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IJCP Group of Publications Volume 23, Number 8, January 2013

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

from the desk of group editor-in-chief 425 Govt to Crack Down on Pharma-Doctor Nexus

KK Aggarwal

Padma Shri and Dr BC Roy National Awardee

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

IJCP Editorial Board Obstetrics and Gynaecology Dr Alka Kriplani Dr Thankam Verma, Dr Kamala Selvaraj

clinical review 427 Management of Musculoskeletal Disorders with

Rumalaya, a Polyherbal Formulation: A Review

Hemant Mathur, RK Ghatak, Mrityunjoy Sarker

Cardiology Dr Praveen Chandra, Dr SK Parashar Paediatrics Dr Swati Y Bhave Dr Balraj Singh Yadav Dr Vishesh Kumar, Dr Satish Tiwari Diabetology Dr Vijay Viswanathan Dr CR Anand Moses, Dr Sidhartha Das Dr A Ramachandran, Dr Samith A Shetty ENT Dr Jasveer Singh Dentistry Dr KMK Masthan Dr Rajesh Chandna Gastroenterology Dr Ajay Kumar Dermatology Dr Hasmukh J Shroff Nephrology Dr Georgi Abraham Neurology Dr V Nagarajan

review article 435 Therapeutic and Safety Issues in Pediatric Atopic

Dermatitis

Anand K Gupta

439 CAD: A True Pandemic and a Comprehensive

Surveillance System is the Need of the Hour

G Kannan, NN Rajendran, JSN Murthy, GB Tharani

445 Exercise-induced Bronchoconstriction:

Diagnosis and Management

Michael A. Krafczyk, Chad A. Asplund

Journal of Applied Medicine & Surgery Dr SM Rajendran

clinical Study

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

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

456 Clinical and Laboratory Profile of Typhoid Fever

NS Neki

459 A Study of Maternal and Perinatal

Outcome in Dengue

Laxmi Maru, Astha Jain

case report 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

464 Idiopathic Dilated Cardiomyopathy Complicating

in a Pregnancy with Uterine Fibroid

Debasmita Mandal, Pradip Kumar Saha, Chaitali Dattaray, Saroj Mandal

Printed at IG Printers Pvt. Ltd., New Delhi E-mail: igprinter@rediffmail.com, printer_ig@yahoo.com Š Copyright 2013 IJCP Publications Ltd. All rights reserved.

medilaw

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.

469 Insight on Medicolegal Issues

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.

around the globe 472 News and Views

lighter reading 474 Lighter Side of Medicine

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

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

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

Govt to Crack Down on Pharma-Doctor Nexus ÂÂ

The National Development Council (NDC), led by Prime Minister Manmohan Singh, will meet on December 27 to discuss bringing a legislation requiring drug companies to mandatorily disclose payments made to doctors for research, consulting, lectures, travel and entertainment.

ÂÂ

Doctors involved in ghost writing to promote pharma products will also be disqualified.

ÂÂ

Mandated disclosure by pharmaceutical companies of the expenditure incurred on drug promotion, and penalty on the company and vetting of drug-related material in continuing medical education would be considered.

ÂÂ

The government will also make compulsory the use of generic names or the International Non-proprietary Name (INN), instead of brand names, at all stages of government procurement, distribution, prescription and use.

ÂÂ

Medical Council of India (MCI) received 702 such complaints in 2011-12, of which 343 were referred to state medical councils. In 2010-11, MCI received 824 such complaints following which it cancelled the registration of 10 doctors and warned four others.

ÂÂ

Pharma industry spent more than 25% of its annual turnover on sales promotion alone as compared to a paltry 7% on research and development in 2008-09.

ÂÂ

India plans to soon introduce the ‘Uniform Code of Pharmaceutical Marketing Practices’ after which the word ‘safe’ cannot be used on a drug without qualification and it must be stated categorically that a medicine has no side effects, toxic hazards or risk of addiction.

ÂÂ

The code says, “No gifts, pecuniary advantages or benefits in kind may be supplied, offered or promised to persons qualified to prescribe or supply by a pharmaceutical company. Gifts for the personal benefit of healthcare professionals (such as tickets to entertainment events) also are not be offered or provided.

Companies must not organize meetings to coincide with sporting, entertainment or other leisure events.

Venues that are renowned for their entertainment must not be used.”

ÂÂ

Any hospitality offered to healthcare professionals must not be extended to spouses.

ÂÂ

Funding of healthcare professionals to compensate them for the time spent in attending the event is not permitted.

Source TOI

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clinical review

Management of Musculoskeletal Disorders with Rumalaya, a Polyherbal Formulation: A Review Hemant Mathur*, RK Ghatak**, Mrityunjoy Sarkerâ€

Abstract Despite the availability of analgesics and anti-inflammatory drugs for centuries, satisfactory relief of chronic pain related to musculoskeletal disorders (MSD) remains an important unmet public health need. Rheumatoid arthritis (RA) and osteoarthritis (OA) are two major MSD seen in Indian middle age and elderly age groups. The management of these conditions includes varied modes to achieve desired clinical improvement. The present article reviews five clinical studies conducted on an indigenous polyherbal formulation, Rumalaya in the management of various MSD, specially arthritis. A double-blind placebo-controlled trial on arthritis on 75 patients for eight weeks showed comparable effects to Diclofenac and clearly better than the placebo group.

Unlike Diclofenac group, trial group did not show adverse effects of medication namely gastritis or gastric irritation. Another double-blind study on both OA and RA in a total of 235 patients showed complete relief of symptoms in 78.65 and 84.6% of RA and OA groups, respectively. A controlled study on arthralgia of 60 athletes by Rumalaya tablet along with Rumalaya cream showed its efficacy mainly on knee pain in a total of 84% cases in two weeks, significance clearly above the control group.

Another trial was conducted on OA of knee in 56 patients for four weeks to 2-month duration. Results showed a marked relief of pain in 73 of 88 knees. Another trial comparing Rumalaya tablet with ibuprofen in the management of OA of 80 patients for 2-6 weeks showed results comparable with that of standard comparator along with added advantage of cost-effectiveness.

In all the studies summarized in the review, safety profile was recorded with no adverse reactions even after long-term use and patient compliance to the trial drug was good.

Keywords: Musculoskeletal disorders, osteoarthritis, rheumatoid arthritis, Rumalaya

I

n 2000, the Bone and Joint Decade was proclaimed by the World Health Organization (WHO) in recognition of the significant impact of arthritis and musculoskeletal conditions on population health worldwide.1 This proclamation aimed to raise awareness, promote effective management, empower consumers and encourage research into these important conditions. The terms arthritis and musculoskeletal disorders (MSD) refers to a diverse group of conditions that affect muscle, joints, tendons and other parts of the musculoskeletal system. These conditions are commonly associated with pain and impaired physical function and impact on occupational and psychosocial status often resulting in a reduced quality-of-life or, for some, reduced survival.1

*Professor and Head Dept. of Orthopedics, Govt. Medical College and SSG Hospital, Baroda **Professor and Head National Medical College and Hospital, Kolkata †PMR Specialist, JC Bose Cantt. General Hospital, Ministry of Defence Barrackpore, Kolkata

Arthritis comprises more than 100 different rheumatic diseases and conditions.2 Amongst the many categories of these disorders, osteoarthritis (OA) and rheumatoid arthritis (RA) represent a significant proportion.3 While both diseases fall under the classification or diagnosis of arthritis and rheumatism, they are very different; each has its own distinct characteristics as well as different treatment. These two musculoskeletal conditions are the focus of this review.

An estimated 46 million US adults (about 1 in 5) report doctor-diagnosed arthritis, according to annual estimates and is projected to increase to 67 million by 2030, and more than one-third of these adults will have limited activity as a result. Although arthritis is more common among adults aged 65 years or older, people of all ages (including children) can be affected.

Nearly two-thirds of people with arthritis are younger than age 65. In addition, a recent study indicated that some form of arthritis affects one in every 250 children.

Arthritis is more common among women (24.4%) than men (18.1%) in every age group, and it affects members of all racial and ethnic groups.2 Regardless of the type of arthritis, the common symptoms for all arthritic disorders include varied

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clinical study levels of pain, swelling, joint stiffness and sometimes a constant ache around the joint(s).4 RA has 19th century roots and a 20th century pedigree. Although its name was introduced in the 1850s,5 classification criteria were only developed 50 years ago.6,7 Observational studies using these criteria portray RA as a serious long-term disease with dominant extra-articular features, limited treatment options and poor outcomes.8,9 Findings of population-based studies show that RA affects 0.5-1.0% of adults in developed countries. The disease is three times more frequent in women than men. Prevalence rises with age and is highest in women older than 65 years, suggesting hormonal factors could have a pathogenic role.10 Estimates of the frequency of RA vary depending on the methods used to ascertain its presence.11,12 RA is best considered a clinical syndrome spanning several disease subsets.13 These different subsets entail several inflammatory cascades,14 which all lead towards a final common pathway in which persistent synovial inflammation and associated damage to articular cartilage and underlying bone are present.

Genetic factors contribute 50% of risk of developing RA.15 Identification of genetic regions tagged by structural variation (single nucleotide polymorphisms) show that more than 30 genetic regions are associated with RA.15-19 At present, apart from protein tyrosine phosphatase, nonreceptor type 22 -lymphoid (PTPN22) and human leukocyte antigen (HLA) genes, no major pathogenic insights have come from these genetic associations.

However, progress is shown by the realization that from a putative 2 mM of DNA harboring candidate variants, these 30 regions are all contained within 2 mM of DNA. Smoking is the dominant environmental risk factor and doubles risk of developing RA.20 Its effect is restricted to patients with anti citrullinated protein antibody (ACPA)-positive disease.21,22 Pharmacologic agents are the cornerstone to the management of all patients with RA and are an important treatment option for moderate-to-severe OA. The goals of pharmacologic treatment include pain control, reduction of inflammation and, increasingly, disease modification. Disease-modifying antirheumatic drugs (DMARD) along with short-term treatment with glucocorticoids (oral, intramuscular or intra-articular) is generally considered to rapidly improve symptoms in people with newly diagnosed RA.23 Pharmacologic interventions for people with OA and RA must be prescribed in conjunction with nonpharmacologic interventions including patient

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education, exercise, rehabilitation modalities and referral to specialty services if necessary.

Tumour necrosis factor (TNF) inhibitors and other biological agents have heralded a so-called therapeutic revolution, transforming the outlook for patients with RA. However, improved disease outcomes preceded biological agents, reflecting early use of conventional drugs, ambitious treatment goals, and better management of comorbidities on par with an historic parallel is the 1950s revolution in tuberculosis care.24 New biological agents in development include drugs that target proximal effects on the immune response and growth factors for T-cell subsets (such as interleukin-17).25 New conventional drugs with DMARD-like properties might also have important future roles. Clinical trials of inhibitors of the kinases JAK (Janus kinase) and SYK (Spleen tyrosine kinase) have provided promising data, and other targets are under investigation.26,27 Role of Rumalaya tablet in the management of musculoskeletal disorders Rumalaya tablet, a polyherbal formulation is claimed to be effective in various MSD and indicated in rheumatism and RA, cervical and lumbar spondylosis, OA, arthralgia, gout, Frozen shoulder, sprains, traumatic inflammatory conditions like fibrosis, bursitis, synovitis, capsulitis, tenosynovitis, myositis and sciatica. Rumalaya tablet is safe in chronic conditions necessitating long-term use.

Rumalaya tablet has anti-inflammatory and analgesic properties, reduces swelling, inflammation. Muscle relaxant properties of Rumalaya helps restore mobility of the joints. Rumalaya tablets indicated in long-term Composition Each Rumalaya tablet contains: Pdrs.

Exts.

Mahayograj guggul

0.162 g

Shankha bhasma

65 mg

Shilajeet (purified)

16 mg

Latakasthuri (Hibiscus abelmoschus)

10 mg

Swarnamakshika bhasma

5 mg

Maharasnadi quath

65 mg

Manjishtha (Rubia cordifolia)

19 mg

Shigru (Moringa pterygosperma)

16 mg

Gokshura (Tribulus terrestris)

16 mg

Guduchi (Tinospora cordifolia)

10 mg

clinical study therapy for conditions like RA showed improvement in stiffness of joints, circumference of joint, joint tenderness and range of movements.

Processed in Nirgundi (Vitex negundo), Guduchi (Tinospora cordifolia), Tulasi (Ocimum sanctum), Bhringaraja (Eclipta alba), Ashvagandha (Withania somnifera), Sunthi (Zingiber officinale) and Dashamoola.

Clinical Pharmacology Rumalaya tablet has potent anti-inflammatory, analgesic, antioxidant, antiarthritic and immunomodulatory actions.

Indications: Rheumatism/RA; cervical and lumbar spondylitis; OA; arthralgia; gout; frozen shoulder; traumatic inflammatory conditions like fibrositis, bursitis, synovitis, capsulitis, tenosynovitis, myositis and sciatica.

Dosage: Initially, two tablets twice-daily, followed by 1 tablet twice-daily. Treatment may be continued till pain and inflammation subside.

Adverse effects: No adverse effects have been reported.

Contraindications: Not recommended in pregnancy.

Special precautions: None.

Pharmacological Actions of Individual Ingredients

Antioxidant Activity M. pterygosperma47 and O. sanctum33 have potent antioxidant activity. T. terrestris acts as an antioxidant due to its inducible nitric oxide synthase (iNOS)-inhibitory activity.36 Z. officinale has antioxidant effect comparable to ascorbic acid. It lowers lipid peroxidation while maintaining the activities of other antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase).48 Swarnamakshika bhasma, well-known for its antioxidant action, has a rejuvenating effect.49 Shankha bhasma has antioxidant action due to its cytoprotective activity in the gastrointestinal tract, and reduces gastric irritation.50 Immunomodulatory Activity O. sanctum modulates both humoral and cell-mediated immune responsiveness, and its immunomodulatory effect may be mediated by GABAergic pathways.51 W. somnifera has immunomodulatory activity.30 Z. officinale raises the thymus and spleen indices, phagocytosis, rate of alpha-naphthyl acetate esterase and titer of IgM, which indicate its immunostimulatory actions.52,53 In order to evaluate the safety and efficacy of Rumalaya tablet, several clinical trials have been conducted.

Anti-inflammatory Activity

Clinical trial 1

Shilajeet (purified),28 E. alba,29 W. somnifera30 and Moringa pterygosperma31 have strong anti-inflammatory activity. V. negundo exhibits anti-inflammatory activity mediated via prostaglandin (PG) synthesis-inhibitory and membrane-stabilizing activities.32 O. sanctum33-35 and Tribulus terrestris36 have cyclooxygenase (COX)inhibitory activity, and control acute and chronic inflammation. Z. officinale acts as a potent antiinflammatory agent due to its COX-1, COX-2 and PG biosynthesizing protein-inhibitory actions. Its inhibition of the biotransformation of arachidonic acid is comparable to indomethacin.37-42 Mahayograj guggul has a well-established anti-inflammatory effect in joint disorders.43

Efficacy of Rumalaya Tablets in Arthritis: A Double-blind Placebo-controlled Trial54

Analgesic Activity

Study Procedure

negundo32

alba44

V. and E. exhibit analgesic activities.

O. sanctum exerts analgesic action both centrally as well as peripherally, which involves interplay between various neurotransmitter systems.45 Shilajeet (purified) acts as prospective modifier of analgesic tolerance.46 Mahayograj guggul has a well-established analgesic effect in joint disorders.43

Number of Patients and Method A total of 75 patients with pain, swelling, early morning stiffness and joint immobility were selected for the trial.

Patients in the age group of 40-70 years, having chronic arthritis with pain and with restricted movement for minimum one year duration and who were willing to give informed consent, were included in the trial.

Patients receiving steroids or sedatives, which would influence the analgesic effects of the trial drug and unwilling to provide informed consent or abide by the requirements of the study were excluded from the trial.

The study was a double-blind placebo-controlled trial comparing its efficacy with that of the conventional anti-inflammatory drug, Diclofenac sodium. The patients were divided into three groups. Rumalaya was administered at a dose of two tablets twice-daily for eight weeks. One group of patients also received a placebo to compare the efficacy of Rumalaya

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clinical study tablet with that of placebo. A standard protocol of physiotherapy and heat therapy was used along with drug administration. No other drug or local analgesic application was combined during this period.

Diclofenac sodium was administered as oral sustainedrelease tablet once-daily. The relief from joint and muscular pain, free mobility, reduction in joint swelling and tenderness with the administration of drugs were considered as the criteria of efficacy.

Results Clinical efficacy of Rumalaya tablet was comparable to that of Diclofenac. Both the groups showed significant relief in joint pain and muscular pain. Eighty-eight percent of patients in Rumalaya-treated and 93% of patients in Diclofenac-treated group showed relief from joint pain. All the patients in the Rumalaya-treated group had relief from muscular pain symptoms, whereas in the Diclofenac group, 80% of patients showed relief from muscular pain. Sixty-three percent patients in the Rumalaya group had free mobility of joints, whereas in the Diclofenac group it was only 47%. Seventy-five percent and 90% of patients in the Rumalaya- and Diclofenac-treated groups, respectively had a significant inhibition in joint swelling.

A significant reduction of 57% and 75% in joint tenderness was noticed in the Rumalaya and Diclofenac treated groups, respectively. There was significant difference in the drug intolerance in two groups Rumalaya tablet resulted in no gastritis or gastric intolerance. In the Diclofenac group, 12 patients had to discontinue the drug due to gastritis and gastric intolerance. Rumalaya tablet was completely free from any side effects.

Conclusion From the above findings it can be concluded that, Rumalaya tablet is suitable for patients with arthritis and nonarticular rheumatic conditions associated with pain and restricted movements, especially for elderly patients and patients with a history of hypersensitivity to Diclofenac.

Clinical Trial 2

Rumalaya in RA and OA (A Double-blind Trial)55 Number of Subjects and Method A total of 223 patients were included in the study (88 - RA and 135 - OA).

Patients of mild RA, i.e. without contractures and OA were picked up for study. After essential investigations to confirm the diagnosis patients were put on Rumalaya or placebo. Patients with odd outpatient numbers

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were given Rumalaya and those with even outpatient numbers were given placebo. The research worker did not know whether he was giving Rumalaya/placebo.

Erythrocyte sedimentation rate (ESR), hemoglobin (Hb), total and differential leukocyte count, complete urine examination and stool examination for occult blood were carried out before and after the trial. After 15 days’ treatment, if the patient was having partial relief, then the treatment was continued, till there was complete relief. In cases where there was no relief either the trial was stopped or willing patients were put on the other drug of this trial.

Study Procedure Cases with RA: In this trial 67 females and 21 males were treated with this drug for RA. Eight cases were of monoarticular arthritis (5 of ankle, 2 of knee and 1 of hip joint). In the remaining 80 cases, there were multiple joint involvements. Swelling of the joints was present in 55 cases, none had contractures.

Cases with OA: Out of 135 cases, 115 cases were of the OA of the knee (70 bilateral and 45 unilateral), 17 were of OA of the spine, two of the ankle and 1 of the carpo-metacarpal joint of thumb. Swelling of the joint concerned was present in 54 cases only. The illness in the majority of patients was chronic.

Results Cases with RA: Twenty-nine patients were in placebo group and the results were not favorable in any of them. Eleven out of these and 59 other cases (total 70) were given trial drug. In 55 cases response was complete (78.6%). In the majority of patients response was complete in the third week. Out of the remaining, in eight cases there was partial relief from pain and tenderness, but spasm persisted. Seven cases did not respond to this drug.

Aspiration of the joint was done in 10 cases. Novocaine with hydrocortisone was injected after aspiration in all these cases. The process was not repeated afterwards in anyone of them. Patients with involvement of small joints of hands were encouraged to do active movements of fingers in warm saline. Restriction of movements due to spasm and swelling disappeared in all cases with the disappearance of pain. Fall of ESR after the trial was not consistent in all the cases.

There was general feeling of well-being and increased appetite. There was actual increase in weight in three cases. Six patients volunteered the statement that their constipation was relieved. No side effect was seen in any of these cases.

