Ijcp oct 2015

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Volume 26, Number 5

October 2015, Pages 401–500

Peer Reviewed Journal

yy American Family Physician yy Anesthesiology yy Community Medicine yy Dentistry yy Dermatology yy ENT yy Gastroenterology yy Internal Medicine yy Obstetrics and Gynecology

an i c i ys ians

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Fademy of F n ica Aca

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yy Around the Globe

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

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

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

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

Volume 26, Number 5, October 2015 FROM THE DESK OF THE GROUP EDITOR-IN-CHIEF

406 Harvard’s Medical School’s 4 Exercising Tips for People with Diabetes

KK Aggarwal

AMERICAN FAMILY PHYSICIAN

407 Diagnosis and Management of Generalized Anxiety Disorder and Panic Disorder in Adults

Amy B. Locke, Nell Kirst, Cameron G. Shultz

415 Practice Guidelines 417 Photo Quiz ANESTHESIOLOGY

420 Continuous Spinal Anesthesia in Geriatric Orthopedic Surgeries

Sudivya Sharma, Susheela Taxak, Nikita Jain

COMMUNITY MEDICINE

424 Satisfaction Levels and Recommendation Intentions of Healthcare Consumers: An Exploratory Study Based on Multispecialty Hospitals in North India

Vishal Kamra, Harjot Singh, Kalyan Kumar De

430 A Survey of Public Awareness About Voluntary Body Donation

Shalini Chaudhary, Sarvesh, APS Batra

435 The Rise in Incidence of the Enterococcus: Beyond Vancomycin Resistance: A Review

Deepak Arora, Narinder Kaur

443 Evaluation of Hand Hygiene Practice: Role in Prevention of Infection

Deepak Arora, MK Mahajan

DENTISTRY

447 Desquamative Gingivitis: A Clinician’s Nightmare

Swapan Kumar Purkait, Utpal Mukhopadhyay, Sumanta Kumar Koley, Maitreyi Guha

DERMATOLOGY

454 Study of the Clinico-Epidemiological Pattern and the Precipitating Factors in 100 Melasma Patients in an Urban Town

Pradip Kumar Das, Debjit Panja

ENT

459 Tonsil Schwannoma Presenting as a Tonsillar Cyst: A Rare Case

Saurabh Varshney, Ravi Meher

GASTROENTEROLOGY

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

461 Spectrum of Lesions of Liver in Autopsy in India: One Year Study

Amar Ranjan, Divya Sethi

INTERNAL MEDICINE

464 Dengue Myopericarditis: A Rare Complication of Dengue Fever

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

Pooja Shashidharan, Manish Pangi

OBSTETRICS AND GYNECOLOGY

Copyright 2015 IJCP Publications Ltd. All rights reserved.

468 Interstitial Brachytherapy Using Martinez Universal Perineal Interstitial Template in Locally Advanced Gynecological Malignancies

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.

Meena J Shah, Rakesh K Vyas

PEDIATRICS

473 Managing Iron Deficiency: New Approaches

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.

Dipangkar Hazarika

RESPIRATORY INFECTIONS

477 To Evaluate the Compliance with ICS/NCCP Guidelines in the Management of Community-acquired Pneumonia in a North Indian Tertiary Care Hospital

Payal Preet, Harinder Singh, Vijay K Sehgal, Vishal Chopra

SURGERY

484 What Gravity, Genetics and Smoking, Together can Achieve

Somendra Mohan Sharma

DIAGNOSTICS

486 Dengue Diagnostics for Clinicians MEDILAW

490 Fundamental Rights of Patients and the Consumer Protection Act

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.

KK Aggarwal

AROUND THE GLOBE

493 News and Views LIGHTER READING

495 Lighter Side of Medicine

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FROM THE DESK OF THE GROUP EDITOR-IN-CHIEF

Prof. Dr KK Aggarwal

Group Editor-in-Chief IJCP Group and eMedinewS

Harvard’s Medical School’s 4 Exercising Tips for People with Diabetes 1. Get a "preflight" check Talk with your doctor before you start or change a fitness routine, especially if you are overweight or have a history of heart disease, peripheral vascular disease or diabetic neuropathy.

Go for a complete physical exam and an exercise stress test if you are 35 or older and you have had diabetes for more than 10 years. The results can help determine the safest way for you to increase physical activity.

2. Spread your activity throughout the week Adults should aim for a weekly total of at least 160 minutes of moderate aerobic activity, or 80 minutes of vigorous activity or an equivalent mix of the two.

Be active at least 3-5 days a week.

3. Time your exercise wisely The best time to exercise is 1-3 hours after eating, when your blood sugar level is likely to be higher.

If you use insulin, it’s important to test your blood sugar before exercising. If it is below 100 mg/dL, eat a piece of fruit or have a small snack to boost it and help you avoid hypoglycemia. Test again 30 minutes later to see if your blood sugar level is stable.

Check your blood sugar after any particularly grueling workout or activity.

If you use insulin, your risk of developing hypoglycemia may be highest 6-12 hours after exercising.

Do not exercise if your blood sugar is too high (over 250).

4. Be prepared Should you experience a medical problem while exercising (or at any time) it is important that the people who care for you know that you have diabetes.

Keep card handy or glucose tablets with you while exercising in case your blood sugar takes a sudden nosedive.

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AMERICAN FAMILY PHYSICIAN

Diagnosis and Management of Generalized Anxiety Disorder and Panic Disorder in Adults AMY B. LOCKE, NELL KIRST, CAMERON G. SHULTZ

ABSTRACT Generalized anxiety disorder (GAD) and panic disorder (PD) are among the most common mental disorders in the United States, and they can negatively impact a patient’s quality of life and disrupt important activities of daily living. Evidence suggests that the rates of missed diagnoses and misdiagnosis of GAD and PD are high, with symptoms often ascribed to physical causes.

Diagnosing GAD and PD requires a broad differential and caution to identify confounding variables and comorbid conditions.

Screening and monitoring tools can be used to help make the diagnosis and monitor response to therapy. The GAD-7 and the Severity Measure for Panic Disorder are free diagnostic tools. Successful outcomes may require a combination of treatment modalities tailored to the individual patient. Treatment often includes medications such as selective serotonin reuptake inhibitors and/or psychotherapy, both of which are highly effective. Among psychotherapeutic treatments, cognitive behavior therapy has been studied widely and has an extensive evidence base. Benzodiazepines are effective in reducing anxiety symptoms, but their use is limited by risk of abuse and adverse effect profiles. Physical activity can reduce symptoms of GAD and PD. A number of complementary and alternative treatments are often used; however, evidence is limited for most. Several common botanicals and supplements can potentiate serotonin syndrome when used in combination with antidepressants. Medication should be continued for 12 months before tapering to prevent relapse.

Keywords: Generalized anxiety disorder, panic disorder, screening and monitoring tools, GAD-7, Severity Measure for Panic Disorder, benzodiazepines

G

eneralized anxiety disorder (GAD) and panic disorder (PD) are among the most common mental disorders in the United States and are often encountered by primary care physicians. The hallmark of GAD is excessive, out-of-control worry, and PD is characterized by recurrent and unexpected panic attacks. Both conditions can negatively impact a patient’s quality of life and disrupt important activities of daily living. The rates of missed diagnoses and misdiagnosis of GAD and PD are high, with symptoms often ascribed to physical causes. This article reviews the diagnosis and management of GAD and PD in adults. Diagnosis and care of children and adolescents with these conditions require special considerations that are beyond the scope of this review.

EPIDEMIOLOGY, ETIOLOGY, AND PATHOPHYSIOLOGY

AMY B. LOCKE, MD, FAAFP, is director of the Integrative Medicine Fellowship and an assistant professor in the Department of Family Medicine at the University of Michigan Medical School in Ann Arbor.

NELL KIRST, MD, is assistant residency director of the Family Medicine Residency Program at the University of Michigan Medical School.

CAMERON G. SHULTZ, PhD, MSW, is director of scholarly projects in the Department of Family Medicine at the University of Michigan Medical School.

Source: Adapted from Am Fam Physician. 2015;91(9):617-624.

The etiology of PD is also not well understood. The neuroanatomical hypothesis suggests that a geneticenvironment interaction is likely responsible. Patients with PD may exhibit irregularities in specific brain structures, altered neuronal processes, and dysfunctional corticolimbic interaction during emotional processing.4

The 12-month prevalence for GAD and PD among U.S. adults 18 to 64 years of age is 2.9% and 3.1%, respectively. In this population, the lifetime prevalence is 7.7% in women and 4.6% in men for GAD, and is 7.0% in women and 3.3% in men for PD.1 The etiology of GAD is not well understood. There are several theoretical models, each with varying degrees of empirical support. An underlying theme to several models is the dysregulation of worry.

Emerging evidence suggests that patients with GAD may experience persistent activation of areas of the brain associated with mental activity and introspective thinking following worry-inducing stimuli.2 Twin studies suggest that environmental and genetic factors are likely involved.3

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AMERICAN FAMILY PHYSICIAN TYPICAL PRESENTATION AND DIAGNOSTIC CRITERIA

Generalized Anxiety Disorder Patients with GAD typically present with excessive anxiety about ordinary, day-to-day situations. The anxiety is intrusive, causes distress or functional impairment, and often encompasses multiple domains (e.g., finances, work, health). The anxiety is often associated with physical symptoms, such as sleep disturbance, restlessness, muscle tension, Table 1. Diagnostic Criteria for Generalized Anxiety Disorder A. Excessive anxiety and worry (apprehensive expectation), occurring more days than not for at least 6 months, about a number of events or activities (such as work or school performance).

B. The individual finds it difficult to control the worry.

C. The anxiety and worry are associated with three (or more) of the following six symptoms (with at least some symptoms having been present for more days than not for the past 6 months): Note: Only one item is required in children.

1. Restlessness or feeling keyed up or on edge.

2. Being easily fatigued.

3. Difficulty concentrating or mind going blank.

4. Irritability.

5. Muscle tension.

6. Sleep disturbance (difficulty falling or staying asleep, or restless, unsatisfying sleep).

D. The anxiety, worry, or physical symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

E. The disturbance is not attributable to the physiological effects of a substance (e.g., a drug of abuse, a medication) or another medical condition (e.g., hyperthyroidism).

gastrointestinal symptoms, and chronic headaches.5 Diagnostic and Statistical Manual of Mental Disorders, 5th ed, (DSM-5) diagnostic criteria for GAD are listed in Table 1.5 Some factors associated with GAD include female sex, unmarried status, lower education level, poor health, and presence of life stressors.6 The age of onset is variable, with a median age of 30 years.1 A number of scales are available to establish diagnosis and assess severity. The GAD-7 (Table 27) has been validated as a diagnostic tool and a severity assessment scale, with a score of 10 or more having good diagnostic sensitivity and specificity.8 Greater GAD-7 scores Table 2. GAD-7 Screening Tool Over the last 2 weeks, how often have you been bothered by the following problems?

Not at all

Several days

More than half the days

Nearly every day

(Use “” to indicate your answer) 0

1

2

3

2. Not being able 0 to stop or control worrying

1

2

3

3. Worrying too much about different things

0

1

2

3

4. Trouble relaxing 0

1

2

3

5. Being so 0 restless that it is hard to sit still

1

2

3

6. Becoming easily annoyed or irritable

0

1

2

3

7. Feeling afraid as if something awful might happen

0

1

2

3

Total score____

=_____ +_____

+_____

+_____

1. Feeling nervous, anxious, or on edge

F. The disturbance is not better explained by another mental disorder (e.g., anxiety or worry about having panic attacks in panic disorder, negative evaluation in social anxiety disorder [social phobia], contamination or other obsessions in obsessive-compulsive disorder, separation from attachment figures in separation anxiety disorder, reminders of traumatic events in posttraumatic stress disorder, gaining weight in anorexia nervosa, physical complaints in somatic symptom disorder, perceived appearance flaws in body dysmorphic disorder, having a serious illness in illness anxiety disorder, or the content of delusional beliefs in schizophrenia or delusional disorder).

Note: Total score for the 7 items ranges from 0 to 21. Scores of 5, 10, and 15 represent cutoffs for mild, moderate, and severe anxiety, respectively. Although designed primarily as a screening and severity measure for GAD, the GAD-7 also has moderately good operating characteristics for panic disorder, social anxiety disorder, and posttraumatic stress disorder. When screening for anxiety disorders, a recommended cutoff for further evaluation is a score of 10 or greater.

Reprinted with permission from the American Psychiatric Association.

Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Washington, DC: American Psychiatric Association; 2013:222.

