Positive biomarkers: CK-MB, cardiac troponins.

RESULTS

≤40% = 55% (n = 22)

Triple vessel - 2.5% (n = 1)

of which 22.5% patients had homocysteine level between 15-30 µmol/L and 20% had levels between 30-100 µmol/L. The mean level was 21.11 µmol/L. Anterior wall MI was found in 75% patients, 20% patients had inferior wall MI, while 5% of patients had anterolateral MI. On coronary angiography, 65% patients had single vessel disease, 12.5% had double vessel disease, 20% had normal coronaries and 2.5% had multivessel disease. Left anterior descending (LAD) was involved in 62.5%, right coronary artery (RCA) in 22.5% and left circumflex (LCx) in 7.5%. Inflammatory marker C-reactive protein was positive in 47.5% patients. DISCUSSION AMI is rare before 35 years of age, but there is a rising trend in young population now-a-days. Most of the patients belonged to higher range of age group that is 31-35 years, which contributed 82% of the patients and only 5% of the patients were below 25 years of age. The mean age was 32.12 years for females and 33.12 years for males. The distribution of age group showed a striking increase in the disease with

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CARDIOLOGY increasing age. Thus, in accordance to previous studies which also showed increasing trend with increasing age even in young patients. In a study done by SriCharan et al12 also the maximum numbers of the patients (70%) were within in the age of 35-40 years and 3.33% patients being in the age group of 25-30 years. Also in a study by Prajapati et al, the mean age was 34.5 ± 4.7 years.13 Male sex is an important risk factor for CAD. In t h e present study, 80% of the patients were male. Similarly in a study by Prajapati et al13 also 89.9% patients were male. Thus, the demographic profile of present study was similar to previous studies. Tobacco smoking is an established coronary risk factor for CAD. Casual association between tobacco chewing (smokeless tobacco) and CAD is found in some casecontrol studies.14 Tobacco increases the risk of CVD by raising blood pressure, damaging vascular endothelium, increasing low-density lipoprotein cholesterol (LDL-C) oxidation and lowers the high-density lipoprotein cholesterol (HDL-C). Smoking was found to be most prevalent risk factor (70%) in the present study. This was similar to a previously reported prevalence of 77% in Swiss patients aged ≤35 years by Schoenenberger and colleagues.15 Studies done in India (Prajapati et al, SriCharan et al and Jamil et al) also showed that smoking was the most prevalent risk factor.12,16,17 Thus, an effort should be made to educate people about the hazards of cigarette smoking and people should be educated at an early age to avoid smoking and smoking cessation programs need to be established. In the present study, 15% of the patients were diabetic, of which 10% were newly detected and hypertension was present in 30% of the patients. BMI >25 kg/m2 was seen in 30% of the patients. Family history of premature CAD was present in 12.5% of the patients. In a study done in London among young patients with MI, positive family history of premature coronary heart disease ( CHD) was found in 39% of participants.18 In a study by Zimmerman et al, family history of CAD was more common only in young men,11 while in young patients with MI, positive family history of premature CAD was found in 39% participants. Study by SriCharan et al12 and Jamil et al16 also showed similar trend. However, in the study by Hassan et al, when compared to diabetes mellitus (12%), hypertension was more prevalent (40%).19 In the present study also hypertension (30%) was more prevalent as compared to diabetes mellitus (15%). The excess burden of CAD

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among South Asians appears to be primarily due to dyslipidemia that is characterized by: High levels of triglycerides (TGs), Lp(a), borderline high levels of LDL-C, low levels of HDL-C. Total cholesterol (TC) level and LDL-C levels are correlated with extent and severity of CAD in Asian Indians as in whites. But at any given TC or LDL-C level, Asian Indians have a greater CAD risk than whites. In the present study, hyperlipidemia was present in 65% of the patients, with 45% of the patients having increased LDL-C levels and LDL-C levels were in very high range in 12.5% of the patients. HDL-C level was below 40 mg/dL in 60% of patients. In previous studies also, hyperlipidemia was found to be a common risk factor. In a study by SriCharan et al, hyperlipidemia was the second most common risk factor (36.67%).12 Hyperlipidemia was documented in 46% of study population in the study by Hassan et al.19 Similar results were obtained in study by Prajapati et al.13 Therefore, Asian Indians with dyslipidemia should be treated as aggressively as if they had a CAD risk equivalent–similar to the treatment of patients with diabetes or heart disease. Lp(a) appears to be a major risk factor in Asian Indians as compared to whites. Elevated Lp(a) found in 35-40% of all Indians.20 High Lp(a) levels are highly correlated with the severity of ACS, recurrent events, poor prognosis and increased mortality.20 A high level of Lp(a) is shown to be the most prevalent dyslipidemia in our young patients with premature CAD. Lp(a) levels are governed almost exclusively by race, ethnicity and genetics, unlike other lipids, where the levels are influenced by age, gender, diet and other environmental factors. The effect of Lp(a) on the atherogenicity is not additive but multiplicative. It constitutes an important inherited risk factor for atherosclerosis and is also regarded as biological marker for familial CAD. In the present study, Lp(a) levels were above 30 mg/dL in 27% of the patients representing an important risk factor in young patients with MI. In the study by Prajapati et al, 21.5% patients had high levels of Lp(a)13 similar to present study. Similarly in the studies by Schaefer et al (elevated in 21.5% of patients) and by Isser et al, the Lp(a) levels were significantly higher in young patients with MI as compared with controls.21,22 In the present study, the mean Lp(a) level was 25.63 mg/dL, whereas in a study by Kamariya et al and Prajapati et al the mean Lp(a) levels were 44.04 ±

CARDIOLOGY 8.52 mg/dL and 37.1 Âą 31.9 mg/dL in young patients with MI.13,23 The lower mean level of Lp(a) in present study may be due to the fact most of the patients had levels skewed around 26-30 mg/dL. Homocysteine levels are higher among Asian Indians than others. In India, most people adhere to a vegetarian diet and vegetarians have 3 times higher risk of hyperhomocysteinemia compared to those who eat nonvegetarian food. In the present study, homocysteine levels were above normal in 42.5% of the patients; whereas, homocysteine levels were elevated in 72.55% of the patients in study done by Puri et al.24 Also in the study done by Arumalla et al,25 hyperhomocysteinemia was found in 66% of the patients with AMI. So, one should encourage higher intake of fruits and avoid overcooking of vegetables to prevent hyperhomocysteinemia. Present study showed that 60% patients had multiple risk factors, 36% had a single risk factor and 4% of the patients had no risk factors. In the study by SriCharan et al,12 46.67% of the patients had multiple risk factors for AMI, 46.67% had a single risk factor, while 6.67% had none of the risk factors. The most common presenting complaint in the present study was chest pain (95%) followed by sweating (20%) and breathlessness (7.5%). The study by SriCharan et al showed that the most common symptom was chest pain, which was present in 90% of the patients, followed by sweating (50%), breathlessness (20%), restlessness (6.7%) and palpitations (3.3%).12 However, in study by Hassan et al, 69% of the patients denied any chest pain.19 The chest pain was absent in the present study mainly in females and diabetics. In t h e present study, most common presentation was with anterior wall MI, which was found in 75% of the patients. It was followed by inferior wall MI in 20% and anterolateral wall M I in 5% of the patients. These results are similar to the prior studies done by Sricharan et al and Prajapati et al, where also anterior wall MI was t h e most common presentation followed by inferior wall MI. 12,13 Regarding coronary angiography, LAD was the most common artery involved (67.5%) followed by RCA (22.5%). Prior studies also (Hassan et al, Jamil et al, Sricharan et al)12,16,19 showed LAD as the most common artery involved followed by RCA and LCx. In the present study, single vessel disease (SVD) was seen in 65%, normal coronary in 20%, double vessel disease (DVD) in 12.5% and multivessel in 2.5%. Study by SriCharan et al, shows pattern similar to our study;

majority of the patients (57.14%) had SVD, followed by normal coronaries (22.45%), 16.3% had DVD and 4% patients had multivessel disease.12 SUMMARY AND CONCLUSIONS Although AMI is less common in young adults <35 years of age, it constitutes an important problem for both the patient and the treating physician. The young patients have different risk factor profile, clinical presentation, angiographic presentation and prognosis in comparison to older patients. In this study, most of the patients were male suggesting male sex as a risk factor for the occurrence of AMI in young. Smoking remained the most prevalent risk factor in young AMI patients with cocaine abuse contributing further to the increased risk amongst youngsters. Next common risk factor was dyslipidemia characterized by high levels of TG, Lp(a), borderline elevation of LDL-C and low levels of HDL-C. Regarding novel risk factors for accelerated atherosclerosis, Lp(a) and hyperhomocysteinemia contributed as important risk factors AMI apart from traditional risk factors. These risk factors usually get underdiagnosed. More detailed investigations of these risk factors should be done. These risk factors can be genetically determined, so these should be properly evaluated in children of families with premature CAD. Female patients tends to have higher prevalence of diabetes and multiple risk factors when they present with AMI at younger age. A sizeable proportion of the patients had normal coronaries. Since, young person form the main working population of the country and are the main financial back-up of their families, important steps should be taken to keep them healthy and prevent such a devastating disease to occur in them at an early age. The most important thing is to do risk factor modification, which is a quite challenging task. Since, cigarette smoking is highly prevalent in young, preventive educational programs along with smoking cessation clinics need to be established. REFERENCES 1. Gupta R, Joshi P, Mohan V, Reddy KS, Yusuf S. Epidemiology and causation of coronary heart disease and stroke in India. Heart. 2008;94(1):16-26. 2. Gupta R. Burden of coronary heart disease in India. Indian Heart J. 2005;57(6):632-8. 3. Joshi P, Islam S, Pais P, Reddy S, Dorairaj P, Kazmi K, et al. Risk factors for early myocardial infarction in South Asians compared with individuals in other countries. JAMA. 2007;297(3):286-94. 4. Mammi MV, Pavithran K, Abdu Rahiman P, Pisharody R, Sugathan K. Acute myocardial infarction in north

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CARDIOLOGY Kerala - a 20 year hospital based study. Indian Heart J. 1991;43(2):93-6. 5. Negus BH, Willard JE, Glamann DB, Landau C, Snyder RW 2nd, Hillis LD, et al. Coronary anatomy and prognosis of young, asymptomatic survivors of myocardial infarction. Am J Med. 1994;96(4):354-8. 6. Achari V, Thakur AK. Association of major modifiable risk factors among patients with coronary artery disease a retrospective analysis. J Assoc Physicians India. 2004;52:103-8. 7. Goel PK, Bharti BB, Pandey CM, Singh U, Tewari S, Kapoor A, et al. A tertiary care hospital-based study of conventional risk factors including lipid profile in proven coronary artery disease. Indian Heart J. 2003;55(3):234-40. 8. Marinou K, Antoniades C, Tousoulis D, Pitsavos C, Goumas G, Stefanadis C. Homocysteine: a risk factor for coronary artery disease? Hellenic J Cardiol. 2005;46(1): 59-67. 9. Zorio E, Falco C, Arnau MA, España F, Osa A, Ramon LA, et al. Lipoprotein (a) in young individuals as a marker of the presence of ischemic heart disease and the severity of coronary lesions. Haematologica. 2006;91(4):562-5.

Investigators. Acute coronary syndromes in young patients: presentation, treatment and outcome. Int J Cardiol. 2011;148(3):300-4. 16. J amil G, Jamil M, Alkhazraji H, Haque A, Chedid F, Balasubramanian M, et al. Risk factor assessment of young patients with acute myocardial infarction. Am J Cardiovasc Dis. 2013;3(3):170-4. 17. Al-Khadra AH. Clinical profile of young patients with acute myocardial infarction in Saudi Arabia. Int J Cardiol. 2003;91(1):9-13. 18. Egred M, Viswanathan G, Davis GK. Myocardial infarction in young adults. Postgrad Med J. 2005;81(962):741-5. 19. H assan Z, Farooq S, Nazir N, Iqbal K. Coronary artery disease in the young: A study of risk factors and angiographic characterization in the valley of Kashmir. Int J Sci Res Pub. 2014;4(7). 20. Nordestgaard BG, Chapman MJ, Ray K, Borén J, Andreotti F, Watts GF, et al; European Atherosclerosis Society Consensus Panel. Lipoprotein(a) as a cardiovascular risk factor: current status. Eur Heart J. 2010;31(23): 2844-53.

10. Klein LW, Agarwal JB, Herlich MB, Leary TM, Helfant RH. Prognosis of symptomatic coronary artery disease in young adults aged 40 years or less. Am J Cardiol. 1987;60(16):1269-72.

21. Isser HS, Puri VK, Narain VS, Saran RK, Dwivedi SK, Singh S. Lipoprotein (a) and lipid levels in young patients with myocardial infarction and their first-degree relatives. Indian Heart J. 2001;53(4):463-6.

11. Zimmerman FH, Cameron A, Fisher LD, Ng G. Myocardial infarction in young adults: angiographic characterization, risk factors and prognosis (Coronary Artery Surgery Study Registry). J Am Coll Cardiol. 1995;26(3):654-61.

22. Schaefer EJ, Lamon-Fava S, Jenner JL, McNamara JR, Ordovas JM, Davis CE, et al. Lipoprotein(a) levels and risk of coronary heart disease in men. The lipid Research Clinics Coronary Primary Prevention Trial. JAMA. 1994;271(13):999-1003.

12. SriCharan KN, Rajesh S, Rashmi, Meghana HC, Badiger S, Mathew S. Study of acute myocardial infarction in young adults: risk factors, presentation and angiographic findings. J Clin Diagnos Res. 2012;6(2):257-60. 13. Prajapati J, Jain S, Virpariya K, Rawal J, Joshi H, Sharma K, et al. Novel atherosclerotic risk factors and angiographic profile of young Gujarati patients with acute coronary syndrome. J Assoc Physicians India. 2014;62(7):584-8. 14. Ram RV, Trivedi AV. Behavioral risk factors of coronary artery disease: A paired matched case control study. J Cardiovasc Dis Res. 2012;3(3):212-7.

23. Kamariya CP, Gorasia JH, Vachhani U, Gohel M. Evaluation of serum lipoprotein(a) in young patients with myocardial infarction. Int J Med Public Health. 2014;4(1):107-9. 24. Puri A, Gupta OK, Dwivedi RN, Bharadwaj RP, Narain VS, Singh S. Homocysteine and lipid levels in young patients with coronary artery disease. J Assoc Physicians India. 2003;51:681-5.

25. Arumalla VK, Reddy KR. Plasma homocysteine and traditional risk factors in young acute myocardial infarction patients. Int J Appl Biol Pharm Technol. 15. Schoenenberger AW, Radovanovic D, Stauffer JC, Windecker S, Urban P, Niedermaier G, et al; AMIS Plus 2011;2(4):54-7. ■■■■

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CARDIOLOGY

A Prospective, Comparative Evaluation of Efficacy and Safety of Olmesartan versus Telmisartan in Stage 1 Hypertensive Patients VARUN GUPTA*, SHALINI CHANDRA†, AK KAPOOR†, NITIN AGARWAL‡

ABSTRACT Angiotensin receptor blockers (ARBs) are the prime first-line agents and mainstay of therapy of hypertension as they modulate renin-angiotensin-aldosterone system (RAAS) and play an important role in the pathogenesis of atherosclerosis and pathophysiology of cardiovascular outcomes. Both olmesartan and telmisartan are not only long-acting but have antihypertensive efficacy, safety and tolerability, and prevent hypertension-related end-organ damage. A prospective, randomized, comparative study of 1 year duration was conducted to evaluate the antihypertensive efficacy, safety and tolerability of olmesartan versus telmisartan in stage 1 hypertensive patients, of either sex, attending the medicine OPD of Rohilkhand Medical College and Hospital, Bareilly, Uttar Pradesh. Clearance from Institutional Ethical Committee and written informed consent of each participant was taken. Of 260 enrolled patients, 130 patients each in olmesartan and telmisartan group were included by simple randomization; of these only 238 patients completed the study. The data obtained were statistically analyzed by paired and unpaired - t-test using SPSS software. Prevalence of stage 1 hypertension was more in 41-50 years age group, in females (M:F ratio 0.95:1) and in urban populace (U:R ratio 1.13:1). Baseline blood pressure (BP) values in the two groups were evenly matched. The mean systolic BP (SBP) and diastolic BP (DBP) values were consistently and statistically significantly reduced from baseline till the end of study in both the groups. Olmesartan reduced SBP and DBP by 27.3 mmHg and 9.32 mmHg as compared to 25.1 mmHg and 8.72 mmHg in the telmisartan group and thus was characterized more effective and potent on prolonged use. Biochemical parameters were almost similarly affected by the two agents. There was no significant difference between the two groups in respect to fasting blood sugar values. Regarding adverse effects, both agents were found safe and well-tolerated as they caused only mild adverse events, hence olmesartan be preferred.

Keywords: Olmesartan, telmisartan, efficacy, safety

ypertension is a multifactorial disease affecting 1 billion people worldwide and is one of the world’s great public health problems.1 It is the most common, readily identifiable and reversible risk factor for myocardial infarction, stroke, heart failure, atrial fibrillation, aortic dissection and peripheral arterial disease.1 Currently, high blood pressure (BP) causes

*3rd Year Resident †Professor Dept. of Pharmacology ‡Assistant Professor Dept. of Medicine Rohilkhand Medical College and Hospital, Bareilly, Uttar Pradesh Address for correspondence Dr AK Kapoor Professor Dept. of Pharmacology Rohilkhand Medical College and Hospital, Bareilly, Uttar Pradesh E-mail: dr.arunkumarkapoor@rediffmail.com

about 54% of stroke and 47% of ischemic heart disease (IHD) worldwide.2 Hypertension is an important risk factor for cardiovascular diseases (CVDs), which are responsible for roughly 30% of deaths worldwide.3,4 Hypertension substantially increases the risk of both macro- and microvascular complications, including stroke, coronary artery disease, peripheral vascular disease, retinopathy, nephropathy and neuropathy.5 The prevalence of hypertension in urban population at Rohtak, India was 59.9 and 69.9 per 1,000 males and females, respectively, and in the rural population in a village in Haryana, India was 35.5 and 35.9 per 1,000 males and females, respectively.6,7 Pooled epidemiological studies show that the average prevalence of hypertension in India is 25% in urban and 10% of the rural population. The rennin-angiotensin-aldosterone system (RAAS) plays an important role in the pathogenesis of atherosclerosis and pathophysiology of CVD.8

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CARDIOLOGY A large number of antihypertensive agents belonging to different pharmacological classes and groups are being currently available and agents modifying RAAS particularly angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are being used as first-line agents for the management of hypertension. Modulation of RAAS with ACE inhibitors, ARB and aldosterone inhibitors reduces a range of adverse cardiovascular outcomes in patients with or at risk of CVD. In the present study, only olmesartan and telmisartan are selected because these agents not only are long-acting, but have demonstrated clinically documented antihypertensive efficacy, safety and tolerability as well as prevented hypertension-related end-organ damage, thus conferring cardiovascular protection.9 Telmisartan not only controls BP but also early morning rise of BP, thus offering cardiovascular protection both in uncomplicated and complicated hypertension and possesses favorable metabolic profile (particularly on insulin sensitivity).10 Moreover, olmesartan is thought to have significantly stronger BP-lowering effect than losartan and valsartan with their respective starting doses.11 It additionally adequately achieved ambulatory BP monitoring goals during the early morning surge period than did candesartan.12 De Luis et al13 observed that both telmisartan and olmesartan, the two angiotensin II AT1 (AT1) receptor blockers had the same beneficial effect on BP. In contrast, Nakayama et al14 observed that olmesartan 20 mg/day caused more potent arterial BP-lowering and anti-inflammatory effect than telmisartan 40 mg/day. Since, limited data are available with olmesartan in respect to Indian populace, hence the aim of the present study was to comparatively evaluate the antihypertensive efficacy, safety and tolerability of olmesartan versus telmisartan in stage 1 hypertensive (JNC VII) patients attending to outdoor patient department (OPD) of medicine. MATERIAL AND METHODS A prospective, randomized, interventional, open level, fix dose, comparative clinical study of 1 year duration (Dec 2014 to Dec 2015) was conducted amongst hypertensive patients attending to the OPD of Rohilkhand Medical College and Hospital, Bareilly, Uttar Pradesh. Approval of the study protocol was taken from Institutional Ethical Committee. The experimental protocol was explained to the participants and those

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willing were enrolled in the study after obtaining the informed consent from each of the participants and one could withdraw without prejudice at any time. A total of 260 eligible patients of both sexes, aged 30-80 years and who were diagnosed with stage 1 hypertension (JNC VII) were selected and enrolled in the study. Both newly diagnosed and those who had discontinued antihypertensive medication voluntarily for more than 4 weeks comprised study population. All recruited patients were assigned a serial/study number on first come first serve basis, the odd numbers were allotted to olmesartan (20 mg once-daily in morning) and even numbers to telmisartan group (40 mg once-daily in the morning) were administered study drug continuously for 12 months. Doses of both antihypertensive agents were fixed throughout the study period and no upward titration of doses was done. Participants were emphatically told that they have to take the prescribed medicine regularly for 1 year (study period) despite adequate control of BP. The exclusion criteria included subjects with history of any acute or chronic disease that would affect the study variables, patients of diabetes, hypersensitivity to the agents, patients on other antihypertensive agents, patients of secondary hypertension, history of significant CVD, symptomatic heart failure, significant valvular heart disease, congenital heart diseases, pregnant and lactating females, females using oral contraceptives, significant renal or liver diseases, chronic use of corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), etc. Predesigned, structured questionnaire was used to record sociodemographic informations, medical history and lifestyle habits. All recruited patients underwent a detailed physical examination inclusive of routine investigations and special investigations were conducted only in limited number of patients as per requirements. At baseline and at each visit, BP was recorded by standardized calibrated mercury column type sphygmomanometer and stethoscope in right arm in seated position after patient had taken rest for 15 minutes. Throughout the study period, a goal BP of <140/90 mmHg was targeted. Further, at each visit, the patients were enquired for objective and subjective adverse effects due to drug, which were recorded. The first follow-up was at 2 weeks and subsequently monthly follow-up were done till end of 9 months. Of 260 enrolled patients, 22 patients did not turn up either for regular follow-up or due to poor compliance (noted by tablet count) owing to high cost of medicine, or

CARDIOLOGY due to unawareness that they have to take medicine continuously despite adequate control almost throughout their life, or due to some other reasons and were excluded for the purpose of the study. The data obtained were statistically analyzed by paired and unpaired t-test using SPSS software version 23 and Microsoft Office Excel 2007. P value <0.05 was taken as significant. RESULTS Of the 260 enrolled patients, 130 each in olmesartan and telmisartan group, only 238 patients (118 in olmesartan and 120 patients in telmisartan group) completed the study. Table 1 shows distribution of patients as per age, educational status and habits in both the groups. Maximum 93 (36%) patients were in the age group of 41-50 years followed by 75 (29%) cases in 51-60 years age group. Minimal incidence of 15% was observed in elderly patients beyond 60 years of age. There were 68 illiterate and 62 literate in olmesartan group and 71 illiterate and 59 literate in telmisartan group.

Thus, incidence of hypertension was more prevalent in illiterates. Education-wise two groups were evenly matched. There were 59 alcoholics and 57 smokers in olmesartan group and 53 alcoholics and 61 smokers in telmisartan group. In these respects, the two groups were comparable. Table 2 shows a predominance of females, M:F ratio 0.95:1 (127/133), urban-rural ratio was 1.13:1 (138/122). Table 3 shows no significant difference in socioeconomic status between olmesartan and telmisartan groups. Regarding body mass index (BMI), the two groups were evenly matched (p = 0.429). Table 4 shows comparative effects on systolic BP (SBP) by olmesartan and telmisartan in different follow-up visits. Both agents caused a significant reduction in SBP as early as 2 weeks and there was significant, regular, consistent reduction in SBP values at each follow-up till the end of study by both agents (p < 0.0001). Olmesartan caused a reduction of 27.3 mmHg compared to 25.1 mmHg by telmisartan in SBP at the end of study.

Table 1. Distribution of Patients as per Age, Educational Status and Habits Age (years)

OLM (n = 130)

TEL (n = 130)

Total No. (%)

Variables

OLM No. (%)

TEL No. (%)

30-40

53 (20)

Illiterates

68 (52.3)

71 (54.6)

41-50

93 (36)

Literates

62 (47.6)

59 (45.3)

51-60

75 (27)

Alcoholics

59 (45.3)

53 (40.7)

>60

39 (15)

Smokers

57 (43.8)

61 (46.9)

OLM = Olmesartan; TEL = Telmisartan.

Table 2. Distribution of Patients as per Residence and Sex in Olmesartan and Telmisartan Groups Variables

Rural

Urban

Male

Female

Male

Female

OLM

TEL

Total (260)

Table 3. Distribution of Patients as per Socioeconomic Status and BMI Socioeconomic status

OLM No. (%)

TEL No. (%)

Upper

11 (8.4)

12(9.2)

Upper middle

47 (36.1)

44 (33.8)

Lower middle

35 (26.9)

34 (26.1)

Upper lower

23 (17.6)

24 (18.4)

Lower

14 (10.7)

16 (12.3)

26.38 Âą 3.35

26.74 Âą 3.96

BMI (kg/m2)

P value

0.429

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CARDIOLOGY Table 4. Comparative Follow-up Mean SBP Values with Olmesartan and Telmisartan SBP

OLM

TEL

't' value

P value

Baseline

152.44 ± 5.43

151.41 ± 6.11

1.375

0.1705

2 weeks

140.44 ± 5.43

141.9 ± 4.62

2.131

0.0342

1 month

138.01 ± 4.61

139.4 ± 4.79

2.171

0.0309

2 months

136. 03 ± 4.81

137.5 ± 5.35

2.177

0.0305

3 months

135.96 ± 4.81

137.11 ± 5.34

2.325

0.0204

4 months

133. 91 ± 4.31

135.59 ± 5.26

2.338

0.0429

5 months

133.21 ± 4.63

135.43 ± 5.56

2.335

0.0204

6 months

131.57 ± 4.34

132.85 ± 5.17

2.045

0.0419

7 months

131.51 ± 4.64

132.65 ± 5.27

2.035

0.0409

8 months

127.52 ± 4.47

128.8 ± 4.85

2.058

0.0407

9 months

125.11 ± 3.81

126.31 ± 5.02

2.077

0.0389

-27.33

-25.1

<0.0001

Reduction from baseline P value P value <0.05 = Significant.

Table 5. Comparative Follow-up of Mean DBP Values with Olmesartan and Telmisartan DBP

OLM

TEL

't' value

P value

Baseline

89.52 ± 6.33

90.35 ± 5.29

1.085

0.279

2 weeks

83.81 ± 5.76

85.8 ± 4.2

2.003

0.0463

1 month

83.5 ± 5.5

85.6 ± 4.3

2.523

0.0123

2 months

83.61 ± 5.17

85.2 ± 4.3

2.544

0.0116

3 months

82.35 ± 5.54

84.05 ± 4.2

2.557

0.0112

4 months

81.35 ± 5.37

82.86 ± 4.64

2.577

0.0106

5 months

81.15 ± 5.57

82.48 ± 4.64

2.577

0.0106

6 months

80.57 ± 5.18

82.08 ± 4.86

2.322

0.0211

7 months

80.37 ± 5.28

82.01 ± 4.89

2.322

0.0211

8 months

80.24 ± 5.08

81.68 ± 4.55

2.244

0.0257

9 months

80.2 ± 5.02

81.63 ± 4.56

2.244

0.0257

Reduction from baseline P value

-27.33

-25.1

<0.0001

Table 5 shows comparative effects on diastolic BP (DBP) by both agents, from baseline till the end of study. Both the agents caused significant fall in DBP at 2 weeks and significant, consistent reduction in DBP values persisted till the end of study. Olmesartan showed a reduction of 9.3 mmHg compared to 8.7 mmHg by telmisartan at the end of study. This shows that when two groups were compared, then olmesartan (20 mg/d) was more efficacious in causing reductions both in SBP as well as DBP in comparison to telmisartan (40 mg/d) though onset of action was almost similar with both agents.