Cases with OA: Out of 135 cases, 69 were males and 66 were females. The youngest patient of this series

clinical study was of 28 years age and the oldest, of 85 years. The majorities were of the age group between 40 and 60 years. Rumalaya was given to 92 cases and placebo to 43 cases. Out of these 43 cases, 19 cases were again put on Rumalaya, as they had no relief with placebo. So, the total number of cases, where complete relief in Rumalaya was administered was 111. There was complete relief from symptoms in 94 cases (84.6%) on Rumalaya.

The drug was partially effective in 10 cases and ineffective in 7. There were no side effects in any case.

Active Quadriceps exercises against gravity and then against resistance were advised to the patients with OA of the knee. Short-wave diathermy was given to seven cases of OA of the knee. In cases of OA of the spine, hard bed and spinal exercises were advised.

Five patients complained of loose motions after taking the drug. In all these patients the trial was stopped.

Placebo was ineffective in all the 43 cases.

Dose: One tablet three times a day after meals was the dose prescribed to every patient except in seven cases, where two tablets t.d.s. for the first three days was prescribed.

Conclusion A double-blind study of the therapeutic effects of Rumalaya in cases of rheumatoid and OA without deformity shows that out of 70 cases of RA-treated with Rumalaya, 78.6% had complete relief and 11.4% had partial relief. Out of 111 cases of OA on Rumalaya, 84.6% had complete relief and 9% had partial relief.

These results have been arrived at by a controlled double-blind clinical trial, and could well be compared with published series and trials with other drugs.

The drug acts slowly and can be given for long periods.

No toxic effects of this drug were observed during the trials.

Clinical trial 3

Role of Rumalaya Tablets and Rumalaya Cream in Arthralgia of Athletes56 Number of Patients and Method Sixty patients suffering from arthralgia of sportsmen for periods ranging between 6-24 weeks were selected for the trial. Male patients aged between 25-35 years, suffering from arthralgia and who were willing to give informed consent, were included in the trial. Patients unwilling to provide informed consent or abide by the requirements of the study were excluded from the trial.

respectively, were selected at random for the present study. Complete medical history, general physical and local examinations were carried out and findings were recorded in a standard proforma. Two Rumalaya tablets along with local application of Rumalaya cream, thrice-daily, were given to each case of study group for a period of two weeks. In some cases, the study was carried over to third and fourth week; but, these cases have not been tabulated in the present study.

The control subjects were put on placebo tablets and ordinary vaseline for a similar duration.

The results were recorded according to the degree of clinical relief. Four grades, namely `poor’, `fair’, `satisfactory’ and `good’ were formulated. Poor cases were those which did not respond to the treatment.

Fair cases were those in whom there was complete disappearance of subjective feeling of pain; however, in such cases swelling and even slight tenderness were present. In satisfactory cases, there was no swelling and tenderness only on deep pressure and slight pain on extremes of active movement. Good results were recorded as complete disappearance of symptoms and signs.

Results It was observed that the drug was most effective in cases of pain in the knee. In the first week 40% of the total number of cases of knee involvement showed good results and further, in the second week 56% more cases of knee involvement showed good results. For the remaining 4% of cases, the treatment was continued for the third and fourth week with `satisfactory’ to `good’ results. Overall success rate in terms of `fair’, `satisfactory’ and `good’ results of the two weeks’ trial in the study group was approximately 84%. The remaining 16% were carried to the third and fourth week of treatment with satisfactory response in 50% of these cases. The control subjects did not show any appreciable change in the two weeks’ period on placebo.

No side effects were observed in any of the cases.

Conclusion From the findings of this study, it is clearly established that Rumalaya improves the signs and symptoms of arthralgia. The drugs are most effective in relieving arthralgic manifestations of knee joint of sportsmen.

Clinical Trial 4

A Clinical Trial of Rumalaya in OA of Knee57

Study Procedure

Number of Patients and Method

Sixty patients were selected for the trial. Two groups, control and study, consisting of 10 and 50 subjects,

Fifty-six patients suffering from OA of knee without any known local cause for the onset of the disease

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clinical study were selected for the study. There were 34 males and 22 females, ranging in age from 35 to 68 years.

All cases were advised Quadriceps exercises and given Rumalaya tablets; two tablets three times a day. The dosage was reduced to 1 tablet three times a day, when patients showed some improvement and was discontinued when they were asymptomatic for 4-6 weeks. Duration of treatment varied from four weeks to 2 months in 32 cases and 2 months in 32 cases and 2 months to six months in the remaining 16 cases. Total number of joints involved by OA was 88; 24 patients with unilateral involvement and 32 patients with bilateral involvement.

After randomization in the two groups of 40 patients each, patients were asked to take indigenous drug Rumalaya or Ibuprofen tablet (400 mg) at 8-hourly intervals after meals. All the patients were assessed for swelling, stiffness, range of joint motion and for joint pain before drug therapy and after drug therapy at two weeks and at 6 weeks time interval. Patients with any other major illness were excluded from the study.

Results

There was marked symptomatic and clinical relief in 73 knees. There were excellent results in 46 knees, good in 21, fair in six, poor in 3 knees. Eight cases were lost in follow-up. There were no untoward toxic effects in any of the cases.

The assessment of pain relief was done on a numerical scale (1-10) before starting drug therapy and at two weeks and 6 weeks after drug therapy. On statistical analysis (two way analysis of variance) of mean pain intensity scores the results show that indigenous drug and ibuprofen provided significant pain relief at two weeks (p < 0.001) and six weeks time interval (p < 0.00), when compared to pain at the initiation of the study, at rest, on walking and squatting. On statistical analysis between the two treatment groups, no significance was observed (p > 0.05) was observed at two weeks and six weeks interval. No significant changes were observed also in their swelling, stiffness and range of motion of joint. No patient reported any side effect with either the medication.

Conclusion

Conclusion

It is seen that Rumalaya therapy with Quadriceps exercises gives excellent results in patients suffering from OA of knee. Rumalaya tablets can be given for longer duration without any untoward reactions, which are commonly observed with salicylates, phenylbutazone, oxyphenbutazone, indomethacin, dextropropoxyphene, naproxen, etc. From this study, it is seen that pain in OA of knee is a common symptom and one can use Rumalaya tablets for a long duration; they are effective and safe and without any toxicity.

Though both the drugs are equally effective, the indigenous drug is cost-effective. Thus, indigenous drug may be prescribed in patients suffering from OA.

Study Procedure All these cases were regularly observed, clinically examined and improvements were followed up regularly. Eight patients were lost to follow-up study (4 with bilateral involvement of knee).

Results

Clinical Trial 5

Comparative Clinical Study of Indigenous Drugs with Ibuprofen in Patients of OA58 Number of Patients and Method A total number of 80 patients (age range 36-73 years) with diagnosis of OA were selected all the patients enrolled in this study had their history recorded; general physical examination and detailed joint examination was done. All patients had their X-ray of the joint, hemogram, urine examination, blood sugar and serum uric acid levels done. All the patients were asked not to take any drug without informing us.

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Status of Rumalaya Tablet in Musculoskeletal Disorders Arthritis is a leading cause of pain, physical disability and healthcare utilization. People living with arthritis, their families and society as a whole are affected by the outcomes of the disease. The increased burden of this disease will have a significant impact on health care resources and is also costly from an economic standpoint. Approximately two-thirds of the costs of arthritis are indirect costs due to disability, a measure of lost productivity. Current pain management is largely limited to opioids and nonsteroidal anti-inflammatory drugs, indicating a gap in the translation of new knowledge to the development of improved pain treatments. Indigenous formulation, Rumalaya tablet a polyherbal formulation was evaluated in various MSD-like arthritis and RA and review of five clinical studies are summarized in this review. To summarize, Rumalaya tablets produces beneficial effects in cases of varied types of MSD-like RA, OA, arthralgia, myalgia,

clinical study sports injuries and others. The natural ingredients in the product act synergistically to provide multiple benefits like anti-inflammatory, analgesic, antioxidant, antiarthritic and immunomodulatory actions. By regulating the mediators of inflammation, Rumalaya tablet exerts a significant anti-inflammatory action.

Muscle relaxant properties of Rumalaya help restore mobility of the joints and reduce muscle pain. Studies have confirmed the safety profile of the product without any toxic or adverse effects with long-term use and also showing good patient compliance in all the studies.

To conclude the review, Rumalaya tablet is found to be effective and safe in chronic conditions necessitating long-term use.

References 1. WHO. Bulletin of the WHO, editorials. http://www.who. int/bulletin/volumes/81/9/en/Editorial%201.pdf 2000.

2. National Arthritis Action Plan: A Public Health Strategy, please contact, Centers for Disease Control and Prevention; National Center for Chronic Disease Prevention and Health Promotion, 2009:p.1-4.

3. National Institute of Health and Welfare. National health priority area: arthritis and musculoskeletal conditions. In: http://www.health.gov.au/internet/wcms/publishing.nsf/ Content/health-pq-arthritisindex. htm: Federal Australian Government; 2004.

4. Lisse J, et al. J Gerontol A Biol Sci Med Sci 2001;56(3): M167-75.

5. Storey GO, et al. Ann Rheum Dis 1994;53(9):557-60.

23. Rheumatoid arthritis: The management of rheumatoid arthritis in adults, NICE Clinical Guideline 79 Developed by the National Collaborating Centre for Chronic Conditions. February 2009:p.12.

24. Wilson LG. Int J Epidemiol 2005;34(3):521-4.

25. Evans HG, et al. Proc Natl Acad Sci U S A 2009;106 (15):6232-7.

26. Kremer JM, et al. Arthritis Rheum 2009;60(7):1895-905.

27. Weinblatt ME, et al. Arthritis Rheum 2008;58(11):3309-18.

28. Goel RK, et al. J Ethnopharmacol 1990;29(1):95-103.

29. Leal LK, et al. J Ethnopharmacol 2000;70(2):151-9.

30. Mishra LC, et al. Altern Med Rev 2000;5(4):334-46.

31. Anwar F, et al. Phytother Res 2007;21(1):17-25.

32. Dharmasiri MG, et al. J Ethnopharmacol 2003;87(2-3): 199-206.

33. Kelm MA, et al. Phytomedicine 2000;7(1):7-13.

34. Godhwani S, et al. J Ethnopharmacol 1987;21(2):153-63.

35. Singh S. Indian J Exp Biol 1998;36(10):1028-31.

36. Hong CH, et al. J Ethnopharmacol 2002;83(1-2):153-9.

37. Kiuchi F, et al. Chem Pharm Bull (Tokyo) 1992;40(2):387-91.

38. Tjendraputra E, et al. Bioorg Chem 2001;29(3):156-63.

39. Nurtjahja-Tjendraputra E, et al. Thromb Res 2003;111(4-5): 259-65.

40. Surh YJ. Food Chem Toxicol 2002;40(8):1091-7.

41. Thomson M, et al. Prostaglandins Leukot Essent Fatty Acids 2002;67(6):475-8.

42. Srivastava KC, et al. Med Hypotheses 1992;39(4):342-8.

7. Arnett FC, et al. Arthritis Rheum 1988;31(3):315-24.

43. Anonymous. Ayurveda Sarasangraha. Mahayograj guggul. Shree Baidyanath Ayurveda Bhawan Ltd., Nagpur 1996: 18th Edn. p. 518-9.

8. Scott DL, et al. Lancet 1987;1(8542):1108-11.

44. Sawant M, et al. Phytother Res 2004;18(2):111-3.

6. Ropes MW, et al. Arthritis Rheum 1959;2(1):16-20.

9. Pincus T, et al. Ann Intern Med 1994;120(1):26-34.

45. Khanna N, et al. J Ethnopharmacol 2003;88(2-3):293-6.

10. Symmons D, et al. Rheumatology (Oxford) 2002;41(7): 793-800.

46. Tiwari P, et al. Phytother Res 2001;15(2):177-9.

11. Jordan K, et al. Br J Gen Pract 2007;57(534):7-14.

48. Ahmed RS, et al. Indian J Exp Biol 2000;38(6):604-6.

12. RodrĂ­guez LA, et al. Scand J Rheumatol 2009;38(3):173-7.

13. Van der Helm-van Mil AH, et al. Arthritis Res Ther 2008;10(2):205.

14. Van Oosterhout M, et al. Arthritis Rheum 2008;58(1):53-60.

15. van der Woude D, et al. Arthritis Rheum 2009;60(4):916-23.

16. Barton A, et al. Arthritis Rheum 2009;61(10):1441-6.

17. Orozco G, et al. Ann Rheum Dis 2010;69(5):813-6.

18. Stahl EA, et al. Nat Genet 2010; 42(6):508-14.

47. Kumar NA, et al. J Med Food 2003;6(3):255-9.

49. Mishra S. Swarnamakshika bhasma. Ayurvediya Rasashastra. Chaukhamba Orientalia, Varanasi. 1996: 7th Edn., p. 383.

50. Mishra S. Shankha bhasma. Ayurvediya Rasashastra.

Chaukhamba Orientalia Varanasi. 1997: 7th Edn. p. 688.

51. Mediratta PK, et al. J Ethnopharmacol 2002;80(1):15-20.

52. Wilasrusmee C, et al. Am Surg 2002;68(10):860-4.

53. Liu H, et al. Wei Sheng Yan Jiu 2002;31(3):208-9.

19. Plenge RM. Curr Opin Rheumatol 2009;21(3):262-71.

54. Rastogi S, et al. Antiseptic 2001;98(5):172-3.

20. Carlens C, et al. Am J Respir Crit Care Med 2010;181(11):1217-22.

55. Aggarwal ND, et al. Probe 1971;X(2):45-9.

56. Bansal MK, et al. J Indian Med Profess 1972;XIX(3):8343-5.

21. Källberg H, et al. Am J Hum Genet 2007;80(5):867-75.

57. Lahkar S. Med Surg 1981: August, 21.

22. Morgan AW, et al, Arthritis Rheum 2009;60(9):2565-76.

58. Singh U, et al. IJPMR 1997;8-9:29-30.

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review article

Therapeutic and Safety Issues in Pediatric Atopic Dermatitis Anand K Gupta

Abstract Atopic dermatitis (AD), a chronic-recurrent inflammatory dermatosis characterized by pruritus, eczematous lesions, xerosis and lichenification and accompanied by cutaneous physiological dysfunction, is one of the most common disorders in children.

Infants, whose immune system and epidermal barrier are still developing, have a higher incidence of AD. Genetic, immune and environmental factors interact in a complex fashion to contribute to disease expression. Dysfunction of the skin barrier, overreaction and abnormal reaction of the immune system against external antigens and/or autoantigens, and immunoglobulin (Ig) E-mediated sensitization to food and environmental allergens have been proposed as atopic cofactors in patients with AD. Successful management of AD includes patient education, trigger avoidance, excellent skin care and treatment involving pharmacologic and nonpharmacologic measures. Increased understanding of skin barrier dysfunction in AD has led to the formulation of a variety of new products containing a mixture of ingredients that are reported to help alleviate inflammation and pruritus associated with AD. Atopiclair cream is a new nonsteroidal therapeutic option for AD, containing glycyrrhetinic acid (GrA), Vitis vinifera (grapevine) extract, telmesteine, hyaluronic acid and shea butter (derivative of shea nut oil) which repairs, calms and protects the skin barrier function.

Keywords: Atopic dermatitis, pruritus, skin barrier dysfunction

A

topic dermatitis (AD), a chronic relapsing eczematous skin disease characterized by pruritus and inflammation and accompanied by cutaneous physiological dysfunction, is one of the most common disorders in children with a worldwide prevalence of 8-20%.1,2 Though the prevalence of AD is low in India as compared to the developed countries, a rising trend is observed in recent years. It occurs primarily during infancy, a critical period, during which the immune system and epidermal barrier are still developing. Kay et al reported that 45% of all cases of AD begin within the first six months after birth, 60% during the first year and 85% before five years of age.3

epidermal barrier function is thought to be related to the downregulation of cornified envelope genes such as the filament-aggregating protein, filaggrin, reduced ceramide levels, increased levels of endogenous proteolytic enzymes and enhanced transepidermal water loss (TEWL). Barrier function can be damaged further by a lack of certain endogenous protease inhibitors in atopic skin, exogenous proteases from Staphylococcus aureus and house dust mites, and the use of soaps and detergents that can raise the local pH and increase activity of endogenous proteases such as stratum corneum chymotryptic enzyme.

Dysfunction of the skin barrier, overreaction and abnormal reaction of the immune system against external antigens and/or autoantigens, and immunoglobulin (Ig) E-mediated sensitization to food and environmental allergens have been proposed as atopic cofactors in patients with AD.4 However, in recent years, it has been suggested that AD is a complicated syndrome that results from a complex interplay of genetic, immune, metabolic, infectious, neuroendocrine and environmental factors. Defective

Clinical features

Skin Specialist New Delhi

AD encompasses an array of features. They can be broadly classified into: The atopic itch, the atopic dry skin, the atopic eczema and the stigmata of AD. Sleep disruption and pruritus/scratching are the most prevalent physical symptoms experienced by affected children, with more than half of the AD effects on children directly or indirectly related to pruritus.

Pruritus often leads to an â&#x20AC;&#x2DC;itch-scratchâ&#x20AC;&#x2122; cycle that can compromise the epidermal barrier, resulting in increased TEWL, visible signs of xerosis, microbial colonization, especially with S. aureus and secondary infection.5

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review article Impact on Quality-of-Life in Patients and Children Childhood AD has a significant social and emotional impact on the child and the family. Mothers of young children with AD have reported poor social support, stress-related to parenting and difficulty with discipline.

It has also been shown that there is a positive correlation between the severity of AD and its impact on the quality- of-life of pediatric patients and their families.

Parents of children with AD are commonly plagued by several persistent â&#x20AC;&#x2DC;worries,â&#x20AC;&#x2122; including concerns regarding what triggers disease flares in their child, the costs of care, proper use of medications and their child's health and well-being in the long-term. The physical changes in AD can affect pediatric patients in a variety of ways, including lack of sleep, an inability to focus in school, behavioral problems, low self-esteem, stress and anxiety. It has been reported that sleep disturbance (e.g., poor sleep, lack of sleep) occurs in 60% of patients as a result of frequent and often intractable pruritus that is such a consistent and predominant symptom of AD. Documented sleep dysfunctions in AD include delayed onset of sleep, multiple awakenings and reduced sleep efficiency. As expected, the natural consequence of poor sleep is adverse impact on daytime behavior and productivity.5 Safety Concerns in Management of PediaTric AD There is no known cure for AD, but the fundamentals of a daily skin care routine are essential for hydration and maintenance of the skin barrier.6 The care of patients with AD has evolved considerably over the last decade.

Treatment consists of daily skin hydration and emollient therapy but most patients still require symptomatic treatment with topical corticosteroids (TCS) and/or topical calcineurin inhibitors (TCIs).7 TCS have been associated with adverse effects like skin atrophy, telangiectasia, striae, hypopigmentation, rosacea, hypothalamic-pituitary-adrenal axis suppression, growth retardation, reduced bone density and flare relapse after discontinuation of treatment.8 Parents also commonly worry about the use of TCS and their side effects. In one questionnaire-based study, 73% of participants worried about using TCS on their own or their child's skin, leading to nonadherence in 24% of individuals.5 This has led to suboptimal use of TCS by both caregivers and parents resulting in ineffective treatment.9 Balancing safety concerns with efficacious treatment is of particular importance in the pediatric population since the stratum corneum and epidermis of

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infants (6-24 months of age) are 30% and 20% thinner, respectively, versus adults.6 Efforts must be made to minimize exposure of children to TCS. To this end, steroid-sparing approaches should be sought when severity necessitates the use of a TCS. TCIs, on the other hand, have been associated with cases of malignancy, leading to a black box warning regarding risk of cancer with the use of these agents.10 Calcineurin inhibitors are reserved for second-line treatment only and are not recommended for children under two years of age.10 Management of AD in Infants and Children Successful management of AD includes patient education, trigger avoidance, excellent skin care and treatment involving pharmacologic and nonpharmacologic measures. Since most cases of AD begin in infancy or early childhood, it is important to determine a course of treatment in this population that is efficacious, easy to use and with minimal potential for side effects. With the heavy social, emotional and financial impact of childhood AD on patients, parents and other family members, it is believed that reversal of epidermal barrier impairment and restoration of stratum corneum function from the outset of treatment of a flare is important to integrate into management of all patients with AD. Increased understanding of skin barrier dysfunction in AD has led to the formulation of a variety of new products. Introduction of Atopiclair cream, a clinically proven nonsteroidal flare remission preparation is a step in this direction. Atopiclair, with its ingredients, tackles the problem of AD with a multifactorial approach which repairs, calms and protects the skin barrier function with anti-inflammatory, antierythematic and antipruritic activities.