Reprinted from Spitzer RL, Williams JB, Kroenke K, et al., with an educational grant from Pfizer Inc. Patient health questionnaire (PHQ) screeners. http://www.phqscreeners. com/overview.aspx?Screener=03_GAD-7. Accessed July 22, 2014.

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GAD = generalized anxiety disorder.

AMERICAN FAMILY PHYSICIAN correlate with more functional impairment.8 The scale was developed and validated based on DSM-IV criteria, but it remains clinically useful after publication of the DSM-5 because the differences in GAD diagnostic criteria are minimal. The PROMIS Emotional Distress– Anxiety–Short Form for adults and the Severity Measure for Generalized Anxiety Disorder–Adult, available from the American Psychiatric Association at http://www. psychiatry.org/practice/dsm/dsm5/online-assessmentmeasures, are intended to aid clinical evaluation of GAD and monitor treatment effectiveness.

Panic Disorder PD is characterized by episodic, unexpected panic attacks that occur without a clear trigger.5 Panic attacks are defined by the rapid onset of intense fear (typically peaking within about 10 minutes) with at least four of the physical and psychological symptoms in the DSM-5 diagnostic criteria (Table 3).5 Another requirement for the diagnosis of PD is that the patient worries about further attacks or modifies his or her behavior in maladaptive ways to avoid them. The most common physical symptom accompanying panic attacks is palpitations.9 Although unexpected panic attacks are required for the diagnosis, many patients with PD also have expected panic attacks, occurring in response to a known trigger.9 The Severity Measure for Panic Disorder–Adult (http://www.psychiatry.org/ File%20Library/Practice/DSM/DSM-5/SeverityMeasure ForPanicDisorderAdult.pdf) is an assessment scale that can complement the clinical assessment of patients with PD. DIFFERENTIAL DIAGNOSIS AND COMORBIDITY When evaluating a patient for a suspected anxiety disorder, it is important to exclude medical conditions with similar presentations (e.g., endocrine conditions such as hyperthyroidism, pheochromocytoma, or hyperparathyroidism; cardiopulmonary conditions such as arrhythmia or obstructive pulmonary diseases; neurologic diseases such as temporal lobe epilepsy or transient ischemic attacks). Other psychiatric disorders (e.g., other anxiety disorders, major depressive disorder, bipolar disorder); use of substances such as caffeine, albuterol, levothyroxine, or decongestants; or substance withdrawal may also present with similar symptoms and should be ruled out.5 Complicating the diagnosis of GAD and PD is that many conditions in the differential diagnosis are also common comorbidities. Additionally, many patients with GAD or PD meet criteria for other psychiatric disorders, including major depressive

Table 3. Diagnostic Criteria for Panic Disorder A. Recurrent unexpected panic attacks. A panic attack is an abrupt surge of intense fear or intense discomfort that reaches a peak within minutes, and during which time four (or more) of the following symptoms occur: Note: The abrupt surge can occur from a calm state or an anxious state.

1. Palpitations, pounding heart, or accelerated heart rate.

2. Sweating.

3. Trembling or shaking.

4. Sensations of shortness of breath or smothering.

5. Feelings of choking.

6. Chest pain or discomfort.

7. Nausea or abdominal distress.

8. Feeling dizzy, unsteady, light-headed, or faint.

9. Chills or heat sensations.

10. Paresthesias (numbness or tingling sensations).

11. Derealization (feelings of unreality) or depersonalization (being detached from oneself).

12. Fear of losing control or “going crazy.”

13. Fear of dying.

Note: Culture-specific symptoms (e.g., tinnitus, neck soreness, headache, uncontrollable screaming or crying) may be seen. Such symptoms should not count as one of the four required symptoms.

B. At least one of the attacks has been followed by 1 month (or more) of one or both of the following: 1. Persistent concern or worry about additional panic attacks or their consequences (e.g., losing control, having a heart attack, “going crazy”).

2. A significant maladaptive change in behavior related to the attacks (e.g., behaviors designed to avoid having panic attacks, such as avoidance of exercise or unfamiliar situations).

C. The disturbance is not attributable to the physiological effects of a substance (e.g., a drug of abuse, a medication) or another medical condition (e.g., hyperthyroidism, cardiopulmonary disorders).

D. The disturbance is not better explained by another mental disorder (e.g., the panic attacks do not occur only in response to feared social situations, as in social anxiety disorder; in response to circumscribed phobic objects or situations, as in specific phobia; in response to obsessions, as in obsessive-compulsive disorder; in response to reminders of traumatic events, as in posttraumatic stress disorder; or in response to separation from attachment figures, as in separation anxiety disorder).

Reprinted with permission from the American Psychiatric Association.

Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Washington, DC: American Psychiatric Association; 2013:208-209.

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AMERICAN FAMILY PHYSICIAN disorder and social phobia. Evidence suggests that GAD and PD usually occur with at least one other psychiatric disorder, such as mood, anxiety, or substance use disorders.10 When anxiety disorders occur with other conditions, historic, physical, and laboratory findings may be helpful in distinguishing each diagnosis and developing appropriate treatment plans.

TREATMENT Some studies evaluating anxiety treatments assess nonspecific anxiety-related symptoms rather than the set of symptoms that characterize GAD or PD. When possible, the treatments described in this section will differentiate between GAD and PD; otherwise, treatments refer to anxiety-related symptoms in general.

Medication or psychotherapy is a reasonable initial treatment option for GAD and PD.11 Some studies suggest that combining medication and psychotherapy may be more effective for patients with moderate to severe symptoms.12 The National Institute for Health and Care Excellence (NICE) guidelines on GAD and PD in adults are a useful review of available evidence; however, information about self-help and group therapies may have less utility in the United States because of their relative lack of availability.11

Education Compassionate listening and education are an important foundation in the treatment of anxiety disorders.11 Patient education itself can help reduce anxiety, particularly in PD.13 The establishment of a therapeutic alliance between the patient and physician is important to allay fears of interventions and to progress toward treatment.

Common lifestyle recommendations that may reduce anxiety-related symptoms include identifying and removing possible triggers (e.g., caffeine, stimulants, nicotine, dietary triggers, stress), and improving sleep quality/quantity and physical activity.

Caffeine can trigger PD and other types of anxiety. Those with PD may be more sensitive to caffeine than the general population because of genetic polymorphisms in adenosine receptors.14 Smoking cessation leads to improved anxiety scores, with relapse leading to increased anxiety. Many studies show an association between disordered sleep and anxiety, but causality is unclear.15 In addition to decreased depression and anxiety, physical activity is associated with improved physical health, life satisfaction, cognitive functioning, and psychological well-being. Physical activity is a

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cost-effective approach in the treatment of GAD and PD.16,17 Exercising at 60% to 90% of maximal heart rate for 20 minutes three times weekly has been shown to decrease anxiety16; yoga is also effective.18

Medication First-Line Therapies. A number of medications are available for treating anxiety (Table 4). Selective serotonin reuptake inhibitors (SSRIs) are generally considered first-line therapy for GAD and PD.19-22 Tricyclic antidepressants (TCAs) are better studied for PD, but are thought to be effective for both GAD and PD.19,20 In the treatment of PD, TCAs are as effective as SSRIs, but adverse effects may limit the use of TCAs in some patients.23 Venlafaxine, extended release, is effective and well tolerated for GAD and PD, whereas duloxetine has been adequately evaluated only for GAD.24 Azapirones, such as buspirone, are better than placebo for GAD25 but do not appear to be effective for PD.26 Mixed evidence suggests bupropion may have anxiogenic effects for some patients, thus warranting close monitoring if used for treatment of comorbid depression, seasonal affective disorder, or smoking cessation.27 Bupropion is not approved for the treatment of GAD or PD. Medications should be titrated slowly to decrease the initial activation. Because of the typical delay in onset of action, medications should not be considered ineffective until they are titrated to the high end of the dose range and continued for at least four weeks. Once symptoms have improved, medications should be used for 12 months before tapering to limit relapse.11 Some patients will require longer treatment.

Benzodiazepines are effective in reducing anxiety, but there is a dose-response relationship associated with tolerance, sedation, confusion, and increased mortality.28 When used in combination with antidepressants, benzodiazepines may speed recovery from anxietyrelated symptoms but do not improve longer-term outcomes. The higher risk of dependence and adverse outcomes complicates the use of benzodiazepines.29 NICE guidelines recommend only short-term use during crises.11 Benzodiazepines with an intermediate to long onset of action (such as clonazepam) may have less potential for abuse and less risk of rebound.30 Second-Line Therapies. Second-line therapies for GAD include pregabalin and quetiapine, although neither has been evaluated for PD. Pregabalin is more effective than placebo but not as effective as lorazepam for GAD. Weight gain is a common adverse effect of

AMERICAN FAMILY PHYSICIAN Table 4. Medications for the Treatment of Generalized Anxiety Disorder and Panic Disorder Medication

Estimated cost*

First line Selective serotonin reuptake inhibitors Escitalopram

$25 ($190)

Fluoxetine

$5 ($250)

Fluvoxamine for PD

$15 (NA)

Paroxetine

$5 ($150)

Sertraline

$10 ($200)

Serotonin-norepinephrine reuptake inhibitors Duloxetine for GAD

$50 ($210)

Venlafaxine, extended release

$15 ($230)

Azapirone Buspirone for GAD

$5 ($87)

Second line Tricyclic antidepressants Amitriptyline†

$5 (NA)

Imipramine‡

$10 ($265)

Nortriptyline†

$10 ($725)

Antiepileptics Pregabalin† for GAD

NA ($145)

Antipsychotics Quetiapine† for GAD Hydroxyzine

$15 ($130) $12 ($200)

Third line Monoamine oxidase inhibitors§ Isocarboxazid†

NA ($130)

Phenelzine†

$20 ($50)

Tranylcypromine†

$50 ($185)

Augmentation Benzodiazepines|| Alprazolam¶

$10 ($70)

Clonazepam**

$10 ($70)

Diazepam for GAD

$10 ($90)

Lorazepam‡

$10 ($300)

Note: Medications are used for GAD and PD unless otherwise noted. They are listed from most to least commonly used.

FDA = U.S. Food and Drug Administration; GAD = generalized anxiety disorder; NA = not available; PD = panic disorder. *Estimated retail price for one month’s treatment based on information obtained at http://www.goodrx.com (accessed January 19, 2015). Generic price listed first; brand price listed in parentheses. †Not FDA approved for this use, although there is some evidence to support its use. ‡Not FDA approved for PD, although there is some evidence to support its use; approved for GAD. §Consideration of monoamine oxidase inhibitors should prompt referral to psychiatry. ||Benzodiazepines may be used for augmentation during acute treatment. Dependence, tolerance, and escalating doses to get the same effect over the long term can be problematic with use of benzodiazepines. Short-term prescribing with emphasis on acute management of uncontrolled anxiety is preferred. Slowly tapered dosing can prevent rebound symptoms. ¶Short-acting benzodiazepines, such as alprazolam, are not preferred because they have a higher risk of addiction and adverse effects. **Not FDA approved for GAD, although there is some evidence to support its use; approved for PD.

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AMERICAN FAMILY PHYSICIAN pregabalin. There is limited evidence for the use of antipsychotics to treat anxiety disorders. Although quetiapine seems to be effective for GAD, the adverse effect profile is significant, including weight gain, diabetes mellitus, and hyperlipidemia.31 Hydroxyzine is considered a second-line treatment for GAD,32 but there are minimal data for its use in PD. Its rapid onset can be appealing for patients needing immediate relief, and it may be a more appropriate alternative if benzodiazepines are contraindicated (e.g., in patients with a history of substance abuse). Based on clinical experience, gabapentin is sometimes prescribed by psychiatrists to treat anxiety on an as-needed basis when benzodiazepines are contraindicated. Of note, the placebo response for medications used to treat GAD and PD is high.13

Psychotherapy and Relaxation Therapies Psychotherapy includes many different approaches, such as cognitive behavior therapy (CBT) and applied relaxation (Table 5).33,34 CBT may use applied relaxation, exposure therapy, breathing, cognitive restructuring, or education. Psychotherapy is as effective as medication for GAD and PD.11 Although existing evidence is insufficient to draw conclusions about many psychotherapeutic interventions, structured CBT interventions have consistently proven effective for the treatment of anxiety in the primary care setting.34-36 Psychotherapy may be used alone or combined with medication as first-line treatment for PD37 and GAD,11

based on patient preference. Psychotherapy should be performed weekly for at least eight weeks to assess its effect.