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Table 6 depicts effect on mean fasting blood sugar (FBS) levels with the two regimens. No significant changes were observed in FBS from baseline till the end of study and the differences in values of FBS between the two groups were statistically not significant. Table 7 depicts that in olmesartan group, there was statistically no significant alterations in mean serum creatinine, blood urea and SGPT (serum glutamate pyruvate transaminase) from baseline till the end of study, but there was statistically significant increase in mean serum potassium levels compared to baseline

CARDIOLOGY Table 6. Comparative Values of Mean FBS in Both Groups FBS (mg/dL)

Group A (OLM)

Group B (TEL)

't' value

P value

Baseline

90.92 ± 11.6

90.53 ± 12.05

0.552

0.582

9 months

89.08 ± 15.5

89.88 ± 13.41

0.568

0.57

Table 7. Comparative Biochemical Parameters in Olmesartan and Telmisartan Laboratory parameters

OLM

P value

TEL

P value

Baseline

Last follow-up

Baseline

Last follow-up

Serum creatinine

1.140 ± 0.25

1.072 ± 0.33

0.0622

1.130 ± 0.24

1.091 ± 0.34

0.2863

Blood urea

30.11 ± 5.94

28.84 ± 10.32

0.2251

29.83 ± 6.0

27.85 ± 10.47

0.0625

Serum potassium

3.85 ± 0.27

3.92 ± 0.29

0.0488

3.86 ± 0.27

3.94 ± 0.27

0.0176

23.43 ± 6.24

23.05 ± 6.18

0.6222

23.3 ± 5.24

23.1 ± 6.4

0.7830

SGPT

209.53 ± 3079

199.61 ± 30.15

0.0092

210 ± 28.41

199.56 ± 27.48

0.0029

139.96 ± 39.06

125.63 ± 22.31

0.0003

139.81 ± 41.25

133.62 ± 18.97

0.1213

LDL

114.83 ± 15.32

112.6 ± 15.02

0.2600

116.83 ± 14.05

115.06 ± 13.4

0.3231

HDL

42.58 ± 5.32

43.08 ± 4.77

0.4479

42.63 ± 5.28

43.32 ± 4.33

0.2503

Table 8. Comparative Adverse Drug Effects of Olmesartan and Telmisartan Adverse effect

OLM (n = 118)

TEL (n = 120)

Total

Headache

2 (1.69%)

3 (2.5%)

5 (2.1%)

GI upset

3 (2.54%)

2 (1.66%)

5 (2.1%)

Dizziness

2 (1.69%)

1 (0.83%)

3 (1.26%)

Total

07 (5.92%)

06 (4.99%)

13 (5.4%)

(p = 0.0488). Further, total cholesterol (TC), triglycerides (TGs), low-density lipoprotein (LDL) showed reduction in values, whereas high-density lipoprotein (HDL) showed an upward trend. Whereas telmisartan like olmesartan showed statistically no significant alterations in serum creatinine, blood urea and SGPT, but there was statistically significant increase in serum potassium levels compared to baseline. TC, TG and LDL were lowered and HDL showed on upward trend. Thus, both olmesartan and telmisartan regimens exhibited almost similar effects on biochemical parameters. Table 8 shows adverse events encountered with both regimens. Seven patients in olmesartan and 6 patients in telmisartan showed adverse events. No serious adverse effect, requiring hospitalization was recorded till the end of study. DISCUSSION Hypertension is a highly prevalent, chronic, incurable ailment yet hypertension remain inadequately treated

and high BP is the leading cause of death worldwide. Hypertension in characterized as major associated risk factor for cardiovascular morbidity and mortality.14-16 Recently, rennin-angiotensin system (RAS) blockers in particular AT1 blockers, were included as firstline agents for management hypertension. ARBs are widely used for the treatment of hypertension.17 Olmesartan and telmisartan are being preferred since these agents are quite effective, long-acting, cause minimal adverse effects, are better tolerated and have demonstrated better compliance. Besides exhibiting clinically documented antihypertensive efficacy, they prevent hypertension related end-organ damage thus conferring cardiovascular protection.9 Moreover, these agents possess superior renoprotective effects compared to other antihypertensive agents. ARBs block RAS by antagonizing the binding of angiotensin II to AT1 receptors. AT1 receptors, predominantly mediate the pathological effects of angiotensin II including vasoconstriction and other mechanisms that raise BP as well as vascular

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CARDIOLOGY hypertrophy, endothelial dysfunction, atherosclerosis, inflammation and apoptosis.18 Actions of angiotensin II type 2 (AT2) receptors are generally opposed to those of the AT1 receptors. ARBs are selective for the AT1 receptors and exhibit minimal affinity for AT2 receptors. Besides lowering BP, ARBs have antiatherogenic effects by blocking angiotensin II, which promotes oxidative stress, inflammation, vasoconstriction and thrombosis.19,20 They also have beneficial effects on hypertension-related cardiovascular end-organ damage, partly through a reduction of oxidative stress and inflammation.19,20 Additionally, ARBs substantially lower the risk of type 2 diabetes, compared with other antihypertensive agents probably by regulating the insulin sensitivity.21,22 The present study was a prospective, comparative, interventional study comprising of 238 patients who completed the study. Twenty-two patients dropped out during the study period and were not considered for the statistical analysis. The dropouts were probably due to high cost of medicine particularly with olmesartan or due to ignorance and poor awareness that, despite adequate control, patients had to take the medicine almost throughout their life. Lack of compliance and adverse events were other important associated factors. The two groups olmesartan and telmisartan were evenly balanced in demographic characteristics with respect to age, sex, locality, educational status, socioeconomic status and BMI. Further, patients of the two groups were also comparable with regards to initial SBP and DBP for comparative evaluation. Females predominated males, M:F ratio 0.95:1. The increased prevalence of females in hypertension is in conformity with the observations of Shaifali et al23 who have also reported almost similar M:F ratio of 0.92:1. Majority of patients in our study were in the age group of 41-50 years. Our observations are in line with those of Shaifali et al23 and Kumar et al8 who also reported the highest incidence of hypertension in the age groups of 41-50 years. Dubey et al24 have also noted the highest incidence of hypertension 44% (275/623) in 41-60 years age group. These authors have also observed that age, education, lifestyle and socioeconomic status are significantly associated with hypertension. A rising trend in incidence of hypertension with increasing age in our study, is consistent with studies of Sidhu et al25 in Punjab, Mehan et al26 in Assam, Deshmukh et al27 in Wardha and Prasanath et al28 in South India. Although prevalence of hypertension in India is showing an increasing trend in both rural and urban populace yet in our study, a higher prevalence in

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urban area was noted, U:R ratio being 1.13:1. A greater involvement of urban subjects has probably been due to stressful urban lifestyles, increased livelihood burden, unhealthy dietary intake and lack of exercise. Contrasting observations have been reported by Kumar et al8 who noted larger involvement of rural subjects (U:R ratio 0.6:1). Our observations are in line with those of Midha et al,29 Chadha et al30 and Shaifali et al23 who reported greater involvement of urban population. Further, review of various epidemiological studies have also shown that prevalence of hypertension is more in urban adults (25%) as compared to rural adults (10-15%).31 Interestingly, we have observed that incidence of hypertension was more prevalent in illiterates compared to literates probably owing to their careless attitude, failure to participate in hypertension detection and unawareness about complications of untreated hypertension. Dubey et al,24 concurring with our findings, observed that subjects with higher education are suffering less from hypertension as compared to subjects who are less educated. Concurring observations have also been noted by Shaifali et al23 and Kumar et al8 of our institution earlier. Contrasting views were expressed by Chadha et al.30 Authors have opined that literacy is a significant independent predictor of BP control. In the present study, monotherapy with once-daily administration of either agents was found significantly effective in lowering BP and the therapy not only improved compliance but was also convenient as both agents have long duration of action. Previous studies have also shown that both telmisartan and olmesartan effectively reduced BP when used alone. In a large cohort of patients in Italy, the rate of discontinuation of initial single antihypertensive drug treatment was lower for ARBs compared with ACE inhibitors. Since, the baseline of mean SBP and DBP in the two groups were evenly matched, hence the efficacy between the two drugs can well be accounted for. Previous investigators in the field32,33 have also observed an almost similar baseline values of SBP and DBP. We have observed that both olmesartan and telmisartan showed a statistically significant reduction in both SBP and DBP at each follow-up till the end of study. Further, the fall in values was noted as early as at 2 weeks with both the agents. Other investigators in the field have also observed a similar trend in respect to fall in BP, which was statistically significant.14 Further, our observations are qualitatively and quantitatively similar to observations of Yusuf et al32 and Teo et al.33 We observed that olmesartan effectively

CARDIOLOGY and significantly lowered both SBP and DBP and that statistically significant fall in BP continues till the end of study and this finding is consistent with the result of other investigators.14 Moreover, these authors observed that olmesartan and telmisartan have been shown to have a significantly stronger BP-lowering effect than losartan, valsartan with their respective starting doses.14 Regarding antihypertensive effects of telmisartan, it has been observed that similar to olmesartan, it also caused a fall in SBP and DBP which is statistically significant, the fall in BP was noted at 2-week (first follow-up). These results are in conformity with those of other workers.32,33 In reference to comparative efficacy or effectiveness, it was noted that olmesartan caused a maximum fall of 27.33 mmHg in SBP and 9.32 mmHg fall in DBP compared with a fall of 25.10 mmHg in SBP and 8.71 mmHg in DBP with telmisartan, thus demonstrating that olmesartan is more efficacious and potent than telmisartan in doses used. Moreover, the fall in BP recorded in our study was more than a subtle change. Though, telmisartan has been identified as a gold standard treatment of hypertension and has been recommended as a preferred ARB treatment option, yet in the present study, olmesartan in usual therapeutic dose caused a greater fall in SBP and DBP as compared to telmisartan. Nakayama et al14 have observed that olmesartan 20 mg/day had more potent BP-lowering effect thus supporting our observations. These authors also noted that olmesartan has a more potent anti-inflammatory effect than telmisartan 40 mg/day and that olmesartan significantly reduced both day time and night-time mean BP levels compared with telmisartan, thus showing the superiority of olmesartan BP-lowering effect might depend on its strength rather than the duration of its pharmacological action. In reference to biochemical parameters, both agents caused minimal alterations in FBS and in blood urea, serum creatinine and SGPT, though notable alterations were observed in respect to mean serum potassium level, which required repeated investigations. Interestingly, in the doses used, telmisartan did not cause alterations in FBS values though previous investigators labeled telmisartan having effects similar to those of peroxisome proliferator-activated receptor (PPAR-γ) agonists and improving insulin resistance and increasing serum adiponectin levels.13,34 Furuhashi et al35 also observed that ARBs decreased adipocyte size with improvement in insulin sensitivity. In contrast to our observations, De Luis et al13 noted a greater impact of telmisartan on glucose control. Previous investigators34,36 have also

observed that telmisartan but not other ARBs could act as a partial PPAR-γ agonist and improve insulin sensitivity. Olmesartan caused significant fall in TC, TGs, but LDL decrease was not significant. HDL showed an upward trend though not significant. Telmisartan on the other hand, like olmesartan, showed no statistically significant alterations in blood urea, serum creatinine and SGPT though there was statistically significant increase in serum potassium levels compared to baseline. There was a statistically significant fall in TC but serum TGs, LDL showed minimal alterations though a mild increase in HDL, which was not significant, was noted. Regarding the adverse events, safety and tolerability, it was noted that both the agents are well-tolerated and none of the patient developed serious toxicity requiring hospitalization during use course of the therapy. Adverse events were mild and both agents were found safe in the administered doses even for 1 year long duration. CONCLUSION Both olmesartan and telmisartan are powerful antihypertensive agents but olmesartan in the administered dose is a more effective and potent antihypertensive than telmisartan. Both these agents are fairly safe and well-tolerated even on long duration use. Additionally, they exhibited minimal alternation in biochemical parameters including FBS and lipid profile. REFERENCES 1. Victor RG. Systemic hypertension: Mechanisms and diagnosis. In: Bonow RO, Mann DL, Zipes DP, Libby P (Eds.). Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine. 9th Edition, Philadelphia, Pa: Saunders Elsevier; 2011. pp. 935-54. 2. Lawes CM, Vander Hoorn S, Rodgers A; International Society of Hypertension. Global burden of blood-pressurerelated disease, 2001. Lancet. 2008;371(9623):1513-8. 3. Fauci AS, Braunwald E, Kasper DL, et al (Eds.). Harrison’s Principle of Internal Medicine. 18th Edition. New York: McGraw-Hill; 2008, WHO (1999), Health situation in the South East Asian Region, 1997, regional officer for SEAR, New Delhi. 4. Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J. Global burden of hypertension: analysis of worldwide data. Lancet. 2005;365(9455):217-23. 5. Arauz-Pacheco C, Parrott MA, Raskin P; American Diabetes Association. Treatment of hypertension in adults with diabetes. Diabetes Care. 2003;26 Suppl 1:S80-2.

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CARDIOLOGY 6. Gupta SP, Siwach SB, Moda VK. Epidemiology of hypertension. Based on total community survey in the urban population of Haryana. Indian Heart J. 1978;30(6):315-22. 7. Gupta SP, Siwach SB, Moda VK. Epidemiology of hypertension based on total community survey in the rural population of Haryana. Indian Heart J. 1977;29(2): 53-62. 8. Kumar P, Kapoor AK, Singh HK, Kulshrestha M. Randomized, interventional prospective, comparative study to evaluate the antihypertensive efficacy and tolerability of ramipril versus telmisartan in stage 1 hypertensive patients with diabetes mellitus. IJMU. 2015;10(1):15-25. 9. Victor RG. Pathophysiology of target-organ disease: does angiotensin II remain the key? J Clin Hypertens (Greenwich). 2007;9(11 Suppl 4):4-10. 10. Grassi G, Quarti-Trevano F, Mancia G. Cardioprotective effects of telmisartan in uncomplicated and complicated hypertension. J Renin Angiotensin Aldosterone Syst. 2008;9(2):66-74. 11. Oparil S, Williams D, Chrysant SG, Marbury TC, Neutel J. Comparative efficacy of olmesartan, losartan, valsartan, and irbesartan in the control of essential hypertension. J Clin Hypertens (Greenwich). 2001;3(5):283-91, 318. 12. Brunner HR, Arakawa K. Antihypertensive efficacy of olmesartan medoxomil and candesartan cilexetil in achieving 24-hour blood pressure reductions and ambulatory blood pressure goals. Clin Drug Investig. 2006;26(4):185-93. 13. De Luis DA, Conde R, González-Sagrado M, Aller R, Izaola O, Dueñas A, et al. Effects of telmisartan vs olmesartan on metabolic parameters, insulin resistance and adipocytokines in hypertensive obese patients. Nutr Hosp. 2010;25(2):275-9. 14. Nakayama S, Watada H, Mita T, Ikeda F, Shimizu T, Uchino H, et al. Comparison of effects of olmesartan and telmisartan on blood pressure and metabolic parameters in Japanese early-stage type-2 diabetics with hypertension. Hypertens Res. 2008;31(1):7-13. 15. Egan BM, Zhao Y, Axon RN. US trends in prevalence, awareness, treatment, and control of hypertension, 1988-2008. JAMA. 2010;303(20):2043-50. 16. Ezzati M, Oza S, Danaei G, Murray CJ. Trends and cardiovascular mortality effects of state-level blood pressure and uncontrolled hypertension in the United States. Circulation. 2008;117(7):905-14. 17. Ostchega Y, Dillon CF, Hughes JP, Carroll M, Yoon S. Trends in hypertension prevalence, awareness, treatment, and control in older U.S. adults: data from the National Health and Nutrition Examination Survey 1988 to 2004. J Am Geriatr Soc. 2007;55(7):1056-65. 18. Steckelings UM, Kaschina E, Unger T. The AT2 receptor a matter of love and hate. Peptides. 2005;26(8): 1401-9.

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19. Dzau VJ. Theodore Cooper Lecture: Tissue angiotensin and pathobiology of vascular disease: a unifying hypothesis. Hypertension. 2001;37(4):1047-52. 20. Zhang C, Hein TW, Wang W, Kuo L. Divergent roles of angiotensin II AT1 and AT2 receptors in modulating coronary microvascular function. Circ Res. 2003;92(3): 322-9. 21. Pfeffer MA, Swedberg K, Granger CB, Held P, McMurray JJ, Michelson EL, et al; CHARM Investigators and Committees. Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme. Lancet. 2003;362(9386): 759-66. 22. Dahlöf B, Devereux RB, Kjeldsen SE, Julius S, Beevers G, de Faire U, et al; LIFE Study Group. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet. 2002;359(9311):995-1003. 23. Shaifali I, Kapoor AK, Singh HK. Patial RK. A comparative evaluation of losartan/hydrochlorothiazide versus amlodipine monotherapy in patients with hypertension in Rohilkhand region. IJMU. 2014;9(2):9-16. 24. Dubey RK, Singh RG, Singhal A, Sharma S, Tiwari S, Dwivedi M. Effects of contemporary lifestyle and socioeconomic status on hypertension in eastern UP, India. Int Res J Pharm. 2013;4(12):50-2. 25. Sidhu S, Kumari K, Prabhajot. Socio-demographic variables of hypertension among adult Punjabi females. J Hum Ecol. 2015;17(3):211-5. 26. Mehan MB, Srivastava N, Pandya H. Profile of non communicable disease risk factors in an industrial setting. J Postgrad Med. 2006;52(3):167-71; discussion 171-3. 27. Deshmukh PR, Gupta SS, Dongre AR, Bharambe MS, Maliye C, Kaur S, et al. Relationship of anthropometric indicators with blood pressure levels in rural Wardha. Indian J Med Res. 2006;123(5):657-64. 28. Prasanath TS, Vijaykumar K. Prevalence of systemic hypertension among rural residents of Kerala. Calicut Med J. 2008;6(3):1-4. 29. Midha T, Nath B, Kumar R. Prevalence of hypertension in India: A meta-analysis. World J Meta-Anal. 2013;1(2):83-9. 30. Chadha SL, Gopinath N, Shekhawat S. Urban-rural differences in the prevalence of coronary heart disease and its risk factors in Delhi. Bull World Health Organ. 1997;75(1):31-8. 31. Dreisbach AW, Prisant LM, Talavera F, et al. Epidemiology of hypertension. Supplement to JAPI. 2013;61:12-3. 32. Yusuf S, Teo K, Anderson C, Pogue J, Dyal L, Copland I, et al; Telmisartan Randomised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease (TRANSCEND) Investigators. Effects of the angiotensinreceptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: a randomised controlled trial. Lancet. 2008;372(9644):1174-83.

CARDIOLOGY 33. Teo K, Yusuf S, Sleight P, Anderson C, Mookadam F, Ramos B, et al; ONTARGET/TRANSCEND Investigators. Rationale, design, and baseline characteristics of 2 large, simple, randomized trials evaluating telmisartan, ramipril, and their combination in high-risk patients: the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial/Telmisartan Randomized Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease (ONTARGET/TRANSCEND) trials. Am Heart J. 2004;148(1):52-61.

as a unique angiotensin II receptor antagonist with selective PPARgamma-modulating activity. Hypertension. 2004;43(5):993-1002. 35. Furuhashi M, Ura N, Takizawa H, Yoshida D, Moniwa N, Murakami H, et al. Blockade of the renin-angiotensin system decreases adipocyte size with improvement in insulin sensitivity. J Hypertens. 2004;22(10):1977-82.

36. Schupp M, Janke J, Clasen R, Unger T, Kintscher U. Angiotensin type 1 receptor blockers induce peroxisome proliferator-activated receptor-gamma activity. 34. Benson SC, Pershadsingh HA, Ho CI, Chittiboyina A, Circulation. 2004 ;109(17):2054-7. Desai P, Pravenec M, et al. Identification of telmisartan ■■■■

Study Identifies Risk Factors Predicting Early Post-procedural Morality Following VT Ablation According to a study published in the Journal of the American College of Cardiology, poorer clinical status (low left ventricular ejection fraction [LVEF], chronic kidney disease, ventricular tachycardia (VT) storm and unmappable VTs) and post-procedural VT recurrence are risk factors for early post-procedural mortality following radiofrequency (RF) catheter ablation of VT.

Air Pollution Increases Risk of Heart Disease by Lowering the Good Cholesterol Air pollution is a reality today and has been a subject of much discussion recently. Several studies have demonstrated the association of poor air quality with diseases such as respiratory and heart diseases, global warming making it a major public health problem of concern. Yet another new study reported in the journal Arteriosclerosis, Thrombosis, and Vascular Biology has highlighted the increased risk of cardiovascular diseases due to traffic-related air pollution and proposed an explanation for the relationship between air pollution and cardiovascular disease. The study says that traffic-related air pollution may increase risk of developing heart diseases via its effects on the good high-density lipoprotein cholesterol (HDL-C). The study involving more than 6,000 middle-aged and older adults in the United States found that people who live in areas with high levels of air pollution, especially traffic-related air pollution, have lower levels of the good HDL-C. Over a period of 1 year, those with higher exposure to black carbon, emitted from vehicles, had considerably lower levels of HDL-C compared to those with lower exposure to black carbon. Higher particulate matter exposure over 3 months was associated with a lower HDL particle number. Compared to men, women had much lower levels of HDL-C. Keep your total cholesterol <160 mg/dL. HDL is good cholesterol, keep it >40 mg/dL. LDL is bad cholesterol and should be kept as low as possible; keep it <80 mg/dL. A 1% rise in bad cholesterol increases the chances of heart attack by 2% and 1% reduction in good HDL-C reduces the chances of heart attack by 3%. (Source: AHA News Release, April 13, 2017)

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CARDIOLOGY

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

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

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

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

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

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

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

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

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

Patient Selection Patients presented with ischemic systolic HF [i.e. left ventricular ejection fraction (LVEF) ≤35% as diagnosed by two-dimensional (2D) echocardiography] and undergoing CABG were included. Patients of age above 70 years, previous or recent history of second or third degree atrioventricular block, renal failure (serum creatinine >2.6 mg%), hepatic dysfunction (SGPT >45 IU/L), cerebrovascular events, previous history of revascularization or valve replacement surgery were excluded from the study. Groups of Patients: They were divided into two groups. Group I included male patients and Group II included female patients. Assessment of Patients: Biographic, clinical as well as biochemical parameter evaluation carried out at the time of hospitalization for CABG was collected. Their functional status as per New York Heart Association (NYHA) class for HF and 2D echocardiogram and color Doppler measurements recorded at the time of hospitalization and following CABG were also collected.

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

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

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

Clinical Assessment Clinical assessment was done in presence of physician. Patients’ hemodynamic parameters, i.e. pulse rate, systolic and diastolic blood pressure were measured in patient’s seating position with elbow at the level of heart. They were evaluated for the coronary artery disease (CAD) characteristic using coronary angiography pattern carried out preoperatively. Functional status was determined as per NYHA class for HF.9 This system assigns patients to 1 of 4 functional classes depending on the degree of effort needed to elicit symptoms.10

Data Analysis The results were analysed by finding mean ± standard error of mean (SEM) for continuous variables and percentage of number (n) of patients for discrete variables. Chi-square test was used to find significant difference of discrete variables between two groups. For continuous variables under consideration, the results were analysed by applying Student’s “t” test to find the change in characteristics from baseline levels and to find the significant difference between two groups. Difference, from baseline in the same group or between two groups, was considered statistically significant if the probability value (P) was found to be less than 0.05 (p < 0.05). RESULTS Out of 293 patients, 265 were males and 28 were female patients. The biographic characteristics were similar in female and male groups. However, smoking and alcoholism—the disease worsening habits were found in men but not in women (Table 1). Biochemical parameters and angiographic characteristics did not differ significantly between two groups (Tables 2 and 3). The hemodynamic status of the two group at the time of hospitalization and following CABG is shown in Table 4. Medicines used, in both

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CARDIOLOGY Table 1. Biographic Characteristics at the Time of Hospitalization

Table 3. Coronary Angiographic Characteristics of Patients

Parameter

Group I (Male)

Group II (Female)

Coronary Angiography

Number (%)

265 (90.44%)

28 (9.55%)

Age (years)

59.22 ± 0.57

60.38 ± 1.40

Body weight (kg)

66.56 ± 0.63

59.58 ± 2.00

Dyspnea

129 (48.67%)

18 (64.28%)

Fatigue

5 (1.88%)

2 (7.14%)

160 (60.37%)

19 (67.85%)

Chest pain Habits Smoking

60 (22.64%)*

0 (0%)

Tobacco

57 (21.5%)

1 (3.57%)

10 (3.77%)

0 (0%)

Diabetes mellitus

105 (39.62%)

14 (50%)

Hypertension

97 (36.60%)

15 (53.57%)

Family history of IHD

34 (12.83%)

7 (25%)

Past history of MI

139 (52.45%)

11 (39.28%)

Alcohol

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

Table 2. Biochemical Parameters at Baseline Level Biochemical parameter

Group I (Male)

Group II (Female)

Blood sugar (mg%)

160.17 ± 4.09

186.85 ± 8.74

Serum urea (mg%)

33.69 ± 1.07

28.46 ± 2.18

Serum creatinine (mg%)

1.23 ± 0.03

1.12 ± 0.08

SGPT (IU/L)

30.41 ± 0.80

26.05 ± 1.86

Serum K+ (mEq/L)

4.87 ± 0.55

4.34 ± 0.09

136.57 ± 0.33

135.47 ± 0.52

Serum

Na+ (mEq/L)

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

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

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3 (1.13%)

1 (3.57%)

DVD

47 (17.73%)

5 (17.85%)

TVD

215 (81.13%)

22 (78.57%)

LMCA ≥50% stenosis

45 (16.98%)

6 (21.42%)

106 (40.0%)

8 (28.57%)

34 (12.83%)

0 (0%)

103 (38.86%)

5 (17.85%)

LAD stenosis LCx 100% RCA 100%

Risk factors

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Group II (Female)

SVD

100%

Symptoms

Group I (Male)

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

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

Group I (Male)

Group II (Female)

Baseline

82.08 ± 1.00

83.89 ± 2.03

Post CABG

79.90 ± 1.57

81.85 ± 1.13

Baseline

124.33 ± 1.13

124.68 ± 3.40

Post CABG

122.42 ± 1.61

120.38 ± 2.68

Baseline

79.92 ± 0.62

78.36 ± 1.63

Post CABG

81.48 ± 1.70

80.43 ± 1.37

HR (beats/min)

SBP (mmHg)

DBP (mmHg)

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

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

Group I (Male)

Group II (Female)

Digoxin

152 (57.36%)

13 (46.43%)

Diuretics

195 (73.58%)

18 (64.29%)

β-adrenoceptor blocker

130 (49.06%)

16 (57.14%)

Angiotensin-converting enzyme inhibitor

265 (100%)

28 (100%)

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

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

Group I (Male)

Group II (Female)

% change from baseline

Baseline

27.92 ± 0.39

Post CABG

33.37 ± 0.51*

32.58 ± 1.09† 22.25 ± 1.63

40.7 ± 1.1†,*

27.13 ± 4.03†

LVEDd (mm) Baseline

54.7 ± 0.43

Post CABG

54.11 ± 0.46

50.93 ± 1.12† 1.55 ± 0.90

45.93 ± 0.98†,*

9.32 ± 1.84†

LVEDs (mm) Baseline

42.53 ± 0.49

Post CABG

41.46 ± 0.48

37.13 ± 1.52† 1.14 ± 1.03

34.14 ± 0.87†,*

4.22 ± 4.71†

MR-grade Baseline

0.66 ± 0.04

Post CABG

0.50 ± 0.03*

1.2 ± 0.11† 24.63 ± 3.05

0.7 ± 0.09*

30.0 ± 7.96

NYHA class for HF Baseline

3.0 ± 0.05

Post CABG

2.08 ± 0.03*

3.09 ± 0.17 20.04 ± 2.76

2.02 ± 0.18*

36.46 ± 5.64†

†Significantly

45 40 35 30 25 20 15 10 5 0

†* *

†

Baseline Post CABG †

†

50 LVEDd (mm)

LVEF (%)

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

†*

40 30 20

†

10 0 Male

Female

Male Female (% change) (% change)

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

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

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

Baseline Post CABG

Male

Female

Male Female (% change) (% change)

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

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

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

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LVEDs (mm)

CARDIOLOGY

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

†

Baseline Post CABG †*

DISCUSSION † Male

Female

Male Female (% change) (% change)

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

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

Baseline Post CABG

40 35 MR-grade

30 25 20 15 10 5 0

* Male

† * Female

Male Female (% change) (% change)

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

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

NYHA class for HF

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

†

* Male

* Female

Male Female (% change) (% change)

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

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

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

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Gender is an independent risk factor associated with differential presentation and outcomes of treatment in patients with HF. In our study, Indian female patients of western region with systolic HF were found to be less in number to have systolic dysfunction as compared to men. Ours is the first study carried out to find out gender differences in the prognosis of systolic HF in patients undergoing CABG. Earlier reports have shown that men are at higher risk of developing systolic HF than women.11,12 Furthermore, it is reported that over the past 50 years (i.e. from 1950 to 1999), the incidence of LV dysfunction has declined among women but not among men.13 In our study, we found that male patients were significantly greater in number for having habit of smoking. Although a direct correlation between smoking and development as well as prognosis of systolic dysfunction is not reported, it is listed as a one of the hazards for the development of systolic HF.7,9 Coexistence of other diseases such as hypertension (HT), diabetes mellitus (DM) and positive family history of IHD were found to be more in women making them more prone to LV systolic dysfunction. It is reported that the presence of DM and HT raises the risk of developing LV dysfunction rather than just being primary comorbid conditions.14 DM has negative effect on prognosis of LV dysfunction. Diabetic women with HF have shown poorer prognosis than diabetic men. DM eliminates the female coronary protection probably by reducing beneficial effects of estrogen.15 No report is available on relation between presence of family history of IHD and development of systolic dysfunction and HF. However, Schildkraut et al16 reported that the relation between presence of family history of IHD and development of CAD is stronger for women as compared to men. In the present study, women were found to be symptomatic with marginal worse functional status at the time of hospitalization for CABG. These findings are consistent to earlier reports of Vaccarino et al14 and Riedinger et al17 which suggested that female patients with HF are more symptomatic with worse capacity of physical activity as compared to males.

CARDIOLOGY Earlier studies have shown greater occurrence of myocardial infarction (MI) as underlying cause of LV systolic dysfunction in men as compared to women patients.18-19 Furthermore, ischemia and/or hibernation may lead to myocyte apoptosis which results in the progression of LV dysfunction without a clear ischemic event.20-22 However, myocyte death by apoptosis, necrosis or both following ischemia and LV remodeling is reduced in women.23,24 In our study, female patients presented with relatively more preserved LV function as LVEF was significantly greater and LV diameters (systolic as well as diastolic) were significantly smaller in the female group as compared to male group. Vaccarino et al14 also suggested that women presented with HF have more preserved LV systolic function than men. In our study, the improvement in LVEF was greater in female patients as compared to that found in males after 10 weeks of CABG. A controversy prevails with regard to survival rate on the basis of gender difference in patients undergoing CABG.25 The original Framingham data showed that the prognosis of women with HF was better than that of men.26 Kurlansky et al27 also reported favorable results in 327 women in terms of hospital mortality, low postoperative morbidity, excellent functional improvement and enhanced longterm of survival following CABG. Bypass Angioplasty Revascularization Investigation (BARI) trial has also shown that female sex is an independent predictor of improved 5-year survival after controlling multiple risk factors.28 In our study, CABG produced significant reversal of diastolic as well systolic indices of LV remodeling in female group as there was a significant reduction in diastolic and systolic diameters in female group but not in male patients. At the time of hospitalization for CABG, MR was found to be significantly worse in women as compared to men in our study. However, the reduction in MR from baseline following CABG was statistically significant in female group as well as in male group. This may be secondary to significant cardiac function improvement including that in LV size and shape in females.29 Improvement in functional capacity produced following CABG was also significantly greater in women than that found in men. Thus, overall postoperative improvement was significantly greater in Indian women than men. Though no report is available on gender difference in improvement of the above-mentioned parameters following CABG, it is well-accepted that CABG in

general improves overall health status of patients with ischemic LV systolic dysfunction and HF.9,30 CONCLUSION In conclusion, out results suggest that among patients with systolic HF undergoing CABG, women seem to have less systolic dysfunction as compared to men. Women also seem to have better prognosis in terms of improvement in LV contractility, reversal of LV remodeling and improvement in functional status following CABG as compared to men. REFERENCES 1. Ho KK, Anderson KM, Kannel WB, Grossman W, Levy D. Survival after the onset of congestive heart failure in Framingham Heart Study subjects. Circulation. 1993;88(1):107-15. 2. Simon T, Mary-Krause M, Funck-Brentano C, Jaillon P. Sex differences in the prognosis of congestive heart failure: results from the Cardiac Insufficiency Bisoprolol Study (CIBIS II). Circulation. 2001;103(3):375-80. 3. McKee PA, Castelli WP, McNamara PM, Kannel WB. The natural history of congestive heart failure: the Framingham study. N Engl J Med. 1971;285(26):1441-6. 4. Adams KF Jr, Sueta CA, Gheorghiade M, Oâ&#x20AC;&#x2122;Connor CM, Schwartz TA, Koch GG, et al. Gender differences in survival in advanced heart failure: insights from the FIRST study. Circulation. 1999;99(14):1816-21. 5. Adams K, Dunlap S, Sueta C, Clarke SW, Patterson JH, Blauwet MB, et al. Relation between gender, etiology and survival in patients with symptomatic heart failure. J Am Coll Cardiol. 1996;28(7):1781-8. 6. Schocken, DD, Arrieta MI, Leaverton PE, Ross EA. Prevalence in mortality rate of congestive heart failure in the United States. J Am Coll Cardiol. 1992;20(2):301-6. 7. Alexander M, Grumbach K, Remy L, Rowell R, Massie BM. Congestive heart failure hospitalizations and survival in California: patterns according to race/ethnicity. Am Heart J. 1999;137(5):919-27. 8. Schiller NB, Shah PM, Crawford M, DeMaria A, Devereux R, Feigenbaum H, et al. Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. J Am Soc Echo. 1989;2(5):358-67. 9. Hunt SA, Abraham WT, Mancini DM, Chin MH, Michl K, Feldman AM, et al. American College of Cardiology/ American Heart Association 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult. Circulation. 2005;112(12):e154-235. 10. Brown L. Diseases of the Heart and Blood Vessels: Nomenclature and Criteria for Diagnosis, 6th Edition. Boston: Mass; 1964. p. 114. 11. Diller PM, Smucker DR, David B, Graham RJ. Congestive heart failure due to diastolic or systolic dysfunction.