Atopiclair, a novel nonsteroidal therapeutic option for AD Atopiclair is a nonsteroidal preparation, which contains glycyrrhetinic acid (GrA), Vitis vinifera (grapevine) extract, telmesteine, hyaluronic acid and shea butter (derivative of shea nut oil).8,11 Hyaluronic acid and shea butter target the disrupted skin barrier element of AD. Hyaluronic acid has hydrating and moisturizing properties and essential skin lipids, such as triglycerides and polyunsaturated fatty acids in the form of shea butter, help to restore skin barrier function.11 The antiinflammatory, antierythematic and antipruritic activity of Atopiclair is attributed to 2% GrA, which blocks the degradation of endogenous cortisol through inhibition of 11-β-hydroxysteroid dehydrogenase and potentiates the effect of hydrocortisone on skin.8,12 The extract of

review article V. vinifera has antioxidant and antiprotease activity, which may protect against epidermal breakdown.8 Telmesteine has antiprotease action and inhibits elastase, collagenase and matrix metalloproteinase, which are expressed at high levels in AD.8 The benefits of improving barrier function and hydration, coupled with steroid-sparing effects, renders Atopiclair cream a safe and effective option for managing patients with AD, particularly for infants and young children who have a continuously maturing epidermal barrier. Atopiclair cream thus represents a new level of treatment for AD by allowing physicians and patients to more effectively manage their symptoms.

Atopiclair cream is being used extensively for the relief of symptoms of AD in USA and the EU. Clinical Safety and Efficacy The use of Atopiclair is supported by two published, well-controlled clinical trials. Early and lasting relief of itch has been demonstrated as early as Day 3, as well as a reduction in the use of steroid rescue therapy during the study periods with use of Atopiclair.3,12,13 It has also been shown that Atopiclair cream is an effective and safe therapeutic option for the treatment of symptoms of mild-to-moderate AD in infants and children. Preliminary findings from a recent pilot study undertaken by Cimaz have demonstrated that Atopiclair is safe and effective as an intervention option to manage atopic, contact and diaper dermatitis in infants as young as one months of age.14 In a multicenter, randomized, double-blind, vehiclecontrolled clinical study, the efficacy and safety of Atopiclair was demonstrated in 60 pediatric patients affected by AD, aged between two and 17 years. Using the Investigators Global Assessment (IGA) score for AD, patients with a score of 2 (mild) or 3 (moderate) were enrolled in the study. Twenty patients were randomly selected to receive Atopiclair, 20 patients received MAS060, a similar formulation with key ingredients at lower concentration and no preservatives, and 20 patients received vehicle only. The study consisted in a treatment period of 43 days, with clinical evaluations at baseline (Day 1), Days 8, 15, 22, 29 and 43, at which time the treatment was stopped. It was seen that Atopiclair showed nearly 80% improvement in IGA score at Day 22, compared with 16.6% and 26.3% with the MAS060 and vehicle, respectively. A statistically significant difference was found by comparing Atopiclair with MAS060 (p < 0.0001); a similar result was evidenced comparing Atopiclair and vehicle (p = 0.001). By contrast, no significant difference was

found between MAS060 and vehicle. A statistically significant difference was sustained until the end of the study.

Safety analysis of all the treated patients was also undertaken. It was seen that no serious adverse event occurred during the study.15 In another multicenter, randomized, vehicle-controlled clinical study undertaken to examine the efficacy and safety of Atopiclair in the management of mild-tomoderate AD in infants and children, 142 patients aged six months to 12 years were administered Atopiclair (n = 72) or vehicle (n = 70) cream 3 times/day to affected areas and sites prone to develop AD.8 The primary endpoint for efficacy was the IGA at Day 22. Secondary endpoints included IGA at other time-points, patient's/ caregiver's assessment of pruritus, onset, duration of itch relief, Eczema Area and Severity Index (EASI), subject's/caregiver's assessment of global response and need for rescue medication in the event of an AD flare.

It was seen that Atopiclair cream was statistically more effective (p < 0.0001) than vehicle cream for the primary endpoint and all secondary endpoints. No serious adverse events were related to Atopiclair although stinging (8.3%), burning (6.9%), and fever (6.9%) were common adverse events (the latter 2 occurring more frequently in the vehicle group). Rates of treatment discontinuation because of adverse events were 9.9% in the Atopiclair group and 16% in the vehicle group.

Atopiclair cream was thus found to be effective and safe as monotherapy for the treatment of symptoms of mild-to-moderate AD in infants and children.8 Conclusions AD is a prevalent inflammatory skin disorder characterized by intense pruritus and inflamed skin.

The care of patients with AD has evolved considerably over the last decade. Increased understanding of skin barrier dysfunction in AD has led to the formulation of a variety of new products. Atopiclair cream, a clinically proven nonsteroidal flare remission preparation, tackles the problem of AD with a multi-factorial approach which repairs, calms and protects the skin barrier function with anti-inflammatory, antierythematic and antipruritic activities. It breaks the vicious itchscratch cycle and can be used as monotherapy or in combination with other topical creams. The benefits of improving barrier function and hydration, coupled with steroid-sparing effects, renders Atopiclair cream a safe and effective option for managing patients with AD, particularly for infants and young children who have a continuously maturing epidermal barrier. It can

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review article be used in all areas of skin and there is no restriction to duration of use. Atopiclair cream is being used extensively for the relief of symptoms of AD in USA and the EU. References 1. Williams H, Stewart A, von Mutius E, Cookson W, Anderson HR; International Study of Asthma and Allergies in Childhood (ISAAC) Phase One and Three Study Groups. Is eczema really on the increase worldwide?

J Allergy Clin Immunol 2008;121(4):947-54.e15.

2. Lee SI, Kim J, Han Y, Ahn K. A proposal: Atopic Dermatitis Organizer (ADO) guideline for children. Asia Pac Allergy 2011;1(2):53-63.

3. Kay J, Gawkrodger DJ, Mortimer MJ, Jaron AG. The prevalence of childhood atopic eczema in a general population. J Am Acad Dermatol 1994;30(1):35-9.

4. Tanaka A, Amagai Y, Oida K, Matsuda H. Recent findings in mouse models for human atopic dermatitis. Exp Anim 2012;61(2):77-84.

5. Kircik LH, Del Rosso JQ. Nonsteroidal treatment of atopic dermatitis in pediatric patients with a ceramidedominant topical emulsion formulated with an optimized ratio of physiological lipids. J Clin Aesthet Dermatol 2011;4(12):25-31.

6. Blume-Peytavi U, Metz M. Atopic dermatitis in children: management of pruritus. J Eur Acad Dermatol Venereol 2012;26 Suppl 6:2-8.

7. Ong PY. Emerging drugs for atopic dermatitis. Expert Opin Emerg Drugs 2009;14(1):165-79.

8. Boguniewicz M, Zeichner JA, Eichenfield LF, Hebert

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AA, Jarratt M, Lucky AW, et al. MAS063DP is effective monotherapy for mild to moderate atopic dermatitis in infants and children: a multicenter, randomized, vehiclecontrolled study. J Pediatr 2008;152(6):854-9.

9. Krakowski AC, Eichenfield LF, Dohil MA. Management of atopic dermatitis in the pediatric population. Pediatrics 2008;122(4):812-24.

10. Correa MCM, Nebus J. Management of patients with atopic dermatitis: the role of emollient therapy. Dermatol Res Pract 2012;2012:836931.

11. A closer look at an up-and-coming therapy. In: Atopic Dermatitis: Emerging Therapies. Supplement to Skin & and Aging 2006:p.10.

12. Abramovits W, Perlmutter A. Atopiclair: its position within a topical paradigm for the treatment of atopic dermatitis. Expert Rev Dermatol 2007;2(2):115-9.

13. Abramovits W, Boguniewicz M; Adult Atopiclair Study Group. A multicenter, randomized, vehicle-controlled clinical study to examine the efficacy and safety of MAS063DP (Atopiclair) in the management of mild to moderate atopic dermatitis in adults. J Drugs Dermatol 2006;5(3):236-44.

14. Cimaz R. Efficacy and safety of Atopiclair in pediatric dermatoses: preliminary findings from an open pilot study. Unpublished study conducted at a paediatric practice in Milan, Italy.

15. Patrizi A, Capitanio B, Neri I, Giacomini F, Sinagra JL, Raone B, et al. A double-blind, randomized, vehiclecontrolled clinical study to evaluate the efficacy and safety of MAS063DP (ATOPICLAIR) in the management of atopic dermatitis in paediatric patients. Pediatr Allergy Immunol 2008;19(7):619-25.

review article

CAD: A True Pandemic and a Comprehensive Surveillance System is the Need of the Hour G Kannan*, NN Rajendran**, JSN Murthy†, GB Tharani‡

Abstract Coronary artery disease (CAD) occurs when the arteries that supply blood to the heart muscle harden and narrow. According to the Global Burden of Disease Study, the developing countries contributed 3.5 million of the 6.2 million global deaths from CAD in 1990. The prevalence of CAD in India has more than doubled in the past two decades. India topped the world with 1,531,534 cardiovascular disease-related deaths in 2002, and based on WHO report, 2009, CAD currently occupies the first place in cause of death. A comprehensive surveillance system of risk factors and CAD will be an invaluable public health research tool for monitoring population health status, guiding resource allocation and policy, identifying and prioritizing interventions for subpopulations at particular risk that would help to bring down the true pandemic which is on the climb.

Keywords: Coronary artery disease, pandemic, surveillance system, health status

C

oronary artery disease (CAD) occurs when the arteries that supply blood to the heart muscle harden and narrow (Bhati K, 2011; Heart Diseases, 2011). The result is the loss of oxygen and nutrients to myocardial tissue because of diminished coronary blood flow (Springhouse, 2005). This reduction in blood flow can lead to acute coronary syndrome (angina or myocardial infarction). CAD is on the climb and has become a true pandemic that respects no borders.

Prevalence of CAD

Global Scenario The term ‘prevalence’ of CAD usually refers to the estimated population of people who are managing CAD at any given time (American Heart Association, 2004). The proportion of deaths due to CAD is projected to rise from 59% in 2002 to 69% in 2030 (Mathers and

*Assistant Professor Dept. of Pharmacy Practice, Faculty of Pharmacy Sri Ramachandra University, Porur, Chennai **Professor Swami Vivekananda College of Pharmacy, Erode, Chennai †Professor and Head Dept. of Cardiology, Sri Ramachandra University, Porur, Chennai ‡Professor and Head Saveetha Medical College, Thandalam, Chennai Address for correspondence Dr G Kannan Assistant Professor, Dept. of Pharmacy Practice, Faculty of Pharmacy Sri Ramachandra University, Porur, Chennai - 600 116 E-mail: kannagg2@yahoo.ca

Loncar, 2006). The WHO (2006) estimates that at least 20 million people survive CAD-related heart attacks and strokes every year around the world; many require continuing costly clinical care. By 2030, almost 23.6 million people will die from CADs, mainly from heart disease and stroke. These are projected to remain the single leading causes of death (WHOCardiovascular Disease: Prevention and Control, 2006).

A recent evaluation of WHO in the cause of death in 2009, CAD and stroke were placed as first (7,185,353 deaths) and second (5,704,843 deaths) in rank among total deaths (6,830,586,985) of all kind of diseases.

Moreover, the rate of death is rising more in the underdeveloped countries than the developed countries, because of their lifestyle and socioeconomic factors (WHO, 2009).

According to the Global Burden of Disease Study, the developing countries contributed 3.5 million of the 6.2 million global deaths from CAD in 1990. The projections estimate that these countries will account for 7.8 million of the 11.1 million deaths due to CAD in 2020 (Murray et al, 1996). Disability-adjusted life years (DALYs) lost can be thought of as ‘healthy years of life lost’. They indicate the total burden of a disease, as opposed to simply the resulting deaths. Murray et al (1996) calculate that in India and China, a spectacular rise in the number of DALYs is expected in the coming years - from a figure of <25 million DALYs in each country in 1990, to 30 million and 35 million in India and China, respectively, in 2020. CAD is decreasing

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review article in many developed countries, but is increasing in developing and transitional countries, partly as a result of increasing longevity, urbanization and lifestyle changes. CAD is responsible for 10% of DALYs lost in low and middle-income countries and 18% in highincome countries (Global Burden of Coronary Heart Disease, 2002).

CAD is the most common cause of death (and premature death) in the UK. One in 5 men and one in 7 women die from CAD. There are 94,000 deaths from CAD in the UK each year (Greenlund et al, 2006). With regard to incidence, data from the Atherosclerosis Risk In Communities (ARIC) and Cardiovascular Health Study indicate that annually, 7,85,000 Americans have a new coronary attack and 4,70,000 have a recurrent attack; in addition, approximately 1,95,000 silent myocardial infarctions occur each year. This assumes that 21% of the 9,35,000 first and recurrent myocardial infarctions are silent (Thom et al, 2001; Boland et al, 2002).

Tables 1 and 2 depict the CAD prevalence in urban and rural population of developed countries and developing countries.

in urban than in rural population, with a greater prevalence in affluent groups (Chadha et al, 1990; Enas et al, 1992; Singh et al, 1997). Enas et al (1996) and Enas et al (1999). It is estimated that 9.2 million productive years of life were lost in India in 2000, with an expected increase to 17.9 million years in 2030. Table 3 depicts the CAD prevalence with respect to age group, sample size of the study population in different parts of India.

Salient features of the CAD epidemic in India: ÂÂ

Incidence of CAD in young Indians is about 12-16%, which is higher than any other ethnic group (Mammi et al, 1991).

ÂÂ

Age-standardized estimates for DALYs lost due to CAD per 1,000 population in India are three times higher than in developed countries (Negus et al, 1994).

ÂÂ

About 5-10% of heart attacks occur in Indian men and women younger than 40 years (Mackay and Mensah, 2004).

ÂÂ

India topped the world with 1,531,534 cardiovascular disease-related deaths in 2002, and occupied first place in cause of death in current moment based on WHO report, 2009 (Yusuf et al, 2004; WHO, 2009).

ÂÂ

Median age of first heart attack in Indians is 53 years (WHO, 2009).

ÂÂ

1,55,88,000 DALYs (WHO, 2009).

Indian Scenario The prevalence of CAD in India has more than doubled in the past two decades. This has occurred both in the rural and urban populations, although it is higher

Table 1. CAD in Urban and Rural Population of Developed Countries Author

Year

Age group

Place

Sample size

CAD prevalence (%)

Calvet et al.

2010

45-75

France

300

50.0

Arzamendi et al.

2010

20-65

Developed countries

1,260

49.0

Iwasaki et al.

2011

30-70

Japan

135

9.20

Icaza et al.

2009

35-74

USA

General population

6.95

Kivimaki et al.

2011a

30-70

UK

5,533

0.70

Jain et al.

2011

35-75

London (UK)

2,369

22.0

Kivimaki et al.

2011b

30-70

London (UK)

7,095

0.027

Ong et al.

2011

30-70

UK

698

5.00

Stansby et al.

2011

68

UK

473

30.0

Ebrahim et al.

2011

20-70

UK

1,63,471

4.35

Secrest et al.

2011

24-32

USA

317

2.50

Oizumi et al.

2008

30-70

Japan

2,938

3.19

Idris et al.

2008

30-70

UK

1,087

50.0

Konishi et al.

1990

40-59

Japan

8,835

88.0

Urban population

Rural population

440

Indian Journal of Clinical Practice, Vol. 23, No. 8 January 2013

review article Table 2. CAD in Urban and Rural Population of Developing Countries (Excluding India) Author

Year

Age group

Place

Sample size

CAD prevalence (%)

Grau et al.

2010

30-70

France + Spain

420 + 562

0.98

Chin et al.

2009

30-70

Malaysia

2,030

10.35

Hatmi et al.

2007

20-45

Iran

3,000

25.75

Hariharan et al.

2010

30-70

Trinidad + Tobago

1,082

1.20

Sadeghi et al.

2006

35-70

Iran

6,498

29.90

Kalra et al.

2011

35-86

Nepal

142

38.00

Icaza et al.

2009

35-74

Chile

General population

1.80

Icaza et al.

2009

35-74

China

General population

0.85

Icaza et al.

2009

35-74

Spain

General population

3.70

Ozdemir et al.

2010

30-70

Turkey

24

33.33

Vaidya et al.

2009

35 - <

Eastern Nepal

-

5.70

Onat et al.

2010

45-74

Turkey

1,655

11.50

Pitsavos et al.

2008

30-70

Greek

2,172

1.36

PavloviÄ&#x2021; et al.

2004

37-56

Croatia

3,544

3.70

Urban population

Rural population

Table 3. Prevalence of CAD in Population of India Author

Year

Age group

Place

Sample size

CAD prevalence (%)

Geetha et al.

2011

30-70

Chennai (Tamil Nadu)

2,350

2.93

Mohan et al.

2010a

30-70

Chennai (Tamil Nadu)

-

5.40

South India

Mohan et al.

2010b

30-70

Chennai (Tamil Nadu)

-

11.0

Kumaran et al.

2002

30-70

Mysore

435

21.75

Mohan et al.

2001

20-70

Chennai (Tamil Nadu)

1,262

11.0

Stein et al.

1996

Mysore

517

10.0

Begom et al.

1995

25-65

South India (Urban)

506

13.9

Singh et al.

2011

<15

Chandigarh

196

0.000045

Kumar et al.

2006

>35

North India (Urban + Rural)

7,169

3.96

Ahmad et al.

2005

25-70

Delhi (Urban)

14,000

0.2-0.9

Ahmad et al.

2005

25-70

Delhi (Rural)

14,000

0.1-0.4

North India

Singh et al.

1997

25-64

Moradabad

3,575

1.5-3.0

Chadha et al.

1997

25-64

Delhi (Urban + Rural)

13,723

96.7 (Urban) + 27.1 (Rural)

Begom et al.

1995

25-65

North India (Urban)

506

61.6

Lanjewar et al.

2005

25-70

Mumbai

3,871

4.20

Rastogi et al.

2004

30-70

Western India

350

1.88

Pinto et al.

2004

35-64

Goa

371

13.2

Hazarika et al.

2002

30-70

Assam

1,015

61.0

Bhattacharyya

2003

30-70

Kolkata

28 + 62

39 + 60

West India

East India

Indian Journal of Clinical Practice, Vol. 23, No. 8 January 2013

441

review article Need of the Hour Prospective studies on the relative role and importance of traditional and newer risk factors are urgently needed in Indians within the subcontinent as much of the knowledge of risk factors for CAD has been acquired from studies conducted in the Western population. It is widely believed that the association of these risk factors with CAD in different subpopulations needs to be ascertained, and there is speculation that differences might range from the frequency of presence of classical risk factors to their total absence or irrelevance in these populations. A cost-effective preventive strategy will need to focus on reducing risk factors both in the individual and in the population at large.

Effective screening, evaluation and management strategies for CAD are well-established in high-income countries, but these strategies have not been fully implemented in India which was noted by Mohan et al (2001). A key factor that hampers the development of such preventive strategies in developing countries such as India is the meager amount (8%) of published literature on CAD research available from these countries (Mackay and Mensah, 2004). Of particular concern to India is not only the high burden of CAD, but also the effects of these diseases on the productive workforce aged 35-65 years. Heart diseases are rising in Asian Indians 5-10 years earlier than in other populations around the world. The mean age for first presentation of acute myocardial infarction in Indians is 53 years. CAD that manifests at a younger age can have devastating consequences for an individual, the family and society. Prevention of these deaths in young people is a nationâ&#x20AC;&#x2122;s moral responsibility (Sharma and Ganguly, 2005). A strategy involving prevention of CADs long before their onset will be more costeffective than providing interventions at a stage when the disease is well-established.