Mindfulness has similar effectiveness to traditional CBT or other behavior therapies,38 particularly mindfulnessbased stress reduction.39 A meta-analysis of 36 randomized controlled trials on meditation showed that meditative therapies reduce anxiety symptoms, but most studies looked at anxiety symptoms rather than anxiety disorders.40 Transcendental meditation has similar effectiveness to other relaxation therapies.41 After a treatment course, rebound symptoms may occur less often with psychotherapy than with medications.

Successful treatment requires tailoring options to individuals and may often include a combination of modalities.11,37,42 Combined treatment with medications and psychotherapy reduces relapse even at two years.43

Complementary and Alternative Medicine Therapies Although a number of complementary and alternative products have evidence for treating depression, most lack sufficient evidence for the treatment of anxiety.

Botanicals and supplements sometimes used to treat GAD and PD are listed in Table 6. Kava extract is an effective treatment for anxiety44; however, case reports of hepatotoxicity have decreased its use.45 St. John’s wort, tryptophan, 5-Hydroxytryptophan, and S-adenosyl-l-methionine should be used with caution in combination with SSRIs because of the increased risk

Table 5. Possible Behavior Interventions for the Treatment of Generalized Anxiety Disorder, Panic Disorder, and Anxiety-Related Symptoms Intervention

Comments

Cognitive behavior therapy* This intervention is useful in treating anxiety disorders. The cognitive portion assists change in thinking patterns that support fears, whereas the behavior portion often involves training patients to relax deeply and helps desensitize patients to anxiety-provoking triggers.

To be effective, therapy must be directed at the patient’s specific anxieties and tailored to his or her needs. There are minimal adverse effects, except that behavior desensitization is typically associated with temporary mild increases in anxiety.33 Mindfulness based stress reduction†

This intervention promotes focused attention on the present, acknowledgment of one’s emotional state, and meditation for further stress reduction and relaxation.

Key features include moment to moment awareness cultivated with a nonjudgmental attitude, formal meditation techniques, and daily practice.34

Note: Formal use of these interventions requires specialized training. In patients whose anxiety and impairment are severe, referral to a trained behavior health specialist should be considered. *For more information, see DiTomasso RA, Golden BA, Morris HJ, eds. Handbook of Cognitive-Behavioral Approaches in Primary Care. New York, NY: Springer; 2010, and Craske MG. Cognitive-Behavioral Therapy. Washington, DC: American Psychological Association; 2010. †For more information, see Brantley J. Mindfulness-based stress reduction. In: Orsillo SM, Roemer L, eds. Acceptance and Mindfulness-Based Approaches to Anxiety: Conceptualization and Treatment. New York, NY: Springer; 2005:131-145.

Information from references 33 and 34.

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AMERICAN FAMILY PHYSICIAN Table 6. Botanicals and Supplements Sometimes Used to Treat Generalized Anxiety Disorder and Panic Disorder Therapy

Potential significant adverse effects*

Botanicals Kava (Piper methysticum)

Possible hepatotoxicity, sedation, interference with P450 substrates

Lavender oil (Lavandula Minimal angustifolia) Passionflower (Passiflora incarnata)

Dizziness, sedation, decreased blood pressure

St. John’s wort (Hypericum perforatum)†

Similar to serotonin reuptake inhibitors, interference with P450 substrates

Valerian (Valeriana officinalis)

Headache, gastrointestinal upset

Supplements 5-Hydroxytryptophan†

Gastrointestinal upset, possible eosinophilia-myalgia syndrome

Inositol

Nausea, headache

l-theanine

May lower blood pressure; may lower effect of stimulant medication

l-tryptophan†

Gastrointestinal upset, possible eosinophilia-myalgia syndrome

S-adenosyl-lmethionine†

Gastrointestinal upset, mania in patients with bipolar disorder

Vitamin B complex

Yellow urine

*This list includes important adverse effects but is not exhaustive. †Can potentiate serotonin syndrome when used in combination with antidepressants.

of serotonin syndrome.46 Evidence indicates that music therapy, aromatherapy, acupuncture, and massage are helpful for anxiety associated with specific disease states, but none have been evaluated specifically for GAD or PD. REFERRAL AND PREVENTION For patients with GAD or PD, psychiatric referral may be indicated if there is poor response to treatment, atypical presentation, or concern for significant comorbid psychiatric illness. There is insufficient evidence to support a concise recommendation on the prevention of PD and GAD in adults.

United States. Int J Methods Psychiatr Res. 2012;21(3): 169-184.

2. Paulesu E, Sambugaro E, Torti T, et al. Neural correlates of worry in generalized anxiety disorder and in normal controls: a functional MRI study. Psychol Med. 2010; 40(1):117-124.

3. Mackintosh MA, Gatz M, Wetherell JL, Pedersen NL. A twin study of lifetime generalized anxiety disorder (GAD) in older adults: genetic and environmental influences shared by neuroticism and GAD. Twin Res Hum Genet.

2006;9(1):30-37.

4. Dresler T, Guhn A, Tupak SV, et al. Revise the revised?

New dimensions of the neuroanatomical hypothesis of panic disorder. J Neural Transm. 2013;120(1):3-29.

5. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed.

Washington, DC: American Psychiatric Association; 2013.

6. Wolitzky-Taylor KB, Castriotta N, Lenze EJ, Stanley MA, Craske MG. Anxiety disorders in older adults: a comprehensive review. Depress Anxiety. 2010;27(2): 190-211.

7. Spitzer RL, Williams JB, Kroenke K, et al. Pfizer Inc. Patient health questionnaire (PHQ) screeners. http:// www.phqscreeners.com/overview.aspx?Screener=03_ GAD-7. Accessed July 22, 2014.

8. Spitzer RL, Kroenke K, Williams JB, Löwe B. A brief measure for assessing generalized anxiety disorder: the GAD-7. Arch Intern Med. 2006;166(10):1092-1097.

9. Craske MG, Kircanski K, Epstein A, et al.; DSM V Anxiety; OC Spectrum; Posttraumatic and Dissociative Disorder Work Group. Panic disorder: a review of DSM-IV panic disorder and proposals for DSM-V. Depress Anxiety. 2010; 27(2): 93-112.

10. Zimmerman M, McGlinchey JB, Chelminski I, Young D. Diagnostic co-morbidity in 2300 psychiatric out-patients presenting for treatment evaluated with a semi-structured diagnostic interview. Psychol Med. 2008;38(2):199-210.

11. National Institute for Health and Care Excellence.

Generalised anxiety disorder and panic disorder (with or without agoraphobia) in adults: management in primary, secondary and community care. January 2011. http: // www.nice.org.uk/Guidance/CG113. Accessed July 10, 2014.

12. Van Apeldoorn FJ, Van Hout WJ, Timmerman ME, Mersch PP, den Boer JA. Rate of improvement during and across three treatments for panic disorder with or without agoraphobia: cognitive behavioral therapy, selective serotonin reuptake inhibitor or both combined. J Affect Disord. 2013;150(2):313-319.

REFERENCES

13. Shearer SL. Recent advances in the understanding and treatment of anxiety disorders. Prim Care. 2007;34(3): 475-504, v-vi.

1. Kessler RC, Petukhova M, Sampson NA, Zaslavsky AM, Wittchen HU. Twelve-month and lifetime prevalence and lifetime morbid risk of anxiety and mood disorders in the

14. Charney DS, Heninger GR, Jatlow PI. Increased anxiogenic effects of caffeine in panic disorders. Arch Gen Psychiatry.

1985;42(3):233-243.

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AMERICAN FAMILY PHYSICIAN 15. Chapman DP, Presley-Cantrell LR, Liu Y, Perry GS, Wheaton AG, Croft JB. Frequent insufficient sleep and anxiety and depressive disorders among U.S. community dwellers in 20 states, 2010. Psychiatr Serv. 2013;64(4):385-387.

32. Guaiana G, Barbui C, Cipriani A. Hydroxyzine for generalised anxiety disorder. Cochrane Database Syst Rev. 2010;(12):CD006815.

16. Smits JA, Berry AC, Rosenfield D, Powers MB, Behar E, Otto MW. Reducing anxiety sensitivity with exercise.

Depress Anxiety. 2008;25(8):689-699.

33. National Institutes of Health. What is anxiety disorder?

Treatments. http: //www.nimh.nih.gov/health/topics/ anxiety-disorders/index. shtml#part6. Accessed August 1, 2014.

17. Carek PJ, Laibstain SE, Carek SM. Exercise for the treatment of depression and anxiety. Int J Psychiatry Med. 2011;41(1):15-28.

34. Grossman P, Niemann L, Schmidt S, Walach H. Mindfulness-based stress reduction and health benefits: a meta-analysis. J Psychosom Res. 2004;57(1):35-43.

18. Chugh-Gupta N, Baldassarre FG, Vrkljan BH. A systematic review of yoga for state anxiety: considerations for occupational therapy. Can J Occup Ther. 2013;80(3):150-170.

19. Otto MW, Tuby KS, Gould RA, McLean RY, Pollack MH. An effect-size analysis of the relative efficacy and tolerability of serotonin selective reuptake inhibitors for panic disorder. Am J Psychiatry. 2001;158(12):1989-1992.

20. Kapczinski F, Lima MS, Souza JS, Schmitt R. Antidepressants for generalized anxiety disorder.

Cochrane Database Syst Rev. 2003;(2):CD003592.

21. Zohar J, Westenberg HG. Anxiety disorders: a review of tricyclic antidepressants and selective serotonin reuptake inhibitors. Acta Psychiatr Scand Suppl. 2000;403:39-49.

22. Baldwin D, Woods R, Lawson R, Taylor D. Efficacy of drug treatments for generalised anxiety disorder: systematic review and meta-analysis. BMJ. 2011;342:d1199.

23. Ravindran LN, Stein MB. The pharmacologic treatment of anxiety disorders: a review of progress. J Clin Psychiatry.

2010; 71(7):839-854.

24. Carter NJ, McCormack PL. Duloxetine: a review of its use in the treatment of generalized anxiety disorder. CNS Drugs. 2009;23(6):523-541.

25. Chessick CA, Allen MH, Thase M, et al. Azapirones for generalized anxiety disorder. Cochrane Database Syst Rev. 2006;(3):CD006115.

26. Imai H, Tajika A, Chen P, et al. Azapirones versus placebo for panic disorder in adults. Cochrane Database Syst Rev. 2014;(9):CD010828.

27. Wiseman CN, Gören JL. Does bupropion exacerbate anxiety? Curr Psychiatry Rep. 2012;11(6):E3-E4.

28. Weich S, Pearce HL, Croft P, et al. Effect of anxiolytic and hypnotic drug prescriptions on mortality hazards: retrospective cohort study. BMJ. 2014;348:g1996.

29. Furukawa TA, Streiner DL, Young LT. Antidepressant plus benzodiazepine for major depression. Cochrane Database Syst Rev. 2001;(2):CD001026.

30. Hoge EA, Ivkovic A, Fricchione GL. Generalized anxiety disorder: diagnosis and treatment. BMJ. 2012;345:e7500.

35. Hunot V, Churchill R, Silva de Lima M, Teixeira V. Psychological therapies for generalised anxiety disorder.

Cochrane Database Syst Rev. 2007;(1):CD001848.

36. Cape J, Whittington C, Buszewicz M, Wallace P, Underwood L. Brief psychological therapies for anxiety and depression in primary care: meta-analysis and metaregression. BMC Med. 2010;8:38.

37. Furukawa TA, Watanabe N, Churchill R. Combined psychotherapy plus antidepressants for panic disorder with or without agoraphobia. Cochrane Database Syst Rev. 2007;(1):CD004364.

38. Khoury B, Lecomte T, Fortin G, et al. Mindfulness-based therapy: a comprehensive meta-analysis. Clin Psychol Rev. 2013;33(6):763-771.

39. Marchand WR. Mindfulness-based stress reduction, mindfulness-based cognitive therapy, and Zen meditation for depression, anxiety, pain, and psychological distress.

J Psychiatr Pract. 2012;18(4):233-252.

40. Chen KW, Berger CC, Manheimer E, et al. Meditative therapies for reducing anxiety: a systematic review and meta-analysis of randomized controlled trials. Depress Anxiety. 2012; 29(7):545-562.

41. Krisanaprakornkit T, Krisanaprakornkit W, Piyavhatkul N, Laopaiboon M. Meditation therapy for anxiety disorders.

Cochrane Database Syst Rev. 2006;(1):CD004998.