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CARDIOLOGY Frequency and patient characteristics in an ambulatory setting. Arch Fam Med. 1999;8(5):414-20. 12. Halm MA, Penque S. Heart failure in women. Prog Cardiovasc Nurs. 2000;15(4):121-33. 13. Levy D, Kenchaiah S, Larson MG, Benjamin EJ, Kupka MJ, Ho KKL, et al. Long-term trends in the incidence of and survival with heart failure. N Engl J Med. 2002;347(18):1397-402. 14. Vaccarino V, Chen Y-T, Wang Y, Radford MJ, Krumholz HM. Sex differences in the clinical care and outcomes of congestive heart failure in the elderly. Am Heart J. 1999;138(5):835-42. 15. Merz BNB, Juhnson BD, Bittner V, Hodgson TK, Berga SL, Braunstein GD, et al. Diabetes and estrogen deficiency in premenopausal women: the NHLBI-sponsored WISE study. Circulation. 2002;106(II):508. 16. Schildkraut JM, Myers RH, Cupples LA, Kiely DK, Kannel WB. Coronary risk associated with age and sex of parental heart disease in the Framingham study. Am J Cardiol. 1989;64(10):555-9. 17. Riedinger MS, Dracup KA, Brecht ML, Padilla G, Sarna L, Ganz PA. Quality of life in patients with heart failure: do gender differences exist? Heart Lung. 2001;30(2): 105-16. 18. Kannel WB. Epidemiological aspects of heart failure. Cardiol Clin. 1989;7(1):1-9. 19. Kimmelstiel C, Goldberg RJ. Congestive heart failure in women: focus on heart failure due to coronary artery disease and diabetes. Cardiology. 1990;77(Suppl 2):71-9. 20. Colucci WS. Apoptosis in the heart. N Engl J Med. 1996;335(16):1224-6. 21. Chen C, Ma L, Linfert DR, Lie T, Fallon JT, Gillam LD, et al. Myocardial cell death and apoptosis in hibernating myocardium. J Am Coll Cardiol. 1997;30(5):1407-12.

Outcomes Nationwide in Heart Failure. Consensus recommendations for the management of chronic heart failure. Am J Cardiol. 1999;83(2A):1A-38A. 23. Olivetti G, Giordano G, Corradi D, Melissari M, Lagrasta C, Gambert SR, Anversa P. Gender differences and aging: effects in the human heart. J Am Coll Cardiol. 1995;26(2A):1068-79. 24. Adams K, Dunlap S, Sueta C, Clarke SW, Patterson JH, Blauwet MB, et al. Relation between gender, etiology and survival in patients with symptomatic heart failure. J Am Coll Cardiol. 1996;28(7):1781-8. 25. Vaccarino V, Lin ZQ, Kasl SV, Mattera JA, Roumanis SA, Abramson JL, et al. Gender differences in recovery after coronary artery bypass surgery. J Am Coll Cardiol. 2003;41(2):307-14. 26. Kannel W, Sorlie P, McNamara P. Prognosis after initial myocardial infarction: the Framingham study. Am J Cardiol. 1979;44(1):53-9. 27. Kurlansky PA, Dorman MJ, Galbut DL, Moreno NL, Traad EA, Carrillo RG, et al. Bilateral internal mammary artery grafting in women: a 21-year experience. Ann Thorac Surg. 1996;62(1):63-9. 28. Jacobs AK, Kelsey SF, Brooks MM, Faxon DP, Chaitman BR, Bittner V, et al. Better outcome for women compared with men undergoing coronary revascularization: a report from the bypass angioplasty revascularization investigation (BARI). Circulation. 1998;98(13):1279-85. 29. Kono T, Sabbah HN, Rosman H, Alam M, Jafri S, Goldstein S. Left ventricular shape is the primary determinant of functional mitral regurgitation in heart failure. J Am Coll Cardiol. 1992;20(7):1594-8.

30. Elefteriades JA, Tolis G, Levi E, Mills LK, Zaret BL. Coronary artery bypass grafting in severe left ventricular dysfunction: excellent survival with improved ejection fraction and functional state. J Am Coll Cardiol. 22. Packer M, Cohn JN. On behalf of the Steering Committee and Membership of the Advisory Council to Improve 1993;22(5):1411-7. ■■■■

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INTERNAL MEDICINE

Symmetrical Peripheral Gangrene - A Rare Clinical Manifestation of Hodgkin’s Lymphoma: A Case Report PRAVEEN KUMAR*, KALPANA CHANDRA†

ABSTRACT Symmetrical peripheral gangrene is a cutaneous manifestation of wide array of infective and noninfective etiological factors and is due to hypoxemia, vasoconstriction, primary endothelial damage and/or decreased cardiac output. It is a devastating complication of underlying septicemia and disseminated intravascular coagulation with a high mortality rate and commonly requiring amputation of the affected limb in those who survives. We here describe a case presented with fever, cough, blackish discoloration of fingers and generalized lymphadenopathy. Investigation revealed anemia, leukocytosis, coagulopathy and positive D-dimer test. Fine needle aspiration cytology showed evidence of Hodgkin’s lymphoma.

Keywords: Symmetrical peripheral gangrene, disseminated intravascular coagulation, Hodgkin’s lymphoma

ymmetrical peripheral gangrene (SPG), a rare clinical condition known for decades, was first described by Hutchison in the year 1891 in a 37-year-old male who developed gangrene in fingers, toes and ear lobule after shock.1 It manifests as marked coldness, pallor and cyanosis of the acral parts of the body followed by acral ischemic damage and frank gangrene in two or more extremities without any evidence of obstruction or vasculitis of the related artery. Rarely, it may be the presenting manifestation of malignancy or heralds its recurrence or metastasis. Here, we are discussing a case of SPG with Hodgkin’s lymphoma. CASE REPORT

120/min, regular, normal in volume and character without radio-radial or radio-femoral delay. All peripheral pulses including dorsalis pedis were palpable bilaterally. Respiratory rate was 22/min, regular, thoracoabdominal. Jugular venous pressure was normal. Generalized lymphadenopathy was present in cervical, axillary and inguinal areas. Systemic examination revealed splenomegaly and scattered bilateral crepitations in lungs with normal cardiovascular and nervous systems. Local examination of both hands showed blackish discoloration, shrunken and dry index and middle fingers with a definite line of demarcation without any local rise of temperature or ulceration (Figs. 1 and 2).

A 60-year-old female, without any premorbidities, presented with chief complaints of fever for 5 months, cough with sputum and blackish discolorations of the fingers of both hands for 1 month. General examination revealed fever, palor and dehydration. Pulse was

*Associate Professor Dept. of General Medicine †Associate Professor Dept. of Pathology Shri Ram Murti Smarak Institute of Medical Sciences, Bhojipura, Bareilly, Uttar Pradesh Address for correspondence Dr Praveen Kumar Associate Professor, Dept. of General Medicine, Shri Ram Murti Smarak Institute of Medical Sciences, Bhojipura, Bareilly - 243 202, Uttar Pradesh E-mail: praveen_kmr_23@yahoo.co.in

Figure 1. Symmetrical peripheral gangrene of index and middle fingers of both hands (palmar aspect).

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INTERNAL MEDICINE including various infections, myocardial infarction, congestive heart failure, hypersplenism, dog bite, Hodgkin’s lymphoma, polymyalgia rheumatica, etc. It can also occur as a complication of malignant diseases, ergotism or protein deficiency. Existing data show that disseminated intravascular coagulation (DIC) might be associated with up to 85% of cases of SPG.2

Figure 2. Symmetrical peripheral gangrene of index and middle fingers of both hands (dorsal aspect).

Investigations revealed hemoglobin (Hb) - 10.5 g/dL; white blood cell (WBC) count - 28,700/mm3; differential leukocyte count (DLC) - N89%L08%Eo1%Mo1%; erythrocyte sedimentation rate (ESR) - 47 in first hour; red blood cell (RBC) - 3.8 million/cm3; peripheral blood smear (PBS) - normocytic and normochromic with mild anisocytosis, mild poikilocytosis with few schistocytes and helmet cells; leukocytosis with neutrophilia with occasional myeloid precursors, no hemoparasite; platelet count - 1.2 lacs; hepatitis B surface antigen (HbsAg) and anti-HCV (hepatitis C virus) - nonreactive; antinuclear antibodies (ANA) - negative; random blood sugar (RBS) - 109 mg/100 mL; renal function text (RFT) - within normal limit; urine routine examination within normal limit; blood and urine culture - sterile; prothrombin time/partial thromboplastin time (PT/PTT) - prolonged; D-dimer - positive; lipid profile normal; liver function test (LFT) - within normal limit. Chest X-ray - P/A view showed bilateral lung infiltrates and bilateral pleural effusion. Ultrasonography showed bilateral pleural effusion with moderate ascites. Fine needle aspiration cytology (FNAC) of the cervical lymph node: Cytomorphologically lymphoproliferative disorders suggestive of Hodgkin’s lymphoma.

Final Diagnosis Hodgkin’s lymphoma with septicemia and SPG. DISCUSSION SPG is defined as symmetrical distal ischemic damage in two or more sites in the absence of major vascular occlusive disease. It is a rare syndrome associated with a multitude of underlying medical problems

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This rare syndrome is typically sudden in onset, symmetrical in nature and predominantly affects the upper extremities, and progresses rapidly to acral gangrene. The lower extremities, tip of the nose, borders of the ears, genitalia and scalp are the other areas of predilection. There is no evidence of occlusion of large vessels or vasculitis with intact distal pulses. This makes the pathogenesis behind its causation difficult to explain with the current understanding of its pathology. The pathogenesis of SPG may involve the Shwartzman reaction, bacterial endotoxin release and platelet plugging in peripheral arterioles due to vascular collapse and DIC.3 DIC seems the most common final pathway of its pathogenesis4 because of high association between DIC and SPG. The paradoxical syndrome seen in DIC is of consumptive coagulopathy with abnormal uncontrollable hemorrhages and intravascular clotting at microscopic level. It would explain the acral gangrenous changes of SPG, the lack of vasculitis in small vessels and the lack of thrombi in large vessels. Histopathological examination of amputated parts often reveal thrombi in the small vessels with sparing of large vessels without any features of vasculitis or inflammatory cell infiltrates on walls of the blood vessels.5 In our case, the cause of gangrene was not clear. Sepsis seemed to be responsible for SPG in this case. Sepsis and the underlying malignancy might have caused some degree of abrupt hypofibrinogenemia. The low level of fibrinogen might be associated with inappropriate microscopic clot formation. The patient was given treatment for septicemia, other supportive care and was planned for further management, which was declined and lost to follow-up. CONCLUSION SPG is cause of significant morbidity and mortality often requiring multiple limb amputations. DIC is an almost universal finding and is probably the final common event in the microvascular insult that gives rise to the prototypical clinical features of this syndrome. No

INTERNAL MEDICINE treatment is effective. Early recognition, awareness of the condition and vigorous therapy of sepsis and DIC may prevent progression of gangrene and dramatic fall in high mortality rate associated with this syndrome. We present this case because of rare manifestation of Hodgkin’s lymphoma with SPG.

Acknowledgment The authors are highly thankful to Dept. of Medicine and Pathology of SRMS-IMS, Bareilly for providing adequate facilities, which helped in working out this study.

REFERENCES 1. Hutchinson J. Severe symmetrical gangrene of the extremities. Br Med J. 1891;2:8-9. 2. Molos MA, Hall JC. Symmetrical peripheral gangrene and disseminated intravascular coagulation. Arch Dermatol. 1985;121(8):1057-61. 3. Tripathy S, Rath B. Symmetric peripheral gangrene: Catch it early! J Emerg Trauma Shock. 2010;3(2):189-90. 4. Sharma BD, Kabra SR, Gupta B. Symmetrical peripheral gangrene. Trop Doct. 2004;34(1):2-4.

5. Kashyap R, Behl RK, Mahajan S, Jaret P, Patial RK, The authors are thankful to the Dean SRMS-IMS, Bareilly for Kaushal SS. Symmetrical peripheral gangrene due to viral gastroenteritis. J Assoc Physicians India. 2004;52:500-1. permitting us to publish this case report. ■■■■

ACP Terms Substance Use Disorders as Chronic Medical Conditions Substance use disorders related to illicit and prescription drugs, including opioids, are chronic medical conditions that are treatable through public and individual health interventions, says the American College of Physicians (ACP) in a new policy statement published online March 27, 2017 in the Annals of Internal Medicine. The new ACP policy statement includes public policy recommendations for the prevention and treatment of substance use disorders involving illicit and prescription drugs. Some of the key recommendations to combat the epidemic of prescription drug misuse are as follows: ÂÂ

Physicians should familiarize themselves with and follow as appropriate clinical guidelines related to pain management and controlled substances such as prescription opioids as well as nonopioid drugs and nondrug interventions

ÂÂ

Expansion of access to naloxone to opioid users, law enforcement and emergency medical personnel

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Expansion of access to medication-assisted treatment of opioid use disorders

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Improved training in the treatment of substance use disorders including buprenorphine-based treatment

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Establishment of a national Prescription Drug Monitoring Program and improvement of existing monitoring programs.

ACP also recommends public and individual health interventions rather than excessive reliance on criminalization and incarceration to prevent and treat substance use disorders. It proposes education and training of healthcare professionals to substance use disorders. Health insurance should cover mental health conditions including substance use disorders. (Source: ACP News Release, March 28, 2017)

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NEUROLOGY

Hereditary Spastic Paraplegia with Thin Corpus Callosum and Dementia: A Rare Presentation CHANDRAMOHAN SHARMA*, BANSHI LAL KUMAWAT†, TARACHAND SAINI‡, MOHIT SHAH‡

ABSTRACT Hereditary spastic paraplegia (HSP) is a genetically and clinically heterogeneous group of disorders rather than a single entity. Common clinical feature to all cases is progressively worsening spasticity of the lower extremities with variable degrees of weakness. Autosomal recessive HSP with thin corpus callosum (ARHSP-TCC) is a subtype of complicated HSP characterized by slowly progressive spastic paraparesis, cognitive decline, muscle atrophy, optic atrophy, dysphagia, dysarthria and peripheral neuropathy. ARHSP-TCC is mainly seen in Japanese, very few cases of ARHSP-TCC from India, described in the literature. Herein, we report a patient of HSP from North India, presented with spastic paraparesis and beginning of cognitive decline in the second decade of life.

Keywords: Hereditary spastic paraplegia, corpus callosum, cognitive decline

ereditary spastic paraplegia (HSP) is a diverse group of neurodegenerative disorders characterized by gradually progressive weakness and spasticity of the lower extremities. Mostly, patients present with difficulty in walking or gait disturbance, noticed either by themselves or a relative. Most common mode of inheritance is autosomal dominant, but it can be inherited in autosomal recessive or X-linked recessive manner, and 12-13% of cases occur with apparently sporadic mutations. HSP manifests in two forms, pure and complicated. Age of onset is variable, from infancy to the eighth decade, although majority of cases present in the second to fourth decades. Clinically, pure HSP is defined when isolated progressive spastic paraparesis, brisk reflexes and extensor plantar responses are present. Complicated form have many other features beside spastic paraparesis like mental retardation, optic atrophy, retinopathy, amyotrophy, ataxia, cerebellar sign, peripheral neuropathy, deafness.1 HSP with thin

*Head †Senior Professor ‡Senior Resident Dept. of Neurology SMS Medical College, Jaipur, Rajasthan Address for correspondence Dr Tarachand Saini E-379, Bank Colony, Murlipura Scheme, Jaipur - 302 013, Rajasthan E-mail: drtcsaini20@gmail.com

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corpus callosum (HSP-TCC) is classified as complicated form of HSP with autosomal recessive transmission. CASE PRESENTATION A 26-year-old male presented with history of insidious onset, gradually progressive, spastic weakness of lower limbs, behavioral changes and cognitive decline for the past 13 years. He was born out of nonconsanguineous marriage with history of full-term normal vaginal delivery and normal developmental milestones during childhood. He was 2nd order child among five siblings. No history of similar symptoms in the parents or siblings was present. General physical examination was normal. Neurologic examination revealed impaired attention, calculation, recall, judgment, reasoning power and abstract thinking, although he was able to comprehend simple verbal commands. Mini-mental state examination score was 20/30. Cranial nerves examination including fundus was normal. Speech was slow and spastic. He had normal muscle bulk with spasticity of lower limbs. The power in upper limb and lower limb was Medical Research Council (MRC) Grade V/V and IV/V in all groups of muscles, respectively. Deep tendon reflexes in both upper and lower limbs were brisk and plantar response was bilaterally extensor. Sensory examination was normal. He was able to walk with one person support with spastic gait. Rest of the neurological examination was normal.

NEUROLOGY Investigation On investigation, complete blood count, blood sugar, renal and liver functions, thyroid profile, electrolytes, serum vitamin B12 was in the normal range. Human immunodeficiency virus (HIV) status was negative. Routine cerebrospinal fluid analysis was normal. Human T-cell lymphotropic virus type 1 (HTLV-1)antibody assay was negative in both serum and cerebrospinal fluid. Electromyography and nerve conduction studies were also normal. Magnetic resonance imaging (MRI) brain (Figs. 1 and 2) showed thin corpus callosum, periventricular cone-shaped hyperintensities near the

frontal horn of lateral ventricles resembling tuft of hair on ear of Lynx (Ear of Lynx sign), enlarged lateral ventricles, frontoparietal atrophy and symmetrical white matter lesions. On the basis of clinical history and investigations diagnosis of autosomal recessive HSP with thin corpus callosum (ARHSP-TCC) was made and other possible diagnoses were excluded by relevant investigations. Patient was treated with supportive treatment including antispastic agent. DISCUSSION ARHSP-TCC is a complicated form of HSP. Majority of cases of ARHSP-TCC to attributed to mutation in Spastic Paraplegia gene 11 (SPG11) on chromosome 15 encoding protein SPATACSIN.2 SPATASCIN is widely distributed in the nervous system, especially in the cerebellum and cerebral cortex.3

Figure 1. MRI brain axial view T2 FLAIR image showing dilated lateral ventricles; periventricular cone-shaped hyperintensities near the frontal horn resembling tuft of hair on ears of Lynx (Ear of Lynx sign).

Motor development was normal in early life in our patient and he developed slowly progressive spastic paraparesis and cognitive decline in the early second decade. This clinical profile is similar to cases reported by Okubo et al.4 Pathologically, axonal degeneration was present in the long descending and ascending tracts of the spinal cord.5 In our patient, MRI brain revealed thin corpus callosum, frontoparietal atrophy and enlargement of lateral ventricles; similar MRI findings are described in cases reported by Nakamura et al.6 Presence of thin corpus callosum is not specific for this syndrome and whether it represents a congenital hypoplasia or a progressive atrophy is not known.7 The diagnosis of ARHSP-TCC was made based on following essentials: (1) Autosomal recessive inheritance, (2) slowly progressive spastic paraparesis and mental impairment, (3) thinning of the corpus callosum revealed by CT or MRI brain and (4) exclusion of other disorders.8 REFERENCES 1. McDermott C, White K, Bushby K, Shaw P. Hereditary spastic paraparesis: a review of new developments. J Neurol Neurosurg Psychiatry. 2000;69(2):150-60. 2. Stevanin G, Azzedine H, Denora P, Boukhris A, Tazir M, Lossos A, et al; SPATAX consortium. Mutations in SPG11 are frequent in autosomal recessive spastic paraplegia with thin corpus callosum, cognitive decline and lower motor neuron degeneration. Brain. 2008;131(Pt 3):772-84.

Figure 2. MRI brain sagittal view T2 - weighted image showing thin corpus callosum and frontoparietal atrophy.

3. Paisan-Ruiz C, Dogu O, Yilmaz A, Houlden H, Singleton A. SPG11 mutations are common in familial

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NEUROLOGY cases of complicated hereditary spastic paraplegia. Neurology. 2008;70(16 Pt 2):1384-9.

with mental impairment and thin corpus callosum. J Neurol Sci. 1995;131(1):35-42.

4. Okubo S, Ueda M, Kamiya T, Mizumura S, Terashi A, Katayama Y. Neurological and neuroradiological progression in hereditary spastic paraplegia with a thin corpus callosum. Acta Neurol Scand. 2000;102(3):196-9.

7. Teive HA, Iwamoto FM, Della Coletta MV, Camargo CH, Bezerra RD, Minguetti G, et al. Hereditary spastic paraplegia associated with thin corpus callosum. Arq Neuropsiquiatr. 2001;59(3-B):790-2.

5. Behan WM, Maia M. Strümpell's familial spastic paraplegia: genetics and neuropathology. J Neurol Neurosurg Psychiatry. 1974;37(1):8-20.

8. Shibasaki Y, Tanaka H, Iwabuchi K, Kawasaki S, Kondo H, Uekawa K, et al. Linkage of autosomal recessive hereditary spastic paraplegia with mental impairment and thin corpus callosum to chromosome 15q13-15. Ann 6. Nakamura A, Izumi K, Umehara F, Kuriyama M, Neurol. 2000;48(1):108-12. Hokezu Y, Nakagawa M, et al. Familial spastic paraplegia ■■■■

PTSD is a Systemic Disorder with Comorbidities Post-traumatic stress disorder (PTSD) has been traditionally regarded as a psychological disorder. However, the findings of a new study suggest that PTSD should be considered a systemic disorder and not just a psychological disorder as it is associated with several comorbidities independent of exposure to trauma. Researchers analysed the health status of 298 Australian veterans aged between 60 and 88 years who had fought in the Vietnam War between February 2014 and July 2015. Of these, 108 had confirmed PTSD, while 106 acted as trauma-exposed controls. Compared to trauma-exposed controls, patients with PTSD had higher frequency (14.1% vs. 17.7%, respectively) of comorbid conditions of the gastrointestinal, hepatic, cardiovascular and respiratory systems. It was also associated with sleep disorders. Comorbid depression was found in 22% of subjects with PTSD. These patients also had a higher prevalence of risk factors such as smoking, alcohol dependence and higher BMI. Hence, not just psychological health, but physical health including control of risk factors should also be part of management of patient with PTSD to improve their quality-of-life and survival. The study is published April 3, 2017 in the Medical Journal of Australia. (Source: Med J Aust. 2017 Apr 3;206(6):251-7)

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Every citizen of India should have the right to accessible, affordable, quality and safe heart care irrespective of his/her economical background

Sameer Malik Heart Care Foundation Fund An Initiative of Heart Care Foundation of India

E-219, Greater Kailash, Part I, New Delhi - 110048 E-mail: heartcarefoundationfund@gmail.com Helpline Number: +91 - 9958771177

“No one should die of heart disease just because he/she cannot afford it” About Sameer Malik Heart Care Foundation Fund

Who is Eligible?

“Sameer Malik Heart Care Foundation Fund” it is an initiative of the Heart Care Foundation of India created with an objective to cater to the heart care needs of people.

Objectives Assist heart patients belonging to economically weaker sections of the society in getting affordable and quality treatment. Raise awareness about the fundamental right of individuals to medical treatment irrespective of their religion or economical background. Sensitize the central and state government about the need for a National Cardiovascular Disease Control Program. Encourage and involve key stakeholders such as other NGOs, private institutions and individual to help reduce the number of deaths due to heart disease in the country. To promote heart care research in India.

All heart patients who need pacemakers, valve replacement, bypass surgery, surgery for congenital heart diseases, etc. are eligible to apply for assistance from the Fund. The Application form can be downloaded from the website of the Fund. http://heartcarefoundationfund.heartcarefoundation. org and submitted in the HCFI Fund office.

Important Notes The patient must be a citizen of India with valid Voter ID Card/ Aadhaar Card/Driving License. The patient must be needy and underprivileged, to be assessed by Fund Committee. The HCFI Fund reserves the right to accept/reject any application for financial assistance without assigning any reasons thereof. The review of applications may take 4-6 weeks. All applications are judged on merit by a Medical Advisory Board who meet every Tuesday and decide on the acceptance/rejection of applications. The HCFI Fund is not responsible for failure of treatment/death of patient during or after the treatment has been rendered to the patient at designated hospitals.

To promote and train hands-only CPR.

Activities of the Fund Financial Assistance

The HCFI Fund reserves the right to advise/direct the beneficiary to the designated hospital for the treatment.

Financial assistance is given to eligible non emergent heart patients. Apart from its own resources, the fund raises money through donations, aid from individuals, organizations, professional bodies, associations and other philanthropic organizations, etc.

The financial assistance granted will be given directly to the treating hospital/medical center.

After the sanction of grant, the fund members facilitate the patient in getting his/her heart intervention done at state of art heart hospitals in Delhi NCR like Medanta – The Medicity, National Heart Institute, All India Institute of Medical Sciences (AIIMS), RML Hospital, GB Pant Hospital, Jaipur Golden Hospital, etc. The money is transferred directly to the concerned hospital where surgery is to be done.

Drug Subsidy

The HCFI Fund has the right to print/publish/webcast/web post details of the patient including photos, and other details. (Under taking needs to be given to the HCFI Fund to publish the medical details so that more people can be benefitted). The HCFI Fund does not provide assistance for any emergent heart interventions.

Check List of Documents to be Submitted with Application Form Passport size photo of the patient and the family A copy of medical records Identity proof with proof of residence Income proof (preferably given by SDM)

The HCFI Fund has tied up with Helpline Pharmacy in Delhi to facilitate

BPL Card (If Card holder)

patients with medicines at highly discounted rates (up to 50%) post surgery.

Details of financial assistance taken/applied from other sources (Prime Minister’s Relief Fund, National Illness Assistance Fund Ministry of Health Govt of India, Rotary Relief Fund, Delhi Arogya Kosh, Delhi Arogya Nidhi), etc., if anyone.

The HCFI Fund has also tied up for providing up to 50% discount on imaging (CT, MR, CT angiography, etc.)

Free Diagnostic Facility

Free Education and Employment Facility

The Fund has installed the latest State-of-the-Art 3 D Color Doppler EPIQ 7C Philips at E – 219, Greater Kailash, Part 1, New Delhi.

HCFI has tied up with a leading educational institution and an export house in Delhi NCR to adopt and to provide free education and employment opportunities to needy heart patients post surgery. Girls and women will be preferred.

This machine is used to screen children and adult patients for any heart disease.

Laboratory Subsidy HCFI has also tied up with leading laboratories in Delhi to give up to 50% discounts on all pathological lab tests.

About Heart Care Foundation of India

Help Us to Save Lives The Foundation seeks support, donations and contributions from individuals, organizations and establishments both private and governmental in its endeavor to reduce the number of deaths due to heart disease in the country. All donations made towards the Heart Care Foundation Fund are exempted from tax under Section 80 G of the IT Act (1961) within India. The Fund is also eligible for overseas donations under FCRA Registration (Reg. No 231650979). The objectives and activities of the trust are charitable within the meaning of 2 (15) of the IT Act 1961.

Heart Care Foundation of India was founded in 1986 as a National Charitable Trust with the basic objective of creating awareness about all aspects of health for people from all walks of life incorporating all pathies using low-cost infotainment modules under one roof. HCFI is the only NGO in the country on whose community-based health awareness events, the Government of India has released two commemorative national stamps (Rs 1 in 1991 on Run For The Heart and Rs 6.50 in 1993 on Heart Care Festival- First Perfect Health Mela). In February 2012, Government of Rajasthan also released one Cancellation stamp for organizing the first mega health camp at Ajmer.

Objectives Preventive Health Care Education Perfect Health Mela Providing Financial Support for Heart Care Interventions Reversal of Sudden Cardiac Death Through CPR-10 Training Workshops Research in Heart Care

Donate Now... Heart Care Foundation Blood Donation Camps The Heart Care Foundation organizes regular blood donation camps. The blood collected is used for patients undergoing heart surgeries in various institutions across Delhi.

Committee Members

Chief Patron

President

Raghu Kataria

Dr KK Aggarwal

Entrepreneur

Padma Shri, Dr BC Roy National & DST National Science Communication Awardee

Governing Council Members Sumi Malik Vivek Kumar Karna Chopra Dr Veena Aggarwal Veena Jaju Naina Aggarwal Nilesh Aggarwal H M Bangur

Advisors Mukul Rohtagi Ashok Chakradhar

Executive Council Members Deep Malik Geeta Anand Dr Uday Kakroo Harish Malik Aarti Upadhyay Raj Kumar Daga Shalin Kataria Anisha Kataria Vishnu Sureka

This Fund is dedicated to the memory of Sameer Malik who was an unfortunate victim of sudden cardiac death at a young age.

Rishab Soni

HCFI has associated with Shree Cement Ltd. for newspaper and outdoor publicity campaign HCFI also provides Free ambulance services for adopted heart patients HCFI has also tied up with Manav Ashray to provide free/highly subsidized accommodation to heart patients & their families visiting Delhi for treatment.

http://heartcarefoundationfund.heartcarefoundation.org

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OBSTETRICS AND GYNECOLOGY

Timing of Elective Repeat Cesarean Section at Term and Neonatal Outcomes in a Peripheral Tertiary Hospital in West Bengal TAMAL KUMAR MANDAL*, PRATIMA GARAIN†, SANKAR MURMU‡, SIB SANKAR MURMU*, DEBJANI DEB#

ABSTRACT Background: Births by elective cesarean section (CS) have risen over the last decade worldwide, particularly before 39 weeks’ gestation in mothers with previous cesarean deliveries, which may be associated with unacceptably high risk of adverse neonatal outcomes. So, the optimal timing of these deliveries needs to be determined with recent recommendations to delay births by elective CS until 39 weeks. Aims: To evaluate the association between the gestational age at delivery and neonatal outcomes after elective repeat CS between 37 and 40 completed weeks, so that timing of elective repeat CS can be mapped out without compromising neonatal and maternal outcomes among the low and middle socioeconomic mothers in a peripheral tertiary hospital of West Bengal whose outcome was not studied extensively. Material and methods: This is a prospective observational comparative study of viable singleton neonates delivered by elective repeat CS at Bankura Sammilani Medical College and Hospital, Bankura, West Bengal. During the study period, from 1st January 2016 to 31st December 2016, a total of 101 mothers, delivered by elective repeat CS at term, were stratified into two gestational age groups with early term Group A (between 37 weeks, 0 day and 38 weeks, 6 days) compared with the reference group of full-term Group B (between 39 weeks, 0 day and 40 weeks, 6 days). The neonatal outcomes examined were serious respiratory morbidity (respiratory distress syndrome, transient tachypnea of newborn), depression at birth, neonatal sepsis, nursery admission. Results: Out of 101 elective repeat cesarean deliveries at term, 46.53% were performed between 37 weeks, 0 day and 38 weeks, 6 days; 53.46% between 39 weeks, 0 day and 40 weeks, 6 days. We found a significant risk in the early term Group A in comparison to the reference group of full-term Group B for development of neonatal respiratory complications i.e., respiratory distress syndrome (p = 0.031), transient tachypnea of newborn (p = 0.003); neonatal sepsis (p = 0.031), admission in sick newborn care unit (p = 0.003). Conclusion: Elective repeat CS performed at 37-38 completed weeks is associated with poorer neonatal outcomes compared to those delivered at 39-40 completed weeks. This study supports recent recommendations to delay delivery by elective repeat CS until 39 week of gestation if possible.