Therefore, it is imperative to undertake large populationbased, prospective studies in developing countries such as India to identify CAD risk factors, both conventional and novel. Careful scrutiny of available scientific evidence for modifiable CAD risk factors (elevated serum total and LDL-C, low HDL-C, smoking, diabetes, hypertension, low level of physical activity and central obesity) in association with genetically predisposing factors like Lp(a) in Indian population may be helpful in formulating a more immediate CAD prevention strategy.

Given the explosion of diabetes and CAD in India and in view of the differences in race, culture, way of life,

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diet, stress and strain and the myriad other factors, increased emphasis on lifestyle modification, including diet, exercise, weight reduction and whenever relevant, stress reduction, is urgently needed. A comprehensive surveillance system of risk factors and CAD will be an invaluable public health research tool for monitoring population health status, guiding resource allocation and policy, identifying and prioritizing interventions for subpopulations at particular risk, identifying disparities in outcomes and planning and evaluating health programs. Carefully planned prevention programs with intervention strategies by catching the vulnerable individuals at an early age could also be taken up in different parts of the country to prevent the twin epidemic of diabetes and CAD; as both have common causative factors, and prevention strategies could also be combined judiciously to prevent both disorders, as this would make it more cost-effective.

Resources should be directed towards applying the existing knowledge base to tackle the CAD epidemic in policy, capacity building and research arenas. Control of the CAD epidemic in the Indian subcontinent is tenable in the foreseeable future, provided that policy makers, health professionals and the lay public in the Indian subcontinent acknowledge its potential impact and promptly act to address to make a major step towards CAD free society.

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2. American Heart Association, 2004. Prevalence of Coronary heart disease. http://www.wrongdiagnosis. com/c/coronary_heart_disease/prevalence.htm.

3. Arzamendi D, Benito B, Tizon-Marcos H, Flores J, Tanguay JF, Ly H, et al. Increase in sudden death from coronary artery disease in young adults. Am Heart J 2011;161(3):574-80.

4. Bhattacharyya M. Coronary heart disease prevention in Kolkata, India. J R Soc Promot Health 2003;123(4): 222-8.

5. Begom R, Singh RB. Prevalence of coronary artery disease and its risk factors in the urban population of South and North India. Acta Cardiol 1995;50(3):227-40.

6. Bhati K. Causes and herbal remedies for coronary artery disease or heart problem. Available at: http://www. sooperarticles.com/health-fitness-articles/heart-diseasearticles/causes-herbal-remedies-coronary-artery-diseaseheart-problem-368593.html. Published on 28th Mar. 2011.

7. Boland LL, Folsom AR, Sorlie PD, Taylor HA, Rosamond WD, Chambless LE, et al. Occurrence of

review article unrecognized myocardial infarction in subjects aged 45 to 65 years (the ARIC study). Am J Cardiol 2002;90(9): 927-31.

21. Heart diseases (2011). The Heart and Stroke Foundation.

Available at: http://www.heartandstroke.com/site/c.ikI QLcMWJtE/b.3483991/k.34A8/Statistics.htm.

8. Calvet D, Touzé E, Varenne O, Sablayrolles JL, Weber S, Mas JL. Prevalence of asymptomatic coronary artery disease in ischemic stroke patients: the PRECORIS study. Circulation 2010;121(14):1623-9.

22. Icaza G, Núñez L, Marrugat J, Mujica V, Escobar MC, Jiménez AL, et al. Estimation of coronary heart disease risk in Chilean subjects based on adapted Framingham equations. Rev Med Chill 2009;137(10):1273-82.

9. Chadha SL, Radhakrishnan S, Ramachandran K, Kaul U, Gopinath N. Epidemiological study of coronary heart disease in urban population of Delhi. Indian J Med Res 1990;92:424-30.

23. Idris I, Deepa R, Fernando DJ, Mohan V. Relation between age and coronary heart disease (CHD) risk in Asian Indian patients with diabetes: a cross-sectional and prospective cohort study. Diabetes Res Clin Pract 2008;81(2):243-9.

10. Chin CY, Pengal S. Cardiovascular disease risk in a semirural community in Malaysia. Asia Pac J Public Health 2009;21(4):410-20.

24. Iwasaki M, Kuroda S, Nakayama N, Hokari M, Yasuda H, Saito H, et al. Clinical characteristics and outcomes in carotid endarterectomy for internal carotid artery stenosis in a Japanese population: 10-year microsurgical experience. J Stroke Cerebrovasc Dis 2011;20(1):55-61.

11. Ebrahim S, Taylor F, Ward K, Beswick A, Burke M, Davey Smith G. Multiple risk factor interventions for primary prevention of coronary heart disease. Cochrane Database Syst Rev 2011;(1):CD001561.

12. Enas EA, Garg A, Davidson MA, Nair VM, Huet BA, Yusuf S. Coronary heart disease and its risk factors in firstgeneration immigrant Asian Indians to the United States of America. Indian Heart J 1996;48(4):343-53.

25. Jain P, Kooner JS, Raval U, Lahiri A. Prevalence of coronary artery calcium scores and silent myocardial ischaemia was similar in Indian Asians and European whites in a cross-sectional study of asymptomatic subjects from a UK population (LOLIPOP-IPC). J Nucl Cardiol 2011;18(3):435-42.

13. Enas EA, Salim Yusuf. Third Meeting of the International Working Group on Coronary Artery Disease in South Asians. 29 March 1998, Atlanta, USA. Indian Heart J 1999;51(1):99-103.

26. Kivimäki M, Batty GD, Hamer M, Ferrie JE, Vahtera J, Virtanen M, et al. Using additional information on working hours to predict coronary heart disease: a cohort study. Ann Intern Med 2011b;154(7):457-63.

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

27. Kivimäki M, Nyberg ST, Batty GD, Shipley MJ, Ferrie JE, Virtanen M, et al. Does adding information on job strain improve risk prediction for coronary heart disease beyond the standard Framingham risk score? The Whitehall II study. Int J Epidemiol 2011a May 9. (Epub ahead of print)

15. Geetha L, Deepa M, Anjana RM, Mohan V. Prevalence and clinical profile of metabolic obesity and phenotypic obesity in Asian Indians. J Diabetes Sci Technol 2011; 5(2):439-46.

16. Grau M, Bongard V, Fito M, Ruidavets JB, Sala J, Taraszkiewicz D, et al; REGICOR, GENES Investigators.

Prevalence of cardiovascular risk factors in men with stable coronary heart disease in France and Spain Arch Cardiovasc Dis 2010;103(2):80-9.

17. Greenlund KJ, Giles WH, Keenan NL, et al. Heart disease and stroke mortality in the 20th century. In: Silent Victories: The History and Practice of Public Health in 20th Century America. Ward J, Warren C (Eds.), Oxford University Press: Oxford, England; 2006.

28. Konishi M, Iso H, Iida M, Naito Y, Sato S, Komachi Y, et al. Trends for coronary heart disease and its risk factors in Japan: epidemiologic and pathologic studies. Jpn Circ J 1990;54(4):428-35.

29. Kumar R, Singh MC, Singh MC, Ahlawat SK, Thakur JS, Srivastava A, et al. Urbanization and coronary heart disease: a study of urban-rural differences in northern India. Indian Heart J 2006;58(2):126-30.

30. Kumaran K, Fall CH, Martyn CN, Vijayakumar M, Stein CE, Shier R. Left ventricular mass and arterial compliance: relation to coronary heart disease and its risk factors in South Indian adults. Int J Cardiol 2002;83(1):1-9.

18. Hariharan S, Chen D, Vialva M, Exeter H, Billingy I, Bobb KA, et al. Outcome evaluation of coronary artery bypass grafting surgery applying the EuroSCORE in a Caribbean developing country. Heart Surg Forum 2010;13(5):E287-91.

31. Lanjewar C, Jolly S, Mehta SR. Effects of aspiration thrombectomy on mortality in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention: a meta-analysis of the randomized trials. Indian Heart J 2009;61(4):335-40.

19. Hatmi ZN, Tahvildari S, Gafarzadeh Motlag A, Sabouri Kashani A. Prevalence of coronary artery disease risk factors in Iran: a population based survey. BMC Cardiovasc Disord 2007;7:32.

32. Mackay J, Mensah G. The atlas of heart disease and stroke.

World Health Organization, Centers for Disease Control and Prevention; 2004.

20. Hazarika NC, Biswas D, Narain K, Kalita HC, Mahanta J. Hypertension and its risk factors in tea garden workers of Assam. Natl Med J India 2002;15(2):63-8.

33. Mammi MV, Pavithran K, Abu Rahiman P, Pisharody R, Sugathan K. Acute myocardial infarction in north Kerala. A 20-year hospital based study. Indian Heart J 1991;43(2):93-6.

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review article 34. Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med 2006; 3(11):e442.

35. Mohan V, Deepa R, Rani SS, Premalatha G; Chennai Urban Population Study (CUPS No. 5). Prevalence of coronary artery disease and its relationship to lipids in a selected population in South India: The Chennai Urban Population Study (CUPS No. 5). J Am Coll Cardiol 2001;38(3):682-7.

36. Mohan V, Vassy JL, Pradeepa R, Deepa M, Subashini S. The Indian type 2 diabetes risk score also helps identify those at risk of macrovascular disease and neuropathy (CURES-77). J Assoc Physicians India 2010a; 58:430-3.

37. Mohan V, Venkatraman JV, Pradeepa R. Epidemiology of cardiovascular disease in type 2 diabetes: the Indian scenario. J Diabetes Sci Technol 2010;4(1): 158-70.

38. Murray CJL, Lopez AD. The Global Burden of Disease: A Comprehensive Assessment of Mortality and Disability from Disease, Injuries and Risk Factors in 1990 and Projected to 2020. Harvard University Press: Boston, Ma; 1996.

39. Oizumi T, Daimon M, Jimbu Y, Wada K, Kameda W, Susa S, et al. Impaired glucose tolerance is a risk factor for stroke in a Japanese sample - the Funagata study.

Metabolism 2008;57(3):333-8.

40. Onat A, Uğur M, Ciçek G, Ayhan E, Doğan Y, Kaya H, et al. The Turkish Adult Risk Factor survey 2009: similar cardiovascular mortality in rural and urban areas. Turk Kardiyol Dern Ars 2010;38(3):159-63.

41. Ong P, Athanasiadis A, Borgulya G, Voehringer M, Sechtem U. 3-year follow-up of patients with coronary artery spasm as cause of acute coronary syndrome: the CASPAR (coronary artery spasm in patients with acute coronary syndrome) study follow-up. J Am Coll Cardiol 2011;57(2):147-52.

42. Ozdemir H, Ciftçi E, Tapisiz A, Ince E, Tutar E, Atalay S, et al. Clinical and epidemiological characteristics of children with Kawasaki disease in Turkey. J Trop Pediatr 2010;56(4):260-2.

43. Pavlović M, Corović N, Gomzi M, Simić D, Jazbec A, Tiljak MK. Smoking habits, signs of chronic diseases and survival in inland and coastal regions of Croatia: a followup study. Coll Antropol 2004;28(2):689-700.

44. Pinto RJ, Bhagwat AR, Loya YS, Sharma S. Coronary artery disease in premenopausal Indian women: risk factors and angiographic profile. Indian Heart J 1992;44(2):99-101.

45. Pitsavos C, Kavouras SA, Panagiotakos DB, Arapi S, Anastasiou CA, Zombolos S, et al; GREECS Study Investigators. Physical activity status and acute coronary syndromes survival The GREECS (Greek Study of Acute Coronary Syndromes) study. J Am Coll Cardiol 2008; 27;51(21):2034-9.

46. Rastogi T, Vaz M, Spiegelman D, Reddy KS, Bharathi AV, Stampfer MJ, et al. Physical activity and risk of coronary heart disease in India. Int J Epidemiol 2004;33(4):759‑67.

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47. Secrest AM, Costacou T, Gutelius B, Miller RG, Songer TJ, Orchard TJ. Associations between socioeconomic status and major complications in type 1 diabetes: the Pittsburgh epidemiology of diabetes complication (EDC) Study. Ann Epidemiol 2011;21(5):374-81.

48. Sharma M, Ganguly NK. Premature coronary artery disease in Indians and its associated risk factors. Vasc Health Risk Manag 2005;1(3):217-25.

49. Singh RB, Rastogi SS, Rao PV, Das S, Madhu SV, Das AK, et al. Diet and lifestyle guidelines and desirable levels of risk factors for the prevention of diabetes and its vascular complications in Indians: a scientific statement of The International College of Nutrition.

Indian Consensus Group for the Prevention of Diabetes.

J Cardiovasc Risk 1997;4(3):201-8.

50. Singh S, Aulakh R, Bhalla AK, Suri D, Manojkumar R, Narula N, et al. Is Kawasaki disease incidence rising in Chandigarh, North India? Arch Dis Child 2011;96(2): 137-40.

51. Springhouse (2005). Professional Guide to Diseases 8th edition, Lippincott Williams and Wilkins; 2005.

52. Stansby G, Mister R, Fowkes G, Roughton M, Nugara F, Brittenden J, et al; Prospective Registry and Evaluation of Peripheral Arterial Risks, Events and Distribution Investigators. High risk of peripheral arterial disease in the United Kingdom: 2-year results of a prospective registry. Angiology 2011;62(2):111-8.

53. Stein CE, Fall CH, Kumaran K, Osmond C, Cox V, Barker DJ. Fetal growth and coronary heart disease in South India. Lancet 1996;348:1269-73.

54. Thom TJ, Kannel WB, Silbershatz H, D’Agostino RB. Cardiovascular disease in the United States and preventive approaches. In: Hurst’s The Heart, Arteries and Veins. 10th edition, Fuster V, Alexander RW, O’Rourke RA (Eds.), McGraw-Hill: New York, NY 2001:3-7.

55. Vaidya A, Pokharel PK, Nagesh S, Karki P, Kumar S, Majhi S. Prevalence of coronary heart disease in the urban adult males of eastern Nepal: a population-based analytical cross-sectional study. Indian Heart J 2009;61(4):341-7.

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58. Yusuf S, Hawken S, Ôunpuu S, Dans T, Avezum A, Lanas F, et al; INTERHEART Study Investigators.

Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet 2004;364:937-52.

review article

Exercise-induced Bronchoconstriction: Diagnosis and Management MICHAEL A. KRAFCZYK, CHAD A. ASPLUND

Abstract Exercise-induced bronchoconstriction describes the narrowing of the airway that occurs with exercise. More than 10â&#x20AC;Żpercent of the general population and up to 90 percent of persons previously diagnosed with asthma have exercise-induced bronchoconstriction. Common symptoms include coughing, wheezing, and chest tightness with exercise; however, many athletes will present with nonspecific symptoms, such as fatigue and impaired performance. Spirometry should be performed initially to evaluate for underlying chronic asthma, although results are often normal. An empiric trial of short-acting beta2 agonists or additional bronchial provocation testing may be necessary to confirm the diagnosis. Nonpharmacologic treatment options include avoiding known triggers, choosing sports with low minute ventilation, warming up before exercising, and wearing a heat exchange mask in cold weather. Short-acting beta2 agonists are recommended first-line agents for pharmacologic treatment, although leukotriene receptor antagonists or inhaled corticosteroids with or without long-acting beta2 agonists may be needed in refractory cases. If symptoms persist despite treatment, alternative diagnoses such as cardiac or other pulmonary etiologies, vocal cord dysfunction, or anxiety should be considered.

Keywords: Airway, wheezing, chest tightness, sports

E

xercise-induced bronchoconstriction (EIB) is a common problem in physically active persons. EIB is defined as transient, reversible bronchoconstriction that happens during or after strenuous exercise. It can occur in persons with or without underlying asthma.1 Bronchoconstriction that is triggered by exercise in persons with underlying asthma is considered exercise-induced asthma. This article discusses the diagnosis and management of EIB in persons without underlying asthma. The National Asthma Education and Prevention Program also provides guidelines for the diagnosis and management of asthma.2

Epidemiology and Etiology EIB is more common in persons who participate in endurance sports and sports that require high minute ventilation. More than 10 percent of the general population and up to 90 percent of persons previously

diagnosed with asthma have EIB.3 The prevalence of EIB in athletes ranges from 11 to 50 percent, although it approaches 90 percent in athletes with asthma.3 EIB also commonly occurs in cold-weather athletes and has been found to be present in approximately 50 percent of Olympic cross-country skiers.4 In persons without asthma, the rapid breathing of cold, dry air over a prolonged period is an ideal setting for EIB. When a person finishes exercising, the airway responds with vasodilation to warm the airway, resulting in water loss and engorgement of the airways. This process causes bronchoconstriction and the release of proinflammatory mediators. Another possible etiology may be environmental irritants, such as chlorine gas in a swimming pool or gases from ice-resurfacing equipment. Persons with EIB and underlying asthma usually experience exacerbation of underlying inflammation and airway hyperactivity caused by any of these mechanisms or by poorly controlled chronic asthma.5 Diagnosis

MICHAEL A. KRAFCZYK, MD, FAAFP, is the associate program director of the Primary Care Sports Medicine Fellowship Program and a faculty member in the Family Medicine Residency Program at St. Lukeâ&#x20AC;&#x2122;s Hospital and Health Network in Bethlehem, Pa. CHAD A. ASPLUND, MD, FACSM, is a staff family physician and a primary care sports medicine physician at Eisenhower Army Medical Center in Fort Gordon, Ga. Source: Adapted from Am Fam Physician. 2011;84(4):427-434.

Symptoms Typical symptoms of EIB include wheezing, shortness of breath, dyspnea, cough, or chest tightness during or after exercise. These symptoms usually occur during strenuous exercise and peak about five to 10 minutes after exercise. Atypical symptoms include

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review article fatigue, feeling out of shape, feeling unable to keep up with peers, and abdominal discomfort. Self-reported symptoms have been shown to be poor predictors of EIB because other conditions, such as vocal cord dysfunction, can cause similar symptoms.6-8 Therefore, symptoms alone should not be used to diagnose EIB.

Diagnosis of Exercise-induced Bronchoconstriction Symptoms suggestive of EIB Perform spirometry

The physical examination in patients with EIB is often unremarkable. If patients are evaluated when symptomatic, the most common findings are tachypnea and wheezing during end expiration.

Testing

Spirometry results normal

Spirometry results normal

Elite athlete?

Treat for EIB and asthma

Yes

In patients with possible EIB, spirometry should be performed to rule out underlying asthma2 (Fig. 1). Normal resting spirometry results are common in patients with EIB. If spirometry reveals an obstruction, additional testing before and after albuterol use is recommended. Obstruction with reversibility is indicative of underlying chronic persistent asthma.

If the patient is not an elite athlete, the next step is to prescribe an empiric trial of a short-acting beta2 agonist.

Only athletes who participate in high-level competition will need documentation of objective testing to use banned asthma medication. Follow-up, usually after one to two weeks, is necessary to determine whether treatment is successful. If the patientâ&#x20AC;&#x2122;s response to treatment is inadequate, additional testing is warranted.

No

Perform bronchial provocation testing

Initiate trial of short-acting beta2 agonist 15 to 30 minutes before exercise

Results abnormal; treat EIB

Results normal; consider alternative diagnoses

Adequate response; continue treatment

Inadequate response; perform bronchial provocation testing

Figure 1. Algorithm for the diagnosis of exercise-induced bronchoconstriction (EIB).

For elite athletes or for persons with EIB that does not respond to a trial of a short-acting beta2 agonist, bronchial provocation tests can be used to identify provoked decreases in forced expiratory volume in one

Table 1. Indirect Testing for the Diagnosis of Exercise-Induced Bronchoconstriction Test

Description

Advantages

Disadvantages

Eucapnic voluntary hyperpnea test

Patient hyperventilates a mixture of cold, dry air

Sensitive and specific

Need to control inspired gases and humidity

Spirometry performed before and after hyperventilation

Less laboratory space and equipment needed

Need to monitor minute ventilation Relatively expensive Not readily available

Field-based exercise challenge

Usually performed in the environment Sensitive and specific for coldthat causes symptoms weather athletes Spirometry performed before and after exercise

Not standardized Unable to control environment

Readily available Minimal equipment Inexpensive

Hypertonic saline test

Patient is given nebulized hypertonic saline Spirometry performed before and after nebulization

Laboratorybased exercise challenge

Usually performed on a treadmill or stationary bike Spirometry performed before and after exercise

Sensitive and specific Less laboratory space and equipment needed Sensitive and specific Standardized

Not as reliable if patient is already being treated with inhaled corticosteroid Need to control inspired gases and humidity Need to monitor heart rate and minute ventilation Relatively expensive

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review article Table 2. Differential Diagnosis of Exercise-induced Bronchoconstriction Anxiety Cardiac abnormalities (e.g., congestive heart failure, coronary artery disease, dysrhythmias, hypertrophic cardiomyopathy, valvular abnormalities) Deconditioning Hyperventilation syndrome Myopathies Obesity

as football, baseball, wrestling, or sprinting. Although nonpharmacologic treatment options can be effective, all athletes with EIB need to have a short-acting beta2 agonist available.