42. Pull CB. Combined pharmacotherapy and cognitivebehavioural therapy for anxiety disorders. Curr Opin Psychiatry. 2007;20(1):30-35.

43. Cuijpers P, Sijbrandij M, Koole SL, Andersson G, Beekman AT, Reynolds CF 3rd. Adding psychotherapy to antidepressant medication in depression and anxiety disorders: a meta-analysis. World Psychiatry.

2014;13(1):56-67.

44. Pittler MH, Ernst E. Kava extract for treating anxiety.

Cochrane Database Syst Rev. 2002;(2):CD003383.

45. Rowe A, Ramzan I. Are mould hepatotoxins responsible for kava hepatotoxicity? Phytother Res. 2012;26(11): 1768-1770.

31. Depping AM, Komossa K, Kissling W, Leucht S. Second46. Sarris J. St. John’s wort for the treatment of psychiatric generation antipsychotics for anxiety disorders. Cochrane disorders. Psychiatr Clin North Am. 2013;36(1):65-72.

Database Syst Rev. 2010;(12):CD008120.

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Practice Guidelines AAP RELEASES POLICY STATEMENT ON SCREENING FOR NONVIRAL SEXUALLY TRANSMITTED INFECTIONS IN ADOLESCENTS AND YOUNG ADULTS Many sexually transmitted infections (STIs) have a higher prevalence in the adolescent population. The objectives of screening for STIs include identifying persons with infection or possible infection, providing treatment, reducing transmission, avoiding or lessening consequences of the infection, and decreasing the prevalence of STIs. This policy statement from the American Academy of Pediatrics (AAP) provides recommendations on routine screening for nonviral STIs in adolescents and young adults (25 years and younger).

Recommendations Physicians should develop clinical processes to include STI risk assessment, screening, treatment, and prevention counseling when providing routine health care for sexually active adolescents. This should include providing staff with education and training related to procedures and other issues such as consent, confidentiality, and billing. Additionally, physicians should become proficient in screening for STIs with nucleic acid amplification testing. They should strive to reduce barriers to STI screening, including access to and stigma of screening, while being careful to avoid breaching confidentiality. Recommendations about specific STIs are outlined below.

Chlamydia Chlamydia trachomatis infection, which is the most common reportable communicable disease in the United States, has the highest rates in women 20 to 24 years of age and the second highest rates in female adolescents 15 to 19 years of age. Typically, chlamydia does not cause symptoms; however, if not treated, the infection can persist.

Chlamydia can cause cervicitis, urethritis, proctitis, and rarely, pharyngitis. Complications and sequelae of infection include adverse outcomes in pregnancy and

Source: Adapted from Am Fam Physician. 2015;91(9):652-654.

for the infant, including neonatal infections, chronic pelvic pain, ectopic pregnancy, epididymitis, increased transmission of human immunodeficiency virus (HIV), pelvic inflammatory disease (PID), reactive arthritis, and tubal-factor infertility. Additionally, recurrent chlamydia is associated with increased reproductive sequelae.

All sexually active female adolescents and adults 25 years and younger should be screened every year for C. trachomatis infection. Sexually active adolescent males and young adult males who have sex with males should be screened ever year for rectal chlamydia if having receptive anal intercourse and urethral chlamydia if having insertive intercourse. Males who have sex with males who are high risk (e.g., multiple sex partners, sex combined with illicit drug use) should be screened every three to six months. Annual screening should be considered in sexually active males in settings with a high prevalence of chlamydia (e.g., jail, high school clinics, national job training programs).

Additionally, because of their increased risk of infection, sex partners of persons with chlamydia (in the 60 days before diagnosis) should also be screened.

All adolescents found to have the infection should be screened again three months after treatment; this should be done whether or not the patient thinks his or her sex partner was treated. If it is not possible to perform screening again at three months, repeat screening should be performed when the patient next presents, in the year after treatment of the initial infection.

Gonorrhea Gonorrhea, the second most common reportable communicable disease in the United States, has the highest rates in women 20 to 24 years of age and the second highest rates in female adolescents 15 to 19 years of age. Many times, the infection does not cause symptoms. Neisseria gonorrhoeae infection can manifest as cervicitis, urethritis, proctitis, and pharyngitis, and rarely can lead to conjunctivitis. The upper genital tract can be affected by gonorrhea, causing PID and other problems (e.g., ectopic pregnancy, infertility, and chronic pelvic pain in females; epididymitis in males).

Additionally, gonorrhea infection is linked to increased transmission of HIV. In pregnant women, gonorrhea can cause chorioamnionitis, premature rupture of

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AMERICAN FAMILY PHYSICIAN membranes, and preterm labor, and transmission perinatally can lead to ophthalmia neonatorum.

and prostatitis in males. Additionally, it may increase transmission of HIV.

All sexually active female adolescents and adults younger than 25 years should be screened every year for N. gonorrhoeae infection. Sexually active adolescent and young adult males who have sex with males should be screened every year for pharyngeal gonorrhea if having receptive oral intercourse, rectal gonorrhea if having receptive anal intercourse, and urethral gonorrhea if having insertive intercourse. Males who have sex with males who are high risk (e.g., multiple sex partners, sex combined with illicit drug use) should be screened every three to six months. Annual screening should be considered in other sexually active young adult males based on individual and population-based risk factors; local epidemiology should be used to decide if gonorrhea screening is appropriate in a particular patient population.

In asymptomatic adolescents, routine screening is not recommended. However, female adolescents and young women may be at higher risk of infection because of individual or population-based factors (e.g., new or multiple partners, a history of STIs, exchanging sex for money, injecting drugs); these patients may need more extensive evaluation, including screening for T. vaginalis infection. Rescreening females previously diagnosed with trichomoniasis should be considered three months after treatment; rescreening in males has not been discussed in the literature. If it is not possible to perform screening again at three months, repeat screening should be performed when the patient next presents, in the year after treatment of the initial infection.

Because reinfection is common, sex partners of persons with gonorrhea (in the 60 days before diagnosis) should also be screened. All adolescents found to have gonorrhea should be screened again three months after treatment; this should be done whether or not the patient thinks his or her sex partner was treated.

If it is not possible to perform screening again at three months, repeat screening should be performed when the patient next presents, in the year after treatment of the initial infection.

In recent years, rates of syphilis have significantly increased, particularly among males who have sex with males. If the infection is left untreated, serious complications can occur, including neurosyphilis and, in infants of pregnant women with syphilis, congenital syphilis, which causes a variety of multisystem problems, including intrauterine death.

Trichomoniasis Based on population studies, Trichomonas vaginalis genital tract infection is thought to be the most common nonviral STI. Rates of T. vaginalis infection in adolescent females are 2.1% to 14.4%. T. vaginalis infection is also common in older women. It usually does not have symptoms; however, it can cause vaginitis, PID, and preterm labor in females, and urethritis, epididymitis,

Syphilis

Routine screening in nonpregnant, heterosexual adolescents is not recommended. However, sexually active adolescent and young adult males who have sex with males should be screened every year; those who are high risk should be screened every three to six months. Additionally, screening can be considered in adolescents and young adults with higher risk behaviors. Local health departments can provide local prevalence rates and risks, which may affect screening decisions.

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Photo Quiz A GEOMETRIC SUMMERTIME RASH A 17-year-old girl presented with a bruise-like rash on her legs. The rash had appeared three days prior, after she had eaten limes and rolled down a grassy hill with friends. The rash was initially brightly erythematous, and it was associated with a burning sensation. She had a history of asthma and eczema.

The physical examination revealed multiple linear and geometric hyperpigmented patches on her medial thighs bilaterally (Figures 1 and 2). The rash was in a “kissing” pattern in the flexural aspect of her knee.

Figure 1.

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

A. Allergic contact dermatitis.

B. Chemical burn.

C. Child abuse.

D. Phytophotodermatitis.

Figure 2.

SEE THE FOLLOWING PAGE FOR DISCUSSION.

Source: Adapted from Am Fam Physician. 2015;91(9):649-650.

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AMERICAN FAMILY PHYSICIAN Summary Table Condition

Rash characteristics

Exposures

Allergic contact dermatitis

Pruritic papules and vesicles on an erythematous base, at the site of exposure or diffusely across the body

Plants (e.g., poison ivy and oak), topical medications (e.g., bacitracin), metals (e.g., nickel), personal care products (e.g., cosmetics, perfumes, lotions, soaps); prior sensitization is required

Chemical burns

Erythematous plaques and vesicles that resolve Cleaning agents, car battery acid, bleach, ammonia, denture with hyperpigmentation cleaners, teeth whitening products, swimming pool chlorinating products

Child abuse

Geometric lesions resembling hands or fingers in various stages of healing; bruising in atypical locations (e.g., ear, soft tissue, cheek)

Injury secondary to foreign objects; patterns that are incongruous with history

Phytophotodermatitis

Brightly erythematous geometric patches associated with burning; resolves with hyperpigmentation, which may last for months

Psoralen; common sources include citrus fruits (e.g., lemons, limes, bergamot oranges), figs, parsnips, celery, carrots, dill, and mustard

Discussion The correct answer is D: phytophotodermatitis.

Phytophotodermatitis is a phototoxic eruption (i.e., an enhanced sunburn) that occurs when the skin is exposed to a photosensitizing compound called a psoralen, then exposed to sunlight. The most common source of psoralen is citrus fruits such as lemons, limes, and bergamot oranges. Other sources include figs, parsnips, celery, carrots, dill, and mustard. Heat, sweating, and wet skin intensify the process. Phototoxic reactions differ from photoallergic reactions in that they can happen at any time, without prior sensitization.1-3 Phytophotodermatitis is more common in the summer.

It may occur as an occupational hazard of bartenders, agricultural workers, florists, gardeners, and grocers.4 Phytophotodermatitis typically presents 24 hours after exposure with an erythematous rash that is accompanied by vesicles and a burning sensation.

Symptom severity peaks within 48 to 72 hours, then characteristic hyperpigmentation gradually develops.

The hyperpigmentation lasts weeks to months, but may occasionally last years in individuals with darker skin. The distribution offers diagnostic clues. Irregular or bizarre sunburns, preferential involvement of the dorsal hands and fingers, drip marks, hyperpigmented handprints, or kissing lesions on flexural surfaces suggest phytophotodermatitis.1-3 The treatment of choice is cool compresses, with topical corticosteroids if the reaction is severe and edematous.

To prevent recurrence, sun protection and hand washing after exposure to foods known to contain psoralen should be emphasized.1-3 Allergic contact dermatitis manifests as an acute eczematous dermatitis after prior sensitization. The rash is characterized by pruritic papules and vesicles on an erythematous base. Causes

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include exposure to plants such as poison ivy and oak, topical medications such as bacitracin, metals such as nickel, and personal care products such as cosmetics, perfumes, lotions, and soaps. Allergen exposure, pruritus, and expansion of the rash slightly beyond the site of exposure differentiate allergic contact dermatitis from phytophotodermatitis. Chemical burns may be difficult to distinguish from phytophotodermatitis because both present with erythema, vesicles, and eventual hyperpigmentation in odd, geometric shapes.

Clinical history of exposure can differentiate between these two diagnoses.

Child abuse should be considered in the differential diagnosis of any injured child. Clues to abuse include an unusual distribution or location of lesions, a handprint bruise that is adult-sized, or a pattern of bruises or marks in various stages of healing and incongruous with the patient’s history.5,6 REFERENCES 1. Goskowicz MO, Friedlander SF, Eichenfield LF. Endemic “lime” disease: phytophotodermatitis in San Diego County. Pediatrics. 1994; 93(5):828-830.

2. Egan CL, Sterling G. Phytophotodermatitis: a visit to Margaritaville. Cutis. 1993;51(1):41-42.

3. Hankinson A, Lloyd B, Alweis R. Lime-induced phytophotodermatitis. J Community Hosp Intern Med Perspect. 2014;4(4):25090.

4. Seligman PJ, Mathias CG, O’Malley MA, et al.

Phytophotodermatitis from celery among grocery store workers. Arch Dermatol. 1987;123(11):1478-1482.

5. Committee on Child Abuse and Neglect, American Academy of Pediatrics. When inflicted skin injuries constitute child abuse. Pediatrics. 2002;110(3):644-645.

6. McDonald KC. Child abuse: approach and management.

Am Fam Physician. 2007;75(2):221-228.