Keywords: Previous cesarean delivery, elective repeat cesarean section, neonatal outcomes, respiratory complications

INTRODUCTION, REVIEW OF LITERATURE, AIMS AND OBJECTIVES Elective cesarean section (CS) i.e., (a delivery performed in the absence of labor or other recognized medical or obstetrical indications for delivery) rates

*RMO cum Clinical Tutor †Associate Professor ‡Postgraduate Trainee #Assistant Professor Dept. of Obstetrics and Gynecology Bankura Sammilani Medical College and Hospital, Bankura, West Bengal Address for correspondence Dr Tamal Kumar Mandal North Pratapbagan, Sarani No - 5, Bankura - 722 101, West Bengal E-mail: tamal.cool2011@gmail.com

have risen over the last decade worldwide because of increasing maternal age, advanced fetal monitoring, assisted reproductive technology (ART), post cesarean pregnancy, breech delivery and ultimately maternal request. This has the potential for a significant impact on public health and healthcare costs because of the morbidity associated with this subgroup.1,2 Elective cesarean delivery may be scheduled to accommodate patient and physician convenience and there is a risk that it may be performed earlier than is appropriate. Infants born before 39 weeks of gestation are at increased risk for neonatal adverse respiratory outcomes and the risk increases progressively as gestational age at birth declines.3,4 As compared with the infants born vaginally, those born by CS are at increased risk for adverse respiratory outcomes,

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OBSTETRICS AND GYNECOLOGY especially when delivery occurs before the onset of labor.3-6 This increased risk persists even in the infants who are delivered by CS at term (i.e. at or beyond 37 completed weeks of gestation). Human lung development begins at early embryonic life (3-7 weeks) and it continues through several stages up to the early childhood. Period of saccular development extends from 24th to 28th weeks. Final developmental of alveolar period extends from 36th weeks to 2 years after birth. The main determinants of extrauterine survival are with two issues. First is formation of surfactant, the phospholipids secreted by the type II pneumocytes, situated in the pulmonary alveoli. Several hormones and growth factors regulate the surfactant synthesis of which glucocorticosteriod is the most important to accelerate the process. The second important issue is the transition in the mechanics of breathing from intermittent fetal to continuous in neonatal life following the process of birth. Here comes the role of chest wall respiratory muscles and the diaphragm. For effective gas exchange to occur, alveolar spaces must be cleared of excess fluid and pulmonary blood flow must be increased to match ventilation with perfusion. Failure of either of these events can jeopardize neonatal transition and cause the infant to develop respiratory distress- transient tachypnea of newborn and hyaline membrane disease.7 The ability of a neonate to self-resuscitate itself at birth after remaining “submerged” in fluid for much of its life is truly remarkable, considering victims of neardrowning faced with similar amounts of fluid in the lungs do so poorly. Bland et al, Jain et al8,9 said that amiloride-sensitive sodium transport by lung epithelia through epithelial sodium channels (ENaC) has emerged as a key event in the transepithelial movement of alveolar fluid. Canessa et al10,11 said indeed, cDNAs that encode amiloride-sensitive sodium channels in other sodium transporting epithelia have also been cloned from airway epithelial cells. The lung epithelium is believed to switch from a predominantly chloride secreting membrane at birth to a predominantly sodium absorbing membrane after birth. We are still far from a complete understanding of the mechanisms by which fetal lungs are able to clear themselves of excessive fluid at birth. The evidence-based management of term pregnancy with a history of previous CS is cesarean delivery but the timing of such delivery at term has been a subject of debate in obstetrics. Obstetricians need to consider

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Indian Journal of Clinical Practice, Vol. 27, No. 12, May 2017

several areas while deciding the timing of delivery. The few important issues are: ÂÂ

Risk of mother and newborn if the pregnancy continued

ÂÂ

The resources available at the place of delivery and even after discharge for such neonates

ÂÂ

The benefits of delivery need to be weighed against the risk to the mother or the newborn or the mother and the newborn both. Ultimately, the decision of delivery is based on individual woman.

Approximately, 40% of the 1.3 million cesarean deliveries performed annually in the United States are repeat procedures and the number of cesarean deliveries continues to rise, so the timing of elective cesarean delivery has increasingly important public health implications.12,13 A major reason for this increase is the decline in the rate of attempted vaginal birth after cesarean delivery.14 Tita et al15 said that delivery at 37-38 completed weeks as compared with delivery at 39 weeks (for neonatal benefit) is not associated with improved composite adverse maternal outcomes. A composite of severe adverse maternal outcomes only that included maternal death, uterine rupture or need for hysterectomy was also not decreased by earlier delivery compared with elective delivery at 39 weeks. Tita et al15 also noticed those elective repeat cesareans before 39 weeks of gestation are common and are associated with respiratory and other adverse neonatal outcomes. Early elective delivery was associated with a twofold increased frequency of maternal hospitalization for 5 days or more, as compared to elective delivery at 39 weeks. Additional analyses suggested that this increase in prolonged maternal hospital stay may be more attributable to prolonged neonatal hospitalization (women remain longer in the hospital because of their babies) than to increased maternal morbidity. With the recent trend of increasing elective repeat CS rates, it is important to confirm and quantify the impact on neonatal outcomes. The aim of this study was to report the effect of the timing of elective repeat CS deliveries at term on neonatal outcomes. The results will provide further evidence to guide the policy on the optimal timing of these deliveries. MATERIAL AND METHODS A prospective, observational, comparative study was carried out in the Dept. of Obstetrics and Gynecology in Bankura Sammilani Medical College and Hospital, Bankura, West Bengal from 1st January 2016 to 31st December 2016. During the study period, the

OBSTETRICS AND GYNECOLOGY mothers with gestational age between 37 weeks, 0 days to 40 weeks, 6 days with a history of one previous CS, not in labour, without scar tenderness, with hemoglobin % (Hb%) â&#x2030;Ľ10 gm%, hemodynamically stable (normal maternal pulse rate and blood pressure [BP]) with a singleton live fetus, in cephalic presentation, without any congenital anomaly with adequate liquor were included in the study. Patients with gestational age <37 weeks, 0 day and >40 weeks, 6 days; more than one previous CS, with scar tenderness, multifetal pregnancy, malpresentation, scanty liquor, intrauterine growth restriction (IUGR), intrauterine fetal death (IUFD), antepartum hemorrhage, Hb% <10 gm%, hemodynamically unstable (maternal tachycardia, low or high BP), pregnancy-induced hypertension (PIH), heart disease, chronic renal disease, liver disease were excluded. All the mothers were assessed by history, clinical examination and ultrasonography for fetal maturity. Data about sociodemographic variables, detailed obstetrical history, indication for CS were collected in data sheet. Gestational age was determined by treating surgeons with the use of standard criteria16 that took into consideration the clinical history and the results of the earliest ultrasound examination. If the findings on ultrasound examination were consistent with a gestational age based on first date of the last menstrual period, gestational age was determined according to the date of the last menstrual period; if the date of the last menstrual period was uncertain or the findings on ultrasound examination were inconsistent with a gestational age based on the date of the last menstrual period, gestational age was determined according to the results of the ultrasound examination. Decision about the timing of cesarean delivery was taken by the respective treating surgeons. Where a conservative approach was taken till an optimum gestational age the mothers were followed up by daily clinical monitoring (maternal pulse rate, BP, pallor and uterine contractions, scar tenderness), daily fetal movement count, twice in a week CTG, routine USG for fetoplacental profile, liquor volume (AFI) and umbilical artery Doppler study after every 2 weeks. Ethical clearance was obtained from College Ethical Committee. Appropriate written consent was taken from the pregnant women and relatives. Data sheets were given to the sick newborn care unit (SNCU) and to the operation theater (OT). All cesarean deliveries were conducted by experienced resident surgeons. After the delivery of the baby in OT-indication of elective CS, Apgar score at 1 and 5 minutes, resuscitation needed or not, birth weight, need of SNCU admission were

documented by resident doctors and submitted to the OT sister-in-charge. Subsequent neonatal outcomes were documented until the baby was discharged. All the pregnant mothers fulfilling the inclusion criteria were stratified into two gestational age groups with early term Group A (between 37 weeks, 0 day and 38 weeks, 6 days) compared with the reference group of full-term Group B (between 39 weeks, 0 day and 40 weeks, 6 days). Collected data were put into Microsoft excel version 7 (Microsoft Corporation, Redmond, WA, USA) and analyzed by Epi Info version 3.5.1 Software (Centers for Disease Control and Prevention, Atlanta, gestational age, USA). Categorical data was described as frequency and percentage. The chi-square (Ď&#x2021;2) test was performed to compare categorical data. P < 0.05 was considered as statistically significant. OBSERVATION AND DISCUSSION In this study, total 101 antenatal mothers with previous one CS with 37-40 completed weeks of gestational age were selected for elective CS. About 46.53% (47/101) CS were done between 37 weeks, 0 day and 38 weeks, 6 days i.e., at early term and 53.46% (54/101) in between 39 weeks, 0 day and 40 weeks, 6 days i.e., at full-term (Table 1 and Fig. 1) and this is supported by Tita et al15 who showed that 35.8% of CS were performed before 39 completed weeks of gestation and 49.1% at 39 weeks of gestation. Table 1. Distribution of Mothers According to Gestational Age Gestational age

No. of mothers

Percentage (%)

Group A

46.53

Group B

53.46

Group A

53.46%

Group B

46.53%

Figure 1. Distribution of mothers according to gestational age.

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OBSTETRICS AND GYNECOLOGY We found that there was significantly higher risk in the early cesarean group (early term Group A) of various neonatal outcomes including respiratory complications. In the early cesareans group, the respiratory complications were statistically significant, manifested most often as respiratory distress syndrome (85.7%) (p = 0.031), transient tachypnea of the newborn (84.6%) Table 2. Different Neonatal Outcomes Between Two Groups Parameters

Group A Group B (%) (%)

Total (%)

Chi-square (P value)

TTN Yes

11 (84.6)

2 (15.4) 13 (100)

36 (40.9) 52 (59.1) 88 (100)

0.003

Apgar score at 5 minutes <7 at 5 minutes 5 (71.40) 2 (28.60) 7 (100)

0.171

â&#x2030;Ľ7 at 5 minutes 42 (44.70) 52 (55.30) 94 (100) Birth asphyxia Yes

5 (62.5)

3 (37.5)

8 (100)

0.346

42 (45.2) 51 (54.8) 93 (100)

SNCU admission Yes

11 (84.65) 2 (15.40) 13 (100)

36 (40.90) 52 (59.10) 88 (100) 6 (85.7)

41 (43.6) 53 (56.4) 94 (100)

1 (14.3)

7 (100)

9 (81.8)

38 (42.7) 52 (57.3) 90 (100)

2 (18.2) 11 (100)

0.031

0.013

TTN

Apgar score at 5 minutes

Birth asphyxia

SNCU admission

8 6

RDS

6 5

3 2

2 0

2 1

Group A

Group B

Figure 2. Different neonatal outcomes between two groups.

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2. Martin JA, Hamilton BE, Ventura SJ, Osterman MJ, Kirmeyer S, Mathews TJ, et al. Births: final data for 2009. Natl Vital Stat Rep. 2011;60(1):1-70. 3. Morrison JJ, Rennie JM, Milton PJ. Neonatal respiratory morbidity and mode of delivery at term: influence of timing of elective caesarean section. Br J Obstet Gynaecol. 1995;102(2):101-6. 4. Zanardo V, Simbi AK, Franzoi M, SoldĂ G, Salvadori A, Trevisanuto D. Neonatal respiratory morbidity risk and mode of delivery at term: influence of timing of elective caesarean delivery. Acta Paediatr. 2004;93(5):643-7. 5. Richardson BS, Czikk MJ, daSilva O, Natale R. The impact of labor at term on measures of neonatal outcome. Am J Obstet Gynecol. 2005;192(1):219-26. 6. Levine EM, Ghai V, Barton JJ, Strom CM. Mode of delivery and risk of respiratory diseases in newborns. Obstet Gynecol. 2001;97(3):439-42.

Neonatal sepsis

This study focuses the light on a new dark corner of neonatal morbidities secondary to unjustified early elective repeat CS. Conversely, a significant reduction in the neonatal morbidities may be obtained if the timing of planned elective repeat CS is postponed till or beyond 39 weeks of gestation if possible. It seems to be the first logical step in reducing iatrogenic prematurity and excess risk of respiratory distress in newborns. Of course thanks to the presence of a SNCU nearby.

1. Ramachandrappa A, Jain L. Elective cesarean section: its impact on neonatal respiratory outcome. Clin Perinatol. 2008;35(2):373-93, vii.

TTN = Transient tachypnea of newborn; SNCU = Sick newborn care unit; RDS = Respiratory distress syndrome. 12

CONCLUSION

REFERENCES

Neonatal sepsis Yes

In this study, we found a very significant association between early cesareans group and neonatal sepsis (81.8%) (p = 0.013) and subsequent admission in SNCU (84.65%) (p = 0.003). This is also supported by Wilmink et al.18

0.003

RDS Yes

(p = 0.003) and this risk decreased as advancing the gestational age (Table 2 and Fig. 2) that is in line with those found by Tita et al,15 Signore et al,17 Wilmink et al,18 Levine et al6 and Van den Berg et al.19 Our data did not find any difference in Apgar score at 5 minutes (p = 0.171) or birth asphyxia (p = 0.345) between early and late cesareans.

Indian Journal of Clinical Practice, Vol. 27, No. 12, May 2017

7. Jain L, Eaton DC. Alveolar fluid transport: a changing paradigm. Am J Physiol Lung Cell Mol Physiol. 2006;290(4):L646-8. 8. Bland RD. Loss of liquid from the lung lumen in labor: more than a simple "squeeze". Am J Physiol Lung Cell Mol Physiol. 2001;280(4):L602-5.

OBSTETRICS AND GYNECOLOGY 9. Jain L, Chen XJ, Ramosevac S, Brown LA, Eaton DC. Expression of highly selective sodium channels in alveolar type II cells is determined by culture conditions. Am J Physiol Lung Cell Mol Physiol. 2001;280(4): L646-58.

15. Tita AT, Landon MB, Spong CY, Lai Y, Leveno KJ, Varner MW, et al; Eunice Kennedy Shriver NICHD MaternalFetal Medicine Units Network. Timing of elective repeat cesarean delivery at term and neonatal outcomes. N Engl J Med. 2009;360(2):111-20.

10. Canessa CM, Horisberger JD, Rossier BC. Epithelial sodium channel related to proteins involved in neurodegeneration. Nature. 1993;361(6411):467-70.

16. American Academy of Pediatrics, American College of Obstetricians and Gynecologists. Guidelines for Perinatal Care. 6th Edition, Elk Grove Village, IL: American Academy of Pediatrics; 2007.

11. Canessa CM, Schild L, Buell G, Thorens B, Gautschi I, Horisberger JD, et al. Amiloride-sensitive epithelial Na+ channel is made of three homologous subunits. Nature. 1994;367(6462):463-7. 12. M enacker F. Trends in cesarean rates for first births and repeat cesarean rates for low-risk women: United States, 1990-2003. Natl Vital Stat Rep. 2005;54(4):1-8. 13. Menacker F, Declercq E, Macdorman MF. Cesarean delivery: background, trends, and epidemiology. Semin Perinatol. 2006;30(5):235-41.

17. Signore C, Klebanoff M. Neonatal morbidity and mortality after elective cesarean delivery. Clin Perinatol. 2008;35(2):361-71, vi. 18. Wilmink FA, Hukkelhoven CW, Lunshof S, Mol BW, van der Post JA, Papatsonis DN. Neonatal outcome following elective cesarean section beyond 37 weeks of gestation: a 7-year retrospective analysis of a national registry. Am J Obstet Gynecol. 2010;202(3):250.e1-8.

19. Van den Berg A, van Elburg RM, van Geijn HP, Fetter WP. Neonatal respiratory morbidity following elective 14. Gregory KD, Curtin SC, Taffel SM, Notzon FC. Changes in caesarean section in term infants. A 5-year retrospective indications for cesarean delivery: United States, 1985 and study and a review of the literature. Eur J Obstet Gynecol Reprod Biol. 2001;98(1):9-13. 1994. Am J Public Health. 1998;88(9):1384-7. ■■■■

Cab Safety Measures for Women Included in the New Taxi Policy Guidelines The safety measures, recommended by the Ministry of Women and Child Development (WCD), concerning safety of women commuters availing of cab services have been included in the new Taxi Policy Guidelines. Recommendations of WCD Ministry included in the New Taxi Policy Guidelines are: ÂÂ

The taxis should be mandatorily fitted with GPS panic devices.

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For the safety of women and child passengers, the central locking system in the taxis should not be allowed.

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The driver's identification along with the photo and registration number of the vehicle should also be prominently displayed in the taxi.

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Violation of the stipulated rules by the taxi operators/drivers should be strictly dealt in accordance with law.

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Sharing of seat should be subject to willingness of passengers. (Press Information Bureau, Ministry of Women and Child Development, April 12, 2017)

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OBSTETRICS AND GYNECOLOGY

Analysis of Cesarean Deliveries According to Robson’s Ten Group Classification at a Tertiary Care Hospital in Jaipur MEETA GUPTA*, SHAILESH JAIN*, RP KHUTETA†

ABSTRACT Objective: To analyze cesarean section (CS) rate, classify according to the Robson’s classification and interpret them clinically. Material and methods: This retrospective study was conducted at Dept. of Obstetrics and Gynecology, RUHS College of Medical Sciences, a tertiary teaching hospital in Jaipur (Rajasthan), North India. The data were collected for all women delivered between 1st January 2016 to 31st December 2016 and proportions in various groups as per Robson’s Ten Group Classification System (TGCS), were calculated. Results: The Robson’s TGCS was easily applied in this dataset of 2,959 deliveries. The overall CS rate was 31.46%. Groups 1 and 3 represented 61.9% of the total obstetric population. The largest contributions to the total CS rate are Group 1 (30.0%) and Group 5 (32.2%). Group 3 which was the second largest group contributed 4.5% to the overall CS rate. Group 2 and Group 4 had high group CS rates of 42.1% and 27.1%, respectively, although the total group size was small (n = 470; 15.88%). Conclusion: The Robson’s TGCS is based on well-defined parameters. It helped to identify the main groups of subjects who contribute most to the overall CS rate. It also helped to identify subgroups requiring close monitoring for more in-depth analysis of the indications for CS. It is important to focus on the first four groups of Robson’s TGCS, which constitute about 77.7% of all deliveries. It is in these low risk groups that one is likely to find the highest and medically unjustified indications for CS.

Keywords: Robson’s ten group classification, cesarean section

he cesarean section (CS) rate has been increasing worldwide in last 50 years and in some regions it exceeds 30%.1 The rise in CS rates is becoming a major public health concern. The factors that are causing this phenomenon as well as the strategies to reduce cesarean birth were analyzed intensively.3

There are major difficulties in evaluation and comparing the results of studies according to the mode of deliveries. A variety of classification systems have been proposed with some limitation. In 2001, Robson presented a new classification system, the Ten Group Classification System (TGCS),4 which fulfils current international

*Assistant Professor †Professor and Head Dept. of Obstetrics and Gynecology RUHS College of Medical Sciences, Jaipur, Rajasthan Address for correspondence Dr Meeta Gupta Swasthya Mangalam Plot No. 4, Moti Nagar, Gurjar Ki Thadi, Jaipur - 302 019, Rajasthan E-mail: swasthyamangalam@gmail.com

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Indian Journal of Clinical Practice, Vol. 27, No. 12, May 2017

and local needs, allows auditing and comparing CS rates across different settings and, the most important, helps to create and implement effective strategies specifically targeted to optimize CS rates.5 Robson’s TGCS categorizes women into 10 groups which are mutually exclusive and totally inclusive, clinically relevant and prospectively identifiable.5 Robson’s classification depends on women’s previous obstetric history, gestation age, onset of labor, fetal presentation and number of fetuses without needing the indication of induction. The objective of this study was to analyze CS birth rates using Robson's TGCS and to identify the main contributors to the overall CS rate at the Dept. of Obstetrics and Gynecology, RUHS College of Medical Sciences, Jaipur, Rajasthan. MATERIAL AND METHODS This was a retrospective study, done at Dept. of Obstetrics and Gynecology, RDBP Jaipuria Hospital, RUHS College of Medical Sciences, Jaipur, Rajasthan.

OBSTETRICS AND GYNECOLOGY All women who delivered between 1st January 2016 to 31st December 2016 were included. An approval was sought from Hospital Ethical and Research Committee, RUHS College of Medical Sciences, Jaipur, Rajasthan. The data were compiled from the departmental records according to the Robson’s TGCS. All relevant obstetric information namely parity, gestational age, mode of previous delivery, spontaneous or induced labor, number of fetuses and presentation were entered into Microsoft Excel sheet and an analysis was carried out. Total birth in the year was calculated. The deliveries were classified according to Robson’s TGCS as follows: Robson’s Ten Group Classification System Group

Description

Nulliparous, single cephalic, ≥37 weeks, in spontaneous labor

Nulliparous, single cephalic, ≥37 weeks, induced or CS before labor

Multiparous (excluding previous CS), single cephalic, ≥37 weeks, in spontaneous labor

Multiparous (excluding previous CS), single cephalic, ≥37 weeks, induced or CS before labor

Previous CS, single cephalic, ≥37 weeks

All nulliparous breeches

All multiparous breeches (including previous CS)

All multiple pregnancies (including previous CS)

All abnormal lies (including previous CS)

All single cephalic, ≤36 weeks (including previous CS)

For data analysis, the distribution of cases among all 10 groups of Robson’s TGCS for total births, for CS deliveries and contribution of each group to the overall CS rates was done. CS rates were calculated as the ratio of cesarean deliveries to total deliveries. RESULTS There were 2,028 vaginal deliveries and 931 cesarean deliveries during this study period. The overall CS rate was 31.46%. Table 1 shows that the Robson’s Group 1 had the maximum number of subjects (n = 946), of which 29.59% (n = 280) had CS. The second largest group of subjects were in Robson’s Group 3 (n = 890) of which 4.71% (n = 42) underwent CS. The group CS rate% for induced labor in Robson’s Group 2 and Group 4 were high at 42.07% and 27.05%, respectively. The smallest group was Group 9, with only 9 (0.30%) women having abnormal lies. The rates of CS were 100% for the Group 9, 72.46% for Group 6 and 85.71% for Group 5. Table 2 shows that Group 5 (32.22%) made the greatest contribution to the total CS rate. Group 1 (30.02%) had the second highest contribution to the CS rate and then Group 2 (17.40%) placed third. DISCUSSIONS Robson’s TGCS was successfully applied to this dataset of 2,959 deliveries. In our study, the CS rate was 31.46%. Similar high rates were observed in study by Patel et al6 around 40%, 25.7% by Katke et al,7 25.17% by Yadav et al8 and 32.6% by Dhodapkar et al9 from various hospitals in India.

Table 1. Robson’s Group Specific, Group CS Rate (%) Robson’s Group

Total deliveries

Vaginal deliveries

Cesarean deliveries

Group CS rate

(%)

946

31.97

666

70.41

280

29.59

385

13.01

223

27.93

162

42.07

890

30.07

848

95.29

04.71

2.87

72.95

27.05

350

11.82

14.29

300

85.71

2.33

27.54

72.46

1.89

51.79

48.21

0.74

63.64

36.36

0.30

00.00

100.0

145

4.90

115

79.32

20.68

Total

2,959

2,028

931

31.46

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OBSTETRICS AND GYNECOLOGY Table 2. Relative Contribution of Each Group to Total CS Rate Robson’s Group Total deliveries Vaginal deliveries Cesarean deliveries No. % No. % 1 946 666 70.41 280 29.59 2 385 223 27.93 162 42.07 3 890 848 95.29 42 04.71 4 85 62 72.95 23 27.05 5 350 50 14.29 300 85.71 6 69 19 27.54 50 72.46 7 56 29 51.79 27 48.21 8 22 14 63.64 8 36.36 9 9 00 00.00 9 100.0 10 145 115 79.32 30 20.68

Similar high rates of 32-38% were also observed in a study done by Abdel-Aleem et al10 in Egypt. A study from Iran reported an increase from 35% to 40%.11 A World Health Organization (WHO) global survey using the Ten-group classification found that the overall rate of CS was 35.4%.12 Dr M Robson in 2001 proposed that Groups 1 and 2 usually account for 35-40% of all deliveries. Group 1 should be larger than Group 2. Groups 3 and 4 usually account for 30-40% of women; Group 3 should be larger than Group 4. Group 5 should comprise no more than 10% of women. Groups 6 and 7 should include 3-4% of all women, and Group 6 is usually twice the size of Group 7. Group 8 should include 1.5-2% of women, unless the site has an IVF program or is a referral center. Group 9 should comprise 0.2-0.6% of women with a CS rate of 100%. Group 10 includes approximately 5% of women. In our study, Groups 1 and 2 accounted for 44.98% and Group 1 (n = 946) was larger than Group 2 (n = 385); 32.94% women were in Groups 3 and 4 and Group 3 (n = 890) was larger than Group 4 (n = 85). Group 5 comprised of 11.82% of women. In a WHO study, women with single cephalic pregnancy at term without previous CS and who entered into labor spontaneously (Group 1 and 3) represented 60% of total obstetric population.3 In our study, these groups constituted 62.04%, similar to WHO study. Groups 6 and 7 included 4.22% of all women. Group 8 had 0.74% of women. Group 9 comprised of 0.30% of women and 4.90% women were in Group 10. In our study, the CS rate in Group 1 was 29.59% which was in accordance with studies done in other parts of India by Shirsath et al13 (19.6%), Kansara et al14 (20.11%), Yadav et al8 (25.44%) and Dhodapkar et al9 (23.5%) and

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Contribution to total CS rate (%) 30.02 17.40 04.51 02.47 32.22 05.37 02.90 00.85 00.96 03.22

is closer to the WHO Global Survey in Latin America18 (27.7%), but was higher than a similar study done in Oman by Kazmi at al15 (13%). According to Dr Robson, a CS rate for Group 1 less than 15% is desirable. The higher-than–acceptable CS rate is probably because of high CS rate for nonreassuring fetal status (NRFS) pattern.16 Group 2 had high group CS rate i.e., 42.07%, very similar to Yadav et al8 (47.28%), but higher than Dhodapkar et al9 (33.5%), although the total group size was small (13.0%). Its contribution to the overall CS rate was 17.40%, similar to Dhodapkar et al9 (14.2%). Dr Robson stated that the CS rate for Group 3 should be 2.5-3%. Compared with other groups, these women are less likely to have obstetric indication for CS, since they present very low risk in general. Hence, the CS rate in this group can be expected to be low. In our study, the CS rate in Group 3 was 4.71% which again was in accordance with the studies by Shirsath et al13 (4.8%) and Kansara et al14 (5.4%). The CS rate in our study in Group 4 was 27.05%, which was higher than other Indian studies, Dhodapkar et al9 (12.2%) and Shirsath et al13 (6.6%) but lower than Yadav et al8 (34.74%). According to Dr Robson, the CS rate in Group 4 should be below 20%. The higher-than–acceptable CS rate is probably because of high CS rate for NRFS pattern.16 According to Dr Robson, with good perinatal outcomes, a CS rate of 50-60% in Group 5 is excellent. In our study, the CS rate in Group 5 was 85.71% which is in accordance with those observations done by Shirsath et al13 (87.2%) and Dhodapkar et al9 (89.6%) and this was lower than the CS rate in study by Kansara et al14 (98.3%). Group 6 through 9 presented high rate of CS due to the particular obstetric condition within which these are defined. However, their contribution to the overall CS rate was 10.08% similar to Yadav et al8

OBSTETRICS AND GYNECOLOGY (11.44%) and Dhodapkar et al9 (13.0%). In Group 10, CS rate in our study is 20.68%, very similar to other Indian study by Yadav et al8 (21.58%) and this was lower than the CS rate in study by Dhodapkar et al9 (32.9%). If the CS rate in Group 10 is 15-16% it suggests a high proportion of women with spontaneous onset of preterm labor. Higher CS rates (30-40%) in this Group reflect more women with CS following preterm labor induction or a cesarean delivery without labor. In our study, Group 10 contributed 3.22% to the overall CSR, lesser than Dhodapkar et al9 (7.4%) and Yadav et al8 (12.9%). Although women with term singleton cephalic pregnancy with a previous CS (Group 5) represented only 11.82% of the obstetric population (similar to WHO Global survey - 11.4%), this group was the largest contributor to the overall CS rate i.e., 32.22%. (similar to WHO Global Survey - 26.7%). According to a study done by Wanjari et al17 in Maharashtra, repeat CS accounted for 32.8% of all CS. Similar results were also obtained by Dhodapkar et al9 (40.1%), Shirsath et al13 (54.5%) and Kansara et al14 (46.1%). Similar observation was made in a study done by Abdel-Aleem et al10 in Egypt where 30% CS were repeat CS. The second and third largest contributors to the overall CS rate were Group 1 and Group 2, which were responsible for 30.02% and 17.40% of all cesarean deliveries, respectively. Our findings were similar to Dhodapkar et al9 (24.0%; 14.2%) The Robson’s TGCS is based on well-defined parameters. It helps to identify the main groups of subjects who contribute most to the overall CS rate. It also helps to identify subgroups requiring close monitoring for more in-depth analysis of the indications for CS. It is important to focus on the first four groups of Robson’s TGCS, which constitute about 77.92% of all deliveries. It is in these low risk groups that one is likely to find the highest and medically unjustified indications for CS. It is thus important that efforts to reduce the overall CS rate should focus on reducing the primary CS rates and also encouraging vaginal birth after CS in patients with previous lower segment CS.