Pre-exercise Warm-up There is some evidence that a pre-exercise interval warm-up may attenuate the bronchoconstriction associated with EIB by inducing a refractory period.2,14 However, this has not been shown to be helpful in elite cold-weather athletes.15

Pulmonary arteriovenous malformations

Heat Exchange Mask

Pulmonary disease (e.g., chronic asthma, chronic obstructive pulmonary disease, cystic fibrosis, interstitial lung disease, pectus excavatum, scoliosis, tracheobronchial malacia)

Heat exchange masks are designed to limit cold air exposure during exercise in athletes with EIB. They typically can be found in running stores or online.

Using a mask has not been shown to be as effective as pretreatment albuterol in the prevention of bronchoconstriction.2,16 One of the main limitations of a heat exchange mask is that it may not be practical during competition.

Vocal cord dysfunction Information from reference 11.

second (FEV1). There are two main types of bronchial provocation tests: direct and indirect. Most pulmonary function laboratories can perform direct challenges, such as methacholine challenge.

Some are also equipped to perform indirect challenges, such as an exercise challenge test, which can accurately diagnose EIB.9 In addition, indirect challenges can be performed with a handheld spirometer at the location in which the athlete develops symptoms. Direct challenges have a lower sensitivity than indirect challenges10; therefore, indirect challenge is the preferred diagnostic test for EIB. Examples of indirect testing are listed in Table 1.9 If bronchial provocation testing results are normal, other diagnoses should be considered (Table 211).

Management EIB can affect many aspects of a patientâ&#x20AC;&#x2122;s life, regardless of the severity of symptoms. The main goal of treatment is to allow patients to exercise safely.

Secondary goals should include keeping athletes of all levels active and helping competitive athletes maximize performance. Asthma symptoms in association with exercise have been shown to reduce health-related quality of life scores in adolescents.12 One report found that among asthma-related deaths during exercise, many athletes had only mild asthma.13

Nonpharmacologic Treatment Several nonpharmacologic options exist for managing EIB. Basic measures include avoiding known triggers (allergen and environmental) and choosing sports with low minute ventilation (short bursts of exercise), such

Nutrition A review of the literature suggests that restricting dietary sodium intake for one to two weeks may reduce bronchoconstriction after exercise in patients with asthma and EIB; however, long-term studies are lacking.17 Additionally, a small, double-blind crossover study showed that high-dose omega-3 fish oil supplementation for three weeks reduced the use of bronchodilators in the treatment group. The limitations of this study included the small size and no mention of adverse effects from the high dosage of omega-3 fish oil.18

Pharmacologic Treatment Medication is the mainstay of treatment for persons with EIB (Table 319,20). Although pharmacologic treatment has been well studied, more research is needed to differentiate between optimal treatment of persons who have EIB with underlying asthma and those who have EIB without asthma.

Beta2 Agonists There are two types of inhaled beta2 agonists: shortacting and long-acting. Short-acting beta2 agonists are recommended first-line treatment in the management of EIB, preventively and for acute symptoms.2,14,21 They should be used 15 minutes before exercise, typically have a peak action of 15 to 60 minutes, and last approximately three hours. There is growing concern about the development of tachyphylaxis with daily use of short-acting beta2 agonists; therefore, they should be used only before more strenuous workouts or before

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review article Table 3. Medications for the Treatment of Exercise-induced Bronchoconstriction Medication

Dosage

Onset of action

Duration

Comments

Albuterol

90 mcg per spray; two puffs 15 minutes before exercise and as needed

Five to seven minutes

Three to six hours

First-line prevention of acute asthma

Levalbuterol

45 mcg per spray; two puffs 15 minutes before exercise and as needed

Five to 10 minutes Three to six hours

First-line prevention of acute asthma; similar to albuterol in safety and effectiveness, but more expensive

Pirbuterol

200 mcg per spray; one or two puffs 15 minutes before exercise and as needed

Five minutes

Five hours

First-line prevention of acute asthma; not available as generic; more expensive than albuterol

Aerolizer: 12 mcg per capsule; one spray twice per day

One to three minutes

12 hours

Second-line prevention of chronic asthma in conjunction with inhaled corticosteroid

30 to 48 minutes

12 hours

Second-line prevention of chronic asthma in conjunction with inhaled corticosteroid

20 mg per 2 mL; 20 mg taken 10 to 60 minutes before exercise or 20 mg four times per day

Less than one week

Unknown

Second-line prevention of chronic asthma

Beclomethasone

40 or 80 mcg per spray; one to four puffs twice per day

One week

Variable

Second-line prevention of chronic asthma

Budesonide

90 or 180 mcg per spray; two puffs twice per day

One week

Variable

Second-line prevention of chronic asthma

Ciclesonide

80 or 160 mcg per spray; one or two puffs twice per day

One week

Variable

Second-line prevention of chronic asthma

Flunisolide

250 mcg per spray; one or two puffs twice per day

One week

Variable

Second-line prevention of chronic asthma

Fluticasone

Diskus: 50, 100, or 250 mcg per blister; one or two puffs twice per day

One week

Variable

Second-line prevention of chronic asthma

One week

Variable

Second-line prevention of chronic asthma

Two hours

24 hours

Second-line prevention of chronic asthma and allergic rhinitis

Short-acting beta2 agonists

Long-acting beta2 agonists Formoterol; combination budesonide/formoterol

Metered-dose inhaler: 4.5 mcg per spray; two puffs twice per day Salmeterol; combination fluticasone/salmeterol

Diskus: 50 mcg per blister; one puff twice per day HFA: 21 mcg per puff; two puffs twice per day

Mast cell stabilizers Cromolyn (nebulizer solution)

Inhaled corticosteroids

HFA: 44, 110, or 220 mcg per spray; two puffs twice per day Mometasone

110 or 220 mcg per spray; one or two puffs, divided, once or twice per day

Leukotriene receptor antagonists Montelukast

Six to 14 years of age: 5 mg per day or two hours before exercise 15 years and older: 10 mg per day or two hours before exercise

Contâ&#x20AC;&#x2122;d...

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review article ...Contâ&#x20AC;&#x2122;d

Table 3. Medications for the Treatment of Exercise-induced Bronchoconstriction Medication Zafirlukast

Dosage Five to 11 years of age: 10 mg twice per day, one hour before or two hours after meal 12 years and older: 20 mg twice per day, one hour before or two hours after meal

Onset of action Unknown

Duration 12 hours

Comments Second-line prevention of chronic asthma

Zileuton, extended-release

Older than 12 years: 1,200 mg twice per day

Two hours

12 hours

Second-line prevention of chronic asthma

17 mcg per spray: two to four puffs, 15 to 30 minutes before exercise and as needed

15 minutes

Two to four hours

Third-line prevention of acute asthma

Anticholinergics Ipratropium

HFA = Hydrofluoroalkane; NA = Not available.

Information from references 19 and 20.

Table 4. NCAA and USOC Restricted Medications Medication class

NCAA

USOC

Anticholinergics

Not prohibited

Not prohibited

Inhaled beta2 agonists

Permitted only by prescription

Salmeterol and albuterol: athletes must declare use All other inhaled beta2 agonists: therapeutic use exemption is needed

Inhaled corticosteroids

Not prohibited

Declaration of use required in competition

Leukotriene receptor antagonists

Not prohibited

Not prohibited

Mast cell stabilizers

Not prohibited

Not prohibited

NCAA = National Collegiate Athletic Association; USOC = United States Olympic Committee.

Information from references 32 and 33.

competition.5 Although long-acting beta2 agonists have been shown to be effective in persons with EIB,2 the U.S. Food and Drug Administration has recommended that they not be used in persons with asthma unless there is concomitant use of a controller medication, such as inhaled corticosteroids.22 Concurrent use of inhaled corticosteroids and long-acting beta2 agonists has been shown to be effective and superior to use of inhaled corticosteroids alone in managing EIB.23 Mast Cell Stabilizers Mast cell stabilizers have been shown to be more effective than anticholinergics but less effective than short-acting beta2 agonists for managing EIB.24 Mast cell stabilizers should be used 15 to 20 minutes before exercise. Metered-dose inhalers have been discontinued because they are difficult to manufacture without chlorofluorocarbon propellants; however, cromolyn is still available as a nebulized solution.

Inhaled Corticosteroids Inhaled corticosteroids are considered controller medications and are the mainstay of treatment in patients with persistent asthma.2,14 A meta-analysis showed that use of inhaled corticosteroids for four weeks or more reduced the percentage decrease in FEV1 after exercise.25 There is a paucity of studies comparing inhaled corticosteroids with other treatments for EIB. Leukotriene Receptor Antagonists Leukotriene receptor antagonists have been shown to have a persistent benefit against EIB.14,26 Montelukast has an onset of action within two hours and continued EIB preventive benefit up to 24 hours after a single oral dose.27 Compared with salmeterol, montelukast is equally effective at preventing EIB at two hours and at eight and one-half hours, but montelukast is more effective at 24 hours.21 Short-acting beta2 agonists have

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review article been shown to be more effective than montelukast in the prevention of EIB.28 Use of montelukast has not been shown to cause tachyphylaxis.29 Other Agents Ipratropium is an anticholinergic that provides some protection against EIB but is not as effective as short-acting beta2 agonists or leukotriene receptor antagonists.14 Inhaled heparin30 and furosemide31 have been shown to be effective for treating EIB, but only small sample sizes have been used in studies.

A Practical Approach to the Patient Chronic, persistent-asthma should be treated according to the National Asthma Education and Prevention Program guidelines.2 In athletes with confirmed EIB, a reasonable approach is to start with a short-acting beta2 agonist before exercise (Fig. 1). If regular dosing of a short-acting beta2 agonist is needed, or if EIB is not controlled with short-acting beta2 agonists, a second-line agent (e.g., leukotriene receptor antagonist, mast cell stabilizer, inhaled corticosteroid with or without a long-acting beta2 agonist) can be added.

Inhaled corticosteroids and leukotriene receptor antagonists are the preferred agents in persons with underlying asthma. Leukotriene receptor antagonists are preferred in persons with allergic rhinitis. When prescribing medications to high-level athletes (e.g., those who participate in the National Collegiate Athletic Association or the Olympics), physicians should be aware of which medicines require a waiver (Table 4).32,33 Patients should be reassessed periodically; if a satisfactory response is not achieved, the diagnosis of EIB should be reconsidered.

References 1. Randolph C. An update on exercise-induced bronchoconstriction with and without asthma. Curr Allergy Asthma Rep. 2009;9(6):433-438.

2. Managing asthma long term—special situations. In: National Heart, Lung, and Blood Institute, National Asthma Education and Prevention Program. Expert panel report 3: guidelines for the diagnosis and management of asthma. NIH publication no. 07-4051. Bethesda, Md.: National Heart, Lung, and Blood Institute; 2007:363-372. http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln. pdf. Accessed May 3, 2010.

3. Parsons JP, Mastronarde JG. Exercise-induced bronchoconstriction in athletes. Chest. 2005;128(6):3966-3974.

4. Wilber RL, Rundell KW, Szmedra L, Jenkinson DM, Im J, Drake SD. Incidence of exercise-induced bronchospasm in Olympic winter sport athletes. Med Sci Sports Exerc. 2000;32(4):732-737.

5. Weiler JM, Bonini S, Coifman R, et al. Ad Hoc Committee of Sports Medicine Committee of American Academy

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of Allergy, Asthma & Immunology. American Academy of Allergy, Asthma & Immunology Work Group report: exercise-induced asthma. J Allergy Clin Immunol.

2007;119(6):1349-1358.

6. Parsons JP, Kaeding C, Phillips G, Jarjoura D, Wadley G, Mastronarde JG. Prevalence of exercise-induced bronchospasm in a cohort of varsity college athletes. Med Sci Sports Exerc. 2007;39(9):1487-1492.

7. De Baets F, Bodart E, Dramaix-Wilmet M, et al. Exerciseinduced respiratory symptoms are poor predictors of bronchoconstriction. Pediatr Pulmonol. 2005;39(4): 301-305.

8. Rundell KW, Im J, Mayers LB, Wilber RL, Szmedra L, Schmitz HR. Self-reported symptoms and exerciseinduced asthma in the elite athlete. Med Sci Sports Exerc.

2001;33(2):208-213.

9. Rundell KW, Slee JB. Exercise and other indirect challenges to demonstrate asthma or exercise-induced bronchoconstriction in athletes. J Allergy Clin Immunol.

2008;122(2):238-246.

10. Holzer K, Anderson SD, Douglass J. Exercise in elite summer athletes: Challenges for diagnosis. J Allergy Clin Immunol. 2002;110(3):374-380.

11. Weiss P, Rundell KW. Imitators of exercise-induced bronchoconstriction. Allergy Asthma Clin Immunol.

2009;5(1):7.

12. Hallstrand TS, Curtis JR, Aitken ML, Sullivan SD. Quality of life in adolescents with mild asthma. Pediatr Pulmonol.

2003;36(6):536-543.

13. Becker JM, Rogers J, Rossini G, et al. Asthma deaths during sports: report of a 7-year experience. J Allergy Clin Immunol. 2004;113(2):264-267.

14. Dryden DM, Spooner CH, Stickland MK, et al. Exerciseinduced bronchoconstriction and asthma. Evidence Reports/Technology Assessments, no. 189. AHRQ publication no. 10-E001. Rockville, Md.: Agency for Healthcare Research and Quality; January 2010.

15. Rundell KW, Wilber RL, Szmedra L, Jenkinson DM, Mayers LB, Im J. Exercise-induced asthma screening of elite athletes: field versus laboratory exercise challenge.

Med Sci Sports Exerc. 2000;32(2):309-316.

16. Beuther DA, Martin RJ. Efficacy of a heat exchanger mask in cold exercise-induced asthma. Chest. 2006;129(5): 1188-1193.

17. Mickleborough TD. Salt intake, asthma, and exerciseinduced bronchoconstriction: a review. Phys Sportsmed.

2010;38(1):118-131.

18. Mickleborough TD, Lindley MR, Ionescu AA, Fly AD. Protective effect of fish oil supplementation on exercise-induced bronchoconstriction in asthma. Chest.

2006;129(1):39-49.

19. Physicians’ Desk Reference. 64th ed. Montvale, N.J.: Physicians’ Desk Reference, Inc.; 2010.

20. Sinha T, David AK. Recognition and management of exercise-induced bronchospasm. Am Fam Physician.

2003;67(4):769-774.

review article 21. Medications. In: National Heart, Lung, and Blood Institute, National Asthma Education and Prevention Program. Expert panel report 3: guidelines for the diagnosis and management of asthma. NIH publication no. 07-4051. Bethesda, Md.: National Heart, Lung, and Blood Institute; 2007:213–276.http://www.nhlbi.nih.gov/ guidelines/asthma/asthgdln.pdf. Accessed May 3, 2010.

22. U.S. Food and Drug Administration. FDA announces new safety controls for long-acting beta agonists, medications used to treat asthma. February 18, 2010. http://www. fda.gov/NewsEvents/Newsroom/PressAnnouncements/ ucm200931.htm. Accessed May 3, 2010.

exercise-induced bronchoconstriction. Chest. 2007;132(3): 875-883.

28. Raissy HH, Harkins M, Kelly F, Kelly HW. Pretreatment with albuterol versus montelukast for exerciseinduced bronchospasm in children. Pharmacotherapy.

2008;28(3):287-294.

29. Edelman JM, Turpin JA, Bronsky EA, et al. Oral montelukast compared with inhaled salmeterol to prevent exercise-induced bronchoconstriction. A randomized, double-blind trial. Exercise Study Group. Ann Intern Med. 2000;132(2):97-104.

23. Pearlman D, Qaqundah P, Matz J, Yancey SW, Stempel DA, Ortega HG. Fluticasone propionate/salmeterol and exercise-induced asthma in children with persistent asthma. Pediatr Pulmonol. 2009;44(5):429-435.

30. Ahmed T, Gonzalez BJ, Danta I. Prevention of exercise-induced bronchoconstriction by inhaled lowmolecular-weight heparin. Am J Respir Crit Care Med. 1999;160(2):576-581.

24. Spooner CH, Spooner GR, Rowe BH. Mast-cell stabilising agents to prevent exercise-induced bronchoconstriction.

Cochrane Database Syst Rev. 2003;(4):CD002307.

31. Melo RE, Solé D, Naspitz CK. Comparative efficacy of inhaled furosemide and disodium cromoglycate in the treatment of exercise-induced asthma in children.

J Allergy Clin Immunol. 1997;99(2):204-209.

25. Koh MS, Tee A, Lasserson TJ, Irving LB. Inhaled corticosteroids compared to placebo for prevention of exercise induced bronchoconstriction. Cochrane Database Syst Rev. 2007;(3):CD002739.

26. Coreno A, et al. Comparative effects of long-acting beta2-agonists, leukotriene receptor antagonists, and a 5-lipoxygenase inhibitor on exercise-induced asthma. J Allergy Clin Immunol. 2000;106(3):500-506.

27. Philip G, Pearlman DS, Villarán C, et al. Single-dose montelukast or salmeterol as protection against

32. National Collegiate Athletic Association. NCAA banned drug list. http://www.ncaa.org/wps/wcm/ connect/public/NCAA/Student-Athlete+Experience/ NCAA+banned+drugs+list. Accessed May 3, 2010.

33. World Anti-Doping Agency. The World Anti-Doping Code: The 2010 Prohibited List: International Standard. http://www.wada-ama.org/Documents/World_AntiDoping_Program/WADP-Prohibited-list/WADA_ Prohibited_List_2010_EN.pdf. Accessed May 3, 2010.

Legal Question Q. I am a lawyer practicing in Delhi. I went to a doctor in Chennai for consultation. I was given ECT by him even though I refused to give consent. He obtained proxy consent from my brother. I understand ECT is banned in many countries. I have filed complaints with DMC and NHRC. What are your comments?

Ans. My comments are as follows: ÂÂ

ECT is given for serious mental disorders usually called psychoses (plural of psychosis). A person with psychosis may or may not have legal capacity to consent depending upon the nature and stage of the disease.

ÂÂ

Proxy consent has no validity in the case of a conscious adult capable of giving consent as held by the SC in Samira Kohli case. Giving any treatment, especially ECT, without valid consent is a grave crime. Valid consent may come from the patient or the guardian.

ÂÂ

The crucial points in your case are:

Were you capable of giving consent at the time of ECT?

Was the consent given by your brother valid in law? If ECT was given without valid consent, the doctor is liable.

ÂÂ

Complaint to DMC is likely to be infructuous if the Chennai doctor was not registered with it. You should find out with which SMC he is registered. You should complain to that SMC. You can find this out from the MCI web site. If you cannot find out, send the complaint to the MCI and they will refer it to the SMC concerned.

ÂÂ

Complaint to the NHRC is likely to be infructuous in the absence of expert medical opinion.

ÂÂ

You can also file a consumer complaint and a police complaint.

–MC Gupta

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clinical Study

Clinical and Laboratory Profile of Typhoid Fever NS Neki

Abstract Objectives: Changing trends have been reported in typhoid fever since last decade. A clinical and laboratory data of 100 patients is presented. Material and methods: Hundred patients in the age groups of 20-60 years (60 males and 40 females) attending the medical OPD and those admitted in the medical wards of GND Hospital/Govt. Medical College, Amritsar were studied. The diagnosis was based on s/s, positive Widal test (rising titer of O agglutinin) or positive blood culture Salmonella typhi. Patients excluded from the study were history of malaria, muscular disorders, myocardial infarction, hepatotoxic drugs, TAB vaccination, liver disease and shock due to reasons other than typhoid fever. The patients were subjected to complete hemogram, BT, CT, platelet count, kidney function tests, LFT, ECG, urine C/E, chest X-ray, blood sugar, Widal test and blood culture. Whenever required patients were even subjected to CT brain, CSF and bone marrow examination.