ANESTHESIOLOGY

Continuous Spinal Anesthesia in Geriatric Orthopedic Surgeries SUDIVYA SHARMA*, SUSHEELA TAXAK†, NIKITA JAIN‡

ABSTRACT Continuous spinal anesthesia (CSA) was first formally described in 1940 by Lemmon, it involved intrathecal placement of a 17- or M-gauge malleable needle connected to rubber tubing. It allowed incremental dosing of an intrathecal local anesthetic drug for an indefinite duration. It is a well-established regional technique with many advantages over single dose spinal blockade, including the ability to titrate level and duration of anesthesia, hemodynamic stability and postoperative analgesia.

It is an underutilized technique in modern anesthesia practice, when compared with other techniques of neuraxial anesthesia.

Most critics of CSA mention two complications: neurological damage and cerebrospinal fluid infection. Spinal microcatheters thinner than 24-gauge, intended for the use in CSA have been banned from the US market. By intermittent administration of small doses of a local anesthetic through the spinal catheter, the spread of the block can be better regulated and the risk of abrupt decreases in arterial pressure can be reduced compared with single-shot spinal anesthesia or epidural anesthesia.

Also, an adequate level of anesthesia can be maintained in prolonged surgery. Finally, the spinal catheter can be utilized for continuous spinal postoperative analgesia. We present case series of geriatric patients undergoing orthopedic surgery under continuous spinal anesthesia.

Keywords: Spinal, continuous, catheter, analgesia, geriatric

C

ontinuous spinal anesthesia (CSA) is a technique of initiating and maintaining spinal anesthesia with small doses of local anesthetic injected intermittently into the subarachnoid space via an indwelling catheter. It allows incremental dosing of an intrathecal local anesthetic for a prolonged duration.1

WHY SPINAL ANESTHESIA? Spinal anesthesia is a widely used anesthetic technique for lower limb surgery in the elderly. It is often preferred for its efficacy, rapidity, minimal effect on mental status, reduction of blood loss and protection against thromboembolic complications. But, there is risk of severe and prolonged hypotension. This is due to the rapid extension of the sympathetic block, hindering

cardiovascular adaptation and causing significant morbidity and mortality.2-4 Spinal and epidural anesthesia has been shown to blunt the stress response to surgery; decrease blood loss intraoperatively; lower the incidence of postoperative thromboembolic event and decrease mortality and morbidity in high-risk patients.

In addition, both spinal and epidural techniques can be used for postoperative analgesia. Inserting a catheter in subarachnoid space increases the utility of spinal anesthesia by permitting repeated drug administration as often is necessary to extend the level and duration of spinal block. The technique is similar to that described for single shot spinal anesthesia except that a large enough needle must be used to accommodate the desired catheter. It is an underutilized technique in modern anesthesia practice, when compared with other techniques of neuraxial anesthesia.

WHY CONTINUOUS SPINAL?

*Clinical Assistant HN Reliance Hospital, Mumbai, Maharashtra †Professor PGIMS, Rohtak, Haryana ‡Senior Resident ESI Hospital, Faridabad, Haryana Address for correspondence Dr Sudivya Sharma E-mail: drsudivyasharma@gmail.com

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The CSA technique offers several advantages over single-shot spinal anesthesia in patients undergoing extensive surgery of the lower part of the body. It has been reported to be more rapid in action, producing more pronounced sensory-motor blockade with fewer hemodynamic alterations and side effects by enabling the reduction and fractionation of the induction dose

ANESTHESIOLOGY through a catheter. But, CSA has been implicated in causing-specific complications, such as infection, headache or cauda-equina syndrome.5,6 By intermittent administration of small doses of a local anesthetic through the spinal catheter, the spread of the block can be better regulated and the risk of abrupt fall in arterial pressure can be reduced. Also, an adequate level of anesthesia can be maintained in prolonged surgery. Finally, the spinal catheter can be utilized for continuous spinal postoperative analgesia.

CASE SERIES Clinical scenarios in which CSA may be of particular benefit include patients with severe aortic stenosis undergoing lower-extremity surgery and obstetric patients with complex heart disease. We present case series of geriatric patients undergoing orthopedic surgery under continuous spinal anesthesia.

METHODOLOGY A similar methodology was applied to these elderly patients with individualization of drug volume according to comorbidities, type of surgery and duration of surgery. The patients were made to lie in the lateral position and under full aseptic precautions 19 G Tuohy epidural needle was inserted into L3-L4 space (Pediatric epidural set-Portex). After obtaining free-flow of cerebrospinal fluid, a 20 G Portex epidural catheter was threaded into the subarachnoid space up to a distance of 2-3 cm. Hyperbaric injection bupivacaine 0.5% (0.6-0.8 mL) was injected slowly intrathecally through the catheter and the catheter was taped to the back. Patients were turned supine. Spinal anesthesia was titrated with incremental boluses (0.2-0.4 mL) of the same bupivacaine solution, until sensory block was attained in the desired dermatomes. Additional boluses of bupivacaine were given during the surgery as and when needed. Postoperatively, 0.2-0.4 mL of 0.5% injection bupivacaine (heavy) with injection fentanyl 12.5 µg were given. The catheter was removed thereafter.

Case 1 A 72-year-old obese female was posted for open reduction and fixation of trochanter fracture due to fall on the ground. She was a known case of chronic obstructive pulmonary disease with deranged arterial blood gas analysis showing raised partial pressure of carbon dioxide (PaCO2). She was also a known hypertensive, had history of ischemic heart disease with

ejection fraction of 40%. Other routine investigations were within normal limits. CSA was considered and 0.6 mL injection bupivacaine 0.5% was given initially and 0.2 mL towards the end of surgery.

Case 2 A 60-year-old male presented with polytrauma i.e., supracondylar femur fracture, olecranon fracture and fracture tibial condyle. He was a knownhypertensive but uncontrolled and had productive cough with exertional dyspnea. He was a chronic smoker with reduced air entry in bilateral lung fields.

The hemoglobin was low (8 g/dL) and blood urea levels were raised, other routine investigations were within normal limits. CSA was given with 0.6 mL plus 0.4 mL injection bupivacaine hyperbaric 0.5% initially and injection fentanyl 12.5 µg postoperatively in the recovery room.

Case 3 A 90-year-old male presented with fracture trochanter with history of fall. He was recently diagnosed with hypertension, on multiple medications but blood pressure was 200/110 mmHg at the time of surgery.

CSA was given with 0.7 mL + 0.4 mL injection bupivacaine hyperbaric 0.5% initially and later injection fentanyl 12.5 µg through catheter.

Case 4 An 83-year-old edentulous male with fracture trochanter with advanced carcinoma prostate was also given CSA with 0.5 mL + 0.3 mL injection bupivacaine hyperbaric 0.5% intraoperatively and injection fentanyl 12.5 µg + 0.2 mL injection bupivacaine hyperbaric 0.5% later in recovery room postoperatively.

Only minimal cardiovascular and respiratory side effects were observed in comparison to single-shot spinal and general anesthesia. In the whole series, no anesthesia-related complications were seen. Another benefit of CSA is the option of applying a second dose with longer duration of surgery to keep the optimal anesthetic level. In addition, the method is suitable for postoperative analgesia over a period of 2-3 days.

DISCUSSION Most critics of CSA mention two complications: neurological damage and cerebrospinal fluid infection. Serious neurological complications such as cauda-equina syndrome after CSA performed with microcatheters were described by Rigler et al in 1991;

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ANESTHESIOLOGY additional cases after CSA administered through microcatheters resulted in a safety alert of the Food and Drug Administration (FDA) in 1992. Spinal microcatheters thinner than 24-gauge intended for the use in CSA were banned from the US market.7 The possible complications are neurologic sequelae, which include post-dural-puncture headache (PDPH), nerve root injury (persistent pain, sensory or motor deficits) and central nervous system complications (meningitis, spinal abscess, spinal hematoma, paraplegia). Catheter insertion, breakage, shearing, knotting or kinking are widely discussed, again mainly when using microcatheters, are not present with macrocatheters.

The observed frequency of neurologic sequelae (excluding PDPH) after continuous spinal anesthesia with a malleable needle or catheter technique ranges from 0% to 1%. Inflammatory reaction develops in the dura surrounding the puncture site, and that when the catheter is removed, edema or fibrinous exudate resulting from the inflammatory reaction seals the hole in the dura, thus preventing leakage of cerebrospinal fluid.

CONCLUSION

trauma to the neurovascular structures and maldistribution with resultant local anesthetic toxicity; but on the other hand, it offers better spread of the block and reduced hemodynamic variations. Geriatric patients are high-risk patients owing to age-related changes and comorbidities. Hence, CSA provides a safe alternative to general anesthesia.

REFERENCES 1. Lemmon WT. A method for continuous spinal anesthesia: a preliminary report. Ann Surg. 1940;111(1):141-4.

2. Sutter PA, Gamulin Z, Forster A. Comparison of continuous spinal and continuous epidural anaesthesia for lower limb surgery in elderly patients. A retrospective study. Anaesthesia. 1989;44(1):47-50.

3. Covert CR, Fox GS. Anaesthesia for hip surgery in the elderly. Can J Anaesth. 1989;36(3 Pt 1):311-9.

4. Chan VW, Chung F, Gomez M, Seyone C, Baylon G. Anesthetic and hemodynamic effects of single bolus versus incremental titration of hyperbaric spinal lidocaine through microcatheter. Anesth Analg. 1994;79(1):117-23.

5. Denny NM, Selander DE. Continuous spinal anaesthesia.

Br J Anaesth. 1998;81(4):590-7.

6. Ellis JE, Klock PA, Klafta JM, Laff SP. Choice of anesthesia and intraoperative monitoring for lower extremity revascularization. Surg Clin North Am. 1995;75(4):665-78.

7. Rigler ML, Drasner K, Krejcie TC, Yelich SJ, Scholnick FT, DeFontes J, et al. Cauda equina syndrome after continuous spinal anesthesia. Anesth Analg. 1991;72(3):275-81.

■■■■

On one hand, the use of an intrathecal catheter introduces an increased risk of technical difficulties,

ÂÂ

Patients with fibromyalgia show deficiencies in red blood cell (RBC) magnesium and insulin-like growth factor 1 (IGF-1), reported a small study presented at the American Academy of Pain Management (AAPM) 2015 Annual Meeting.

ÂÂ

A clinical profile of chronic back pain accompanied by a specific report of severe pain upon standing for too long and leg tremors may suggest an often overlooked diagnosis of arachnoiditis, suggests new research presented at the American Academy of Pain Management (AAPM) 2015 Annual Meeting.

ÂÂ

A noninvasive wearable nerve stimulator improves pain to the point of needing less analgesia in patients with neuropathy, arthritis, and other common forms of chronic pain, suggests a new study presented at PAIN Week 2015.

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COMMUNITY MEDICINE

Satisfaction Levels and Recommendation Intentions of Healthcare Consumers: An Exploratory Study Based on Multispecialty Hospitals in North India VISHAL KAMRA*, HARJOT SINGH†, KALYAN KUMAR DE‡

ABSTRACT Background: Patient satisfaction has been considered as one of the important outcomes of healthcare delivery system. It has not only been emerged as an essential parameter to measure the quality of healthcare service, but also as an indicator of utilization of healthcare services. Aims and objectives: This study was aimed to examine the factors affecting patient satisfaction and their service recommendation decisions with respect to tertiary level healthcare services. Study design: Data were collected from 883 patients of 73 multispecialty hospitals located in seven states, one union territory and national capital territory of India with the help of a structured questionnaire. Methods: Factor analysis and linear discriminant analysis techniques have been employed to analyze the data. Results and conclusion: The study has revealed that factors which affect patient satisfaction are infrastructure and amenities, fulfillment of clinical requirement, facilities at reception and OPD area, nursing and staff care, professional behavior of doctors, affordability and convenience, registration and administrative procedures and general behavior of doctors. The study has also resulted in a model consisting of linear discriminant equation to predict the patients’ recommendation intentions for the services of same hospitals.

Keywords: Consumer behavior, healthcare, India, multispecialty hospitals, patient satisfaction

A

service is not something that is built in a factory, shipped to a store, put on a shelf and then taken home by a consumer. It is executed on behalf of, and often with the involvement of, the consumers. Many definitions of service are available but all contain a common theme of intangibility and simultaneous consumption.1

It is very subjective in nature because of its experience.