Available at: http://www.who.int/healthsystems/topics/ financing/healthreport/29DeterminantsC-section.pdf 4. Robson M. Classification of caesarean sections. Fetal Matern Med Rev. 2001;12(1):23-39. 5. Torloni MR, Betran AP, Souza JP, Widmer M, Allen T, Gulmezoglu M, et al. Classifications for cesarean section: a systematic review. PLoS One. 2011;6(1):e14566. 6. Patel RV, Gosalia EV, Deliwala KJ, Vasa PB, Pandya VM. Indications and trends of caesarean birth delivery in the current practice scenario. Int J Reprod Contracept Obstet Gynecol. 2014;3(3):575-80. 7. Katke RD, Zarariya AN, Desai PV. LSCS audit in a tertiary care center in Mumbai: to study indications and risk factors in LSCS and its effect on early perinatal morbidity and mortality rate. Int J Reprod Contracept Obstet Gynecol. 2014;3(4):963-8. 8. Yadav RG, Maitra N. Examining cesarean delivery rates using the Robson’s Ten-group classification. J Obstet Gynecol India. 2016;66(Suppl 1):1-6. 9. Dhodapkar SB, Bhairavi S, Daniel M, Chauhan NS, Chauhan RC. Analysis of caesarean sections according to Robson’s ten group classification system at a tertiary care teaching hospital in South India. Int J Reprod Contracept Obstet Gynecol. 2015;4(3):745-9. 10. Abdel-Aleem H, Shaaban OM, Hassanin AI, Ibraheem AA. Analysis of cesarean delivery at Assiut University Hospital using the Ten Group Classification System. Int J Gynaecol Obstet. 2013;123(2):119-23. 11. Yazdizadeh B, Nedjat S, Mohammad K, Rashidian A, Changizi N, Majdzadeh R. Cesarean section rate in Iran, multidimensional approaches for behavioral change of providers: a qualitative study. BMC Health Serv Res. 2011;11:159. 12. Betrán AP, Gulmezoglu AM, Robson M, Merialdi M, Souza JP, Wojdyla D, et al. WHO global survey on maternal and perinatal health in Latin America: classifying caesarean sections. Reprod Health. 2009;6:18. 13. Shirsath A, Risbud N. Analysis of cesarean section rate according to Robson’s 10-group classification system at a tertiary care hospital. Int J Sci Res. 2014;3(1):401-2. 14. Kansara V, Patel S, Aanand N, Muchhadia J, Kagathra B, Patel R. A recent way of evaluation of cesarean birth rate by Robson’s 10-group system. J Med Pharmaceut Allied Sci. 2014;01:62-70.

REFERENCES

15. Kazmi T, Saiseema S 5th, Khan S. Analysis of cesarean section rate - according to Robson's 10-group Classification. Oman Med J. 2012;27(5):415-7.

1. National Institutes of Health state-of-the-science conference statement: Cesarean delivery on maternal request. March 27-29, 2006. Obstet Gynecol. 2006;107(6):1386-97.

16. Perinatal Services BC. Examining cesarean delivery rates in British Columbia using the Robson Ten classification. Part 1: Understanding the Ten Groups. Vancouver, BC; 2011.

2. World Health Organization. Appropriate technology for birth. Lancet. 1985;2(8452):436-7.

17. Wanjari SA. Rising caesarean section rate: a matter of concern? Int J Reprod Contracept Obstet Gynecol. 2014;3:728-31.

3. Lauer JA, Betran AP, Merialdi M, Wojdyla D. Determinants of caesarean section rates in developed countries: supply, demand and opportunities for control. World Health Report (2010).

18. Denk CE, Kruse LK, Jain NJ. Surveillance of cesarean section deliveries, New Jersey, 1999-2004. Birth. 2006;33(3):203-9. Indian Journal of Clinical Practice, Vol. 27, No. 12, May 2017

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Hypertensive Disorders in Pregnancy: An Obstetric Catastrophe SURYA MALIK*, KHUSHPREET KAUR†, PARNEET KAUR‡

ABSTRACT Objective: To study the contribution of hypertensive disorders in pregnancy in maternal and fetal morbidity and mortality and to study its relation with various maternal factors like antenatal care during pregnancy, socioeconomic status education and parity. Methods: The present study was conducted on a prospective basis for 1 year from 1st February 2011 to 31st January 2012 in the Dept. of Obstetrics and Gynecology, Govt. Medical College, Patiala, Punjab. All the cases with hypertensive disorders of pregnancy, presenting as obstetrical emergency were included in the study. A detailed history including age, parity, gestational age, antenatal care during pregnancy, socioeconomic status and obstetrical history, medical or surgical disorders was taken into account. Results: Hypertensive disorders of pregnancy contributed 35.32% of all the obstetrical emergencies. Various maternal complications that were encountered were abruptio placenta (23.6%), acute renal failure (2.25%), pulmonary edema (3.37%), HELLP syndrome (5.62%), coagulopathy (2.25%) and postpartum hemorrhage (13.48%). Maternal mortality was 3.45%. Fetal mortality was 33.33%. Conclusions: Through this study, it was concluded that hypertensive disorders of pregnancy is a leading cause of maternal morbidity and mortality. It is more common in unbooked cases with low socioeconomic status and poor access to antenatal care.

Keywords: Hypertensive disorders of pregnancy, HELLP syndrome

ypertensive disorders represent the most common medical condition of pregnancy affecting between 10 to 15% of all gestations and account for approximately a quarter of all antenatal admissions.1 According to World Health Organization’s (WHO’s) systematic review on maternal mortality worldwide, hypertensive disease remains a leading cause of direct maternal mortality. Together with hemorrhage and infection, hypertension forms the deadly triad that contributes to morbidity and mortality during pregnancy and child birth.2 Around 5,85,000 women die each year due to pregnancy related causes, 98% of these occur in developing countries. It is estimated that 13% of maternal deaths are due to hypertensive disorder of pregnancy particularly in eclampsia.3

*Junior Resident †Professor ‡Associate Professor Dept. of Obstetrics and Gynecology Govt. Medical College, Patiala, Punjab Address for correspondence Dr Surya Malik A2A, House No. 159, Janakpuri West, New Delhi E-mail: surya85.sm@gmail.com

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Hypertensive disorders in pregnancy can be divided into four well-defined groups: ÂÂ

Gestational hypertension

ÂÂ

Pre-eclampsia, eclampsia

ÂÂ

Chronic hypertension

ÂÂ

Essential

Secondary

Pre-eclampsia hypertension.

superimposed

chronic

Eclampsia is an extremely severe form of pre-eclampsia characterized by the sudden onset of generalized tonic-clonic seizures. Eclampsia occurs antepartum in 35-45%, intrapartum in 15-20% and postpartum in 35-45% of cases.4 Approximately 1 in 2,000 deliveries is complicated by eclampsia in developed countries, whereas the incidence in developing countries is estimated around 1 in 100 to 1 in 1,700 cases.5 In the developing countries, there is low utilization of both antenatal and intrapartum care and the patients present to the hospital only as a final resort. The opportunity to detect women at the pre-eclamptic stage is therefore usually lost. In addition, the WHO estimates that only 40% of birth in developing countries take place in health facilities.6

OBSTETRICS AND GYNECOLOGY Cases presenting with this morbid condition as emergency were included in the present study. METHODS The present study was conducted on a prospective basis for 1 year from 1st February 2011 to 31st January 2012 in the Dept. of Obstetrics and Gynecology, Govt. Medical College, Patiala, Punjab. All the cases with hypertensive disorder of pregnancy presenting as obstetrical emergency were included in the study. A detailed history including age, parity, gestational age, antenatal care during pregnancy, socioeconomic status, obstetrical history, medical or surgical disorders was taken into account. RESULTS Hypertensive disorders in pregnancy has a major role in maternal and fetal morbidity and mortality. In the Table 1. Demographic Profile of Cases

present study, it is evident that hypertensive disorders in pregnancy were more common in the age group of 18-23 years (51.685%) and primigravida (60.67%). Majority of the patients were unbooked, uneducated and belonged to rural background (Table 1). Maximum cases 57 (64.04%) presented with eclampsia, whereas 31 (34.83%) had severe pre-eclampsia (Table 2). Out of 57 cases of eclampsia, 44 (77.2%) had antepartum eclampsia followed by 11 (19.3%) cases who had postpartum eclampsia (Table 3). It was observed that 51.72% of the cases had vaginal delivery, whereas 48.28% underwent lower segment cesarean section (LSCS) (Table 4). Various maternal complications were encountered; abruptio placenta was seen in 21 (23.6%), postpartum hemorrhage (PPH) in 12 (13.48%), pulmonary edema in 3 (3.37%), coagulopathy in 2 (2.25%), acute renal failure in 2 (2.25%) and HELLP (Hemolysis, Elevated Liver enzymes and Low Platelet count) syndrome in 5 (5.62%) (Table 5). Maternal mortality was 3.45%. In the present study, 44 (50.58%) fetuses were preterm of which 24 were alive and 20 were stillbirths, followed

No.

Percentage (%)

18-23

51.69

24-29

20.22

30-35

16.8

>35

11.23

60.67

1-2

30.34

3-4

5.62

3.37

Table 3. Distribution of Cases According to Pattern of Eclampsia

Rural

76.4

Pattern

No.

Percentage (%)

Urban

23.6

Antepartum

77.2

Intrapartum

3.5

20.22

Postpartum

19.3

79.77

Total

100

Age (years)

Parity

Residence

Literacy Educated Uneducated

Table 2. Details of Hypertensive Disorders (n = 89) Hypertensive disorder

No.

Percentage (%)

Eclampsia

64.04

Pre-eclampsia

34.83

Chronic hypertension

1.12

Total

100

Booking status Booked

13.48

Unbooked

86.52

Lower

67.42

Upper lower

16.86

Lower middle

11.24

Upper middle

3.37

Upper

1.12

Socioeconomic status

Table 4. Distribution of Cases According to Mode of Delivery Mode

No.

Percentage (%)

Vaginal delivery

51.72

LSCS

48.28

Total

100

N = 87 because one case got referred to higher center, while one case died before any intervention can be done.

Indian Journal of Clinical Practice, Vol. 27, No. 12, May 2017

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OBSTETRICS AND GYNECOLOGY Table 5. Distribution of Cases According to Maternal Complications Maternal complications

No.

Percentage (%)

Abruptio placenta

23.6

Acute renal failure

2.25

Pulmonary edema

3.37

HELLP syndrome

5.62

Coagulopathy

2.25

PPH

13.48

Table 6. Fetal Outcome (n = 87) Outcome

No.

Preterm/Term (%)

Alive/Stillbirths (%)

50.58

66.67

49.42

33.33

Preterm (44) Alive

Stillbirth

Term (43) Alive

Stillbirth

Table 7. Complications as Reported by Different Authors Various researchers

Abruptio placenta (%)

Renal dysfunction (%)

Pulmonary edema (%)

HELLP syndrome (%)

Coagulopathy (%)

PPH (%)

Yücesoy et al12 (2005)

7.5

2.35

0.78

2.35

4.8

Shaheen et Liu et

al10

al9

(2008)

Present study

4.96

9.34

23.6

2.2

3.37

5.6

2.2

13.48

by 43 (49.42%) which were term. Out of these 43 fetuses, 34 were alive while 9 were dead (Table 6). Fetal mortality was 33.33%. DISCUSSION

Present study had 23.6% abruption rates which is comparable to the study by Shaheen et al9 (2008), 19%, with some variations. Coagulopathy rates in the present study were similar to that seen in the study by Yücesoy et al12 (2005), 2.2% and 2.35%, respectively (Table 7).

There were 89 cases of hypertensive disorders in pregnancy, which presented as obstetric emergency during the period. Thus incidence came out to be 35.32%, which is similar to that seen in the study done by Oladapo et al7 (2005). Present study had 60.67% hypertensive patients who were primigravida and 39.33% who were multigravida, which is almost similar to the study done by Tukur et al8 (2007), whereas Shaheen et al9 (2008), Liu et al10 (2008) and Kullima et al11 (2009) reported more prevalence in multigravida.

Present study had 3.4% maternal mortality, which is almost similar to that reported by Yücesoy et al12 (2005), 1.17% and Shaheen et al9 (2008), 4.8%.

LSCS was done in 48.28% of cases which is almost similar to that seen in studies by Tukur et al8 (2007), 48.3% and Yücesoy et al12 (2005), 58.8%. Liu et al10 (2008) had high rates of LSCS (87.3%) due to fetal indications.

CONCLUSIONS

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Indian Journal of Clinical Practice, Vol. 27, No. 12, May 2017

In the present study, 66.66% babies were born alive and 33.33% were stillbirths which is almost similar to the study by Shaheen et al9 (2008); 30% as abruption rates were high in both studies, 23.6% and 19%, respectively (Table 7). Tukur et al8 (2007) and Yücesoy et al12 (2005) had same rates of stillbirths 13% and 12.6%, respectively.

From the present study, it is concluded that hypertensive disorders in pregnancy has a major role

OBSTETRICS AND GYNECOLOGY in maternal morbidity and mortality. Hypertensive disorders in pregnancy are more common in subjects who are unbooked, belong to low socioeconomic status and have poor access to antenatal care. Thus, there is a dire need of proper antenatal care, timely referral from periphery of high risk cases to prevent maternal morbidity and mortality.

6. World Health Organization. Coverage of maternity care. A listing of available information. Geneva: Switzerland. Maternal and Newborn Health/Safe Motherhood, 4th Edition; 1997.

REFERENCES

8. Tukur J, Umar BA, Rabi’u A. Pattern of eclampsia in a tertiary health facility situated in a semi-rural town in Northern Nigeria. Ann Afr Med. 2007;6(4):164-7.

1. James PR, Nelson-Piercy C. Management of hypertension before, during, and after pregnancy. Heart. 2004;90(12):1499-504. 2. Khan KS, Wojdyla D, Say L, Gülmezoglu AM, Van Look PF. WHO analysis of causes of maternal death: a systematic review. Lancet. 2006;367(9516):1066-74. 3. World Health Organization. The World Health Report 1998. Life in the 21st century: A Vision for All. Geneva: WHO; 1998. p. 97. 4. Bhide A, Arulkumaran S, Damania KR, Daftary SN. Hypertensive disorders in pregnancy (Chapter 13). In: Arias’ Practical Guide to High-Risk Pregnancy and Delivery: A South Asian Perspective. 4th Edition, Haryana: Reed Elsevier India Private Limited; 2015. pp. 185-232.

7. Oladapo OT, Sule-Odu AO, Olatunji AO, Daniel OJ. “Near-miss” obstetric events and maternal deaths in Sagamu, Nigeria: a retrospective study. Reprod Health. 2005;2:9.

9. Shaheen S, Tahir S. Management and outcome of severe pre-eclampsia. APMC. 2008;2(1):30-4. 10. Liu CM, Cheng PJ, Chang SD. Maternal complications and perinatal outcomes associated with gestational hypertension and severe preeclampsia in Taiwanese women. J Formos Med Assoc. 2008;107(2):129-38. 11. Kullima AA, Kawuwa MB, Audu BM, Usman H, Geidam AD. A 5-year review of maternal mortality associated with eclampsia in a tertiary institution in northern Nigeria. Ann Afr Med. 2009;8(2):81-4.

12. Yücesoy G, Ozkan S, Bodur H, Tan T, Calişkan E, Vural B, et al. Maternal and perinatal outcome in pregnancies complicated with hypertensive disorder 5. Duley L. Pre-eclampsia and the hypertensive disorders of of pregnancy: a seven year experience of a tertiary care pregnancy. Br Med Bull. 2003;67:161-76. center. Arch Gynecol Obstet. 2005;273(1):43-9. ■■■■

Women at Greater Risk for Sports-related Concussion A new study from Columbia University, New York has shown that female athletes, who competed in sports such as soccer, football and basketball were 50% more likely to sustain sports-related concussions than their male counterparts, new research shows. The study results were presented April 26, 2017 at the American Academy of Neurology 2017 Annual Meeting (AAN) in Boston.

Early Prenatal Transvaginal Sonograms at 14-17 Weeks may Help in Determining Trisomy 21 According to the findings of a prospective study that assessed the rate of trisomy 21 identification by transvaginal sonograms at 14-17 weeks gestation, early prenatal transvaginal sonograms during this period are likely to identify nearly 90% of trisomy 21. In addition, they add 14% to the identification rate at the first-trimester screening. These results published in the Israel Medical Association Journal also revealed that isolated abnormal sonographic findings which enhanced the risk for trisomy 21 included common atrioventricular septal canal, duodenal atresia, nuchal edema and hydrocephalus.

Valuable Role of Prophylactic Lower Para-aortic Irradiation Using Intensity-modulated Radiotherapy in Patients with Cervical Cancer According to a 10-year institutional experience that analyzed the effects of prophylactic subrenal vein radiotherapy using intensity-modulated radiotherapy for cervical cancer, it was found that this method reduced the recurrence of para-aortic lymph nodes with tolerable toxicities. The study cohort included 206 patients with Federation of Gynecology and Obstetrics (FIGO) stage IB2-IVA cervical cancer and negative para-aortic lymph nodes who underwent pelvic intensity-modulated radiotherapy or sub-renal vein radiotherapy. The findings of this study published in the Gynecologic Oncology Journal thus support the application of risk-based radiation fields for cervical cancer.

Indian Journal of Clinical Practice, Vol. 27, No. 12, May 2017

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OBSTETRICS AND GYNECOLOGY

A Prospective Study on Acceptability and Safety of IUCD Among Postpartum Mothers SUSHMA SINHA*, SURYA MALIK†

ABSTRACT Aims and objectives: To study the acceptability, safety, efficacy and complications of immediate postpartum intrauterine contraceptive devices (PPIUCD) insertion. Material and methods: This study was conducted in a 100 bedded hospital, Govt. of NCT of Delhi, for the duration of 1 year, 1st January 2016 to 31st December 2016. All patients who satisfied inclusion criteria and willing for this form of contraception were enrolled for this study. Results: Total numbers of deliveries during this period were 1,698; among them 1,510 women were eligible for PPIUCD insertion. Out of these 1,510 women, 227 women (15%) accepted this form of contraception, 194 (85.46%) underwent normal delivery and the remaining 33 (14.54%) underwent lower segment cesarean section (LSCS). Follow-up was done at 6 weeks. Forty-four percent i.e., 100 women came for follow-up visit. Various complications in the form of expulsion (6%), heavy bleeding (17%), failure (1%), pain abdomen (17%) and infections (21%) were studied. Fourteen percent women opted for removal and hence the continuation rates were 80%. Conclusions: Overall immediate postpartum insertion of IUCD appears to be safe and effective method of contraception in the hands of trained personnel. This opportunity should not be missed in countries like ours with high rates of unplanned and short interval pregnancies in women with limited exposure to healthcare providers.

Keywords: PPIUCD, contraception, expulsion

ontraception methods by definition means ways to prevent unwanted pregnancies either temporarily or permanently.1 Contraception use has risen, but the unmet need is still high in some regions. Uses of contraceptive methods contribute to reducing the number of unintended pregnancies, unsafe abortions and maternal deaths. Worldwide, the proportion of women aged 15-49, married or in a union, who were using any methods of contraception has increased from 55% in 1990 to 64% in 2015. In Southern Asia, the proportion increased from 39% to 59% during the same period. Nine in 10 contraceptive users were using effective methods, including female and male sterilization, oral hormonal pills, intrauterine devices, condoms, injectables or an implant. Yet even in 2015, 12% of married or in union women, of reproductive

*Head of Department †Senior Resident Dept. of Obstetrics and Gynecology Acharyashree Bhikshu Govt. Hospital, Moti Nagar, New Delhi Address for correspondence Dr Surya Malik A2A, House No. 159, Janakpuri West, New Delhi E-mail: surya85.sm@gmail.com

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age worldwide, want to delay or avoid pregnancy but are not using any method of contraception.2 India is second largest populated country in the world with 120 crore according to 2011 census.3 It contributes 17.5% of world’s population by adding around 25 million births every year.4 In India, the unmet need is estimated to be 15.8% as estimated by the Demographic and Health Surveys (DHS).5 Around 65% of women are having unmet need of family planning in the first year of postpartum period.4 Till 2 years after delivery, a women will not be ready physically to conceive and deliver. Studies have found that conceiving, within 2 years, leads to adverse events like abortion, premature labor, postpartum hemorrhage, low birth weight babies, fetal loss and sometimes maternal deaths. Hence, advising and practicing contraception within postpartum period is good for women’s health.6 Insertion of an intrauterine contraceptive device (IUCD) immediately after delivery has been recommended by World Health Organization (WHO), as one of the safe and effective methods of temporary contraception.7 In the immediate post delivery period, the women are highly motivated and need an effective method for contraception, so that the child can be brought up with a relaxed mind without the worry of unintended

OBSTETRICS AND GYNECOLOGY pregnancy. On the other hand, if they are made to wait for 6 weeks for initiating an effective method of contraception, they may conceive accidentally or may not come for contraception.8 This approach of immediate postpartum IUCD (PPIUCD) insertion is more applicable in a country where delivery may be the only time when a healthy woman comes in contact with a healthcare professional. Other advantages of insertion are that the discomfort related to interval insertion can be avoided and any bleeding from insertion will be disguised by lochia.9 MATERIAL AND METHODS This, 1 year prospective study was carried out at a 100 bedded hospital, Govt. of NCT of Delhi, New Delhi, from 1st January 2016 to 31st December 2016. Women delivering in the hospital fulfilling inclusion criteria were included in the study after obtaining consent.

Inclusion Criteria ÂÂ 18-40 years old. ÂÂ Desire to have copper T (CuT) after counseling. ÂÂ Anticipate vaginal delivery/cesarean section. ÂÂ No infections. ÂÂ Hemoglobin (Hb) ≥8 g/dL. Exclusion Criteria ÂÂ Prelabor rupture of membranes for ≥18 hours. ÂÂ Chorioamniotis. ÂÂ Temperature ≥38° during or after labor. ÂÂ Continuous excessive postpartum bleeding. The women included in the study underwent immediate postpartum insertion of CuT 380A after delivery of placenta. The IUCD, held by Kelly’s forceps, was introduced in the uterine cavity and placed at the fundus in the women delivering vaginally. In the case of cesarean section, IUCD was placed at the fundus in the uterine cavity through the lower segment incision. Uterine incision was closed routinely. At the time of discharge from hospital, women were advised to come for follow-up visit after 6 weeks. At followup visit, women were asked especially for history of expulsion of IUCD, excessive bleeding, pain or unusual vaginal discharge. Pelvic examination was performed; on per speculum examination, if IUCD threads were long, they were cut 2 cm from external os. If threads of IUCD were not seen and there was no history of expulsion of IUCD, pelvic ultrasound was performed for confirmation of IUCD in place.

Various complications like infection, excessive bleeding, pain discharge per vaginum and failure were reported and their frequencies and percentages were calculated for analysis. RESULTS Total deliveries during this period of 1 year was 1,698. Among these deliveries; 1,510 women were found eligible for PPIUCD insertion. Out of these, only 227 women were willing for this form of contraception i.e., PPIUCD insertion, hence the acceptability was 15%. Of these 227 women, 194 women (85.46%) underwent normal delivery and the remaining 33 (14.54%) women underwent lower segment cesarean section (LSCS) (Fig. 1). Regarding the demographics, maximum women, 151 (66.52%) belonged to the age group of 20-29 years. Only 22.47% of women were primipara and the rest were multiparas. Maximum women in this group belonged to urban background (81.1%) and were educated (66.96%) (Table 1).

Eligible n = 1,510

Accepted (15%) n = 227

Intracesarean n = 33 (14.54%)

Declined (85%) n = 1,283

Post-placental n = 194 (85.46%)

Figure 1. Study design.

Table 1. Demographic Profile of Cases No. of patients Percentage (%) Age (years) <20 12 5.28 20-29 151 66.52 >30 64 28.2 Parity 1 51 22.47 2 91 40.08 ≥3 85 37.45 Residence Urban 184 81.1 Rural 43 18.9 Literacy Educated 152 66.96 Uneducated 75 33.04

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OBSTETRICS AND GYNECOLOGY Follow-up was done at 6 weeks; 100 women (44%) of total 227 came for follow-up visit. Complications and clinical outcomes were studied in each of the women who came for follow-up visit, and presented in Table 2. A complication in the form of expulsion was seen in 6% of women, heavy bleeding was chief complaint in 17% women. These women were prescribed hematinics and antifibrinolytics. Out of these 17 women, 13 responded well to treatment and the rest 4 did not respond well and hence IUCD was removed in these patients. In 4 women threads were not seen and hence pelvic Table 2. Clinical Outcomes Clinical outcomes

No. of patients

Percentage (%)

Expulsion

Heavy bleeding

Pain abdomen

Infection

Long thread

Missed thread

Failure

Nil complaints

Removal

Continuation

Note: Total no. of follow-up patients = 100, one patient may have more than one complication.

Table 3. Reasons for Removal Reasons

No. of patients

Percentage (%)

Heavy bleeding

28.57

Family pressure

14.28

Others methods of contraception

21.43

Partial expulsion

21.43

Planning next issue

14.28

Total

100

USG was done in these patients. IUCD was in situ in all these patients. Failure was seen in 1% women. In this woman thread was not visible, IUCD was in situ. Patient was counseled regarding the complications but the patient was willing to continue her pregnancy thereafter. Seventy women had no complaints and were willing to continue this form of contraception as it was a reversible method and it is also a temporary longacting contraceptive method. Fourteen women were not willing for continuation and hence IUCD was removed in these set of patients. Various reasons that were implicated for removal included heavy bleeding, family pressure, opting for other methods of contraception and planning for next pregnancy (Table 3). DISCUSSION PPIUCD insertion is an opportunity not to be missed in developing countries like ours where delivery may be the only time when a healthy woman comes in contact with healthcare providers and the chance of returning for contraceptive advice is uncertain. It does not interfere with breastfeeding, is convenient for both women and their healthcare providers, is associated with less discomfort and fewer side effects than interval insertions and allows women to obtain safe, long-acting, highly effective contraception, while already within the medical system.10 In the present study, the percentage of women who accepted PPIUCD as a means of contraception was 15%, which is very much similar to the studies done by Mishra et al11 and Jairaj et al12 in which 17.17% and 19.7% women accepted PPIUCDâ&#x20AC;&#x2122;s, respectively. Regarding the demographics, 22.47% of the acceptors were primipara. Mishra et al11 also found 20.7% acceptance among primigravida. Clinical outcomes as reported by different authors are well tabulated in Table 4.11-14 Present study had 14% removal rates which is slightly higher than 9.91% seen in study by Mishra et al.11 Main

Table 4. Clinical Outcomes as Reported by Different Authors Expulsion (%) Mishra et

al11

Jairaj et al12 Afshan et al13 Gautam et

al14

Present study

1168

Missed threads (%)

Pain abdomen (%)

Infection (%)

Heavy bleeding (%)

8.99

11.29

23.5

6.8

17.15

0.9

3.1

12.7

4.3

Indian Journal of Clinical Practice, Vol. 27, No. 12, May 2017

OBSTETRICS AND GYNECOLOGY reason for removal in the present study was heavy bleeding which was responsible for 28.57% cases, which is also similar to study by Mishra et al11 in which 32.56% of women who opted for removal of PPIUCD had heavy bleeding. CONCLUSIONS Overall, immediate postpartum insertion of IUCD appears to be safe and effective method of contraception in the hands of trained personnel. This study suggests that immediate post-placental insertion of IUCD is an effective, useful, safe and convenient opportunity, which should not be missed in countries like ours with high rates of unplanned and short interval pregnancies in women with limited exposure to healthcare providers. REFERENCES 1. Park K. Park’s Textbook of Preventive and Social Medicine. 23rd Edition, Jabalpur: Banarasidas Bhanot; 2015. 2. Catherine Way. The Millennium Development Goals Report 2015, 41-42. Target 5B: UNFPA, UNICEF and United Nations Population Division. 3. India At Glance - Population Census 2011. Census Organisation of India, 2011. Available at: http// censusindia.gov.in/2011-prov-results/Indiaatglance.html. Accessed 21st April 2017. 4. Postpartum IUCD Reference Manual. New Delhi: Family Planning Division; Ministry of Health and Family Welfare, Government of India; 2010.

6. Kanhere AV, Pateriya P, Jain M. Acceptability and feasibility of immediate postpartum IUCD insertion in a tertiary care centre in Central India. Int J Reprod Contracept Obstet Gynecol. 2015;4(1):179-84. 7. World Health Organization. Medical Eligibility Criteria for Contraceptive Use (Internet). Geneva: World Health Organization; 2010. Available at: http://www. who.int/reproductivehealth/publications/family– planning/9789241563888/en/. 8. Suri V. Post placental insertion of intrauterine contraceptive device. Indian J Med Res. 2012;136(3):370-1. 9. Shukla M, Qureshi S; Chandrawati. Post-placental intrauterine device insertion - a five year experience at a tertiary care centre in north India. Indian J Med Res. 2012;136(3):432-5. 10. Kapp N, Curtis KM. Intrauterine device insertion during the postpartum period: a systematic review. Contraception. 2009;80(4):327-36. 11. Mishra S. Evaluation of safety, efficacy, and expulsion of post-placental and intra-cesarean insertion of intrauterine contraceptive devices (PPIUCD). J Obstet Gynaecol India. 2014;64(5):337-43. 12. Jairaj S, Dayyala S. A cross sectional study on acceptability and safety of IUCD among postpartum mothers at tertiary care hospital, Telangana. J Clin Diagn Res. 2016;10(1):LC01-4. 13. Afshan A, Asim SS, Immediate postpartum IUCD (PPIUCD) insertion: an opportunity not to be missed. ASH & KMDC 2014;19(1):15.

14. 5. Klijzing E. Are there unmet family planning needs in Europe? Fam Plann Perspect. 2000;32(2): 74-81, 88. ■■■■

Gautam R, Arya KN, Kharakwal S, Singh S, Trivedi M. Overview of immediate PPIUCD application in Bundelkhand region. J Evolut Med Dent Sci. 2014; 13(36):9518-26.

Evaluating the Prevalence of Postpartum Complications in New Mothers with Juvenile Idiopathic Arthritis A population-based cohort study printed in the Rheumatology Journal assessed the prevalence of postpartum complications, including depression, in new mothers who had juvenile idiopathic arthritis. Moreover, it investigated whether these differ from mothers who never had juvenile idiopathic arthritis. The results showed that mothers with juvenile idiopathic arthritis are associated with a greater risk for complications that are attributed to anesthesia, postpartum hemorrhage and thromboembolism. However, the risk for obstetrical trauma or depression in the first year postpartum appears to be low. It is thus suggested that prevention of postpartum hemorrhage and thromboembolism holds great importance in this set of patients.

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OBSTETRICS AND GYNECOLOGY

Anovulation and Infertility: Focus on Clomiphene Citrate and N-acetylcysteine for Ovulation Induction ANITA KANT

ABSTRACT Infertility is fast becoming a significant health challenge in India. Anovulation is one of the important causes of female factor infertility and disorders of anovulation are responsible for nearly 30% of infertility. Polycystic ovary syndrome (PCOS) is the commonest cause of anovulatory infertility. Clomiphene citrate, an antiestrogen, is the first-line treatment for anovulatory PCOS and also the first choice for ovulation induction therapy with hypothalamic-pituitary dysfunction as the underlying cause. Treatment with clomiphene citrate tends to increase ovulation and pregnancy rates. Clinical efficacy evaluations suggest that clomiphene citrate improves live birth rate and clinical pregnancy rate among women with PCOS. N-acetylcysteine (NAC), a mucolytic drug with insulin sensitizing properties, is a promising adjuvant to clomiphene citrate for ovulation induction in PCOS patients.