Observations: Forty-eight cases (48%), 30 (30%), 14 (14%) and 8 (8%) were in the age group of 20-30, 31-40, 41-50 and 51-60 years, respectively. In all the patients, fever (100-104°F was the major presenting symptom. Duration of fever was one week in 32 (32%), 1-2 weeks 40 (40%), 2-3 weeks 20 (20%), 3-4 weeks seven (7%) and >4 weeks in one (1%) patients 65 (65%) patients presented with continuous fever and 32 (32%) with intermittent fever and three (3%) with remittent fever. Sixty percent patients presented with rigors and chills and 40% without rigors and chills. Headache was reported in 80 (80%), bodyache 60 (60%), abdominal pain 13 (13%), cough 10 (10%), nausea four (4%), constipation two (2%) and vomiting two (2%). Clinical findings were splenomegaly in 70 (70%), tachycardia 65 (65%), hepatomegaly 23 (23%), coated tongue 12 (12%), relative bradycardia three (3%), meningism three (3%) and stupor one (1%). Laboratory findings were anemia (Hb 6-11 g/dl) in 25 cases (25%), severe anemia (Hb <6 g/dl) in 16 cases (16%), neutropenia 9 (9%), lymphopenia four (4%), lymphocytosis two (2%), thrombocytopenia 4 (4%), ↑ SGOT and SGPT 42 (42%), ↑ ALP seven (7%), ↑ serum bilirubin 5 (5%). Conclusion: Continuous and intermittent fever with rigors and chills, headache, bodyaches, abdominal pain, splenomegaly, hepatomegaly, tachycardia and biochemical involvement of liver were more commonly observed in this study.

Keywords: Typhoid fever, blood culture, Widal test, hepatomegaly, splenomegaly

T

yphoid fever is a major health problem now a days as it requires prolonged hospitalization and a major cause of morbidity in the developed countries.1-3 Every year there are more and more episodes of typhoid fever worldwide.1 It is caused by Salmonella group of organisms i.e., Salmonella typhi and S. paratyphi A & B. These organisms are gram-negative motile, nonlactose fermenting bacilli infecting the bowel. Humans are the only reservoir of S. typhi.

Persons with typhoid fever or convalescent or chronic carriers always serve as the ultimate source of infection.

The major vehicles of infection are water and food contaminated by feces or urine of infected patients or carriers in addition to transmission of infection through contaminated hands.2,4,5 In the first week of the disease,

Assistant Professor Dept. of Medicine Govt. Medical College/GND Hospital, Amritsar, Punjab

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70-90% of patients are culture positive and only 30-40% are positive in the third week.2 Changing trends in typhoid fever have been seen since last decade.6,7 The aim of the study was to present the clinical and laboratory data of 100 patients.

Material and Methods Hundred patients (60 males and 40 females in the age group of 20-60 years) attending the medical OPD and those admitted in the medical wards of GND Hospital, Amritsar were enrolled. The sole inclusion criteria was positive Widal test and or positive blood culture for S. typhi. Patients with history of liver disease, myocardial infarction, malaria, muscular disorders, hepatotoxic drugs, TAB vaccination and shock due to reasons other than typhoid fever were excluded from the study.

All the patients were subjected to complete hemogram, platelet count, BT, CT, urine C/E, ECG, chest X-ray, blood urea, serum creatinine, LFT, blood sugar, blood culture and ultrasound abdomen and in required cases CT brain, CSF and bone marrow examination was

clinical study carried out. Suggestive clinical features supported by one or both laboratory findings, either positive blood culture and or positive Widal test was taken as criteria for diagnosis of enteric fever.7,8 Observations Duration of fever in Widal positive cases was one week 20% (20), 1-2 weeks 42% (42), 2-3 weeks 25% (25), 3-4 weeks 8% (8) and >4 weeks 5% (5) subjects.

Widal test was performed using tube agglutination method. Agglutination titers of TO were 1:160 (30%), 1:320 (60%), 1:640 in (8%) and 1:1280 (2%), whereas TH of 1:160 (30%), 1:320 (22%), 1:640 (9%) and 1:1280 (1%) subjects AH titers were 1:160 (8%), 1:320 (6%), 1:640 (3%) and 1:1280 in 0% patients. BH titers were negative.

Table 1. Showing Age Distribution Age (years)

No.

Percentage (%)

Table 3. Showing Characteristics of Fever Type of fever

No. of patients

Percentage (%)

Continuous

65

65

Intermittent

32

32

Remittent

3

3

Table 4. Showing Symptoms Symptoms

No.

Percentage (%)

Headache

80

80

Bodyache

60

60

Abdominal pain

42

42

Rigors and chills

32

32

Diarrhea

13

13

Cough

10

10

Nausea

4

4

Constipation

2

2

Vomiting

2

2

20-30

68

68

31-40

20

20

41-50

7

7

Table 5. Showing associated Features

51-60

5

5

Assoc. features

No. of patients

Percentage (%)

With rigors and chills

60

60

Without rigors and chills

40

40

Males Females

40%

60%

Figure 1. Showing sex distribution.

No. 32 40 20 7 1

Clinical findings

No.

Percentage (%)

Splenomegaly

70

70

Tachycardia

65

65

Hepatomegaly

23

23

Coated tongue

10

10

Relative bradycardia

3

3

Meningism

3

3

Stupor

1

1

Dehydration

1

1

Chest signs

1

1

Discussion

Table 2. Showing Duration of Fever Duration (in weeks) 1 1-2 2-3 3-4 >4

Table 6. Showing Clinical Findings

Percentage (%) 32 40 20 7 1

Infection is imitated by oral ingestion of organisms, which must pass the gastric acid barrier to establish infection. Organisms therefore originate from patients with typhoid or from convalescent or chronic carriers excreting organisms in their stool. Following recovery upto 5% of patients become chronic carriers of S. typhi.5 Clinically the patients present with step like

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clinical study Table 7. Showing Laboratory Findings Findings

No.

Percentage (%)

6-11 g%

25

25

<6 g%

16

16

Neutropenia

9

9

Lymphopenia

4

4

Lymphocytosis

2

2

Anemia

Thrombocytopenia

4

4

↑ SGOT and SGPT

42

42

↑ ALP

7

7

↑ Serum bilirubin

5

5

↑ Urea and creatine

12

12

↑ SGOT, SGPT and hepatomegaly

12

12

Table 8. Showing Grades of Severity-based on Symptomatology Grades of severity

No.

Percentage (%)

Severely ill

10

10

Moderately ill

50

50

Mildly ill

40

40

in 41%, ↑ SGOT and SGTP 42% and SGOT, SGPT and hepatomegaly 12% patients. In S. typhi endemic regions, the rate of clinical typhoid among persons positive for HIV virus is about 25 times higher than that among HIV negative persons in the 15-35 years old age group and is as much as 60 times higher than that in the general population.10 S. typhi can be isolated for blood, stool and urine sample of carriers. It may persist in various sites and later on may present pyogenic lesions.11 Conclusion Clinical picture of typhoid fever is seen no less often.

Fever may be continuous or intermittent. Tachycardia, hepatomegaly and biochemical involvement of liver are more commonly seen in the study. Well-known complications of typhoid fever are rare due to indiscriminate use of antibiotics in clinically suspected fever as antibiotics administration affects the isolation of organisms.

References 1. Park JE, Park K. Textbook of Preventive and Social Medicine. 14th edition 1994:p.161.

2. Keusch GT. Salmonellosis. In: Harrison’s Principles of Internal Medicine. Vol. 1, 14th edition 1998:p.950-2.

3. WHO, World Health Statistics; 26: 2, 1973.

daily increase in temperature (upto 40-41°C) associated with headache, myalgia, malaise, chills, constipation, diarrhea and vomiting in the first week. Delirium, complications then coma and death (if untreated) can occur at the end of second week. Intestinal bleeding and perforation can occur in 3rd or 4th week when the patient is otherwise improving. Bradycardia relative to the height of fever is seen in few patients.2 Patients in the age group of 20-30 years reported maximum incidence of 68%, which is consistent with findings of Guerrant et al4 reporting 75%. Headache was observed as a major complaint in 80% patients and this finding is in tune with other studies.6 Splenomegaly was observed in 70% patients; whereas, it was reported to be 19-86% by Gulati et al.9 Maximum number of patients (78%) were in the age group of 20-40 years. Maximum duration of fever was one week and 1-2 weeks in 32% and 40%, respectively. Headache and bodyaches were observed as most common symptoms in 80% and 60%, respectively.

Regarding clinical signs, splenomegaly was detected in 70%, tachycardia 65% and hepatomegaly 23%.

In the biochemical investigations, anemia was detected

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Indian Journal of Clinical Practice, Vol. 23, No. 8 January 2013

4. Guerrant RL. Salmonella infections. In: Harrison’s Principles of Internal Medicine. 11th edition 1987:p.592.

5. Dastur FD. Salmonellosis: API Textbook of Medicine.

6th edition 1999:p.37-9.

6. Scragg J, Rubidge C, Wallace HL. Typhoid fever in African and Indian children in Durban. Arch Dis Child 1969;44(233):18-28.

7. Gupta S, Meena HS. Changing profile of enteric fever - in summer-91. J Assoc Physicians India 1992;40(11):726-9.

8. Rao BN. An evaluation of modified Widal test in the diagnosis of enteric fever. J Indian Med Assoc 1989;87(8):179-80.

9. Gulati PD, Saxena SN, Gupta PS, Chuttani HK. Changing pattern of typhoid fever. Am J Med 1968;45(4):544-8.

10. Gruenewald R, Blum S, Chan J. Relationship between human immunodeficiency virus infection and salmonellosis in 20- to 59-year-old residents of New York City. Clin Infect Dis 1994;18(3):358-63.

11. Forsyth JRL. Typhoid and paratyphoid. In: Topley and Wilson’s Microbiology and Microbial Infections. Hausler WJ, Sussman M (Ed.), Arnold/Oxford University Press 1998;9(3):461.

Clinical study

A Study of Maternal and Perinatal Outcome in Dengue Laxmi Maru*, Astha Jain**

Abstract Objectives: To study different spectrum of presentations in diagnosed cases of dengue. To study the effects of dengue infection in different trimesters of pregnancy. To evaluate perinatal and maternal outcomes in these cases. Material and methods: The study conducted is a retrospective study of 30 cases who had dengue infection in pregnancy (done by dengue NS1 Ag detection or by serological demonstration of dengue IgM, IgG Ab). The study was conducted in Dept. of Obstetrics and Gynecology, Maharaja Yashwantrao Hospital, Indore over a period of one year (Janâ&#x20AC;&#x2122;09 to Janâ&#x20AC;&#x2122;10).

The interventions were given in the form of proper fluid management therapy, blood transfusions, platelet concentrate, etc.

Data was analyzed taking into consideration varied presentations, different complication, which patient and fetus underwent, and final pregnancy outcomes. Results: Out of 30 cases, nine cases manifested severe disease in the form of dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) i.e., incidence of severe disease manifestations out of total dengue cases in pregnancy was 30%. Out of these three cases succumbed to dengue showing a 33.33% mortality in patients who develop DHF/DSS. Maternal mortality rate in dengue cases is 10%, which otherwise is round about 0.4% (400/1,00,000 live births) in our country (India) and 0.1% (100/1,00,000 live births) in western countries under normal circumstances.

Conclusion: Although the incidence of dengue in pregnancy is very low, but it is on considerable rise specially in regions, where it is endemic i.e., tropical countries like India as sudden outbursts are seen in these regions from time to time thus mandating a need to evaluate the course of disease and study it better. From our study, we would like to conclude that although many cases may remain asymptomatic or manifest a mild form of disease, severe manifestations like DHF/DSS can also occur and these are potentially life-threatening both to the mother and the baby.

Keywords: Dengue in pregnancy, thrombocytopenia, pyrexia, hemorrhage

D

engue is one of the most common mosquitoborne infection (Aedes aegypti - tiger mosquito being the vector), with an estimated 100 million infections worldwide per year. Of this, 250-500 thousand persons manifest severe disease, with the remainder being mild, nonspecific or even asymptomatic.

There are four serotypes of the dengue virus: Infection by one serotype is thought to produce lifelong immunity to that serotype but only a few months of immunity to the others.

Dengue infection is endemic in tropical and subtropical countries, including India. When this viral infection is not asymptomatic, it is diagnosed as dengue fever, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS).

*Professor and Head **Resident Mahatma Gandhi Memorial Medical College, Maharaja Yashwantrao Hospital, Indore, Madhya Pradesh Address for correspondence Dr Laxmi Maru V7 Samwad Nagar Navlakha, Indore, Madhya Pradesh - 452 001

DHF and DSS requires special mention during pregnancy. It must be differentiated from pre-eclampsia as there is an overlap of symptoms between the two conditions, such as thrombocytopenia, impaired liver function, capillary leak, edema, ascites and decreased urinary output. A definite diagnosis can only be confirmed serologically. Pregnant women infected with dengue virus do not require a special treatment, and respond well to bed rest and an antipyretic agent such as paracetamol.

Serial platelet counts and platelet transfusions are mandatory for patients with DHF. As the mortality rate of untreated in DHF may be as high as 40%, early diagnosis and treatment are important. Dengue fever should be suspected in any pregnant woman with fever during epidemics in endemic areas and followed with dengue serology. If the mother acquired infection near term or during labor, perinatal infection is to be excluded with serologic studies and platelet count even if the newborn is asymptomatic.

In severe cases, circulation is compromised, potentially resulting in hypovolemic shock and even demise,

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clinical study without appropriate management. Patients with DHF can also have abnormal blood coagulation, but major hemorrhage is unusual except in association with profound or prolonged shock.

Previous case series on dengue fever in pregnancy reported complications of preterm labor, abruption and severe hemorrhage during cesarean section. Fetal problems include preterm birth, intrauterine death and acute fetal distress during labor. Vertical transmission has also been described.

Pre-eclampsia has been intrapartum dengue fever.

reported

previously

in

presentation into four groups: Those belonging to 1st (0-12 weeks), 2nd (12-28 weeks) and 3rd (28-40 weeks) trimesters and postnatal cases, respectively.

These cases were studied for their various mode of presentations, which included a wide range starting from an: ÂÂ

Asymptomatic stage in which incidental thrombocytopenia on routine investigations during antenatal check-ups was the first sign raising suspicion.

ÂÂ

A mild/moderate symptomatic state in which patient had pyrexia, malaise, upper respiratory tract infection (URTI), rashes, epistaxis, symptoms of threatened abortion or premature pains or bleeding p/v.

ÂÂ

A more severe life-threatening DHF or DSH.

Occasionally, intracranial hemorrhage, cerebral edema or anoxia, micropapillary hemorrhage has been observed with release of toxic products.

Computed tomography (CT) of the brain, done after the seizure, revealed only focal ischemic areas. Moreover, although the blood pressure was normal during the episode, hyperreflexia and raised urinary proteins were present.

The possible mechanism of the blood pressure response as well as the eclamptic fits may be the results of a residual post-dengue leaky vasodilatory state. Conventionally, eclampsia is diagnosed with hypertension, proteinuria and convulsions.

As the average age of dengue infections increases, it is possible that more pregnant women will be exposed.

It is thus important for the obstetrician to be aware of the need for early diagnosis to initiate appropriate management.

MATERIAL and METHODs It is a retrospective study conducted in the Dept. of Obstetrics and Gynecology, MGM Medical College and Maharaja Yashwantrao Hospital, Indore, MP. It included 30 cases who were diagnosed to have dengue in pregnancy. These cases were diagnosed either on the basis of ÂÂ

ÂÂ

Detection of dengue viral antigen (NS1 Ag detection)-70% cases or Positive serological findings i.e., detection of dengue-specific immunoglobulin M (IgM) (30% cases).

Women with DHF/DSS presented either with severe pre-eclampsia/HELLP syndrome like pictures - raised blood pressure, edema, low platelet count and raised liver enzymes or were referred with shock like features following severe blood loss intraoperatively or with severe antepartum hemorrhage (APH) or prepartum hemorrhage (PPH).

Based on the severity of the disease, the management protocol was decided and cases were managed accordingly also keeping in mind the obstetrical parameters, but in most of these cases the perinatal morbidity and mortality was reported and few cases also reported maternal mortality and thereby motivating us to undertake this study to understand dengue in obstetric in a better perspective so that these deaths could be prevented in future.

RESULTS Our cohort consisted of 30 patients with confirmed acute dengue infection during pregnancy or the immediate postpartum period. Twenty-one (70%) cases were diagnosed by the presence of NS1 dengue Ag detection, whereas nine (30%) cases were diagnosed by dengue specific IgM and IgG detection.

Two (6.66%), 6 (20%), 17 (56.66%), five (16.66%) women presented in the 1st, 2nd, 3rd trimester and immediate postpartum period, respectively.

It is present early in infection and can persist for upto six months. The dengue IgM test cross-reacts across all four dengue serotypes.

Table 1. Data Showing Number of Dengue Cases in Different Trimester of Pregnancy Out of Total 30 Cases

The cases were selected over a period of 12 months commencing from Jan’09 to Jan’10. These cases were then arranged on the basis of their gestational age at

Trimester

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Number of Cases

1st

2nd

3rd

Postnatal cases

2

6

17

5

clinical study Table 2. Showing Various Modes of Presentation which Lead to the Suspicion of Dengue in these Patients

9 1

Rashes, epistaxis and bleeding p/v, and bleeding from other sites with h/o fever in the past 2 weeks 4 1

Thrombocytopenia (incidental finding on routine investigations) Platelet count <1,00,000 8 –

Intraoperative excessive blood loss or severe APH or PPH: Mandating further evaluation 9 –

3

1

2

–

5

2

5

5

–

–

1

4

Mode of presentation

Pyrexia

No. of cases (total) No. of cases in 1st trimester No. of cases in 2nd trimester No. of cases in 3rd trimester No. of postnatal cases

Table 3. Gross Outcome Analysis Trimester

Maternal condition

Fetal condition

Intervention received

Mode of delivery

Complications

Conservative

–

–

Group 1st trimester Group 1

No. of cases 1

Improved

Unaffected

Group 2

1

Improved

Aborted spontaneously Blood transfusion 2 units

Sp. Abortion f/b c/c

Anemia; fetal loss

2nd trimester Group 1 4

Improved

Asymmetrical IUGR-1; Conservative Unaffected-3

-

Asymmetrical IUGR

Group 2

2

Improved

1 aborted Blood and platelet spontaneously; 1 intra- transfusion done uterine death reported

1 sp. abortion; 1 2nd trimester induction of abortion

Anemia; fetal loss

3rd trimester Group 1 9

Improved

Vertical transmission-1; asymmetrical IUGR1; MSL-BA: 3; oligohydramnios: 3

Conserevative-4; blood and component transfusions: 5

2 LSCS for MSL, 1 LSCS for MSL with FD, 1 LSCS for severe oligo, 5 NVD

Increased perinatal morbidity; anemia increased operative interference

2 went in shock and revived, 3 patient succumbed after delivery, 3 improved

Twin SVD with severe oligo (AFI 3):1 Intrauterine death with severe oligo: 2; term SVD: 5 2 MSL 1; Chorioamnionitis

All the cases required transfusions, 2 cases were managed for shock and revived, 3 required resuscitative efforts but succumbed

1 LSCS for IUD with severe oligo with failure to progress 7-SVD

Fetal loss, increased maternal morbidity, maternal mortality: 3 cases

Group 2

8

Postnatal cases Group 1 3 Group 2 2

Improved Unaffected Fetus already dead 1 pt revived from the state of shock, 2 required resuscitative measures

Transfusion done PNC PNC Blood and component transfusion done, revived from shock

Anemia Anemia, increased post-op morbidity

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clinical study Eight (26.66%) cases were asymptomatic requiring no intervention, 13 (43.33%) had mild-moderate disease who required a conservative management - fluid replacement therapy, symptomatic therapy and at times blood and component replacement therapy along with a close monitoring. Nine (30%) cases manifested severe disease in the form of DHF/DSS i.e., incidence of severe disease manifestations out of total dengue cases in pregnancy was 30%. Out of these three cases, succumbed to dengue showing a 33.33% mortality in patients who develop DHF/DSS. In 11 (36.66%) cases fetal loss was reported, in one (3.33%) case vertical transmission of dengue infection was seen, two (6.66%) cases reported post-viral asymmetrical intrauterine growth restriction (IUGR) in fetus, in the rest 16 women (53.33%) the fetal condition remained unaffected during the study period.