It purely depends upon the judgment of a person, which he makes from what he expects out of it. In simplest way, services are the deeds, processes and performances provided or coproduced by one entity or person for another entity or person.2

*Research Scholar †Assistant Professor LM Thapar School of Management, Thapar University, Patiala, Punjab ‡Professor Dept. of Business Administration Amity University, Noida, Uttar Pradesh Address for correspondence Dr Vishal Kamra House No. 3, Behind Khairpur Govt. School Chawla Colony, Hissar Road, Sirsa - 125 055, Haryana E-mail: vishalkamra@ymail.com

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Consumer satisfaction has been considered a central concept in the service business.3 It is an overall psychological outcome, a judgment or a fulfillment response, based on experience of a product or service feature or a product or service itself.4 It is the main source of performance feedback of the organizations and employees5 as well as an important tool for the financial measures of any organization.6 Patient satisfaction has become a central part of the healthcare delivery system aiming to improve the quality of care.7 It is the degree to which general and condition-specific healthcare needs are met.8 It is the overall satisfaction from various components of service quality such as technical, functional, infrastructural, interpersonal and environmental.9 Healthcare system is a combination of resources, organizations, financing and management that culminates in the delivery of healthcare services to the population.10 Tertiary level healthcare services refer to a third level of the healthcare system, in which specialized consultative care is provided to the patients suffering from chronic health diseases.

Multispecialty hospitals are the centers of excellence for inpatient surgical procedures and offer comprehensive healthcare treatment across many of the specialties.11

COMMUNITY MEDICINE INDIAN HEALTHCARE SECTOR India has a population of 1.3 billion people residing in 29 states and seven union territories, out of which 31% are situated in the northern part of the country, which consists of seven states and two union territories.

Healthcare services in India have traditionally been provided by the government. In the early postindependence period, the Indian healthcare sector was suffering from a shortage of doctors and nurses, inadequacy of hospitals as well as a lack of modern medical equipments. In the 1980s, approximate 30% decline was witnessed in the use of both urban and rural public healthcare facilities. Thereafter, this sector has achieved tremendous growth and has been growing faster than it was during the last few decades.

It is expected to become US$ 280 billion sector by the end of 2020.12 REVIEW OF LITERATURE In a study on 500 patients in Riyadh city to compare the perceived satisfaction of patients to their expectations prior to admission, researchers have concluded that satisfaction of patients is associated with staff kindness, waiting time, cleanliness of hospital, quality of nursing care, physician’s quality, availability of medicines and advancement in medical technology.13 In an another study on 15 government and 20 private hospitals covering 1,100 patients and 800 management personnel in Bangladesh, authors have affirmed that fast administrative procedures, hygiene, routine visit of doctors and nurses, behavior of service personnel, effective complaint handling and promptness of service are the factors for patient satisfaction in private hospitals. Moreover, high treatment cost, unnecessary medical tests and investigations, no permanent specialist doctors and lack of trained, efficient and experienced nurses are the factors for patient dissatisfaction.14 In a study in PGIMER, Chandigarh on 1,278 OPD patients, researchers have declared that doctor’s professional communication, nursing care, behavior of laboratory staff, basic amenities, staff at waiting area, location of the hospital, timings of OPD, hospital pharmacy and cost of service are the factors affecting patient satisfaction.15 In a study on 223 patients in Iran about their complaints or dissatisfaction with the hospital services, authors have confirmed that accessibility, communication skills, service performance, delay in service delivery, quality of basic amenities, cost of service and administrative procedures are the factors, which lead to patient dissatisfaction.16 In an another study conducted in 34 private hospitals in Jeddah,

Kingdom of Saudi Arabia, researchers have explained that promotional activities, physical evidence, quality of service, staff behavior and processes are the central factors for patient satisfaction.17 On the basis of a study on 471 patients of 26 government hospitals in Jordan, authors have found that waiting time to obtain services, nursing staff care, quality of rooms and bathrooms, quality of food, ambulance service, reputation of doctors, diagnostic facilities, confidentiality of information about treatment and price of the service are the prominent factors for patient satisfaction.18 In a study, which included 268 respondents from three Oriental Medical Hospitals located in Chungnam Province, authors have defined that doctors, nurses, staffs, medical fee, environment, facilities and quality of ward life are the factors for patient satisfaction.19 In a study to access the patient satisfaction at Indian Spinal Injuries Centre, New Delhi, researchers have reported that visiting hours, patient’s interaction with doctors and hospital staff, basic amenities, transport facility, responsiveness of service, rooms, nursing care, treatment process, doctor’s professional behavior and cleanliness of toilets are the important factors for patient satisfaction.11 RESEARCH METHODOLOGY

Objectives of the Study ÂÂ

To identify the factors affecting patient satisfaction with respect to tertiary level healthcare services.

ÂÂ

To predict the patients’ recommendation intention model on the basis of identified factors.

The present study is exploratory-cum-descriptive in nature, as it endeavors to assess the relationship between consumers’ satisfaction and their recommendation intentions for the services of same hospital. Patients in multispecialty hospitals, particularly suffering from tertiary level health diseases based in northern India comprise the population for the study. Patients suffering specifically from eight types of tertiary level health diseases have been considered as respondents.

Table 1 shows the disease-wise distribution of respondents from each region.

Considering the awareness level of the respondents, a questionnaire consisting of 42 questions has been administered to the respondents. They have been requested to rate the importance of factors affecting their satisfaction levels on a 5-point satisfaction scale (1 = Highly dissatisfied, 2 = Dissatisfied, 3 = Neither satisfied nor dissatisfied, 4 = Satisfied, 5 = Highly satisfied). Various demographic variables have also

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COMMUNITY MEDICINE Table 1. Disease-wise Distribution of Respondents from Each Region Knee-joint replacement

Spinal cord operation

Heart bypass surgery

Heart stent implant

Renal failure

Hip-joint replacement

Intestine problem

Lungs disorders

Total

UT 1

33

33

37

51

25

24

7

13

223

State 1

64

26

12

11

33

34

4

8

192

State 2

36

52

33

11

0

0

15

0

147

UT 2

34

22

24

6

2

5

11

10

114

State 3

4

9

13

10

13

3

4

8

64

State 4

9

13

14

3

1

0

9

3

52

State 5

1

3

13

2

5

6

3

5

38

State 6

11

6

11

0

0

1

0

0

29

State 7

5

8

5

0

0

5

0

1

24

197

172

162

94

79

78

53

48

883

Total

UT 1 = Delhi; UT 2 = Chandigarh; State 1 = Haryana; State 2 = Punjab; State 3 = Uttar Pradesh; State 4 = Rajasthan; State 5 = Uttarakhand; State 6 = Himachal Pradesh; State 7 = Jammu and Kashmir.

been considered to understand the diverse behavior of respondents. On the basis of convenience sampling, a total of 1,000 questionnaires have been distributed and 883 fully-filled responses have been received. Data were collected between March and August 2014 and have been analyzed by applying exploratory factor analysis and linear discriminant analysis with the help of SPSS software, version 16.0.

RESULTS

Exploratory Factor Analysis To summarize the data without losing any of the important information20 exploratory factor analysis (EFA) has been conducted. The Kaiser-Meyer Olkin (KMO) value >0.6 can be considered as adequate.21 From Table 2, it can be seen that KMO value (0.816) has been found to be acceptable, and seems to be indicative of a data set considered to be highly desirable for factor analysis.22 The most common method of factor analysis is the principal component analysis and the most common method of factor rotation is the varimax rotation.23 Thus, the factors affecting patient satisfaction have been tested using principal component factor analysis with varimax rotation. With principal component analysis, eight factors have been extracted depending on Eigen values and variance explained as shown in Table 3. The factor structure has explained 68.084% of total variance, which exceeds the threshold level (i.e., 60% commonly used in social sciences).24

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Table 2. Kaiser-Meyer-Olkin and Bartlett’s Test of Sphericity Kaiser-Meyer-Olkin Bartlett's test of sphericity

0.816 Approximate Chi-square

28374.130

Degree of freedom

861

Significance

.000

Table 3. Factors, Eigen Values and Variances Explained Factors

Eigen values

Variance (%)

Cumulative (%)

Infrastructure and amenities

5.255

12.512

12.512

Fulfillment of clinical requirement

4.113

9.792

22.304

Facilities at reception and OPD area

4.004

9.532

31.836

Nursing and staff care

3.869

9.213

41.049

Professional behavior of doctors

3.306

7.870

48.919

Affordability and convenience

3.170

7.548

56.467

Registration and administrative procedures

2.503

6.746

63.213

General behavior of doctors

2.376

4.871

68.084

COMMUNITY MEDICINE Naming of Factors Infrastructure and Amenities This factor has been identified as the first factor affecting patient satisfaction from tertiary level healthcare services. Nine service features which significantly load on this factor are adequacy of utilities like water supply, fan, light and wash rooms, adequate space for parking vehicles, availability of proper sign boards, availability of spacious lifts, clean/airy/lighted stairs and ramps, cleanliness of the toilets, facility of ATM/Bank, facility of canteen and cafeteria and living room facilities. Findings of various studies have also supported these findings.14 Fulfillment of Clinical Requirements This factor has been identified as the second factor affecting patient satisfaction. Five service features which significantly load on this factor are availability of diagnostic facilities, availability of required blood groups, availability of required medicines, correct and timely reports given by the laboratories and quality of ambulance service. Various studies have also shown that these service features are considerable determinants of patient satisfaction.13 Facilities at Reception and OPD Area This factor has been identified as the third factor affecting patient satisfaction. Three service features which significantly load on this factor are adequate sitting area at main reception and respective OPD, availability of trolley/wheel chairs at the reception and cleanliness in the OPD area. Findings of other studies have also shown that cleanliness of the hospital and facilities at OPD are important determinants of patient satisfaction.18 Nursing and Staff Care This factor has been identified as the fourth factor affecting patient satisfaction. Six service features which significantly load on this factor are sufficient nursing staff, sympathetic behavior of staff at waiting area, personal attention and proper time given by the nursing staff and courteous and cooperative behavior of servants, security staff, nursing staff, lab and diagnostic staff. Previous studies have also shown that these service features are significant determinants of patient satisfaction.19 Professional Behavior of Doctors This factor has been identified as the fifth factor affecting patient satisfaction. Five service features

which significantly load on this factor are problem listened carefully by the doctor, schedule and time of the treatment explained properly, required tests and diagnosis were explained properly, doctors advised about the ways to avoid illness and stay healthy, and disease and its consequences were properly explained. Previous studies have also shown that these service features are relevant determinants of patient satisfaction.15 Affordability and Convenience This factor has been identified as the sixth factor affecting patient satisfaction. Five service features which significantly load on this factor are charges for various tests and other medical services, convenient location of the hospital, easy access to the doctors in the hospital, tie-up of hospital with insurance companies and timings of the OPD services. Findings of other studies have also shown that OPD timings, cost of treatment and location of the hospital are significant determinants of patient satisfaction.16 Registration and Administrative Procedures This factor has been identified as the seventh factor affecting patient satisfaction. Five service features which significantly load on this factor are courteous and cooperative behavior of registration staff, efficient system of addressing the complaints, meeting time with patient, waiting time at the registration counter and queries handling at the reception counter. Previous studies have also supported these service features as determinants of patient satisfaction from hospital services.17 General Behavior of Doctors This factor has been identified as the eighth factor affecting patient satisfaction. Four service features which significantly load on this factor are tension free/relaxed environment, personal attention and proper time given by the doctors, privacy during clinical examination and courteous and cooperative behavior of doctors. Findings of various studies have also supported these findings.11

Linear Discriminant Analysis To analyze the association between patient satisfaction and their recommendation intentions of hospital services, step-wise discriminant analysis has been carried out. Eight factors obtained from exploratory factor analysis have been taken as independent variables and categorical variable (“Would you recommend this hospital to others?�) has been taken as dependent

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COMMUNITY MEDICINE variable. The entered variables are significant at 5% level of significance.

In the present study, a positive association has been encountered between patient satisfaction and their recommendation intentions. As seen in Table 4, recommendation intentions have been found to be influenced by the “infrastructure and amenities”, “fulfillment of clinical requirement”, “facilities at reception and OPD area”, “nursing and staff care”, “professional behavior of doctors”, “affordability and convenience”, “registration and administrative procedures” and “general behavior of doctors”.

Discriminant Score Canonical discriminant function coefficients yield coefficients of various factors. The discriminant equation is as follows: Discriminant Score (Recommendation Intentions) = .816 (infrastructure and amenities) + .840 (fulfillment of clinical requirement) - .225 (facilities at reception and OPD area) .199 (nursing and staff care) + .468 (professional behavior of doctors) + .340 (affordability and convenience) + .401 (registration and administrative procedures) + .089 (general behavior of doctors) - .014.

Group centroid values are used to compare the score of discriminant equation. Table 5 shows the values of functions at group centroids for the categorical variable (“Would you recommend this hospital to others?”).