Keywords: Infertility, ovulation induction, clomiphene citrate, N-acetylcysteine, polycystic ovary syndrome, anovulation

he problem of infertility is widely prevalent across the globe. According to a systematic analysis of 277 health surveys, in the year 2010, nearly 48.5 million couples failed to have a child after 5 years, worldwide. The global estimates of primary and secondary infertility have not changed much between 1990 and 2010.1 A recent Indian study conducted among couples in Ambala (urban population) noted the prevalence of primary infertility as 6.1%, and that of secondary infertility as 5.7%. Among women with primary infertility, ovulatory factor surfaced as the commonest cause.2

ANOVULATION Anovulation is one of the important causes of female factor infertility. Disorders of anovulation are responsible for nearly 30% of infertility and are often characterized by irregular periods (oligomenorrhea) or absence of periods (amenorrhea). Anovulation can be treated either medically or surgically, depending upon the cause for anovulation.4 The common causes for anovulation include:4 ÂÂ

Causes suitable for ovulation induction zz

Hypothalamic-pituitary causes: Hypogonadotropic hypogonadism, hyperprolactinemia

Ovarian causes: PCOS.

Saoji3

A case-control study by stated that primary infertility is common among women in urban areas. The study also suggested that the most significant risk factors for primary infertility included higher education, age at marriage >25 years, deferral of childbearing for ≥1 year, obesity, polycystic ovary syndrome (PCOS), irregular menstrual pattern, endometriosis, sexually transmitted infection (STI) and age at menarche >14 years. Infertility is fast becoming a significant health challenge in our country.

*Director, Gynecology and Obstetrics

Asian Institute of Medical Sciences, Faridabad, Haryana

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ÂÂ

Causes not suitable for ovulation induction zz

Premature ovarian failure

Genetic disorders.

PCOS seems to be the commonest cause of anovulatory infertility, accounting for nearly 75% of women having infertility due to anovulation.5 PCOS presents with hirsutism, acne, alopecia and irregular menstruation. Obesity is commonly associated with PCOS.6 The syndrome has the following characteristics:5 ÂÂ

Abnormal ovarian morphology.

ÂÂ

Abnormal steroidogenesis - increased ovarian production of androgens besides increased production of progesterone and estradiol.

OBSTETRICS AND GYNECOLOGY ÂÂ

Hyperinsulinemia - seen in nearly 80% of obese women and 30-40% of women of normal weight with PCOS.

A pulse of gonadotropin-releasing hormone is delivered subcutaneously every 90 minutes, which results in unifollicular ovulation.4

ÂÂ

Abnormal gonadotropin secretion - increased serum luteinizing hormone (LH) with ultrasonically detected polycystic ovary.

Antiestrogen therapy: It is close to 5 decades now that clomiphene citrate has been the choice of therapy for ovulation induction.6 Clomiphene citrate has been the first-line treatment for anovulation on account of hypothalamic-pituitary dysfunction associated with normal basal levels of endogenous estradiol. Nearly 80% of these subjects are oligo- or anovulatory due to PCOS.4 Tamoxifen is another potential agent for treating anovulation.6

MANAGING ANOVULATORY INFERTILITY The goal of treatment is to correct the underlying disorders such as hyperprolactinemia, hypothyroidism and adrenal disorders first. Lifestyle modifications, including correction of body mass index (BMI), smoking cessation and minimalizing alcohol consumption, play a significant role in treatment success.6 The options for ovulation induction and fertility treatment in women with PCOS include:7 ÂÂ Weight loss, exercise and lifestyle modifications ÂÂ Clomiphene citrate ÂÂ Metformin ÂÂ Gonadotropins ÂÂ Ovarian drilling ÂÂ In vitro fertilization (IVF). OVULATION INDUCTION: CAUSE-SPECIFIC TREATMENT Weight change: Underweight women (BMI <18 kg/m2) should be advised to gain weight before offering infertility treatment. Likewise, obese women (BMI >30 kg/m2) should be advised to lose weight.4 In women with PCOS, excess body fat tends to increase insulin resistance. In these women, weight loss can potentially improve ovarian function and the hormonal abnormalities associated with obesity.5 Treating hyperprolactinemia: Dopamine agonists such as bromocriptine, cabergoline and quinagolide are prescribed to these patients.6 Once prolactin levels reach below 1,000 IU/L, the menstrual periods often return and about 70-80% of women begin to ovulate.4 Treating hypothyroidism: Infertile women with subclinical thyroid dysfunction tend to have anovulatory disorders.6 Thyroxine replacement corrects hypothyroidism and brings thyroid-stimulating hormone (TSH) and prolactin levels back to normal.4 MEDICAL INDUCTION OF OVULATION Gonadotropin-releasing hormone: Women with a purely hypothalamic cause for amenorrhea are treated with pulsatile gonadotropin-releasing hormone.

Gonadotropins: Patients who remain anovulatory despite antiestrogen therapy are treated with exogenous gonadotropins.4 Insulin sensitizers: Insulin resistance is linked with hyperandrogenism in PCOS patients. As a result, insulin sensitizers have found use in ovulation induction. A decrease in insulin resistance might cause a reduction in ovarian dysfunction and improve ovarian responsiveness to follicle-stimulating hormone (FSH).4 Aromatase inhibitors: Aromatase inhibitors, such as anastrozole and letrozole, have been used for ovulatory disorders and for superovulation and have shown promising results.4 CLOMIPHENE CITRATE FOR OVULATION INDUCTION

How does Clomiphene Citrate Work? Clomiphene citrate, an antiestrogen, is the first-line treatment for anovulatory PCOS. It is the first choice for ovulation induction therapy where the cause is hypothalamic-pituitary dysfunction.4,6 Antiestrogens promote the release of gonadotropin from the pituitary gland as they occupy the estrogen receptors in the hypothalamus. This interferes with the normal feedback mechanisms, i.e., blocking the negative feedback effect of estradiol. As a result, there is increased FSH secretion that prompts follicular growth.6 Clomiphene citrate, a nonsteroidal compound, is administered orally and is relatively cheaper than some of the injectable alternatives.4 Clomiphene citrate instigates a discharge of FSH from the anterior pituitary, which encourages ovulation and pregnancy in euestrogenic anovulatory women. Clomiphene citrate blocks the estrogen receptors at the level of the hypothalamus.4 It blocks the negative feedback effect of estradiol and stimulates gonadotropin secretion from the pituitary gland. This gives way to follicle selection and estrogen production, resulting in a midcycle LH surge.

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OBSTETRICS AND GYNECOLOGY Of note, in patients treated with clomiphene citrate, exogenous human chorionic gonadotropin (hCG) is not required for follicle rupture, unless ovulation does not occur despite the development of large follicles.8

citrate group. There was no difference in rate of abortion between the two groups.

What is the Optimal Dosage of Clomiphene Citrate?

As mentioned earlier, PCOS is closely linked with anovulatory infertility. Clomiphene citrate is frequently used in patients with PCOS for ovulation induction.4 Most guidelines recommend clomiphene citrate as firstline therapy for PCOS patients.11 Brown and colleagues12 conducted a review to determine the effectiveness of antiestrogen agents in women with subfertility associated with anovulation, possibly caused by PCOS. Clomiphene citrate was effective in increasing pregnancy rate compared to placebo (OR 5.8). In another review by Tang et al,13 clomiphene citrate improved live birth rate (pooled OR 0.3, 95% confidence interval [CI] 0.17-0.52, 2 trials, 500 women) and clinical pregnancy rate (pooled OR 0.34, 95% CI 0.21-0.55, 2 trials, 500 women) among obese women, as compared to metformin.

Clomiphene citrate is given orally in a dose of 50-250 mg/day for a period of 5 days starting from Day 2, 3, 4 or 5 of spontaneous or progestagen-induced bleeding. It is started with the lowest dose and the dose is increased in increments of 50 mg/day per cycle until the attainment of an ovulatory cycle. The starting time of the drug does not affect the outcomes,4,8 50 mg/day is the recommended starting dose; nearly half of the pregnancies are achieved with this dose. With treatment initiation on Day 2, serum progesterone is measured on Days 21 and 28 of the cycle.

Clinical Efficacy of Clomiphene Citrate in Ovulation Induction Treatment with clomiphene citrate has been associated with an ovulation rate of 73% and a pregnancy rate of 36%.4 In well-selected patients with no other causes of infertility, the pregnancy rate can be as high as 60% after 6 cycles and 97% after 10 cycles.8 The administration of clomiphene citrate leads to increased release of pituitary gonadotropins resulting in follicular recruitment. There is continued secretion of estradiol, selection of the dominant follicle and ovulation after stopping the drug.9 Hughes et al9 reviewed published studies to assess the effects of clomiphene citrate on ovulation and pregnancy in women with oligo-ovulatory subfertility. Treatment with clomiphene citrate was associated with increased ovulation, as compared to placebo. The odds ratio (OR) for high doses (50-250 mg/day) was 6.82, while that with low doses (10 mg/day) was 1.29. Clomiphene citrate was associated with an increased pregnancy rate per treatment cycle (OR 3.41). Zadehmodares et al10 conducted a study to compare the effect of clomiphene citrate and letrozole in ovulatory stimulation in infertile women under intrauterine insemination (IUI). Patients were either given 5 mg letrozole daily or 100 mg clomiphene citrate daily for 5 days starting on Day 3 of their menses. Average number of follicles was 2.5 ± 1.65 in letrozole group and 2.36 ± 1.4 in clomiphene citrate group. β-hCG was positive in 20.8% in letrozole and 22.6% in clomiphene citrate group. Pregnancy rate was higher in clomiphene

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Clomiphene Citrate for Ovulation Induction in Women with PCOS

Badawy et al14 investigated the impact of luteal phase administration of clomiphene citrate for ovulation induction in women with PCOS. In all, 212 women (438 cycles) with PCOS were included in the study. Patients were divided into two groups: The early clomiphene citrate group received 100 mg clomiphene citrate daily starting the next day after finishing medroxyprogesterone acetate for 5 days (110 patients, 227 cycles); the late clomiphene citrate group received 100 mg clomiphene citrate daily for 5 days starting on Day 3 of menses (102 patients, 211 cycles). There were more ovulating patients in the early clomiphene citrate group (59.1% vs. 51.9%). The total number of follicles and the number of follicles >14 mm and >18 mm during stimulation were higher in the early clomiphene citrate group. Furthermore, the endometrial thickness at the time of hCG administration was 9.1 ± 0.23 in the early clomiphene citrate group; significantly greater than the late clomiphene citrate group (8.2 ± 0.60 mm). Pregnancy rate was 20.9% in the early clomiphene citrate group compared to 15.7% in the late clomiphene citrate group. Therefore, early administration of clomiphene citrate in patients with PCOS was found to result in more follicular growth and endometrial thickness and a higher pregnancy rate. Ding et al15 also suggested in a recent a systematic review and meta-analysis that luteal phase clomiphene citrate could be a promising method for ovulation induction in women with PCOS compared to conventional clomiphene citrate administration.

OBSTETRICS AND GYNECOLOGY In a comparison of letrozole and clomiphene citrate by Roy et al,16 among patients with anovulatory PCOS with infertility, the mean number of dominant follicles was 1.86 ± 0.26 and 1.92 ± 0.17 in letrozole and clomiphene citrate groups, respectively. Number of ovulatory cycle in letrozole group was 196 (66.6%) versus 216 (67.9%) in clomiphene citrate group. The mean estradiol level was significantly higher in clomiphene citrate group (364.2 ± 71.4 pg/mL) compared to letrozole group (248.2 ± 42.2 pg/mL). Letrozole and clomiphene citrate had comparable ovulation rate. A meta-analysis compared the clinical efficacy and safety of letrozole with clomiphene citrate for ovulation induction in women with PCOS. Six randomized controlled trials involving 841 patients were included. The number of mature follicles per cycle was lower with letrozole (standardized mean difference −1.41; 95% CI −1.54 to −1.28) compared with clomiphene citrate. There were no significant differences in pregnancy rate (relative risk [RR] 0.97; 95% CI 0.79-1.18), abortion rate (RR 1.38; 95% CI 0.48 to −3.96) and multiple pregnancy rate (RR 0.34; 95% CI 0.07 to −1.72) between the two groups.17 N-ACETYLCYSTEINE AS AN ADJUVANT TO CLOMIPHENE CITRATE N-acetylcysteine (NAC) is a mucolytic drug with insulin sensitizing properties. It has several biological effects including improved pregnancy rate.18 NAC is an antioxidant with anti-apoptotic effects. It preserves vascular integrity and decreases homocysteine levels.19 In patients with PCOS, NAC has been shown to improve the parameters of glucose control. It was found to reduce insulin levels and increase peripheral insulin sensitivity. The antioxidant effects of NAC appear to improve the level of circulating insulin and insulin sensitivity in PCOS patients with hyperinsulinemia.20 A study compared the effects of clomiphene citrate plus NAC with clomiphene citrate alone for inducing ovulation in patients with PCOS. Ovulation rate improved with the addition of NAC (17.9% vs. 52.1%). The number of mature follicles was more in the NAC group (2.1 ± 0.88 vs. 3.2 ± 0.93). The mean estradiol levels at the time of hCG injection, serum progesterone levels on Days 21-23 of the cycle and the endometrial thickness were also improved in the NAC group.21 Maged et al22 determined the adjuvant effect of metformin and NAC to clomiphene citrate in ovulation induction in PCOS patients. Patients in Group I were given clomiphene citrate only, Group II received

clomiphene citrate plus NAC and Group III received clomiphene citrate plus metformin. A significant difference was found between Group II and other two groups regarding average number of ovulatory follicles >18 mm (2.25 vs. 1.75 and 1.89, respectively). A significant difference was also noted between Group II and other two groups regarding pregnancy rate per patient (20% vs. 10% and 10%, respectively). Endometrial thickness was also greater in Group II as compared to the other two groups. NAC was thus found to improve ovulation and pregnancy rates in PCOS patients and was beneficial for endometrial thickness as an adjuvant to clomiphene citrate. In another study, NAC appeared to be a safe and welltolerated adjuvant to clomiphene citrate for ovulation induction. It improved ovulation and pregnancy rates in PCOS patients. The number of follicles >18 mm and the mean endometrial thickness on the day of hCG administration were significantly higher in the clomiphene citrate + NAC group. The ovulation and pregnancy rates were also significantly higher in this group.23 CONCLUSION Infertility is widely prevalent globally and is fast becoming a significant health challenge in India. Anovulation is a significant cause of female factor infertility and PCOS is the commonest cause of anovulatory infertility. Treating the underlying disorders including hyperprolactinemia, hypothyroidism and adrenal disorders is important in these patients. Clomiphene citrate is the first-line treatment for anovulatory PCOS and the first choice for ovulation induction therapy where the cause is hypothalamicpituitary dysfunction. Clomiphene citrate provokes a discharge of FSH from the anterior pituitary thus promoting ovulation and pregnancy in euestrogenic anovulatory women. In well-selected patients with no other causes of infertility, the pregnancy rate with clomiphene citrate can be as high as 60% after 6 cycles and 97% after 10 cycles. Treatment with clomiphene citrate is known to increase ovulation rate and pregnancy rate. Most guidelines recommend clomiphene citrate as first-line therapy for PCOS patients. Clinical efficacy evaluations suggest that clomiphene citrate improves live birth rate and clinical pregnancy rate among women with PCOS. NAC is a promising adjuvant to clomiphene citrate for ovulation induction in PCOS patients. It reduces insulin levels and increases peripheral insulin sensitivity in patients with PCOS. Adding NAC to clomiphene

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OBSTETRICS AND GYNECOLOGY citrate improves ovulation and pregnancy rates in PCOS patients. REFERENCES 1. Mascarenhas MN, Flaxman SR, Boerma T, Vanderpoel S, Stevens GA. National, regional, and global trends in infertility prevalence since 1990: a systematic analysis of 277 health surveys. PLoS Med. 2012;9(12):e1001356. 2. Mittal A, Yadav S, Yadav SS, Bhardwaj A, Kaur R, Singh P, et al. An epidemiological study of infertility among urban population of Ambala, Haryana. IJIMS. 2015;2(4):124-30. 3. Saoji AV. Primary infertility problems among female have been a source of concern in India lately. IJMHS. 2014;4(1):332-40.

13. Tang T, Lord JM, Norman RJ, Yasmin E, Balen AH. Insulinsensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility. Cochrane Database Syst Rev. 2012;(5):CD003053. 14. Badawy A, Inany H, Mosbah A, Abulatta M. Luteal phase clomiphene citrate for ovulation induction in women with polycystic ovary syndrome: a novel protocol. Fertil Steril. 2009;91(3):838-41. 15. Ding N, Chang J, Jian Q, Liang X, Liang Z, Wang F. Luteal phase clomiphene citrate for ovulation induction in women with polycystic ovary syndrome: a systematic review and meta-analysis. Gynecol Endocrinol. 2016;32(11):866-71.

4. Katsikis I, Kita M, Karkanaki A, Prapas N, Panidis D. Anovulation and ovulation induction. Hippokratia. 2006;10(3):120-7.

16. Roy KK, Baruah J, Singla S, Sharma JB, Singh N, Jain SK, et al. A prospective randomized trial comparing the efficacy of letrozole and clomiphene citrate in induction of ovulation in polycystic ovarian syndrome. J Hum Reprod Sci. 2012;5(1):20-5.

5. Homburg R. The management of infertility associated with polycystic ovary syndrome. Reprod Biol Endocrinol. 2003;1:109.

17. He D, Jiang F. Meta-analysis of letrozole versus clomiphene citrate in polycystic ovary syndrome. Reprod Biomed Online. 2011;23(1):91-6.

6. Gorthi S, Balen AH, Tang T. Current issues in ovulation induction. TOG. 2012;14(3):188-96. 7. Vause TD, Cheung AP, Sierra S, Claman P, Graham J, Guillemin JA, et al; Society of Obstetricians and Gynecologists of Canada. Ovulation induction in polycystic ovary syndrome. J Obstet Gynaecol Can. 2010;32(5):495-502. 8. Messinis IE. Ovulation induction: a mini review. Hum Reprod. 2005;20(10):2688-97. 9. Hughes E, Collins J, Vandekerckhove P. Clomiphene citrate for ovulation induction in women with oligo-amenorrhoea. Cochrane Database Syst Rev. 2000;(2):CD000056. 10. Zadehmodares S, Niyakan M, Sharafy SA, Yazdi MH, Jahed F. Comparison of treatment outcomes of infertile women by clomiphene citrate and letrozole with gonadotropins underwent intrauterine insemination. Acta Med Iran. 2012;50(1):18-20. 11. Davidson R, Motan T, Korownyk C. Clomiphene for anovulatory infertility. Can Fam Physician. 2016;62(6):492.

18. Youssef G, Makin B, Ali AM, Waly M, Alaa N, Abou-Setta A. N-acetyl-cysteine in anovulatory women: The impact of postcoital test. Middle East Fertil Soc J. 2006;11(2):109-12. 19. Agarwal A, Aponte-Mellado A, Premkumar BJ, Shaman A, Gupta S. The effects of oxidative stress on female reproduction: a review. Reprod Biol Endocrinol. 2012;10:49. 20. Sekhon LH, Gupta S, Kim Y, Agarwal A. Female infertility and antioxidants. Current Women’s Health Reviews. 2010;6(2):84-95. 21. Badawy A, State O, Abdelgawad S. N-Acetyl cysteine and clomiphene citrate for induction of ovulation in polycystic ovary syndrome: a cross-over trial. Acta Obstet Gynecol Scand. 2007;86(2):218-22. 22. Maged AM, Elsawah H, Abdelhafez A, Bakry A, Mostafa WA. The adjuvant effect of metformin and N-acetylcysteine to clomiphene citrate in induction of ovulation in patients with polycystic ovary syndrome. Gynecol Endocrinol. 2015:1-4.

23. Salehpour S, Sene AA, Saharkhiz N, Sohrabi MR, Moghimian F. N-Acetylcysteine as an adjuvant to 12. Brown J, Farquhar C, Beck J, Boothroyd C, Hughes E. clomiphene citrate for successful induction of ovulation in Clomiphene and anti-oestrogens for ovulation induction infertile patients with polycystic ovary syndrome. J Obstet Gynaecol Res. 2012;38(9):1182-6. in PCOS. Cochrane Database Syst Rev. 2009;(4):CD002249. ■■■■

Link Between Obstetrical Complications and Renal Prognosis A study published in the Nephrology, Dialysis, Transplantation Journal assessed the relation between obstetrical complications and renal prognosis among biopsy-confirmed immunoglobulin A nephropathy women who experienced pregnancy after their diagnosis. The findings showed that pregnancy itself did not worsen renal outcomes. However, those with complicated pregnancies experienced poor renal prognosis. This association was found to be significant only in mothers with reduced renal function, overt proteinuria and baseline hypertension.

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OBSTETRICS AND GYNECOLOGY

A Rare Case of Torsion Ovarian Fibroma PRADEEP MUSALE RAMAMCHANDRA*, LALITHA SHIVANNA†, MAMATHA SIDDAPPAJI‡

ABSTRACT Ovarian fibroma is a benign solid tumor, which accounts for 1-4% of ovarian neoplasms. This is commonly seen in postmenopausal women. A 40-year-old para 3 live 3, who had undergone tubectomy and was having regular cycles, was admitted to our hospital with pain abdomen and a 16 weeks pelvic mass. Preoperatively, she was misdiagnosed as pedunculated fibroid with torsion. On table, she was found to have ovarian fibroma with torsion. Total abdominal hysterectomy with bilateral salpingo-ovariotomy was done. Ovarian fibroma cannot be diagnosed accurately in preoperative period. Excision of tumor is the treatment of choice.

Keywords: Ovarian fibroma, postmenopausal women, pedunculated fibroid, torsion, abdominal hysterectomy, bilateral salpingo-ovariotomy

varian fibroma is a type of sex cord cell tumor of ovary. It is a solid tumor which accounts for 1-4% of benign ovarian tumors.1 This tumor commonly occurs in elderly patients, 80.9% were above 40 years and 40.9% were postmenopausal.2 Rarely, it is reported in young females as Gorlin syndrome (ovarian fibroma with nevoid basal cell carcinoma).3 Sometimes it is associated with ascites and pleural effusion, when it is known as Meigs’ syndrome. It is difficult to diagnose preoperatively; may be misdiagnosed as uterine myoma or if it is associated with ascites it may be mistaken for ovarian malignancy. We are reporting one such case of ovarian fibroma operated with misdiagnosis of uterine myoma with torsion. CASE REPORT A 40-year-old para 3 live 3, who had undergone tubectomy and was having regular cycles, was admitted to Mandya Institute of Medical Sciences, Mandya, Karnataka with pain in the lower abdomen, on and off, since 1 week and which became more severe since past

*Assistant Professor †Professor and Head ‡Obs-Gyne Specialist Dept. of Obstetrics and Gynecology Mandya Institute of Medical Sciences, Mandya, Karnataka Address for correspondence Dr Pradeep Musale Ramamchandra Assistant Professor Dept. of Obstetrics and Gynecology Mandya Institute of Medical Sciences, Mandya - 571 401, Karnataka E-mail: majormrp@gmail.com

2 days. Patient was conscious and oriented, afebrile, pallor was present, pulse - 94 beats/min and blood pressure (BP) - 100/70 mmHg. On abdominal examination, a firm and irregular pelvic mass of 16 weeks size was palpable per abdomen. Bimanual examination revealed a pelvic mass of 16-18 weeks, irregular in shape, firm in consistency and tender. Other systemic examinations were normal. Ultrasound pelvis showed a normal-sized uterus with solid mass of 12 × 9.0 × 8.0 cm? Pedunculated fibroid; right side ovary was not seen and left ovary showed a small cyst of 3 cm. Urine pregnancy test was negative, chest X-ray was normal, USG abdomen was normal with no ascites. Preoperatively a diagnosis of a pedunculated subserous fibroid with torsion/ovarian cyst with torsion was made. Her hemoglobin (Hb) was 8.2 g/dL and since pain was increasing after admission she was planned for emergency laparotomy. Peroperatively, uterus of parous size with a rightsided solid ovarian mass of 15 × 10 × 10 cm was seen with torsion three times around itself, and appeared inflamed. There was no ascites (Fig. 1 a and b). Left ovary revealed a cyst of 3 × 3 cm size; total abdominal hysterectomy with bilateral salpingo-ovariotomy was done. Postoperative period was uneventful and the patient was discharged on 7th postoperative day. Histopathology report shows single grey-brown mass 14 × 12 × 10 cm cut section shows solid grey-brown to dark-brown hemorrhagic areas. Microscopy section from ovarian mass showed features of fibroma with hemorrhage consistent with torsion (Fig. 2).

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OBSTETRICS AND GYNECOLOGY misdiagnosed as uterine fibroma, torsion ovarian cyst, ectopic pregnancy and ovarian malignancy. Development of ascites is attributed to inefficient lymphatic drainage through small-sized pedicle and lack of real tumor capsule to the tumor and hydrothorax is secondary to ascites due to transdiaphragmatic passage.8

Figure 1 a and b. Torsion of ovarian fibroma with fallopian tube and uterus.

Treatment is excision of tumor by open or laparoscopic surgery, and life expectancy is same as in general population. Laparoscopy can be a diagnostic tool in detection of tumor and for resection of tumor or for ovariotomy. It can be converted into laparotomy in malignant cases.2 Complete resolution of ascites and pleural effusion takes place after surgery. In young patients with Gorlin syndrome, ovarian preservation can be done by resecting only fibroma.3 CONCLUSION Ovarian fibromas are benign tumors accounting for 1-4% of ovarian neoplasms, seen in elderly patients, generally asymptomatic and cannot be diagnosed accurately preoperatively; excision of tumor is the choice of treatment. REFERENCES 1. Chechia A, Attia L, Temime RB, Makhlouf T, Koubaa A. Incidence, clinical analysis, and management of ovarian fibromas and fibrothecomas. Am J Obstet Gynecol. 2008;199(5):473.e1-4.

Figure 2. Microscopic appearance of ovarian fibroma showing spindle cells.

DISCUSSION Ovarian fibromas account for 1-4% of ovarian neoplasms; 10-15% of these are associated with ascites and 1% have both ascites and pleural effusion.4 Ovarian fibromas are seen in middle-aged women, largely asymptomatic unless they undergo torsion. They are solid ovarian tumors and they are benign, so detection of fibroma is important to decrease patient anxiety and unnecessary extensive surgical procedure. Ovarian fibromas cannot be diagnosed accurately either clinically or by ultrasound.5 Magnetic resonance imaging (MRI) is an excellent modality for detection of ovarian fibroma as they enhance less than myometrium and fibroids.6 In rare cases, carcinoembryonic antigen-125 may be raised.7 But ovarian fibroma is a benign tumor with extremely low malignant potential. It may be

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2. Son CE, Choi JS, Lee JH, Jeon SW, Hong JH, Bae JW. Laparoscopic surgical management and clinical characteristics of ovarian fibromas. JSLS. 2011;15(1):16-20. 3. Ball A, Wenning J, Van Eyk N. Ovarian fibromas in pediatric patients with basal cell nevus (Gorlin) syndrome. J Pediatr Adolesc Gynecol. 2011;24(1):e5-7. 4. Abad A, Cazorla E, Ruiz F, Aznar I, Asins E, Llixiona J. Meigs’ syndrome with elevated CA125: case report and review of the literature. Eur J Obstet Gynecol Reprod Biol. 1999;82(1):97-9. 5. Najmi Z, Mehdizadehkashi A, Kadivar M, Tamannaie Z, Chaichian S. Laparoscopic approach to a large ovarian fibroma: a case report. J Reprod Infertil. 2014;15(1):57-60. 6. Shinagare AB, Meylaerts LJ, Laury AR, Mortele KJ. MRI features of ovarian fibroma and fibrothecoma with histopathologic correlation. AJR Am J Roentgenol. 2012;198(3):W296-303. 7. Morán-Mendoza A, Alvarado-Luna G, Calderillo-Ruiz G, Serrano-Olvera A, López-Graniel CM, Gallardo-Rincón D. Elevated CA125 level associated with Meigs’ syndrome: case report and review of the literature. Int J Gynecol Cancer. 2006;16 Suppl 1:315-8. 8. Nigam A, Jain S, Lal P. Twisted ovarian fibroma mimicking as an ectopic pregnancy. J Case Rep. 2013;3:64-7.

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EXPERTâ&#x20AC;&#x2122;S VIEW

Which Antihypertensive Drugs can be Safely Taken During Pregnancy? SP KALANTRI

s the most common medical disorder of pregnancy, hypertension is reported to complicate one in 10 pregnancies,1 and the challenge is in deciding when to use antihypertensive medications and what level of blood pressure (BP) to target. The choice of antihypertensive agents is easy, because only a small proportion of currently available drugs have been adequately evaluated in pregnant women, and many others are contraindicated. METHYLDOPA

Methyldopa, a centrally-acting a2-adrenergic agonist prodrug, remains one of the most widely used drugs for the treatment of hypertension in pregnancy. It is not thought to be teratogenic-based on limited data and a 40-year history of use in pregnancy. It has been assessed in a number of prospective trials in pregnant women compared with placebo,2-4 or with alternative antihypertensive agents.4-7 Treatment with methyldopa has been reported to prevent subsequent progression to severe hypertension in pregnancy8 and does not seem to have adverse effects on uteroplacental or fetal hemodynamics9 or on fetal well- being.3 CLONIDINE Clonidine, a selective a2-agonist, acts similarly and is comparable to methyldopa with respect to safety and efficacy,10 but of some concern is a small controlled follow-up study of 22 neonates that reported an excess of sleep disturbance in clonidine-exposed infants.11 In pregnancy, it is mainly used as a third-line agent for multidrug control of refractory hypertension. LABETALOL b-blockers have been used extensively in pregnancy although there are still some unresolved issues regarding

their use in pregnancy, largely a result of a few small studies that suggest an association with lower birth weight infants. Labetalol, a nonselective b-blocker with vascular a1-receptor blocking capabilities, has gained wide acceptance in pregnancy. When administered orally to women with chronic hypertension, it is found to be as safe3,7,12,13 and effective as methyldopa. Parenterally, it is used to treat severe hypertension, and because of a lower incidence of maternal hypotension and other adverse effects, its use now supplants that of hydralazine.14 CALCIUM CHANNEL ANTAGONISTS Calcium channel antagonists have been used to treat chronic hypertension, mild pre-eclampsia presenting late in gestation and urgent hypertension associated with pre-eclampsia. Orally, administered nifedipine and verapamil do not seem to pose teratogenic risks to fetuses exposed in the first-trimester.15 Nifedipine does not seem to cause a detectable decrease in uterine blood flow.16,17 DIURETICS Diuretics are commonly prescribed in essential hypertension before conception and, given their apparent safety, the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy concluded that they may be continued through gestation (with an attempt made to lower the dose) or used in combination with other agents, especially for women deemed likely to have salt-sensitive hypertension.1 Hydrochlorothiazide may be continued during pregnancy; the use of low doses (12.5-25 mg daily) may minimize untoward metabolic effects, such as impaired glucose tolerance and hypokalemia.18 Triamterene and amiloride are not teratogenic-based on small numbers of case reports.18 DIRECT VASODILATORS

Address for correspondence Professor and Head Dept. of Medicine, MGIMS, Sevagram, Wardha, Maharashtra

Hydralazine, which selectively relaxes arteriolar smooth muscle has been used in all trimesters of

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EXPERT’S VIEW pregnancy, and data have not shown an association with teratogenicity, although neonatal thrombocytopenia and lupus have been reported.19 It has been widely used for chronic hypertension in the second and third trimesters, but its use has been supplanted by agents with more favorable adverse effect profiles.20 For acute severe hypertension later in pregnancy, intravenous hydralazine has been associated with more maternal and perinatal adverse effects than intravenous labetalol or oral nifedipine. REFERENCES 1. Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy. Am J Obstet Gynecol. 2000;183(1):S1-S22.

uteroplacental and fetal hemodynamics in pregnancyinduced hypertension. Am J Obstet Gynecol. 1993;168(1 Pt 1):152-6. 10. Horvath JS, Phippard A, Korda A, Henderson-Smart DJ, Child A, Tiller DJ. Clonidine hydrochloride - a safe and effective antihypertensive agent in pregnancy. Obstet Gynecol. 1985;66(5):634-8. 11. Huisjes HJ, Hadders-Algra M, Touwen BC. Is clonidine a behavioural teratogen in the human? Early Hum Dev. 1986;14(1):43-8. 12. 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 Gynaecol. 1989;96(1):38-43.