Out of three maternal mortality reported, one was due to spontaneous intracerebral hemorrhage on postnatal Day 1, which manifested as sudden decerebrate rigidity with respiratory arrest, necessary resuscitative measures were taken but patient could not be saved.

This patient had severe thrombocytopenia with reported platelet count 9,000/mm3 at the time of referral with bleeding manifestations and was in active phase of labor, she was managed vigorously and received 1 unit fresh whole blood and 2 unit platelet concentrate at the time of delivery and 1 unit eight hours after.

Her condition was also relatively stable when she developed gross rigidity and respiratory arrest the cause of which was later found to be internal capsule hemorrhage.

Second mortality reported was of a gravida 2 para 1 patient who came in advanced labor and was severely anemic (3 g/dl) with platelet count 37,000/mm3, she delivered and inspite of liberal use of oxytocics, 3 unit blood transfusions, continuous intranasal oxygen inflow at 6-8 lts/min and all resuscitative measures, the patient deteriorated, she was found to be in decompensated state of CCF and tested positive for dengue. Despite our best efforts the patient succumbed eight hours later.

Third mortality reported was in a 27-year-old primigravida patient who came with a picture resembling HELLP syndrome with raised blood pressure, elevated liver enzymes and rapidly falling platelet count (40,000/mm3 at first reading and 27,000/mm3 at second reading two hours after).

This patient was in fulminant form of disease and by the time she was diagnosed to be a case of dengue,

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she succumbed inspite of our best efforts. She received 2 units of platelet concentrate, MgSO4, etc.

DISCUSSION

Summary of the Findings The study shows that although pregnancy does not seem to increase the risk of contracting dengue fever, the disease can be severe in pregnancy, with devastating consequences. Even with primary disease, it can progress to manifestations of typical DHF and its diagnosis and treatment can be hampered by overlapping symptoms and signs with other disease processes such as toxemia, HELLP syndrome and certain forms of sepsis.

Diagnosis was made in the early phase of disease

by NS1 Ag detection in 70% cases and later on by serological demonstration of IgM and IgG Ab in 30%.

Fetal loss was reported in 36.66% cases while mortality was reported in 10% of the total dengue cases.

Complications were more if the infection was acquired near term.

Adequate management protocol should include a high suspicion index during the epidemics of dengue in the endemic regions, an early diagnosis, a vigilant monitoring of even mild-moderate cases and not letting them progress to DHF. A vigorous monitoring with required fluid and blood/component replacement therapy in cases who are already in DHF, as mortality in these cases can be as high as 40%.

CONCLUSION Although the incidence of dengue in pregnancy is very low but it is on considerable rise specially in regions, where it is endemic i.e., tropical countries like India as sudden outbursts are seen in these regions from time to time thus mandating a need to evaluate the course of disease and study it better.

From our study, we would like to conclude that although many cases may remain asymptomatic or manifest a mild form of disease, severe manifestations like DHF/DSS can also occur and these are potentially life-threatening both to the mother and the baby.

Suggested Reading 1. D een JL, Harris E, Wills B, Balmaseda A, Hammond SN, Rocha C, et al. The WHO dengue classification and case definitions: time for a reassessment. Lancet 2006;368(9530):170-3.

clinical study 2. Waduge R, Malavige GN, Pradeepan M, Wijeyaratne CN, Fernando S, Seneviratne SL. Dengue infections during pregnancy: a case series from Sri Lanka and review of the literature. J Clin Virol 2006;37(1):27-33.

8. Chotmongkol V, Sawanyawisuth K. Case report: Dengue hemorrhagic fever with encephalopathy in an adult.

Southeast Asian J Trop Med Public Health 2004;35(1): 160-1.

3. Phupong V. Dengue fever in pregnancy: a case report.

BMC Pregnancy Childbirth 2001;1(1):7.

9. de Souza LJ, Martins AL, Paravidini PC, Nogueira RM, Gicovate Neto C, Bastos DA, et al. Hemorrhagic encephalopathy in dengue shock syndrome: a case report.

Braz J Infect Dis 2005;9(3):257-61.

4. Carles G, Talarmin A, Peneau C, Bertsch M. Dengue fever and pregnancy. A study of 38 cases in French Guiana.

J Gynecol Obstet Biol Reprod (Paris) 2000;29(8):758-762. itayathawornwong P. Parturient and perinatal dengue 5. W hemorrhagic fever. Southeast Asian J Trop Med Public Health 2003;34(4):797-9.

6. J anjindamai W, Pruekprasert P. Perinatal dengue infection: a case report and review of literature. Southeast Asian J Trop Med Public Health 2003;34(4):793-6.

7. B S, Tanawattanacharoen S, unyavejchevin Taechakraichana N, Thisyakorn U, Tannirandorn Y, Limpaphayom K. Dengue hemorrhagic fever during pregnancy: antepartum, intrapartum and postpartum management. J Obstet Gynaecol Res 1997;23(5):445-8.

10. ACOG Committee on Practice Bulletins - Obstetrics.

ACOG practice bulletin. Diagnosis and management of preeclampsia and eclampsia. Number 33, January 2002.

Obstet Gynecol 2002;99(1):159-67.

11. Mattar F, Sibai BM. Eclampsia. VIII. Risk factors for maternal morbidity. Am J Obstet Gynecol 2000;182(2): 307-12.

12. Chames MC, Livingston JC, Ivester TS, Barton JR, Sibai BM. Late postpartum eclampsia: a preventable disease?

Am J Obstet Gynecol 2002;186(6):1174-7.

13. Lubarsky SL, Barton JR, Friedman SA, Nasreddine S, Ramadan MK, Sibai BM. Late postpartum eclampsia revisited. Obstet Gynecol 1994;83(4):502-5.

Legal Question Q. I am private practitioner radiologist. A press reporter is seeking RTI information from the income tax department regarding my income tax returns and from the CMO regarding the USGs done by me. What problems he might create for me? What should I do?

Ans. ÂÂ

He is probably trying to make an allegation against you that you are earning a lot from USGs but not fully reporting your income. A CA may help you regarding this.

ÂÂ

He can also get a few persons to say on affidavit that you performed their USG but never sent the reports to the CMO as required. You must ensure that your USG records, including F forms and monthly reports in order.

ÂÂ

The IT deptt. should not divulge you IT returns to him without the permission of the third party (yourself) as per the RTI Act.

ÂÂ

The CMO should not divulge under RTI the details of patients examined by you because that would be breach of confidentiality to which the patients are entitled.

ÂÂ

You can write to the CMO and the income tax department that if any request as above is received for information under RTI, the same should not be revealed for the reasons mentioned above without your consent. This will ensure that if they do it behind your back, you can sue them.

—MC Gupta

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case report

Idiopathic Dilated Cardiomyopathy Complicating in a Pregnancy with Uterine Fibroid DEBASMITA MANDAL*, PRADIP KUMAR SAHA**, CHAITALI DATTARAY†, SAROJ MANDAL‡

Abstract Idiopathic dilated cardiomyopathy (DCM) during gestation is a rare coincidence. These patients can experience hazardous complications like cardiac failure and even death during pregnancy due to physiologically increased in vascular volume and cardiac output. A previously diagnosed case of idiopathic DCM (ejection fraction [EF] 32% and severe left ventricular systolic dysfunction in Echo Doppler, NYHA functional Class IV) who also had a big uterine fibroid was admitted to our antenatal ward at 33 weeks four days of gestation with signs of left ventricular failure. She required intensive coronary care unit (ICCU) care and was treated with digoxin, inotrops and diuretics, etc. She was managed expectantly upto 36 weeks and cesarean section was done due to intrauterine growth restriction (IUGR). Postpartum period was also eventful with another episode of cardiac failure, which needed ventilator support as well as ICCU back-up. She was followed up with regular echocardiography and ECG and showed improvement at sixth month with EF of 42%. Adequate counseling prenatally and antenatally and good multidisciplinary support may lead to successful pregnancy outcome in patients with idiopathic DCM.

Keywords: Idiopathic dilated cardiomyopathy, pregnancy, fibroid, left ventricular failure

D

ilated cardiomyopathy (DCM) is defined as dilatation of one or both ventricles with reduced left ventricular ejection fraction (LVEF) in the absence of coronary, valvular, congenital or any systemic diseases known to cause myocardial dysfunction.1 The predominant features are evidenced by increased myocardial mass, cardiomegaly with dilatation and enlargement of one or both ventricles with improper contractility and impairment of systolic function.2 It has been observed that young nonpregnant women with DCM have poor prognosis and survival than women with peripartum cardiomyopathy.3 It is only very rare that DCM is well-documented before pregnancy.4 During gestation, the physiologic hemodynamic alteration and procoagulant state of pregnancy can destabilize the cardiac disease as well as the pregnancy outcome itself. Authors have documented a negative impact of pregnancy on clinical course of women with DCM and have also shown an increased incidence of neonatal complications in mothers with DCM.5 *Assistant Professor **RMO cum Clinical Tutor †Associate Professor Dept. of Obstetrics and Gynecology ‡Final Year Post Doctoral Trainee, Dept. of Cardiology IPGME & R, SSKM Hospital, Kolkata Address for correspondence Dr Debasmita Mandal Qr. No. C/11, SSKM Hospital Campus 242, AJC Bose Road, Kolkata, West Bengal - 700 020 E-mail: drdebasmitamondal@yahoo.com

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In this case report, we present the clinical sequel of a young woman with DCM and a big fundal fibroid during antenatal period and subsequent successful pregnancy outcome at 36 weeks gestation.

Case report A 24-year-old primigravida at 33 weeks four days of gestation was referred with chief complaints of acute exacerbation of breathlessness and palpitation for four days. Previously, she required admission at eight weeks gestation at a local health center for severe orthopnea.

Ultrasonography (USG) done then corroborated the gestational age and revealed a big fundal fibroid (14.2 x 13.6 x 13.2 cm3) in USG. Echo Doppler diagnosed DCM with severe left ventricular systolic dysfunction, ejection fraction (EF) of 32%, moderate mitral regurgitation and moderate pulmonary arterial hypertension.

Later, on admission in our antenatal ward she was found to be moderately anemic, afebrile and normotensive. All other peripheral signs like cyanosis, jaundice, clubbing and edema were absent. Uterine height corresponded to 32 weeks gestation. She had dyspnea at rest (New York Heart Association [NYHA] functional Class IV), tachycardia, raised jugular venous pressure (JVP) and left ventricular failure while investigations revealed hemoglobin level of 9.2 g/dl with 29% packed cell volume; liver function

case report Table 1. Overview of Literatures on Idiopathic DCM in Pregnancy (All Case Reports and Study that could be Found Searching MEDLINE from 1980-2010) Authors

No. of pregnancies

Complications during pregnancy

Mode of termination

Gestational age at delivery

Neonatal outcome

Mazor et al2 (1994)

1

Slow progress of labor

LSCS

36 weeks

No morbidity

Chan et al9 (1999)

1

Thromboembolic stroke

LSCS

31 weeks

1.6 kg baby IUGR

Berstein et al7 (2001) 3

PIH

2 by forceps 1 therapeutic abortion

34 Âą 5.9 weeks

2 normal 1 (multiple cardiac anomalies)

Yacoub et al6 (2002)

1

LVF

Therapeutic abortion

20 weeks

Stillbirth

Avila et al8 (2003)

18

CCF, angina, arrhythmia, thromboembolism abortion, maternal death

Majority by NVD

Grewal et al5 (2010)

27

PPH, pre-eclampsia LVF

Majority by NVD

Stillbirth, prematurity

38 weeks

Prematurity, fetal, death, IUGR

LSCS = Lower segment cesarean section; IUGR = Intrauterine growth restriction; PIH = Pregnancy-induced hypertension; LVF = Left ventricular failure; CCF = Congestive cardiac failure; PPH = Postpartum hemorrhage; NVD = Normal vaginal delivery.

test, renal function test and coagulation profile were within normal range. Previously, USG done at showed adequate fetal growth and excluded the absence of congenital anomaly. Chest X-ray on admission revealed a dilated heart with pulmonary venous congestion.

ECG revealed sinus tachycardia and echocardiography showed dilated left atrium and ventricle with global hypokinesia of left ventricle and LVEF was 24%. She was shifted to intensive coronary care unit (ICCU) for better management and treated conservatively with digoxin, diuretics, potassium supplements and heparin and inotropes. After stabilization of heart failure by regular echocardiographies monitoring was continued.

EF of left ventricle was found to vary between 25% and 32% with medical treatment.

Simultaneous USG fetal monitoring and iron and calcium supplementation were continued. At 36 weeks five days, pregnancy was terminated by elective lower segment cesarean section for intrauterine growth restriction (IUGR) and oligohydramnios undergraded epidural anesthesia. A 2.49 kg girl baby was delivered with Apgar score of 9 and 8 at 1 and 5 minutes, respectively.

Postoperatively patient again developed left ventricular failure and cardiogenic shock, which required ICCU admission and multidisciplinary support. She was discharged after two weeks and asked to be on followup. Neonate did not show any congenital affection.

Follow-up echocardiography at sixth month showed relatively improved left ventricular systolic function with EF of 42%. For contraception, she was advised progesterone-only pill.

Discussion While the incidence of DCM (idiopathic and secondary) is observed to be 5-8 cases per 1,00,000 population per year,5 occurrence of idiopathic DCM during gestation is rare.2,4,6 Yacoub et al while reporting such case conducted a MEDLINE search from 1980 to 2000 and found only two pregnant cases with idiopathic or primary DCM.6 From 2001 to 2010, few authors shared their experience and total number of pregnancies reported were 48.5,7,8 Very limited supporting data are available for management guidelines during pregnancy.

Pregnancy outcome of 51 pregnancies showed increased rate of therapeutic abortions and maternal complications included pregnancy-induced hypertension, preterm labor, low birth weight, intrauterine death and ventricular tachycardia, arrhythmia, thromboembolism, infective endocarditis and heart failure, etc.

Grewal et al studied 36 pregnancies with DCM, which included 27 women with idiopathic DCM and observed cesarean deliveries in seven pregnancies for obstetric indications only; no operative interference was present for cardiac indications and preferred method of anesthesia was epidural.5 They observed poor neonatal outcome in women with severe DCM (moderate/ severe LV systolic dysfunction and NYHA functional Class III/IV) if concomitant obstetric risk factors were present.

The present case had severe left ventricular systolic dysfunction with EF of 32% (severe DCM) in first trimester. Adding to this, the presence of big fundal fibroid also increased the obstetric risk. The mode of

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case report delivery was cesarean section under graded epidural anesthesia for an obstetric indication not due to heart disease per se. Maternal morbidity included heart failure twice (33 weeks and immediate postpartum period), oligohydramnios and IUGR. We also concur with other authors regarding the fact that pregnancy is a major determinant for deterioration of DCM cases.5,9 Many have advised against conception with DCM and poor left ventricular systolic function with EF <30-50%.10 But, there is minimal evidence-based data to recommend it. Simultaneously repeated pregnancies should be discouraged in these patients.

Routine administration of anticoagulant is required throughout the pregnancy to avoid thromboembolism.

Though, the present case was managed successfully due to optimal obstetric, ICCU and NICU coordination, undertaking pregnancy in these woman is hazardous and becomes a cause of concern for the family and attending physicians. In our experience, counseling plays a vital role preconceptionally and antenatally.

Conclusion In DCM, prepregnant hemodynamically stable status, good left ventricular function may result in favorable outcome. To avoid such potentially fatal situations of severe DCM in pregnancy like ours, whenever an antenatal patient complains of effort intolerance, dyspnea and palpitation, ECG and Echo Doppler should ideally be recommended.

In a properly monitored environment pregnancy may be allowed to extend to term provided patient is clinically and hemodynamically stable. This is one of the rare case of severe DCM (severe left ventricular systolic dysfunction, EF [32%] and clinically NYHA

Class IV) with big fundal fibroid to have a successful pregnancy outcome at term.

References 1. Elliott P. Cardiomyopathy. Diagnosis and management of dilated cardiomyopathy. Heart 2000;84(1):106-12.

2. Mazor M, Levitas E, Gussarsky Y, Friedman S, Leiberman JR. Idiopathic dilated cardiomyopathy in pregnancy. Arch Gynecol Obstet 1994;255(1):51-3.

3. van Hoven KH, Kitsis RN, Katz SD, Factor SM. Peripartum versus idiopathic dilated cardiomyopathy in young women: a comparison of clinical, pathologic and prognostic features. Int J Cardiol 1993;40(1):57-65.

4. Oakley C, Child A, Jung B, Presbitero P, Tornos P, Klien W, et al. 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 2003;24(8):761-81.

5. Grewal J, Siu SC, Ross HJ, Mason J, Balint OH, Sermer M, et al. Pregnancy outcomes in women with dilated cardiomyopathy. J Am Coll Cardiol 2010;55:45-52.

6. Yacoub A, Martel MJ. Pregnancy with primary dilated cardiomyopathy. Obstet Gynecol 2002;99(5 Pt 2):928-30.

7. Berstein PS, Magriples U. Cardiomyopathy in pregnancy: a retrospective study. Am J Perinatol 2001;18(3):163-8.

8. Avila WS, Rossi EG, Ramires JA, Grinberg M, Bortolotto MR, Zugaib M, et al. Pregnancy in patients with heart disease: experience with 1,000 cases. Clin Cardiol 2003;26(3):135-42.

9. Chan F, Kee WD. Idiopathic dilated cardiomyopathy presenting in pregnancy. Can J Anaesth 1999;46(12): 1146-9.

10. Thorne SA, Nelson-Piercy C, MacGregor A, Gibbs S, Crowhurst J, Panay N, et al. Pregnancy and contraception in heart disease and pulmonary arterial hypertension.

J Fam Plann Reprod Health Care 2006;32(2):75-81.

Legal Question Q. I am a professor, Forensic Medicine and Toxicology (FMT), in a private medical college. On the complaint of the parents of a girl who left her home and married a boy, the police have registered a case under the Prohibition of Child Marriage Act, 2006. The girl, along with her father-in-law has approached me to give an opinion regarding her age. Can I give such opinion?

Ans. ÂÂ

If you are an expert and somebody wants your expert opinion, you are free to do so unless there is a legal impediment. The only legal impediment can be the administrative system/service rules applicable to you.

ÂÂ

It is advisable that you should ask the persons concerned to submit a written application addressed to your employer who should then form a board of experts to give the opinion. It would be upto him to include you in the board and to charge the fees for the services rendered and to remunerate the board members for the service provided as per the rules of the institution.

–MC Gupta

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medilaw

Insight on Medicolegal Issues Can allopathic cardiologist prescribe Ayurveda cardiac drugs?

Many drugs are available in the market, which have originated in the Ayurveda but have been prescribed

by Allopathic Doctors over the years. Ayurveda is the most ancient system of medicine around 5,000 years old and is based on the concept that the body has three humors namely ‘Vata, Pitta and Kapha’ which in the terminology of modern medicine represents ‘movement, metabolism and structure’. Sushruta, Father of Ayurveda, wrote about Ayurveda medicines and described the techniques of surgeries, which are even valid today. All other pathies probably came as an offshoot of Ayurveda later.

Naturopathy came as a science of balancing the five basic elements of nature namely space, air, fire, water and earth with respective therapies. It is now being practised without medicines as a lifestyle promotion pathy. Ayurveda uses traditional herbs (as a whole) as medicines based on their humor or tissue healing properties. As per Ayurveda, when plant is used as a whole, its side effects are countered by the effects of other ingredients present in the same herb.