If the discriminant score of equation is >0.709 then Table 4. Canonical Discriminant Function Coefficients Intention to recommend

Function 1

Infrastructure and amenities

.816

Fulfillment of clinical requirement

.840

Facilities at reception and OPD area

−.225

Nursing and staff care

−.199

Professional behavior of doctors

.468

Affordability and convenience

.340

Registration and administrative procedures

.401

General behavior of doctors

.089

(Constant)

.014

Table 5. Functions at Group Centroids Would you recommend this hospital to others?

Function 1

Yes

.709

No

-1.314

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Table 6. Classification Results Would you recommend this hospital to others?

Predicted group members Yes

No

372

34

Total

Cases selected Original count

Yes

406

No

52

167

219

Percentage (%)

Yes

91.6

8.4

100.0

No

23.7

76.3

100.0

Original count

Yes

151

12

163

No

31

64

95

Percentage (%)

Yes

92.6

7.4

100.0

No

32.6

67.4

100.0

Cases not selected

86.2% of selected original grouped cases correctly classified.

83.3% of unselected original grouped cases correctly classified.

patients are expected to recommend the hospital to others, if score is less than -1.314 then patients are not expected to recommend, and if score is in-between these two then patients may or may not recommend the hospital to others.

The classification results provide the strength of discriminant equation. The patients have been divided into two groups using Bernoulli function. A total of 70% cases have been selected for predicting discriminant equation and rest of 30% cases has been used for checking the strength of discriminant equation.

Discriminant equation correctly classifying the cases more than 80% have been considered good in social sciences.25 Table 6 shows that a total of 86.2% of the selected cases and 83.3% of the unselected cases have been correctly classified for the present study.

CONCLUSION The present study has been undertaken with the primary objective of identifying the factors affecting patient satisfaction from tertiary level healthcare services. To achieve this, exploratory factor analysis has been employed on the collected data. Results have revealed that factors which affect satisfaction levels of patients are infrastructure and amenities, fulfillment of clinical requirement, facilities at reception and OPD area, nursing and staff care, professional behavior of doctors, affordability and convenience, registration and administrative procedures and general behavior of doctors. Findings of various other studies have also supported these findings.16

COMMUNITY MEDICINE Another objective of the study was to predict the patients’ recommendation intention model on the basis of identified factors. Since, the dependent variable is categorical in nature, hence step-wise discriminant analysis has been performed for predicting the equation. The discriminant score >0.709 shows that patients are expected to recommend the hospital to others, score less than -1.314 shows that they are not expected to recommend, and score in-between these two shows that patients may or may not recommend the hospital to others. The discriminant equation has been formed by taking 70% of the total respondents and cross-checked on rest of the 30%. The strength of the discriminant equation has been found 86.2% on selected original grouped cases and 83.3% on unselected original grouped cases.

IMPLICATIONS The results of this study are significant to various stakeholders and have implications on healthcare organizations’ marketing and policy reformulations.

These can be used by the healthcare organizations to improve their service quality and delivery. Doctors and other healthcare professionals can enhance the service quality by improving the service attributes, namely, general behavior of doctors, registration and administrative procedures and affordability and convenience, which have reported lower levels of satisfaction. The healthcare organizations can re-engineer and redesign the service delivery process by making it more patient-centric. This may result in good care of patients and also high returns on investments for the organizations. In addition, this study is expected to make a meaningful contribution to the literature on healthcare marketing. Researchers may also benefit from this study, while undertaking similar studies in future.

LIMITATIONS AND FUTURE RESEARCH One limitation of this study is that it has been conducted in north India. Though the results concur with other studies conducted in other countries, future research exercises can examine the factors affecting patient satisfaction, from different parts of the world. Another limitation is that the study has been conducted with a limited number of respondents using convenience sampling method. Future research can look at increasing the sample size or using other methods of sampling to gain more insight into the factors affecting patient satisfaction. Additionally, the researchers can attempt to explore more factors in this regard and a disease-wise analysis can also be carried out to further

understand the factors, which affect satisfaction levels of patients for tertiary level health diseases.

REFERENCES 1. Fitzsimmons JA, Fitzsimmons MJ. Service Management: Operations, Strategy, and Information Technology. New York: McGraw-Hill Companies; 2001.

2. Wilson A, Zeithaml VA, Bitner MJ, Gremler DD. Services Marketing: Integrating Customer Focus Across the Firm.

UK: McGraw Hill; 2012.

3. Saha GC, Theingi. Service quality, satisfaction, and behavioral intentions: A study of low-cost airline carriers in Thailand. Managing Service Quality. 2009;19(3):350-72.

4. Oliver RL. Satisfaction: A Behavioral Perspective on the Consumer. New York: Irwin-McGraw-Hill; 1997.

5. Hagan CM, Konopaske R, Bernardin HJ, Tyler CL. Predicting assessment center performance with 360‐ degree, top‐down, and customer‐based competency assessments.

Human Resource Management.

2006;45(3):357-90.

6. Gupta S, Zeithaml V. Customer metrics and their impact on financial performance. Market Sci. 2006;25(6):718-39.

7. Rozenblum R, Lisby M, Hockey PM, Levtizion-Korach O, Salzberg CA, Lipsitz S, et al. Uncovering the blind spot of patient satisfaction: an international survey. BMJ Qual Saf. 2011;20(11):959-65.

8. Asadi-Lari M, Tamburini M, Gray D. Patients’ needs, satisfaction, and health related quality of life: towards a comprehensive model. Health Qual Life Outcomes.

2004;2(1):32-46.

9. Zineldin M. The quality of health care and patient satisfaction: an exploratory investigation of the 5Qs model at some Egyptian and Jordanian medical clinics.

Int J Health Care Qual Assur Inc Leadersh Health Serv.

2006;19(1):60-92.

10. Roemer MI. National Health Systems of the World. UK: Oxford University Press; 1993.

11. Mishra PH, Mishra T. Study of patient satisfaction at a super specialty tertiary care hospital. Ind J Clin Pract.

2014;25(7):624-34.

12. Verma DS, Khandelwal U. Consumers preferences towards service industry: a factorial study of health care industry. Int J Multidisc Res. 2011;1(8):83-9.

13. Al-Omar BA. Patients’ expectations, satisfaction and future behavior in hospitals in Riyadh City. Saudi Med J. 2000;21(7):655-65.

14. Chowdhury MU. Customer expectations and management perceptions in healthcare services of Bangladesh. J Serv Res. 2008;8(2):121-40.

15. Sharma R, Sharma M, Sharma RK. The patient satisfaction study in a multispecialty tertiary level hospital, PGIMER, Chandigarh, India. Leadership in Health Service.

2011;24(1):64-73.

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COMMUNITY MEDICINE

A Survey of Public Awareness About Voluntary Body Donation SHALINI CHAUDHARY*, SARVESH†, APS BATRA‡

ABSTRACT Anatomy is one of the basic and very important subjects studied by medical and paramedical students. Teaching and research in anatomy is mainly based on cadaveric dissection. Human cadavers for purpose of study are a scarcity with increased number of medical institutions in this country. Unclaimed bodies are no more origin of cadavers. A voluntary body donation is defined as the act of giving one’s body after death for medical research and education. We have been promoting body donation at our institution for 4 years and started public awareness drive. In this article, a survey was done among faculty members and medical exhibition visitors which included lawyers, engineers, teachers and others during the year of 2014. The body donation including organ donation and various factors such as age, religion, culture and donor’s attitude are discussed.

Keywords: Anatomy, cadaver, voluntary body donation

T

eaching and research in anatomy is mainly based on cadaveric dissection. The dissection is an important part in the anatomical courses of medical students and for anatomical research and special courses devoted to surgeons. Currently, some institutes report a deficit in accessing cadavers because of increasing students numbers and competition with newly established medical schools for limited number of cadavers.

Decades ago, the bodies used for cadaver dissection were mostly those of persons that had died from sickness without relatives. Now-a-day, dissection of unclaimed bodies obtained from the police is not the only source of cadavers, but also those made available from body donation is important. Body donation is the act of giving away one’s body after death without any conditions or rewards for the sake of education and research in medicine. When body donors provide their bodies after death without any conditions students can use their bodies without any limitations.

*Assistant Professor, Dept. of Anatomy †Assistant Professor, Dept. of Anesthesia ‡Professor, Dept. of Anatomy BPS Govt. Medical College for Women, Khanpur Kalan, Sonepat, Haryana Address for correspondence Dr Shalini Chaudhary Assistant Professor, Dept. of Anatomy BPS Govt. Medical College for Women, Khanpur Kalan, Sonepat - 131 305, Haryana E-mail: dr_chaudhary23@rediffmai.com

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Although in India, we have shortage of cadavers but situation in other countries differs completely. In the United States and Europe, the almost overabundant number of bodies is supplied through body donation and bodies are used for various purposes. For example, car crash experiment, in examining the impact of bullet and bombs on human bodies.

A survey was conducted in BPS Govt. Medical College for Women among the teaching, nonteaching staff and visitors who came for medical camp during the year 2014 regarding voluntary body donation.

MATERIAL AND METHODS A cross-sectional analysis was conducted at BPS Govt.

Medical College for Women, Khanpur Kalan, Sonepat among the doctors and nonteaching staff, about 450 members and visitors i.e., the lawyers, engineers, farmers and others, about 3,000 members. Data was collected by giving a questionnaire for the consenting individuals in the age group 20-65 years during the year 2014. Questionnaire provided to the study population was designed to assess the following: ÂÂ

Age

ÂÂ

Sex

ÂÂ

Religion

ÂÂ

Positive and negative attitudes toward voluntary body donation (VBD) and organ donation

ÂÂ

Willingness to donate their body after death to medical institutions

COMMUNITY MEDICINE ÂÂ

Suggestions from existing body donor.

We also gave donor card with due respect to those who filled our donation form.

OBSERVATION AND RESULTS The individuals returned the complete questionnaire.

The medical and paramedical members’ result showed that 75% were not ready to donate their bodies as they believed that there was no need of voluntary body donation and if done their body would not be treated with respect and dignity, moreover, it will be misused.

Only (22%) of youngsters (25-40 years) were willing to donate their bodies to medical colleges. Males were found to be more inclined toward body donation than females.

Only 3% had already registered their names for body donation in other reputed colleges only where they used to go for treatment. Among the nonmedical visitors of the medical exhibition mostly (97%) were not having any prior idea about voluntary body donation. All of them said, it is a noble thing but some of them showed hesitance in donating their bodies because of religious belief.

Above observations show that nonmedical public needs to be educated about voluntary body donation and its need for the medical colleges.

DISCUSSION There are several cited incidences in Indian mythology, about people sacrificing their body for mankind.

Donation of body to science was 1st heard in 1832 when British utilitarian, philosopher, jurist and social reformer Jeremy Bentham’s body was donated in 1832 according to his will.1 Maharishi Dadhichi, who showing the supreme sacrifice donated his bones, from which “Vajra” was made and demon Vritrasura was slain.

In India, the Anatomy Act was enacted in 1948 to provide unclaimed bodies of deceased persons to hospitals and medical and teaching institutions for the purpose of anatomical examination and dissection.

It has been uniformly adopted in all its states.2 In Maharashtra (old Bombay State), the Anatomy Act was adopted as Bombay Anatomy Act 1949. According to Section 5(1) and (2) of this Act, “Where a person under treatment in a hospital whether established by or vesting in, or maintained by the State Government or any local authority, dies in such hospital or a person in a prison and his body is unclaimed, the authorities in-charge of such

hospital or prison shall with the least practicable delay report the fact to the authorized officer and such officer shall then hand over the unclaimed body to the authorities in-charge of an approved institution for any therapeutic purpose or for the purposes of medical education or research including anatomical examination and dissection”. The Section 5(3) of the law states that, “Where a person having no permanent place of residence in the area where his death has taken place dies in any public place in such area and his body is unclaimed, the authorized officer shall take possession of the body and shall hand it over to the authorities incharge of an approved institution for the purpose specified in Subsection (1)”.3 Question of shortage of the cadavers often facing the taboo on trading human anatomical goods.4 As donated body is going to be used to study normal structure of human body, some of the donated bodies may not be suitable for usage and hence liable for rejection. Some frequent reasons for rejection of the body are: ÂÂ

Body of a medicolegal case (e.g., suicide, homicide, accidental death, etc.)

ÂÂ

Postmortem bodies

ÂÂ

Body of a person having contagious/communicable disease (e.g., HIV, AIDS, tuberculosis, hepatitis B and C, gangrene, etc.)