2. Redman CW. Fetal outcome in trial of antihypertensive treatment in pregnancy. Lancet. 1976;2(7989):753-6.

13. Sibai BM, Gonzalez AR, Mabie WC, Moretti M. A comparison of labetalol plus hospitalization versus hospitalization alone in the management of preeclampsia remote from term. Obstet Gynecol. 1987;70(3 Pt 1):323-7.

3. Sibai BM, Mabie WC, Shamsa F, Villar MA, Anderson GD. A comparison of no medication versus methyldopa or labetalol in chronic hypertension during pregnancy. Am J Obstet Gynecol. 1990;162(4):960-6; discussion 966-7.

14. Magee LA, Cham C, Waterman EJ, Ohlsson A, von Dadelszen P. Hydralazine for treatment of severe hypertension in pregnancy: metaanalysis. BMJ. 2003;327(7421):955-60.

4. Leather HM, Humphreys DM, Baker P, Chadd MA. A controlled trial of hypotensive agents in hypertension in pregnancy. Lancet. 1968;2(7566):488-90.

15. Magee LA, Schick B, Donnenfeld AE, Sage SR, Conover B, Cook L, et al. The safety of calcium channel blockers in human pregnancy: a prospective, multicenter cohort study. Am J Obstet Gynecol. 1996;174(3):823-8.

5. Fidler J, Smith V, Fayers P, De Swiet M. Randomised controlled comparative study of methyldopa and oxprenolol in treatment of hypertension in pregnancy. Br Med J (Clin Res Ed). 1983;286(6382):1927-30. 6. Gallery ED, Ross MR, Gyory AZ. Antihypertensive treatment in pregnancy: analysis of different responses to oxprenolol and methyldopa. Br Med J (Clin Res Ed). 1985;291(6495):563-6. 7. Plouin PF, Breart G, Maillard F, Papiernik E, Relier JP. Comparison of antihypertensive efficacy and perinatal safety of labetalol and methyldopa in the treatment of hypertension in pregnancy: a randomized controlled trial. Br J Obstet Gynaecol. 1988;95(9):868-76. 8. Redman CW, Beilin LJ, Bonnar J. Treatment of hypertension in pregnancy with methyldopa: blood pressure control and side effects. Br J Obstet Gynaecol. 1977;84(6):419-26.

16. Lindow SW, Davies N, Davey DA, Smith JA. The effect of sublingual nifedipine on uteroplacental blood flow in hypertensive pregnancy. Br J Obstet Gynaecol. 1988;95(12):1276-81. 17. Rizzo G, Arduini D, Mancuso S, Romanini C. Effects of nifedipine on umbilical artery velocity waveforms in healthy human fetuses. Gynecol Obstet Invest. 1987;24(3):151-4. 18. Magee LA. Drugs in pregnancy. Antihypertensives. Best Pract Res Clin Obstet Gynaecol. 2001;15(6):827-45. 19. Widerlöv E, Karlman I, Storsäter J. Hydralazineinduced neonatal thrombocytopenia. N Engl J Med. 1980;303(21):1235.

20. Task Force on the Management of Cardiovascular Diseases During Pregnancy of the European Society of Cardiology. Expert consensus document on management of cardiovascular diseases during pregnancy. Eur Heart J. 9. Montan S, Anandakumar C, Arulkumaran S, 2003;24(8):761-81. Ingemarsson I, Ratnam SS. Effects of methyldopa on ■■■■

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CONFERENCE PROCEEDINGS

7th World Congress of Diabetes (DiabetesIndia 2017) LONGITUDINAL COHORTS AND UNDERSTANDING DIABETES RISK AND CAUSATION

ÂÂ

Normal endothelium is a smooth layer; nothing permeates it and the blood flow is laminar. Endothelium in diabetes becomes permeable and there is greater adhesion; blood flow is turbulent.

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There is decreased vascular responsiveness in diabetes.

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There is increased RAAS activity in diabetic nephropathy.

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Central aortic pressure is higher in diabetics than controls. Night-time BP is also higher in diabetes. This can lead to CV damage.

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In diabetes, the following 5 mechanisms lead to superoxide generation: ↑ glucose flux pathway through polyol pathway; advanced glycation end-products; ↑ protein kinase C; ↑ glucose flux through hexosamine pathway; ↑ 12/15-lipoxygenase pathway.

Dr Nikhil Tandon, New Delhi ÂÂ

Cohort studies: Observational epidemiological design explicitly incorporating passage of time.

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There are 2 types of cohort studies: Retrospective studies collecting data on events that have already occurred; Prospective - studies in which investigators observe events as they occur in time.

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The Center for Cardiometabolic Risk Reduction in South Asia (CARRS) Surveillance Study is a community-based health survey project in three of the world’s largest cities (Delhi and Chennai, India and Karachi, Pakistan). It involves 12,000 adults aged ≥20 years. CARRS study design: Hybrid model with two cross-sectional serial surveys 3 years apart to monitor trend, with a 3-year prospective follow-up of the first cohort. In the study, every household, census enumeration block (CEB) and 1 km radius around the selected CEB have been geocoded. Dysglycemia (diabetes mellitus or prediabetes) has been noted in 56% males and 65.4% females in Chennai vs. 72.3% males and 73.1% females in Delhi (based on HbA1c and FBS definition). A nested case-control study aimed to assess the association of amount of carbohydrate intake with newly diagnosed T2DM in adults. Baseline fat consumption was found to be related to future risk of diabetes.

MECHANISM OF VASCULAR DISEASES IN DIABETES Dr C Venkata S Ram, Hyderabad ÂÂ

Diabetes = CVD – As soon as you make a diagnosis of diabetes mellitus, you have already made a diagnosis of CVD.

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Increased BP is linked with increased CV risk; diabetes mellitus is linked with increased CV risk; increased BP + diabetes mellitus is linked with a compounded increase in CV risk.

SHOULD DIABETES BE A SEPARATE SPECIALTY OR SUBSPECIALTY IN PG MEDICINE EDUCATION? Prof Dr S Arulrhaj, Thoothukudi, Tamil Nadu ÂÂ

Diabetes is a well-justified separate specialty.

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India needs MCI approved MD and DM/DNB Diabetology.

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It is important to initiate early and meet goals.

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MCI accreditation is the key.

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Yes, diabetes is a specialty.

FIRST ADD-ON AFTER METFORMIN IN INDIAN DIABETICS - GLIPTINS Dr Sanjeev Phatak, Ahmedabad Gliptins are perfect partner to metformin. Gliptins are: Pancreatic beta-cell friendly; are efficient and safe; demonstrate long-term clinical outcomes. DPP-4 inhibitors are durable as they exhibit no cardiovascular harm, cancer, weight gain or fractures. DPP-4 inhibitors are safe and highly effective class of antidiabetic drugs. ÂÂ

Gliptins offer good glycemic control: Reduce HbA1c levels and preserve pancreatic beta cells.

ÂÂ

They protect against weight gain, heart failure and hypoglycemia.

Indian Journal of Clinical Practice, Vol. 27, No. 12, May 2017

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CONFERENCE PROCEEDINGS ÂÂ

They demonstrate long-term clinical outcomes: Due to low mortality and CV events.

(AGIs), dipeptidyl peptidase-4 inhibitors (DPP4i) and GLP-1 agonists are very useful in reducing GV. Use of basal insulin and prandial analogs are also important in improving GV.

Asians are more likely to receive benefit from DPP-4 inhibitors, compared to non-Asians. ÂÂ

The Indian scenario of high postprandial glucose (PPG) can be effectively managed with the use of AGIs. They delay the digestion and absorption of carbohydrates and also do not stimulate insulin release, preventing hypoglycemia.

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According to IDF treatment algorithm in type 2 diabetes mellitus (T2DM), AGIs can be used as second-line of treatment. Studies have shown that, there is decrease in PPG elevation slope more effectively with AGIs in comparison to other oral antidiabetic drugs.

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AGIs decrease glycemic excursion and inhibit pancreatic overwork.

SULFONYLUREAS: WRITTEN OFF? Dr Urman Dhruv, Ahmedabad ÂÂ

It is time to think about safety first in high-risk group of patients with type 2 diabetes mellitus (T2DM).

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Recent trials have concluded beyond doubt that in people having T2DM and established cardiovascular disease (CVD), potent drugs with tendency to produce marked hypoglycemia are best avoided.

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Most of patients having T2DM die of CVD and therefore, an important goal of management of T2DM will be to prevent CV deaths in diabetes.

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Newer molecules have much bigger margin of safety as regards hypoglycemia.

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The next decade belongs to drugs that may have proven safety and effect on CV outcome on longterm basis.

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Sulfonylureas may be potent drugs to reduce HbA1c but at the same time, they have no background trials to suggest CV safety and definitely no evidence to show that they are beneficial in reducing CVD.

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In developing countries where cost plays an important role, one should still remember the cost of managing CVD burden is much more than the cost of nonsulfonylurea drugs, which are safer and beneficial.

AGI: AN INDISPENSABLE PART OF MANAGEMENT OF INDIAN T2DM Dr Banshi Saboo, Ahmedabad ÂÂ

Diabetes is the global health emergency of the 21st century.

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Currently, diabetes control is measured by fasting plasma sugar, postprandial plasma sugar and glycosylated hemoglobin (HbA1c).

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Beyond HbA1c, glycemic variability (GV) is an unnoticed parameter in diabetes management. You can measure it by self-monitoring of blood glucose (SMBG) or continuous glucose monitoring (CGM) or ambulatory glucose profile (AGP). Diet has an important role to play in reducing GV; medications such as alpha-glucosidase inhibitors

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LIPOPROTEIN(A) AND RESIDUAL CARDIOVASCULAR RISK Dr Piyush Jain, New Delhi ÂÂ

Current standards of care for CVD prevention emphasize multifactorial intervention to achieve targets for LDL, BP and glycemic control.

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Significant CVD risk persists despite effective LDL cholesterol-lowering treatment.

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Lp(a) has emerged as an independent risk factor for premature CAD and residual CV risk.

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There is ongoing research for therapy for decreasing the high Lp(a) concentrations.

FEMALE GENDER: THE KEY TO DIABETES PREVENTION Prof V Seshiah, Chennai ÂÂ

The prevalence of diabetes is increasing globally and India is no exception. The increased prevalence is attributed to the aging population structure, urbanization, the obesity epidemic and physical inactivity.

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Early life exposures are emerging as potential risk factors.

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The ‘‘fetal origin of disease’’ hypothesis proposes that gestational programming may critically influence adult health and disease.

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The primary prevention of type 2 diabetes mellitus (T2DM) would mean to keep genetically or otherwise susceptible individuals normoglycemic thus preventing T2DM from developing.

CONFERENCE PROCEEDINGS ÂÂ

Women with gestational diabetes mellitus (GDM) are an ideal group for the primary prevention of diabetes as they are at increased risk of developing diabetes, predominantly T2DM, as are their children. Transgenerational transmission of diabetes occurs.

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Exposure to a diabetic environment in utero is associated with increased occurrence of impaired glucose tolerance, a defective insulin secretory response and higher adiposity in adult offsprings, independent of genetic predisposition to type 2 diabetes.

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A recent publication states that more than 50% doctors do not follow any GDM guidelines, possibly due to lack of awareness. The Ministry of Health, Govt. of India has given the direction to follow the Diabetes in Pregnancy Study Group in India’s (DIPSI) recommendation to diagnose GDM. The need of the hour is that timely action taken now in screening all pregnant women for glucose intolerance, achieving euglycemia in them and ensuring adequate nutrition may prevent in all probability, “the epidemic of diabetes”.

METABOLOMICS IN DIABETES AND METABOLISM Dr GR Sridhar, Visakhapatnam ÂÂ

Metabolomics refers to measurement and characterization of small molecules in biological fluids and tissues.

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They form the bridge between genotype and phenotype.

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While genotype is considered the tip of the iceberg, metabolomics is the iceberg itself.

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The metabolites are measured either as targeted or untargeted by techniques such as NMR spectroscopy and liquid chromatography-mass spectroscopy.

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They are used as biomarkers to identify future risk of diabetes and its complications.

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Metabolomics supplements but does not supplant traditional risk factor assessment.

SGLT2 INHIBITORS CANNOT DISPLACE THE PRIMACY OF DPP-4 INHIBITORS Dr Vinod Mittal, New Delhi ÂÂ

Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder with multiple pathophysiological defects. No single agent can address all these pathophysiologic abnormalities.

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Dipeptidyl peptidase-4 (DPP-4) inhibitors have multiple sites of action and, to a large extent, can address at least 4 major pathophysiological defects, i.e., insulin deficiency, glucagon hypersecretion, incretin defect and apoptosis of pancreatic beta cells.

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DPP-4 inhibitors also have multiple pleiotropic effects such as anti-inflammatory, antithrombotic and lipid-friendly effects. DPP-4 inhibitors are very effective, safe and well-tolerated drugs. These agents are also cardio-renal safe.

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These can be prescribed even in the most vulnerable diabetic population, i.e., elderly (>65 years), severe CKD and high-risk CVD patients.

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Sodium-glucose co-transporter 2 (SGLT2) inhibitors and address only one pathophysiological defect. These agents have no action on beta-cell function, which is the main pathophysiological defect. SGLT2 inhibitors treat only the symptom (i.e., hyperglycemia) and not the disease (diabetes). SGLT2 inhibitors also have a number of safety concerns, which DPP-4 inhibitors do not have.

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Hence, the primacy of DPP-4 inhibitors can never be displaced by SGLT2 inhibitors.

SULFONYLUREA IN MANAGEMENT OF TYPE 2 DIABETES Dr Neeta Deshpande, Belgaum Sulfonylureas (SUs) are the best choice for the management of type 2 diabetic patients due to their high efficacy, neutral cardiovascular safety and most importantly low cost. Further, the weight gain associated with the use of SU is not significant (i.e., 2 kg), hypoglycemic risk is moderate and major side effects are well tolerable. Hence, SUs are constantly used for past 50 years. Recent studies do not show any evidence of SU-mediated progressive beta-cell destruction or decline. Due to high efficacy and low cost of SUs, they are extensively used as initial therapy, second-line therapy and as subsequent add-on therapy for the management of type 2 diabetic patients. THE DEVELOPMENT OF DIABETOLOGY AS A SPECIALTY IN INDIA Dr AH Zargar, Srinagar The Diabetic Association of India was formed in 1955. The All India Institute of Diabetes was established under the aegis of the Diabetic Association of India in 1974. Prof JP Bose started a diabetes clinic way back in 1923 at the School of Tropical Medicine, Kolkata.

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CONFERENCE PROCEEDINGS Prof BB Tripathy did some of the best epidemiological researches at a time when the field of epidemiology was at its nascent stage in India. Dr Hari Vaishnava started diabetes clinic in MAMC in early 60s. Dr Hemraj Chandalia started career as an Endocrinologist and Diabetologist in Bombay in 1971. In the first RSSDI Executive Committee (EC) on September 25, 1972, Prof OP Gupta was in Chair, and Prof BB Tripathy, Dr Vinod Kumar, Dr M Bhaskar Rao, Prof MMS Ahuja and Prof GS Mutalik were present. The second EC met on December 20, 1972.

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Mobile technology could be used as an effective, practical tool for sustained adherence to lifestyle principles in large scale prevention programs.

ALCOHOL AND DIABETES: WHAT DO WE RECOMMEND? Dr Raj Kumar Lalwani, New Delhi ÂÂ

Alcohol has been with human civilizations since ages.

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The first academic activity of the society was a symposium-cum-workshop in Delhi on Etiogenesis of Diabetes Mellitus. In March 2009, the Diabetology Department of Madras Medical College was upgraded as Institute of Diabetology.

Being a drug, it has an abuse and addiction potential. Alcoholism is a well-known clinical entity.

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Despite well-documented health hazards, alcohol drinking continues to be an established and acceptable socio-cultural tradition in many societies.

PRIMARY PREVENTION OF TYPE 2 DIABETES: INDIAN CONTRIBUTION

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As Diabetologists though we should not start preaching against it to all who consume alcohol, but it becomes our duty to educate them on safe and responsible drinking.

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Since, low to moderate drinking has been shown to be a “good lifestyle practice” with documented mortality and cardiovascular benefits, we should counsel and educate our patients on how it can be adapted to their diet plans and how much can be labeled as safe for them?

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Many drugs used for the treatment of diabetes do create complex interactions which can become disastrous, if not understood or recognized in time.

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Even when everything is taken care of and a clinician may find that his patient will not be harmed by mildto-moderate intake of alcohol, it’s use for perceived or so-called health benefits cannot be recommended for all, because of the simple reason that it is a “drug” with great abuse and addiction potential, if not taken responsibly!

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In my opinion, our counseling with a positive note, should be: “Only Champions drink responsibly and just Everybody cannot be a Champion!”

Dr Ambady Ramachandran, Chennai ÂÂ

Primary prevention is a major step in curbing the increasing prevalence of type 2 diabetes.

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Prevention of type 2 diabetes is possible in high risk persons by lifestyle modification or by use of pharmacological agents.

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Normal beta-cell function with improved insulin sensitivity facilitates reversal to normoglycemia and prevents conversion to diabetes.

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Baseline HbA1c is the strongest predictor of future incidence of diabetes.

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Sending text messages on healthy lifestyle principles through mobile phones has been found to be an effective and economical method of educating and motivating participants.

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Lifestyle modification improved cardiovascular risk factors such as dyslipidemia.

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Early reversion to normoglycemia with lifestyle intervention was associated with a significant reduction in subsequent events of diabetes.

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CONFERENCE PROCEEDINGS

54th Annual Conference of Indian Academy of Pediatrics (PEDICON 2017) HYPOTHYROIDISM

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Fever with renal failure: Antipyretics; injection ceftriaxone 100 mg/kg/day IV in 2 divided doses; tablet doxycycline 100 mg BD; IV fluids; renal replacement therapy (intermittent HD/CRRT).

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Fever with jaundice: Antipyretics; injection ceftriaxone 100 mg/kg/day IV in 2 divided doses; tablet doxycycline 100 mg BD; IV fluids; FFP/ cryoprecipitate for bleeding.

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Fever with thrombocytopenia: Antipyretics; IV fluids; avoid aspirin/anticoagulants; platelet transfusion if platelet count <20,000 or clinical bleeding; no role of steroids.

Dr Raghupathy, Bengaluru ÂÂ

Untreated CH results in mental retardation, hence, it is assumed that juvenile hypothyroidism also results in poor school performance and intellectual delay. The fact is that there are no learning problems or intellectual delay or cognitive impairment. The diagnosis may be elusive.

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Adolescent hypothyroidism is most commonly autoimmune thyroiditis and may be detected only with growth failure in chronic hypothyroidism.

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Hashimoto thyroiditis is typically adolescents, rarely in younger age.

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Avoid overdiagnosis, unwarranted treatment. Before advising lifelong thyroxine treatment, confirm data, diagnosis and etiology.

Keep syndromic approach. Follow evidencebased algorithms. Choose reliable rapid diagnostic modalities.

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Start early empiric therapy based on clinical syndromes. Keep update about infections prevalent in your region. Early referral to tertiary care unit in stable condition, if working in periphery.

seen

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Hasty decisions are unjustified. Long-term thyroxine shall surely shrink and fibrose the normal functioning thyroid.

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We should not create hypothyroidism.

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Delay in treatment of CH will results in developmental delay.

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Neonatal thyroid screening is essential for detecting congenital hypothyroidism.

FEVER IN ER Dr Vinay Patil, Mumbai ÂÂ

Japanese encephalitis - Supportive treatment: Airway management, seizure control and management of raised intracranial pressure.

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Enteric fever - First-line: Ceftriaxone for 10-14 days to cover MDR S. typhi; azithromycin and ciprofloxacin are alternatives; consider dexamethasone 3 mg/kg followed by 1 mg/kg 6 hourly for 48 hours in selected cases with encephalopathy, hypotension or DIC.

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Fever with respiratory distress: Antipyretics; IV fluids; oxygen by Venturi mask; injection ceftriaxone 100 mg/kg/day IV in 2 divided doses; injection azithromycin 15 mg/kg/day IV OD; tablet oseltamivir 3 mg/kg BD, if H1N1 is a possibility.

RENAL STONE DISEASE IN CHILDREN Dr Susan Uthup, Kerala Urolithiasis is a common problem in children. Its incidence has increased. Evaluation for metabolic and anatomical abnormalities is important in children. Medical treatment includes analgesics, antiemetics, urinary alkalinization and if required, IV fluids. In selected children, medical expulsion treatment with nifedipine/tamsulosin is an effective and safe modality. Decreased water intake, high salt and meat product intake are major factors contributing to recurrence. Modification of risk factors and follow-up are of prime importance. PREVENTION OF ADOLESCENT HYPERTENSION Dr Kavya Mallikarjun, Bengaluru ÂÂ

The normal BP in children and adolescents is both systolic and diastolic BP <90th percentile. The definition of childhood HT is based upon the normative distribution of BP in healthy children.

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HT is defined as either systolic and/or diastolic BP ≥95th percentile measured on ≥3 occasions.

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CONFERENCE PROCEEDINGS HT is further delineated into two stages: Stage 1 HT (systolic and/or diastolic BP between the 95th percentile and 5 mmHg above the 99th percentile or if in adolescents the BP exceeds 140/90 mmHg even if <95th percentile) and Stage 2 HT (systolic and/or diastolic BP ≥99th percentile plus 5 mmHg). ÂÂ

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Follow-up: If normal (recheck at next scheduled visit), pre-HT (recheck in 6 months), Stage 1 HT (recheck in 1-2 weeks or earlier if symptoms), Stage 2 HT (evaluate immediately, if symptoms; if not evaluate within the week). Avoid food or stimulant drugs prior to measuring BP in children and adolescents. Measure after 5 min of rest in a quiet environment.

Kill Stress with STRESS: Smile, Time management, Relaxation, Exercise, Social activities, Success SLEEP AND ADOLESCENT SCHOOL CHILDREN Dr Sunny Kurian, Sharjah, UAE

A Perspective from the UAE Challenges due to lack of sleep include: Inattentiveness in class and decreased scholastic performance.

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Inability to self-regulate with poor control over emotions/impulse/aggressive behavior/temper. In fact, some of the sleep deprived display symptoms mimicking ADHD.

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Substance use and risky behavior.

Dr Latika Bhalla, New Delhi

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Inability to complete task and assignments on time.

In the right dose, stress can be healthy or even enjoyable because due to stress you get something good in your life and stress adds flavor, challenge and opportunity to our world (positive stress).

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Mood changes especially depression, sometimes predisposing to early mental illness.

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Obesity and later risk of diabetes.

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Dependence on sleep medication and anxiety relieving drugs.

Auscultation is the preferred method of BP measurement, with the right arm supported at the level of the heart. Inflate the cuff to 20-30 mmHg above the anticipated systolic BP and then deflate slowly at a rate of 2-3 mmHg per heartbeat.

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Excessive stress can harm students’ health, happiness, work performance, relationships and personal development (negative stress).

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Stress changes the normal balance and functioning of the immune system. Certain chronic health conditions are linked to stress and may worsen or recur during periods of increased stress (e.g., ulcers, headaches).

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Children need to learn effective techniques to remove surrounding stressors. This will help them to prepare them for school with positive ways to handle competition stress.

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STRESS OF COMPETITION

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Tips on how to manage exam stress: Organize, diet, relax, plan, cross check and positive self talk.

Suggestions and Possible Way Forward

At school: For middle and high schools ÂÂ

‘Later start’ to school time.

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More ‘brightly’ lit classrooms.

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No ‘test’ early in the morning.

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Subjects like mathematics, science and reading to be put later in the day.

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Balancing school and social stressors is necessary.

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To avoid the undesirable disadvantages of competition stress, students should consider the causes of stress important as it helps them make plans to reduce it.

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Explore the possibility of getting into a ‘nap time’ (15-20 min) into the school schedule.

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Initiate classes on ‘sleep health’ for the students.

It is very important to bring about attitudinal change, which may not be possible just by speaking to them often about peace and nontime management as we often do.

At home ÂÂ

Set a sleep time table and sleep discipline and make it a point to stick to it.

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We can help children achieve more of their potential by teaching them positive social skills.

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The ritual toward sleep should start at least 2 hours before the intended sleep time.

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Regular counseling and monitoring should be a part of school health education.

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Dimming of lights and reduction of loud noises (loud music, TV, etc.) should start early.

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CONFERENCE PROCEEDINGS ÂÂ

Avoid stimulating foods/drinks such as tea, coffee, soda pop, chocolates… at least 6 hours before the sleep time.

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Window blinds and curtains should be adequate to keep away external lights.

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The bedroom and the bed should ideally be used to sleep/resting purposes only. Reading, watching TV and texting while in bed should be strongly discouraged and parents should set the example.

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Avoid naps, which last more than 15-20 mins during day time because that would interfere with the child getting enough sleep at night.

REFRACTORY EPILEPSY

artery occlusion (SUSAC syndrome); joints/ kidneys/skin (SLE); GI symptoms (celiac or Whipple’s); DI (histiocytosis); uveitis/mucosal ulcers (Behcet syndrome), facial neuropathy (sarcoid neuroborreliosis), oculomasticatory myorhythmia (Whipple’s). ASTHMA Dr Kishore Baindur, Bengaluru ÂÂ

Asthma is a major cause of morbidity and mortality at all ages. There has been a rise in prevalence that is not entirely explained by changes in diagnostic practices.

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A family history of atopy remains the most useful way of identifying infants at high risk of atopy. A prevalence rate of 40-80% is suggested in children with bi-parental atopy.

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Atopic disease manifests when the genetically predisposed individual is exposed to various trigger factors. Many of these triggers are allergens to which the infant appears to be particularly vulnerable. Avoidance of allergens during infancy may reduce asthma prevalence, including those of other allergic disorders and skin sensitization. The benefit may continue beyond the period of avoidance.

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The prevalence of childhood asthma has continued to rise in the Indian subcontinent in the past decade (ISAAC Phase 3 Thorax. 2007).

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For children, a window of opportunity exists in utero and in early life, but intervention studies are limited.

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Environmental risk factors include nutrition, allergens (inhaled and ingested), pollutants (tobacco smoke), microbes and psychosocial factors.

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Several studies have reported a beneficial effect of breastfeeding on asthma prevention, but results are conflicting. So, exercise caution when advising families that breastfeeding prevents asthma. It should however be encouraged for all the other positive benefits.

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Maternal intake of vitamin D and vitamin E may lower risk of wheezing illnesses in children.

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Probiotics have insufficient evidence to support their preventive role in allergic diseases.

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In children at risk of asthma, dampness, visible mold and mold odor in the home environment are associated with increased risk of developing asthma.

Dr Arun Kumar Agrawal, Ghaziabad ÂÂ

Refractory epilepsy or difficult-to-treat epilepsy is not uncommon; it is a known entity even in the best medical treating hands.

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It is better to revise the whole history before labeling a case as refractory epilepsy. If possible, it should be reviewed by a different specialist. Pseudoseizures should be excluded.

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Alternatives to medical treatment like vagal nerve stimulation and surgery can be tried.

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Each and every disease is not 100% treatable or curable so don’t lose your heart (advice to the treating doctor).

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Do not hesitate in referring to your colleague, may be he can do better though the chances are rare.

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Education program for patient and/or relatives is important.

PEDIATRIC MULTIPLE SCLEROSIS Dr Allison Conravey, USA ÂÂ

Laboratory work-up: B12 and folate, ANA, ESR, RF, HIV and HTLV-1, thyroid, anticardiolipin, ACE, Lyme disease, NMO antibodies, anti-MOG.

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Red flags are: Onset before 1 year of age, h/o developmental delay, consanguineous family, f/h/o severe acute neurologic syndromes, gradual progression of symptoms, multisystemic involvement, MRI (single supratentorial white matter lesion, symmetric white matter involvement or lesions restricted solely to the brain stem and basal ganglia).

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Key points to differential include: Fever, meningismus; hearing loss and branch retinal

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CONFERENCE PROCEEDINGS ÂÂ

Maternal smoking during pregnancy is the most direct route of prenatal environmental tobacco smoke exposure.

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Exposure to outdoor pollutants, e.g., living near a main road, increases risk of asthma.

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Antibiotics, paracetamol during pregnancy and maternal distress have been associated with asthma.

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For primary prevention of asthma, avoid exposure to environmental tobacco smoke during pregnancy or after birth, vaginal delivery should be encouraged where possible, encourage breastfeeding, minimize use of paracetamol and discourage use of antibiotics.

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LRTIs should be characterized by: Type of infection (viral or bacterial), site of infection, nature of episode (acute or acute-on-chronic) and comorbidities e.g., asthma (Pediatr Resp Rev. 2012).

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Prematurity, atopy, passive smoking, indoor and outdoor pollution, congenital respiratory tract abnormalities, CVD and chronic neurological diseases increase risk for recurrent LRTIs.

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Recurrent pneumonia is a symptom of an underlying disease and not a diagnosis in itself.