Allopathy system came in the 18th century with extraction and identification of the ingredient in an herb having the beneficial effect on the body.

The extracted molecule is converted into a small tablet. Being highly concentrated and without the neutralizing properties of other ingredients this science became a branch with side effects and required special qualifications and training to practice. Allopathy research also required evaluation by way of investigations at a molecular level in the form of open or double-blind control trials.

Most Ayurveda drugs once researched in Allopathy are being marketed in the form of tablets and concentrated syrups as allopathic like drugs. Once the ingredients are known they are also manufactured using their chemical properties though chemical processes biotechnology and genetic engineering.

Homeopathy was another offshoot, which used alcohol preparations of either plants or the chemicals. It started with the use of low dilutions

and mother tinctures. Mother tincture means that there are detectable molecules in the preparation.

This preparation is no different from an ayurveda or allopathic medicine. High dilutions homeopathy originate later as a science where the matter was converted into nonmatter (only the energy is left) before use. It became a different science all together and different from Allopathy (nearest to vaccines concept).

Allopathy as a science also started a new system of documentation in the form of journals and online centralized Medline like systems. Once a research was published in indexed journals it became a part of the allopathy prescriptions. With the modern technology and research opportunities modern medicine became evidence based scientific science.

After getting training in modern Allopathy, it became possible for any doctor to prescribe any drug, which has been tested scientifically and for which evidence exists in the indexed journals.

For all other medicine for which literature did not exist, guidelines for “research protocols or drug trial protocols were made for their use in clinical practice”.

These concepts worked for centuries till two Supreme Court judgments created a controversy.

1. Firstly, the Poonam Verma case where a homeopath doctor was found negligent of treating a patient with PUO without investigating him and for using allopathic drugs for which he was not trained. In the order the Supreme Court did not talk about or prohibited allopathic doctors prescribing drugs from other systems of medicine which have been tested under Allopathy. The court gave a verdict and clarified that only those doctors can prescribe a particular drug who has read and whose science has scientifically tested the same medicine under use. It further said that Homeopaths cannot prescribe allopathic drugs.

2. In another landmark judgment of Mukhtiar Chand’s case, the Supreme Court said that Ayurvedic doctors cannot practice allopathic drug system.

In both the judgments, nowhere the courts observed that allopathic doctors cannot write or prescribe

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medilaw Ayurveda medicines. It only had given guidelines for Homeopathic or the Ayurveda doctors when it comes to writing allopathic medicines. Two subsequent Madras High Court Judgment talked about Unani doctors prescribing allopathic drugs.

There are also clear-cut guidelines regarding allopathic drugs use under the drugs and cosmetic acts. It restricts many drugs to be prescribed or dispensed only under medical supervision or to be dispensed only under single or double prescriptions of a registered allopathic medical practitioner.

These medicines in no way can be prescribed by practitioners other than those trained in the modern allopathic system of medicine.

No such directions “to be dispensed only on the prescription of an Ayurveda doctor” are written on Ayurveda drugs.

All Allopathy drugs where it is written “only on the prescription or supervision of a qualified or registered medical practitioner” cannot be prescribed by nonallopathic doctors or pharmacists. Similarly, those Ayurveda drugs or homeopathic medicines where it is written “only on the prescription of an Ayurveda or homeopathic doctor, respectively” cannot be prescribed by doctors from modern system of medicine.

Poonam Verma: Supreme Court Verdict In Poonam Verma’s case (1996, 4 SCC 332) a Homeopathic Doctor Ashwin Patel, treated Pramod Verma by strong Allopathic drugs initially for viral and later for typhoid. After a week of treatment when the condition of Pramod became very serious, Dr Patel transferred him to Hinduja Hospital in an unconscious state where, after about four and half hours of admission, he died. Poonam, wife of the deceased, thereafter filed a petition complaining of negligence on the part of Dr Patel. It was noted by the Supreme Court: 1. That Dr Patel was not qualified in Allopathy and that he was not authorized to practice Allopathic medicine or prescribe Allopathic drugs.

2. That this lack of expertise in the allopathic system of medicines was responsible for the kind of treatment administered by him and resultant death of the patient.

3. That “a person registered under the Bombay Homeopathic Practitioners’ Act, 1959 can practice Homeopathy only. He cannot be registered under the Indian Medical Council Act, 1956 or under

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4.

5.

6.

7.

the State Act, namely, the Maharashtra Medical Council Act, 1965”.

That “a person possessing the qualification mentioned in the schedule appended to the Indian Medical Council Act, 1956, or the Maharashtra Medical Council Act, 1965 cannot be registered as a medical practitioner under the Bombay Homeopathic Practitioners’ Act, 1959 as he does not possess any qualification in Homeopathic system of medicine”.

That “a person having studied one particular system of medicine cannot possibly claim deep and complete knowledge about the drugs of the other system of medicine”.

That “the bane of Allopathic medicine is that it always has a side effect. A warning to this effect is printed on the trade label for the use of the person (doctor) having studied that system of medicine”.

That since Dr Patel was registered as a ‘medical practitioner, he was required to practice in Homeopathy only and was under a statutory duty not to enter the field of any other system of medicine as, admittedly, he was not qualified in the other system, Allopathy, to be precise. This conduct amounted to an actionable negligence”.

8. That “a person who does not have knowledge of a particular system of medicine but practices in that system is a quack and a mere pretender to medical knowledge or skill, or to put it differently, a charlatan”.

It is clear that what has been laid down by the Supreme Court is that unless a doctor possesses adequate knowledge and training in regard to certain drugs, he is not competent to prescribe those drugs because he may-not have sufficient knowledge about those drugs particularly about the adverse effects, etc., to be able to safely prescribe those drugs.

However, the court has, not treated different systems of medicines as being different compartments with no overlapping.

Even though, a particular drug might have had its origin in Ayurveda, there might have been sufficient studies in the allopathic system about those drugs and literature might be available in the allopathic medical journals about these drugs. In such cases enough evidences would be deemed to have been assimilated in the system of modern medicine and the allopathic doctors would be clearly entitled to prescribe those drugs.

Ayurveda system of medicine is more than 5,000 years old. Most medicines invariably have its origin

medilaw Table 1. Some of the Medications with Plant Origins Drug

Common name of herb

Latin name

Atropine

Belladonna

Atropa belladonna

Codeine

Poppy

Papaver somniferum

Colchicine

Autumn crocus

Colchicum autumnale

Digoxin

Foxglove

Digitalis purpurea

Ephedrine

Ephedra

Ephedra sinica

Reserpine

Rauwolfia

Rauwolfia serpentina

Salicylic acid

Willow bark

Salix purpurea

Scopolamine

Jimson weed

Datura stramonium

Taxol

Pacific yew

Taxus brevifolia

Vincristine

Madagascar periwinkle

Catharanthus roseus

from the Ayurveda system. The modern allopathic system was developed in the 18th century only. It has been revalidating all the earlier excising drugs with its own methodology and once done has been reintroducing them as allopathic drugs. Most of the procedures and drugs used for centuries in traditional systems of medicine today have been assimilated into the allopathic system of medicine. Examples of conventional medications with plant origins are given in Table 1.

The drugs in the allopathic system of medicine come into use after they have been studied and the reports of these studies are published in recognized allopathic medical journals. An allopathic doctor gets knowledge about these drugs from, the available literature.

It is not merely new drugs which comprise of modern medicines, but even old drugs which were known long before the modern system of medicines evolved are also being developed and refined and made use of in the modem system of medicine.

Any drug even though its origin might have been Ayurveda or Unani or other system of medicines, if it has been sufficiently studied by the modern allopathic system of medicine and literature exists in the indexed medical journals about these drugs, such drugs would be deemed to have been assimilated in the allopathic system of medicines also.

The Allopathic Doctors are fully entitled to prescribe any of the drugs of which they have sufficient knowledge from the literature relating to these drugs available in the allopathic medical literature including various medical journals of allopathic medicines.

If a drug, even though of Ayurveda origin, has been tested and clinical trials have been performed on that drug by allopathic doctors and the reports of these trials are published in indexed medical journals automatically become a part of modem allopathic medicines. For those drugs, for which allopathic literature do not exist, there are clear cut research protocols cum methodologies and drug trials protocols. One should follow them in the right spirit. They can be very well-prescribed as a part of the trial or research protocol. It is absurd for anybody to speculate that, merely because the origin of a drug was in an ancient system of medicine, it is not legally permissible for allopathic doctors to prescribe that drug.

The only thing the court said was that Dr Patel was not competent in prescribing allopathic medicines. It did not speak anything about the allopathic doctors prescribing Ayurveda medicines. The judgment in the case of Poonam Verma was a case of medical negligence and not a case of cross prescriptions? It is contended that, there is no ban as such upon the allopathic medical practitioners in adhering to cross prescription.

In my opinion the answer is very simple. Check the ingredients and if there are references in medline about them it means that these molecules have been tested the allopathic way.

In any way an allopathic doctor is free to prescribe any drug under consent. In Supreme Court of India Judgment Martin F. D’Souza vs Mohd Ishfaq (3541 of 2002) dated 17.02.2009 Justice Markandey Katju and GS Singhvi write that “54(d): A doctor should not experiment unless necessary and even then he should ordinarily get a written consent from the patient”.

Also under a research project, covering the ICMR guidelines one is free to prescribe Ayurveda drugs.

MCI Act (6.5) under Secret Remedies clarifies it further. “The prescribing or dispensing by a physician of secret remedial agents of which he does not know the composition, or the manufacture or promotion of their use is unethical and as such prohibited. All the drugs prescribed by a physician should always carry a proprietary formula and clear name”. This clause further strengthens the Poonam Verma case mentioned above. As long as you know the ingredients and their action you can prescribe them.

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around the globe

News and Views Hba1c Measures Higher In South Asians Than White Europeans Three measures of blood sugar - glycated hemoglobin (HbA1C) levels, fasting plasma glucose (FPG) and 2-hour β-plasma glucose (2hrPG) - were higher on average in South Asians than white Europeans regardless of other factors associated with glycemic control, according to results from a new study published online June 14 and in the August print issue of Diabetes Care. (Source: Medscape) ICD Outcomes Tied to Cardiac Muscle Scarring A significant amount of magnetic resonance imaging (MRI)-detected scarring in the myocardium is predictive of a poor prognosis in patients with an implantable cardioverter defibrillator (ICD) no matter the left ventricular ejection fraction (LVEF), according to a study in the July 31 issue of the Journal of the American College of Cardiology.

USPSTF Updates Guidelines on Healthy Lifestyle for CVD Prevention The most common cause of death is cardiovascular disease (CVD). Cardiovascular morbidity and mortality rates are lower in adults who adhere to a healthy diet, according to Dietary Guidelines for Americans, 2010, and follow physical activity guidelines, according to the 2008 Physical Activity Guidelines for Americans.

In adults, medium- and high-intensity counseling is linked with reduced intakes of salt, energy, and fats; an increased intake of fruits and vegetables; increased physical activity; decreased body mass index (BMI); decreased total cholesterol and low-density lipoprotein cholesterol levels and decreased blood pressure. The USPSTF finds a small net benefit of medium- and highintensity behavioral counseling in the primary care setting to promote a healthy diet and physical activity in adults without CVD, hypertension, hyperlipidemia or diabetes, given the low risk for adverse events.

Try Flute Yoga To Beat Stress The humble flute, which in Hindu mythology was played by Lord Krishna to charm the maidens, birds

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and animals of Vrindavan and Mathura, is leading a new healing therapy called Bansi Yoga to beat lifestyle stress. Bansi Yoga, created by the S. Vyasa Yoga University using a combination of traditional yoga, breathing exercises and flute melody, will get the official stamp of approval in the capital at the third World Flute Festival, “Raasrang 2012”, Aug. 9-12. The festival will be presented by the Ministry of Culture and the Krishna Prerna Foundation with support from flute maestro Hariprasad Chaurasia.

A team of experts will demonstrate the yoga and discuss its healing powers in 12 workshops over four days at Hotel Ashok in the capital, Arun Buddhiraja, the founder of the Krishna Prerna Foundation, said. “Bansi Yoga is a combination of yoga and flute used as a deep relaxation technique in 40 minutes of cyclic meditations.

The practitioner moves his limbs in a cyclic pattern and the flute, played as an accompaniment, allows him to relax. The relaxation induced is equivalent to eight hours of sleep,” Buddhiraja told IANS. The flute was a symbol of love, peace and water, he said.

Explaining the dynamics of the Bansi Yoga, Buddhiraja said in some postures, the practitioner stands straight with his hands alongside at right angles. The practitioner then moves his hand in a cyclic manner to the music of the flute. The cyclic motion fans from the hand to the fingers and to the shoulders. The meditation is followed by chanting of the words Ukara, Akara, Makara (u, aa, maa) - the essence of the word Omkara to create magnetic sound resonance in the body, Buddhiraja said. “It is a physiological and psychological clean-up,” he said. The Bansi Yoga courses are designed for two groups of people - corporate executives and the common people. (Source: The Pioneer, 21 July 2012) USPSTF: Still No ECG Screens for Low-Risk Adults The US Preventive Services Task Force continues to recommend against using electrocardiography (ECG) to screen asymptomatic adults at low-risk for coronary heart disease. The recommendation, published online in the Annals of Internal Medicine, is consistent with the task force’s 2004 guidance and is based on a update of a review published last September that showed a lack of evidence supporting a reduction in coronary heart

around the globe disease events from screening a low-risk population.

The guidance applies to men and women who do not have any symptoms and have not received a diagnosis of cardiovascular disease. (Source: Medpage Today) Obstructive Sleep Apnea Linked to Diabetic Neuropathy In adults with type 2 diabetes, the prevalence of obstructive sleep apnea (OSA) is 65%.

In adults with type 2 diabetes, the prevalence of neuropathy is higher in those with OSA versus those without OSA (60% vs 27%; OR, 2.82), even after adjustment for confounders. (May 2000 issue of Diabetes Care) Squeezing A Guide To Resynch Targets Out Of CT And ECG Data Computed tomography (CT), used in conjunction with ECG imaging (ECGI), may soon be used to guide the placement of leads for cardiac resynchronization therapy (CRT). At the Society of Cardiovascular Computed Tomography (SCCT) 2012 Annual Scientific Meeting, Dr Fady Dawoud (Johns Hopkins University, Baltimore) presented promising results of an animal study showing that CT and ECGI information can be translated into a map that not only helps to identify the best candidates for CRT therapy but can also guide CRT lead placement. (Source: Medscape) Evidence for TAVI questioned The tens of thousands of transcatheter aortic valve implantations (TAVI) performed worldwide may not have solid evidence behind them, European researchers suggested. (Source: Medpage Today) Radial PCI May Be Best Bet For ACS Patients Among patients undergoing primary percutaneous coronary intervention (PCI) for an ST-segment elevation acute coronary syndrome, transradial access provided better outcomes than transfemoral access, a randomized trial showed. (Source: Medpage Today) Trauma Patients At Risk For Hypothermia Trauma-associated hypothermia evolves from a combination of injury severity and potentially modifiable environmental and treatment-related factors, French investigators reported. Higher Revised Trauma Score (RTS) increased the odds of hypothermia by almost 70%. Intubation, lower temperature inside the transport vehicle, and lower infusion fluid temperature

also increased the risk. The risk declined significantly if patients were clothed and did not have a head injury, as reported online in Critical Care. (Source: Medpage Today) Infusion Pumps Recalled The FDA has issued a Class I recall of two infusion pumps because of potentially fatal product errors.

In one recall, the CareFusion Alaris PC Unit Model 8015’s power supply board issues a “system error” or “missing battery error” alert, which is accompanied by an audible alarm and visual message, due to a malfunctioning component. In the second recall, the B. Braun Infusomat Space Infusion System’s anti-free flow clip catch may break if an infusion is improperly inserted into the pump and the door is forced closed.

Without the clip, a free flow of medication may occur, which can cause potentially life-threatening injury.

(Source: Medpage Today) Endovascular Therapy Improves Outcomes of Internal Carotid Artery Occlusion In patients with stroke from internal carotid artery (ICA) occlusion, adding endovascular intra-arterial therapy to IV thrombolysis can lead to better outcomes, a new analysis shows. (Source: Medscape) Radial Access Better In Acute Coronary Syndrome In patients with ST-segment elevation acute coronary syndrome, outcomes are better with early procedures that use transradial instead transfemoral access, say European researchers. In an August 1 paper in the Journal of the American College of Cardiology, Dr. Enrico Romagnoli of Policlinico Casilino, Rome and colleagues note that in these patients “access site complications still represent a significant source of bleeding, especially when femoral access is used.” (Source: Medscape) Curcumin Capsules Found To Curb Diabetes Risk Supplements containing curcumin, a compound in the curry spice turmeric, may help prevent diabetes in people at high risk, a small clinical trial suggests.

Lab research has suggested curcumin can fight inflammation and oxidative damage to body cells. The new study, published July 6 in Diabetes Care, included 240 Thai adults with prediabetes who were randomly assigned to take either curcumin capsules or a placebo.

In the intervention group, people took six supplement capsules per day, each of which contained 250 mg of curcuminoids. (Source: Medscape) Indian Journal of Clinical Practice, Vol. 23, No. 8 January 2013

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lighter reading

One day the king and his friend were out on a hunting expedition. The friend would load and prepare the guns for the king. The friend had apparently done something wrong in preparing one of the guns, for after taking the gun from his friend, the king fired it and his thumb was blown off.

Examining the situation the friend remarked as usual, ‘This is good!’ To which the king replied, ‘No, this is NOT good!’ and proceeded to send his friend to jail.

About a year later, the king was hunting in an area that he should have known to stay clear of. Cannibals captured him and took them to their village. They tied his hands, stacked some wood, set up a stake and bound him to the stake. As they came near to set fire to the wood, they noticed that the king was missing a thumb. Being superstitious, they never ate anyone that was less than whole. So untying the king, they sent him on his way.

As he returned home, he was reminded of the event that had taken his thumb and felt remorse for his treatment of his friend. He went immediately to the jail to speak with his friend. ‘You were right,’ he said, “it was good that my thumb was blown off.” And he proceeded to tell the friend all that had just happened.

“And so I am very sorry for sending you to jail for so long. It was bad for me to do this.” ‘No,’ his friend replied, ‘This is good!’ “What do you mean, ‘This is good’? How could it be good that I sent my friend to jail for a year?” “If I had NOT been in jail, I would have been with you.”

Situations may not always seem pleasant while we are in them, but the promise of God is clear. If we love Him and live our lives according to His precepts, even that which seems to be bleak and hopeless will be turned by God for His glory and our benefit. Hold on, God is faithful! May God bless you this week as you seek His will in every situation. −Ms. Ritu Sinha

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−Dr GM Singh

Classroom Psychology – Final Exam

Laugh a While

The story is told of a king in Africa who had a close friend with whom he grew up. The friend had a habit of looking at every situation that ever occurred in his life (positive or negative) and remarking, ‘This is good!’

“God grant me the serenity to accept the things I cannot change, the courage to change the things I can, and the wisdom to know the difference.

Serenity Prayer.”

A psychology professor at the University of Miami knew his students expected a terrifyingly long final exam. To play with their minds a little (what do you expect from a psychology professor?) he only put ONE question on the final exam. He watched the reactions of the students as they all opened the exams and saw the one question. Initially, they all looked relieved, but as the difficulty of the question began to sink in, those relieved faces sagged to confusion and consternation. All, that is, except for one student. He read the question, tapped his pencil into his palm a few times, then jotted something down on the test paper. He walked upto the professor, handed him the final, and walked out. The professor blinked in surprise, looked at what the student wrote, and smiled. The professor wrote ‘100%’ on the top of that student’s test.

The Question: What is courage? The Student’s Answer: This is.

−Dr GM Singh

Make Sure

During Medical Practice A patient of suspected MI died after receiving sublingual nitrate.

Oh my God! Why was a history of intake of Viagra drug not taken?

©IJCP Academy

This is Good!

Quote

An Inspirational Story

Lighter Side of Medicine

Make sure to take a history of Viagra drug intake before giving nitrates, because the two drugs coadministered can cause a fatal fall in blood pressure.

KK Aggarwal

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Q. J. Expt. Physiol. 1955;40:89-111.

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Books

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

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