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The normal child with RRTI (50%): Seasonal, milder and often self-limiting infections, complete recovery in between episodes, usually viral; growth and development is normal without any symptoms suggestive of chronic illness; infection limited to the respiratory tract.

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Child with allergy (30%): History and clinical findings of allergic rhinitis, asthma and comorbidities; ↑d susceptibility to RRTI due to ↓d mucociliary clearance, ↑d mucosal permeability and defective innate immune response to pathogens.

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Child with nonimmune cause (10%): Due to ineffective mucus clearance (cystic fibrosis, bronchiectasis), airway obstruction (FB aspiration, tumors, eustachian tube dysfunction), ↑d pulmonary blood flow (CV abnormality), congenital airway abnormality, chronic infection (chronic MTb), recurrent re-infection (day care), exposure to irritants (GERD, cigarette smoke).

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Child with immunodeficiency (10%): Hallmark is SPUR (Severe, Persistent, Unusual or Recurrent infections), f/h/o recurrent infections or early infant death due to infection, failure to thrive, LN ↑, recurrent severe GI and SSTIs.

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Upper and lower respiratory symptoms: Asthma, immunodeficiency, ciliary dyskinesias, cystic fibrosis. Only lower respiratory symptoms: Aspiration syndromes, congenital anomalies, CVS shunts, FB, TB, tumors.

Preventative treatment of RSV infection reduces recurrent wheezing in the first year of life.

Guide to Asthma Prevention in Adolescents Follow asthma action plan. Regular monitoring and treatment. Get vaccinated for influenza and pneumonia. Identify and avoid asthma triggers. Monitor breathing (recognize signs of an asthma

impending attack).

Identify and treat attacks early. Stop any activity and take medication immediately,

if peak flow measurements decrease.

Take medication as prescribed. Pay attention to increasing use of quick-relief

inhaler.

RECURRENT CHEST INFECTIONS Dr Vineet Sehgal, New Delhi ÂÂ

Recurrent pneumonia is usually defined as ≥2 episodes of pneumonia in a year or ≥3 episodes.

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Recurrent LRTIs are very common in childhood, especially in pre-schoolers. ■■■■

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MEDILAW

A Medical Practitioner is not Expected to Achieve Success in Every Case that he Treats

I followed the standard treatment protocol and also followed all due procedures prior to the surgery.

The complainant has alleged deficiency in service and medical negligence in the treatment of her husband who passed away.

A doctor is expected to bring a reasonable degree of skill and care. The negligence to be established by the prosecution must be culpable or gross and not the negligence merely based upon an error of judgement. The complaint is dismissed.

Proceed

Lesson: In its judgement in Kusum Sharma & Ors vs Batra Hospital & Medical Research Centre & Others on 10 February, 2010 Civil Appeal No.1385 of 2001, the Supreme Court of India said “Merely because a complication occurs, it does not mean that the hospital or the doctor was guilty of negligence. A medical practitioner is not expected to achieve success in every case that he treats. The duty of the doctor is to exercise reasonable skill and care. A medical practitioner would be liable only where his conduct fell below that of the standards of a reasonably competent practitioner in his field.”

COURSE OF EVENTS ÂÂ

10.12.1989: Patient visited Hospital ‘X’ with complaints of swelling and difficulty in breathing while climbing stairs. He was very obese and also had high blood pressure. No diagnosis could be made.

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14.3.1990: Patient was examined by Dr ‘A’ (Respondent No. 2) and Dr ‘B’ at Hospital ‘Y’ (Respondent No. 1) and was advised admission.

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20.3.1990: After admission, ultrasonography (USG) abdomen was done followed by computed tomography (CT) scan of abdomen on the next day, which revealed a large left adrenal mass, for which he was advised surgery.

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2.4.1990: Surgery done by Dr ‘C’ (Respondent No. 3) to remove the abdominal tumor after taking consent from the appellants. Tumor was found to be malignant on testing. Pancreas was damaged during surgery, and a drain was fixed to drain out fluids.

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23.5.1990: A second surgery was done to control the flow of fluids in Hospital ‘Y’ by Dr ‘D’ (Respondent No. 4) assisted by Dr ‘C’ (Respondent No. 3) after taking consent from the wife of the patient.

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23.6.1990: Patient was discharged with two bags on his body and an advice to follow-up and change of the dressing regularly.

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14.7.1990: Respondent Nos. 2 and 3 visited the residence of the deceased and found him in a bad condition and asked him to go to AIIMS where he was admitted on 22.7.1990 and treated for pancreatic fistula and chronic fistula. He was discharged on 26.7.1990 with an advice to followup in the OPD.

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30.9.1990: Patient was admitted in a hospital outside Delhi where he was diagnosed as having postoperative complications of adrenalectomy and gluteal abscess. He was discharged on 3.10.1990 with an advice to get further treatment at AIIMS.

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9.10.1990: The patient vomited at home and was shifted to Hospital ‘Y’.

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MEDILAW ÂÂ

11.10.1990: The patient died due to pyogenic meningitis.

The patient’s wife (Appellant No. 1) filed a complaint in the Supreme Court under Section 21 of Consumer Protection Act, 1986 alleging deficiency in services and medical negligence on the part of the doctors (including the hospital) in the treatment of her husband and claimed a compensation of ` 45 lakhs.

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“…there was not even a whisper of any incision or draining of gluteal abscess. The Essentiality Certificate makes it clear that no incision was made to drain out gluteal abscess.”

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Dr ‘E’ (on behalf of Respondent No. 1): “… although the respondents fully sympathized with the appellants’ unfortunate loss, the respondents are constrained to submit that the appellants had presented a malicious, fabricated and distorted account to create a false impression that the respondents were guilty of negligence…”

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“30…appellants have ignored the fact that the medicine is not an exact science involving precision and every surgical operation involves uncalculated risks and merely because a complication had ensued, it does not mean that the hospital or the doctor was guilty of negligence. A medical practitioner is not expected to achieve success in every case that he treats. The duty of the Doctor like that of other professional men is to exercise reasonable skill and care. The test is the standard of the ordinary skilled man… death was attributable to the serious disease with which he was suffering from…”

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“32. … It was clearly recorded in the operation transcript that the body of the pancreas was damaged on its posterior surface. The said fact was recorded in the discharge summary.”

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The operating surgeons “were not obliged to follow every detail of expert recommendation as appropriate decisions were to be made in accordance with the findings at surgery.” The respondents denied any injury to the stomach or that any procedure adopted by them in surgery endangered the life of the patient.

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After following the 2nd surgery, the patient “did not maintain any contact with the answering respondents till 9.10.1990 barring one visit to Respondent No. 2 on 31.8.1990 for the purpose of obtaining fitness certificate. The answering respondent cannot be held responsible for any mishap, which might have taken place when the deceased… was being treated elsewhere.” Also, “no request was received by Respondent No. 1 from AIIMS for supply of the case sheets or the tumor mass.”

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The patient was brought to Hospital ‘Y’ in a critical condition when the disease (pyogenic meningitis) had become very advanced.

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The diagnosis of cancer was not an ‘afterthought’ as alleged, but was a “considered one” after two histopathological reports. All reference to cancer had been deleted from the discharge summary prepared initially on request of the appellants as it would have mentally disturbed the patient.

ALLEGATIONS ÂÂ

No informed consent.

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Preoperatively only USG and CT done to establish the nature of the tumor.

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The deceased had no access to any of the hospitals records before filing the complaint.

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There was nothing on record to conclusively establish malignancy of the tumor prior to the surgery. Appellants had not been informed about the possible surgical complications and alleged that the pancreatic abscess was due to the pancreas being injured during surgery.

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Doctors lacked the experience and skill required to undertake such a complicated operation.

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The appellants also had the grievance that they were not informed in time of the damage caused to the body of pancreas and removal of the spleen. When this fact came to the notice of the deceased, he asked for the details which were not given.

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The ‘anterior’ approach to remove the left adrenal mass during the first surgery was incorrect and not the standard approach. The ‘posterior’ approach should have been used instead. The appellants alleged that the tumor taken out from the body was not malignant.

SOME SALIENT COURT OBSERVATIONS ÂÂ

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Respondent No. 3: “… anterior approach was preferred over the posterior approach in the suspected case of cancer. The risk involved was explained to the patient and the appellants and they had agreed to the surgery after due consultation with the family doctor.” Literature from medical texts was cited for adopting `anterior’ approach supported by two expert witnesses as well… Respondent No. 4: “…there are three well known alternative methods of food supply of nutrition minimizing any leakage of enzymes from the pancreas. Any of the alternative methods could be adopted only after opening the stomach ...”

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MEDILAW ÂÂ

The Court examined the laws on negligence and also explained the nature of evidence required to establish civil and criminal negligence. ÂÂ

“… the law of negligence has to be applied according to the facts of the case.”

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“49. In Bolam v. Friern Hospital Management Committee (1957) I WLR 582: (1957) 2 All ER 118 (Queen’s Bench Division - Lord Justice McNair observed … The direction that, where there are two different schools of medical practice, both having recognition among practitioners, it is not negligent for a practitioner to follow one in preference to the other accords also with American law… a failure to warn the patient of dangers of treatment is not, of itself, negligence.”

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“… Every surgical operation is attended by risks. We cannot take the benefits without taking risks. Every advancement in technique is also attended by risks.”

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“59… A doctor is not guilty of negligence if he has acted in accordance with a practice accepted as proper by a responsible body of medical men in that particular art.”

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“60. The test is the standard of ordinary skilled man exercising and professing to have that special skill.”

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“66 ... a clear distinction exists between “simple lack of care” incurring civil liability and “very high degree of negligence” which is required in criminal cases…”

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“67... There is a marked difference as to the effect of evidence, viz. the proof, in civil and criminal proceedings. In civil proceedings, a mere preponderance of probability is sufficient, and the defendant is not necessarily entitled to the benefit of every reasonable doubt; but in criminal proceedings, the persuasion of guilt must amount to such a moral certainty as convinces the mind of the Court, as a reasonable man, beyond all reasonable doubt. Where negligence is an essential ingredient of the offence, the negligence to be established by the prosecution must be culpable or gross and not the negligence merely based upon an error of judgement.”

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that he is possessed of the requisite skill in that branch of profession which he is practising and while undertaking the performance of the task entrusted to him he would be exercising his skill with reasonable competence...

Dr ‘C’ has impressive credentials and had undertaken training in a well-known cancer hospital in the country and was sufficiently experienced to handle a surgery of this nature.

“69. In a landmark judgement in Jacob Mathew v. State of Punjab & Another (2005) 6 SCC 1, the Court observed as under: A lawyer does not tell his client that the client shall win the case in all circumstances. A physician would not assure the patient of full recovery in every case. A surgeon cannot and does not guarantee that the result of surgery would invariably be beneficial, much less to the extent of 100% for the person operated on. The only assurance which such a professional can give or can be understood to have given by implication is

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“78. A doctor faced with an emergency ordinarily tries his best to redeem the patient out of his suffering. He does not gain anything by acting with negligence or by omitting to do an act… it will be for the complainant to clearly make out a case of negligence before a medical practitioner is charged with or proceeded against criminally.”

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“80. The professional should be held liable for his act or omission, if negligent… at the same time courts have to be extremely careful to ensure that unnecessarily professionals are not harassed and they will not be able to carry out their professional duties without fear.”

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“90 (2) … A simple lack of care, an error of judgement or an accident, is not proof of negligence on the part of a medical professional. So long as a doctor follows a practice acceptable to the medical profession of that day, he cannot be held liable for negligence merely because a better alternative course or method of treatment was also available or simply because a more skilled doctor would not have chosen to follow or resort to that practice or procedure which the accused followed.”

ÂÂ

“90 (3) The standard to be applied for judging… would be that of an ordinary competent person exercising ordinary skill in that profession. …A highly skilled professional may be possessed of better qualities, but that cannot be made the basis or the yardstick for judging the performance of the professional proceeded against on indictment of negligence.”

FINAL JUDGEMENT “95. … As long as the doctors have performed their duties and exercised an ordinary degree of professional skill and competence, they cannot be held guilty of medical negligence. It is imperative that the doctors must be able to perform their professional duties with free mind.” The Court observed that the “Appellants have failed to make out any case of medical negligence against the respondents.” The Hon’ble Court concurred with the National Commission in dismissing the complaint of the appellants as being devoid of any merit. The Court also directed all the parties to bear their own costs. REFERENCE 1. Kusum Sharma & Ors vs Batra Hospital & Medical Research Centre & Others on 10 February, 2010 Civil Appeal No. 1385 of 2001.

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AROUND THE GLOBE

News and Views Medical Device Alert Issued for Bioresorbable Vascular Scaffolds

Monitoring Worry Helps Manage Generalized Anxiety Disorder

The CDSCO has issued a medical device alert for bioresorbable vascular scaffolds (BVS) in a notice posted on its website citing safety concerns. The notice says that “based on the 3-year clinical data analysis from ABSORB II it has been observed that there is an overelevated rate of major adverse cardiac events, specifically myocardial infarction and scaffold thrombosis”. CDSCO has advised patients and healthcare professionals to report adverse events suspected to be associated with the use of Absorb BVS and Absorb GT1 BVS to the manufacturer, importer and CDSCO…(Source: CDSCO)

Maintaining a worry outcome journal is an effective and easy-to-use clinical tool to manage generalized anxiety disorder, says a new study presented April 8, 2017 at the Anxiety and Depression Association of America (ADAA) Conference 2017 in San Francisco, USA.

PAHO Trains Journalists from the Americas on Responsible Coverage of Suicide to Prevent ‘Suicide Contagion’ The World Health Organization (WHO) has identified media coverage of suicide as a strategic area that can help prevent suicide. The Pan American Health Organization (PAHO) recently held a virtual seminar on best practices to report suicide in order to promote responsible reporting. More than 130 journalists, communication specialists and mental health professionals from 30 countries in the region participated. Recommendations for coverage include: ÂÂ

Avoid describing suicide as inexplicable or without warning; include suicide warning signs

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Avoid glorifying or romanticizing the act of suicide or a person who died by suicide; try to present a balanced story on the person

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Avoid relaying the method, location or details of the person who died by suicide; limit details to the facts the audience needs to know

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Avoid portraying suicide as a common or acceptable response to life’s adversities

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Avoid sensationalizing headlines

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Avoid using stigmatizing language

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Avoid harmful graphics

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Do not share the content of a suicide note

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Avoid quoting police or first responders

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Provide resources whenever possible. (Source: PAHO/WHO, April 6, 2017)

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HIV Infection Increase Risk of Heart Failure Results from the Veterans Aging Cohort Study published April 5, 2017 in JAMA Cardiology show that compared with uninfected individuals, those who are infected with HIV have an increased risk of heart failure (HF) with preserved ejection fraction (HFpEF), borderline HFpEF, and HF with reduced ejection fraction (HFrEF). Those who were younger than 40 years at the start of the study were at a 3-fold increased risk of HFrEF.

Study Defines Factors Influencing Response to Monitor Alarms Nurses respond faster to physiologic monitor alarms when they had less than 1 year of experience, when there was a 1 to 1 nursing assignment, when prior alarms requiring intervention had sounded, or when they were responding to an alarm for lethal arrhythmia, says a study reported online April 10, 2017 in JAMA Pediatrics. There was also a 15% longer response time for each hour of a nurse’s shift that had elapsed (6.1 minutes in Hour 2 vs. 14.1 minutes in Hour 8).

Low Urine Ammonium Indicates Poor Outcomes in CKD Patients Data from a new study published online April 6 in the Journal of the American Society of Nephrology show that patients with hypertensive chronic kidney disease (CKD) who had the lowest urine ammonium excretion had a 46% higher risk of dying or needing dialysis, even among those without acidosis, than patients with the highest levels of urine ammonium excretion.

Mepolizumab Effective as Add-on Treatment Option in Severe Eosinophilic Asthma Mepolizumab is an effective add-on treatment option to standard of care in patients with severe eosinophilic asthma. According to a study reported April 5, 2017 in The Lancet Respiratory Medicine, mepolizumab was

AROUND THE GLOBE associated with significant improvements in healthrelated quality-of-life, as well as improvements in lung function and symptoms of asthma.

AHA Survey Finds Patients Uncertain About How to Best Manage Their Cholesterol People who have high cholesterol may understand they need to manage their condition, but many aren’t sure how to do that, nor do they feel confident they can, according to a new survey from the American Heart Association (AHA). The survey was conducted as part of “Check.Change.Control.Cholesterol”, the association’s new initiative to help people better understand and manage their overall risk for cardiovascular disease, especially as it relates to cholesterol.

HIV-AIDS Bill Passed in the Parliament The HIV and AIDS (Prevention and Control) Bill was passed by the Parliament as reported in the Times of India. The Bill had been passed by the Rajya Sabha earlier this year. The Bill seeks to ensure equal rights to people living with HIV while seeking treatment, education and job… (TOI, Sushmi Dey, 11th April, 2017)

Elimination of Leprosy in the Country Analysis of geographical distribution of leprosy by World Health Organization (WHO) shows that India accounted for the largest number of cases of leprosy at 60% of the global new cases reported during 2015 by 136 countries. In a written reply in the Rajya Sabha, the Minister of State (Health and Family Welfare), Sh Faggan Singh Kulaste said that a three-pronged strategy has been adopted for early detection of leprosy cases in the community during 2016-17 to eliminate leprosy from the country viz. Leprosy Case Detection Campaign for high endemic districts, focused Leprosy Campaign for hot spots and a specific plan for Case Detection in Hard to reach areas. All detected cases of leprosy are provided standard treatment in accordance with program guidelines… (Press Information Bureau, Ministry of Health and Family Welfare, 11th April, 2017)

By 2030 Most Common Cancers in People with HIV will be Age-related Cancers The common cancers in patients living with HIV are usually Kaposi sarcoma and non-Hodgkin’s lymphoma. However, according to a new epidemiological data from the University of North Carolin presented at the recently concluded 2017 Annual Meeting of the American Association for Cancer Research (AACR) held in Washington, DC, these cancers are now declining

and cancers related to aging such as prostate cancer, lung cancer, liver cancer, anal cancer and non-Hodgkin’s lymphoma are on the rise and are projected to be the most common cancers in this population group by the year 2030… (Medscape)

Prostate Cancer Screening should be Individualized, Says USPSTF The US Preventive Services Task Force (USPSTF) has released new draft recommendations for prostate cancer screening. It recommends against prostate-specific antigen (PSA)-based screening for prostate cancer in men aged 70 years and older. But, the decision to screen men aged 55-69 years should be individualized. Clinicians should inform men aged 55-69 years about the potential benefits and harms of PSA-based screening for prostate cancer. The new draft recommendations are posted on the website for public comment until May 8.

AHA’s ‘Get with the Guidelines’ Program The American Heart Association/American Stroke Association (AHA/ASA) is launching its acclaimed ‘Get with the Guidelines’ in the United Arab Emirates (UAE), which is the first country outside the United States to implement this cardiovascular hospital care quality improvement program. First launched in the US in 2002, this is an evidence-based, in-hospital continuous quality improvement process-based on an online, interactive assessment and reporting system designed to improve treatment and prevent future cardiovascular and stroke events through consistent adherence to the latest scientific treatment guidelines.

Triple Combination Improves Ovulation in Adolescents with PCOS According to findings from a new research presented April 4, 2017 at ENDO 2017: The Endocrine Society Annual Meeting in Orlando, Florida, compared to oral contraceptive, early intervention with a three-drug combination of low-dose spironolactone, pioglitazone, and metformin (SPIOMET) in adolescents with polycystic ovary syndrome (PCOS) led to a 2.5-fold higher ovulation rate associated with more on-treatment loss of hepatic fat and a 6-fold higher prevalence of normovulation.

First Drug to Treat Tardive Dyskinesia Gets FDA Nod The US Food and Drug Administration has approved Ingrezza (valbenazine) capsules to treat adults with tardive dyskinesia. The side effects include QT

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AROUND THE GLOBE prolongation and drowsiness. Patients with congenital long QT syndrome or with abnormal heart beats associated with a prolonged QT interval should avoid this drug. Similarly, those who drive or operate heavy machinery or do other dangerous activities should avoid taking this drug.

also directed the officers to conduct regular supervisory visits to various hospitals in Delhi for assessing the situation, preparedness and to provide on the spot technical guidance to the health authorities … (Press Information Bureau, Ministry of Health and Family Welfare, April 12, 2017)

Benefits of Eating More Fresh Fruit for Primary and Secondary Prevention of Diabetes

American Heart Association Gets Recognition as Employer of Choice in the US

Eating fresh fruit daily reduced risk of developing diabetes by 12% in individuals who were free of diabetes compared to those who never or only rarely ate fresh fruit. And, in patients with diabetes, consuming fresh fruit more than 3 days a week reduced mortality risk from any cause by 17% and also lowered the risk of diabetes related complications by 13-28%. These results of a 7-year prospective study from China were reported online April 11, 2017 in PLoS Medicine.

The American Heart Association (AHA), the world’s leading voluntary health organization devoted to fighting cardiovascular disease has once again been selected as a top employer in the US in two leading rankings. The global nonprofit was named one of Great Place to Work® and Fortune Magazine’s 2017 Best Workplaces in Health Care and was also named one of The NonProfit Times’ Best Nonprofits To Work For. This is the second year in a row Great Place to Work® and Fortune ranked the association as a top employer and the seventh time The NonProfit Times ranked the association as one of the Best Nonprofits To Work For… (AHA News Release, April 12, 2017).

Open-capsule Budesonide Beneficial in Patients with Refractory Celiac Disease A study reported March 21, 2017 in the American Journal of Gastroenterology has shown 92% clinical and 89% histopathologic improvement with open-capsule budesonide in patients with refractory celiac disease, who failed immunosuppressant therapy suggesting open-capsule budesonide as a first-line therapeutic option for these patients.

Health Minister Reviews Dengue and Chikungunya Preparedness Union Minister for Health and Family Welfare, Shri JP Nadda, held a high level meeting to review the preparedness of the Ministry and Central Government Hospitals for prevention and control of dengue and chikungunya in the country. During the meeting, Shri Nadda asked the States for mounting aggressive IEC campaigns to enhance awareness on prevention and control of vectors in their surrounding areas and neighborhoods. Taking stock of the situation, Shri Nadda was briefed on the preparations of the Health Ministry and was informed that advisories have already been sent to all States as early as January for strengthening their preparedness before the dengue season. The officials further informed him that teams of experts from the Ministry have visited many States to review their preparedness and advised them suitably. The Central Government hospitals informed that they were adequately equipped to combat dengue and chikungunya during this season. The Health Minister

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Endocrine Society Scientific Statement on Screening for Endocrine Hypertension The Endocrine Society has released a new scientific statement about screening for endocrine hypertension published in the April 2017 issue of the journal Endocrine Reviews. The statement provides guidance on screening for 15 hormonal disorders such as primary aldosteronism that may initially present with hypertension that can be potentially cured with surgery or treated with medication. Without effective screening, these conditions are undiagnosed and untreated putting the affected individual at greater risk of developing cardiovascular disease, renal disease leading to dialysis or even dying.

FDA Allows Marketing of First Whole Slide Imaging System for Digital Pathology The US Food and Drug Administration (FDA) has for the first time permitted marketing of the Philips IntelliSite Pathology Solution (PIPS), the first whole slide imaging (WSI) system that allows for review and interpretation of digital surgical pathology slides prepared from biopsied tissue. “The system enables pathologists to read tissue slides digitally in order to make diagnoses, rather than looking directly at a tissue sample mounted on a glass slide under a conventional light microscope,” said Alberto Gutierrez, PhD, Director of the Office of In Vitro Diagnostics and Radiological Health in the FDA’s Center for Devices and Radiological Health.

AROUND THE GLOBE Study Shows Stem Cell Patch as Promising Therapy for Heart Failure According to a Phase I clinical trial reported in Journal of the American Heart Association, heart failure patients treated with patches made from their muscle cells showed improved exercise capacity and heart function after 1 year suggesting stem cell patch as a viable therapy to treat heart failure.

Study Links Both Too Much and Too Little Weight to Migraine Both obesity and being underweight are associated with an increased risk for migraine, according to a metaanalysis published online in the April 12, 2017 issue of the journal Neurology. In the study, obese people were 27% more likely to have migraine than people of normal weight. People who were underweight were 13% more likely to have migraine than people of normal weight.

Women with CHD at Higher Peripartum and Postpartum Risks Women with congenital heart disease (CHD) may be at increased risk for adverse events during pregnancy and delivery. In a retrospective study reported April 12, 2017 in JAMA Cardiology, women with CHD were more likely to undergo cesarean delivery and have longer duration of hospitalization. CHD was significantly associated with incident congestive heart failure, atrial arrhythmias, fetal growth restriction and hospital readmission.

Intensive Glycemic Control Significantly Reduces Microvascular Kidney and Eye Complications Data on more than 27,000 patients reported in The Lancet Diabetes & Endocrinology online March 29, 2017 indicated that intensive glycemic control in patients with type 2 diabetes was associated with a 20% lower risk for kidney events and a 13% lower risk for eye events. However, no effect on nerve events was observed.

improve the Plan and discussed how to integrate Prime Minister’s 10-point agenda on Disaster Risk Reduction (DRR) into the national plan. Earlier in the day, Shri RK Jain, Member, NDMA, set the agenda by appraising the participants on the objectives of the workshop and summarizing the discussions with State Government representatives. Discussions at this workshop will also form a part of the deliberations at the upcoming National Platform for Disaster Risk Reduction (NPDRR), which will be held shortly… (Press Information Bureau, Ministry of Home Affairs, April 13, 2017)

WHO Launches Report by Dr Margaret Chan, Director-General, WHO The World Health Organization (WHO) has launched a report that chronicles the evolution of global public health over the decade that Dr Margaret Chan has served as Director-General at WHO. The report opens with a letter from Dr Chan who offers her reflections on some of the highlights and challenges of the past 10 years working to build a better, healthier future for the world’s people. The first chapter, which examines the key role of WHO in promoting universal health coverage as the most powerful way to improve global health and development and lead the world towards greater fairness, is available on the WHO website. The full series will be published over the next 6 weeks… (WHO, April 13, 2017)

AAOS Guidelines on Hip Osteoarthritis The American Academy of Orthopedic Surgeons (AAOS) has for the first time issued guidelines for hip osteoarthritis, which have been published on the Academy’s website on April 5, 2017. The guidelines recommend use of physical therapy, NSAIDs, intra-articular corticosteroids for symptomatic hip osteoarthritis. But it does recommends against use of glucosamine sulfate because of lack of evidence.

NDMA Reviews National Disaster Management Plan

Traffic-related Air Pollution Lowers ‘Good’ HDL Cholesterol Increasing Heart Disease Risk

The 2-day workshop on the review of the National Disaster Management Plan (NDMP) concluded on a high note with fruitful discussions and inputs from all stakeholders. A 2-day workshop was organized by the National Disaster Management Authority (NDMA). The NDMP, which was launched by Prime Minister Narendra Modi in June last year, provides for periodic reviews. To make this review process participatory and inclusive, NDMA had sought suggestions from State Governments and Ministries of the Central Government. Various Ministries made presentations suggesting ways to

Traffic-related air pollution may increase cardiovascular disease risk by lowering levels of the ‘good’ high-density lipoprotein (HDL), according to new research published in the journal Arteriosclerosis, Thrombosis, and Vascular Biology. In the study, higher exposure to black carbon (a marker of traffic-related pollution) averaged over a 1 year period was significantly associated with a lower “good” cholesterol level. Higher particulate matter exposure over 3 months was associated with a lower HDL particle number. The magnitude of decrease was greater in women.

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LIGHTER READING

HUMOR

Lighter Side of Medicine COLLEGE WRITING A visitor to a certain college paused to admire the new Hemingway Hall that had been built on campus. “It’s a pleasure to see a building named for Ernest Hemingway, “he said. “Actually,” said his guide, “it’s named for Joshua Hemingway. No relation.” The visitor was astonished. “Was Joshua Hemingway a writer, also?” “Yes, indeed,” said his guide. “He wrote a check.” MY KEYBOARD IS NOT WORKING Customer: My keyboard is not working anymore. Tech support: Are you sure it’s plugged into the computer? Customer: No. I can’t get behind the computer.

then asked the tourist, “Do you know Swimology and Escapology from Crocodiology?” The tourist said, “No!” The boat guy replied, “Well, today you will Drownology and Crocodiology will eat you. I will not Helpology and you will Dieology because of your Badmouthology.” TOMATOES A small boy was looking at the red ripe tomatoes growing in the farmer’s garden. “I’ll give you my two pennies for that tomato,” said the boy pointing to a beautiful, large, ripe fruit hanging on the vine. “No,” said the farmer, “I get a dime for a tomato like that one.”

Tech support: Pick up your keyboard and walk 10 paces back.

The small boy pointed to a smaller green one, “Will you take two pennies for that one?”

Customer: OK

“Yes,” replied the farmer, “I’ll give you that one for two cents.”

Tech support: Did the keyboard come with you? BLONDE STOP A police car pulled alongside a speeding car on the motorway. Glancing at the car he was astonished to see that the blond behind the wheel was knitting! Realizing that she was oblivious to his flashing lights and siren, the cop rolled down his window and shouted “Pullover!”

“OK,” said the lad, sealing the deal by putting the coins in the farmer’s hand, “I’ll pick it up in about a week.”

Dr. Good and Dr. Bad SITUATION: A patient with Chikungunya was found to have high ESR.

The blonde rolled down her window and yelled back “No, it’s a scarf!” NEVER BE RUDE TO ANYONE

It may not be Chikungunya.

This is Chikungunya.

An American tourist asked a boat guy in Zanzibar, “Do you know Biology, Psychology, Geography, Geology or Criminology?”

The boat guy said nothing. After a while the boat developed a fault and started sinking. The boatman

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The boat guy said, “No. I don’t know any of these.” The tourist then said, “What the hell do you know on the face of this Earth? You will die of illiteracy!” LESSON: High ESR is seen in Chikungunya.

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

– –

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

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

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

–

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

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

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

Confidence intervals for the measurements should be provided wherever appropriate.

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

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Discussion –

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

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

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

Do not use clips/staples on photographs and artwork.

–

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

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

Books

5. Special requests _____________________________

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

6. Suggestions for reviewers (name and postal address)

Articles in Books

2.____________ 2.________________

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

3.____________ 3.________________

4.____________ 4.________________

Tables –

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

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

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

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Indian 1.____________Foreign 1.________________

7. All authors’ signatures________________________ 8. Corresponding author’s name, current postal and e-mail address and telephone and fax numbers __________________________________________

Online Submission Also e-Issue @ www.ijcpgroup.com For Editorial Correspondence

Dr KK Aggarwal

Group Editor-in-Chief Indian Journal of Clinical Practice E-219, Greater Kailash Part-1 New Delhi - 110 048. Tel: 40587513 E-mail: editorial@ijcp.com Website: www.ijcpgroup.com

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POSTAL REGISTRATION NO. DL (S)-01/3200/2015-2017 Posted in N.D. PSO New Delhi