ÂÂ

Decomposed body

ÂÂ

Extreme obese/emaciated body

ÂÂ

Body with organs removed (except eyes)

ÂÂ

Body of a person with skin diseases like psoriasis, bedsores, etc.

The medical institute has a right to reject the body for any other reason. The decision, whether to accept or reject the body is taken by the medical institution at the time of donation. Even though willingness form is filled by the prospective donor, the execution of donation is not mandatory for both - the donor as well as recipient (the medical institution).

CONCLUSION There is a need for creating an awareness of voluntary body donation and to change the mindset of society about body donation. Organized efforts are needed to raise the awareness about body donation. One has to choose between donating your organs or body to science. Generally, you cannot do both. Donation provides students unparalleled opportunities to study the human body. It can done by adopting the following:

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By developing a VBD program (putting hoardings, posters about body donation) in institutes, so that the shortage of cadaver can be solved

ÂÂ

By use of media increased public awareness will definitely benefit the institutions

ÂÂ

Cadaver pooling can be done at the level of district/ state and national, so that problem of cadaver shortage might be solved

ÂÂ

Honoring of the donor by the medical institute

ÂÂ

Need of religious knowledge.

REFERENCES 1. Richardson R, Hurwitz B. Jeremy Bentham’s self image: an exemplary bequest for dissection. Br Med J (Clin Res Ed). 1987;295(6591):195-8.

2. Ajita R, Singh YI. Body donation and its relevance in anatomy learning - a review. JASI. 2007;56(1):44-7.

3. The Bombay Anatomy Act, 1949. Available at: http:// bombayhighcourt.nic.in/libweb/acts/1949.11.pdf

4. Delmonico FL, Arnold R, Scheper - Hughes N, Siminoff LA, Kahn J, Youngner SJ. Ethical incentives-not payment for organ donation. N Engl J Med. 2002;346(25):2002-5.

■■■■

...Cont’d from page 429

16. Ebrahimipour H, Vafaee-Najar A, Khanijahani A, Pourtaleb A, Saadati Z, Molavi Y, et al. Customers’ complaints and its determinants: the case of a training educational hospital in Iran. Int J Health Policy Manag.

2013;1(4):273-7.

19. Park HS, Seo YJ. Determinants of inpatients satisfaction and intent to revisit oriental medical hospitals. J Korean Med. 2014;35(4):65-73.

17. Ahmad AEMK, Al-Qarni AA, Alsharqi OZ, Qalai DA, Kadi N. The impact of marketing mix strategy on hospitals performance measured by patient satisfaction: an empirical investigation on Jeddah private sector hospital senior managers perspective. Int. J Market Stud.

2013;5(6):210-27.

21. Kaiser HF, Rice J. Educational and psychological measurements. Little Jiffy Mark IV. 1974;34(1):111-7.

18. Aqel IS, Al-Tarawneh KA. Study of the relationship between the quality of the medical service and patient satisfaction in private hospitals operating in Amman area.

Euro J Busin Manage. 2013;5(4):255-74.

24. Hair JF, Anderson RE, Tatham RL, Black WC. Multivariate Data Analysis. New Jersey: Prentice-Hall; 1995.

20. Tabachnick B, Fidell L. Using Multivariate Statistics.

Boston: Pearson; 2007.

22. Kim J, Mueller C. Introduction to factor analysis. Beverly Hills: Sage Publications; 1978.

23. Kinnear PR, Gray CD. PASW statistics 17 made simple.

Hove, East Essex: Psychology Press; 2010.

25. Malhotra NK. Marketing Research: Applied Orientation, 5th Edition. New Delhi: Pearson Publication; 2007.

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A recent case report highlights the possibility of acquiring food allergies following transfusion of a blood product such as platelets. The allergy is transient and is due to food-specific immunoglobulin E (IgE) in the blood product. An allergic reaction to a food can occur in an allergic recipient after receiving a blood product that contains intact allergen consumed by the donor (Ching JC, et al. Peanut and fish allergy due to platelet transfusion in a child. CMAJ. 2015;187(12):905-7).

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Another World Rabies Day has passed by with statistics being espoused about the number of deaths caused by rabies. The fact is that India accounts for 20,000 of the 45,000 deaths due to rabies every year. With over 95% of the time rabies virus being transmitted through dog bites, the focus must be on the animal too.

Doctors say the high number of deaths is due to the low proportion of vaccinated dogs. According to data provided by the Public Health Foundation of India in its Rabies Control Initiative in Tamil Nadu, 2010, the State has around 4,238 dogs per lakh population. “People do not realise that a bite by a pet can also cause rabies. The virus attacks the nervous system and reaches the brain. When a pet licks an open wound, it could transmit the virus even if it has been vaccinated. The risk is higher as not all dogs are vaccinated. We found in our survey that people want free vaccines and don’t want to take up animal birth control,” says S. Elango, president of the State branch of the Indian Public Health Association….(Source: The Hindu, October 3, 2015).

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COMMUNITY MEDICINE

The Rise in Incidence of the Enterococcus: Beyond Vancomycin Resistance: A Review DEEPAK ARORA*, NARINDER KAUR†

ABSTRACT The emergence of microorganisms resistant to commonly used antimicrobial agents has reached global epidemic proportions.

Once regarded as a bacterial genus of little consequence, enterococci, in the past several years, have rapidly emerged as important nosocomial and community-acquired pathogens. These organisms can cause serious invasive infections including, endocarditis, bacteremia, meningitis and urinary tract infections. Enterococcus faecalis is the most common isolate, being associated with 80-90% of human enterococcal infections. Enterococcus faecium ranks second and is isolated from 10% to 15% of infections. In 1988, the first reports of vancomycin-resistant strains surfaced. Vancomycin-resistant enterococci (VRE) infections are especially aggressive and have been associated with mortality rates approaching 60-70%. Transmission of VRE by healthcare workers whose hands become transiently contaminated with the organism while caring for affected patients is probably the most common mode of nosocomial transmission. The Centers for Disease Control and Prevention Hospital Infection Control Practices Advisory Committee (HICPAC) recommends: i) prudent use of vancomycin; ii) education of hospital staff; iii) effective use of the microbiology laboratory and iv) implementation of infection control measures (including the use of gloves and gowns and isolation or cohorting of patients, as appropriate to specific conditions.

Keywords: Centers for Disease Control and Prevention, Enterococcus, vancomycin-resistant enterococci, Hospital Infection Control Practices Advisory Committee

T

he emergence of microorganisms resistant to commonly used antimicrobial agents has reached global epidemic proportions. But antimicrobial resistance in bacteria is neither a new phenomenon nor unexpected in an environment in which potent antimicrobial agents are used. Resistance to antimicrobial agents, which was recognized more than 50 years, continues to be a major cause of increased morbidity, mortality and healthcare cost. New forms of antibiotic resistance can cross international boundaries and spread between continents with ease. Many forms of resistance spread with remarkable speed. World health leaders have described antibiotic-resistant microorganisms as “nightmare bacteria” that “pose a

*Associate Professor Dept. of Microbiology Guru Gobind Singh Medical College, Faridkot, Punjab †Associate Professor Adesh Institute of Medical Sciences and Research, Bathinda, Punjab Address for correspondence Dr Deepak Arora Associate Professor Dept. of Microbiology Guru Gobind Singh Medical College, Faridkot - 151 203, Punjab E-mail: drdeepakarora78@gmail.com

catastrophic threat” to people in every country in the world.

Each year in the United States, at least 2 million people acquire serious infections with bacteria that are resistant to one or more of the antibiotics designed to treat those infections. At least 23,000 people die each year as a direct result of these antibiotic-resistant infections. Many more die from other conditions that were complicated by an antibiotic-resistant infection.

The use of antibiotics is the single most important factor leading to antibiotic resistance around the world.

Antibiotics are among the most commonly prescribed drugs used in human medicine. However, up to 50% of all the antibiotics prescribed for people are not needed or are not optimally effective as prescribed.

Bacteria will inevitably find ways of resisting the antibiotics we develop, which is why aggressive action is needed now to keep new resistance from developing and to prevent the resistance that already exists from spreading. A hospital-acquired infection (HAI) or nosocomial infection is an infection whose development is favored by a hospital environment, such as one acquired by a patient during a hospital visit or one developing among hospital staff. In the United States, the Centers for Disease Control and Prevention (CDC)

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COMMUNITY MEDICINE estimated roughly 1.7 million HAIs, from all types of microorganisms, including bacteria, combined, cause or contribute to 99,000 deaths each year.1 In Europe, where hospital surveys have been conducted, the category of Gram-negative infections are estimated to account for two-thirds of the 25,000 deaths each year.

Nosocomial infections can cause severe pneumonia and infections of the urinary tract, bloodstream and other parts of the body. Many types are difficult to attack with antibiotics, and antibiotic resistance is spreading to Gram-negative and Gram-positive bacteria that can infect people outside the hospital.1,2 The organisms that cause most HAIs are common in the general population, in which setting they are relatively harmless. They may cause no disease or a milder form of disease than in hospitalized patients. This group includes Staphylococcus aureus, coagulase-negative staphylococci, enterococci and Enterobacteriaceae. Factors that increase a patient’s susceptibility to nosocomial infections include young or old age, decreased immune resistance, underlying disease and therapeutic and diagnostic interventions.

The organisms that cause nosocomial infections are often drug-resistant. The regular use of antimicrobials for treatment therapy or prophylaxis promotes the development of resistance.

Antimicrobial resistance is of two types: inherent/ intrinsic resistance and acquired resistance. Intrinsic resistance is species characteristic and thus present in all members of species and is chromosomally mediated.

Organism which currently represent major nosocomial pathogens include enterococci; these organisms exhibit antimicrobial resistant phenotypes, which presently make clinical management difficult.1 Once regarded as a bacterial genus of little consequence, enterococci, in the past several years, have rapidly emerged as important nosocomial and communityacquired pathogens. These organisms can cause serious invasive infections including, endocarditis, bacteremia, meningitis and urinary tract infections (UTIs).3 Enterococci exhibit intrinsic resistance to penicillinase susceptible penicillin (low level), penicillinaseresistant penicillins, cephalosporins, lincosamides, nalidixic acid, low level of aminoglycoside and low level of clindamycin. On the other hand, acquired resistance results from either mutation in DNA or acquisition of new DNA. Examples of acquired resistance include resistance to penicillin by β-lactamases, high level of aminoglycoside resistance, vancomycin, chloramphenicol, erythromycin, high level of clindamycin, tetracycline and fluoroquinolone

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resistance.4 Vancomycin had been in clinical use for more than 30 years without the emergence of marked resistance. Because of their activity against methicillin-resistant staphylococci and other Grampositive bacteria, these drugs have been widely used for therapy and prophylaxis against infections due to these organisms. Oral vancomycin, which is poorly absorbed, has been used extensively for treatment of Clostridium difficile enterocolitis.5 Vancomycin was first marketed for patient use in the United States in 1956. It is a narrow-spectrum glycopeptide antibiotic obtained from cultures of Streptomyces orientalis and is active only against Grampositive bacteria. From a mechanistic standpoint, vancomycin inhibits the synthesis of cell wall peptidoglycan by forming a complex with D-alanyl-Dalanine terminal amino acid structure of peptidoglycan precursor.

For the treatment of systemic infections, vancomycin must be given by intravenous route; when given orally, it remains in gastrointestinal tract and is not appreciably absorbed. Vancomycin was marketed primarily for treatment of staphylococcal and streptococcal infections as an alternative to β-lactam antibiotics, such as penicillins. Vancomycin was not widely used intravenously until the development of methicillin-resistant S. aureus (MRSA) in the late 1980s.

Since then, the increase in use of parenteral vancomycin has been consistent with an increase in the incidence of MRSA. Vancomycin was not used orally until the pathophysiology of pseudomembranous enterocolitis caused by C. difficile toxins was elucidated in the mid 1980s. The use of oral vancomycin has increased with the growing rate of C. difficile associated diarrhea in the US. In the late 1980s and early 1990s, vancomycin became the last resort for treating the patients with specific β-lactam allergies and for wide variety of Gram-positive infections: ÂÂ

Infections caused by MRSA

ÂÂ

Infection caused by methicillin-resistant coagulasenegative staphylococci

ÂÂ

Meningitis caused by highly β-lactam-resistant Streptococcus pneumoniae

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Enterococcal endocarditis (in combination with gentamicin) in patients allergic to penicillin/ ampicillin when the enterococcal isolate maintains susceptibility to vancomycin

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Patients treated for C. difficile colitis who have not responded to oral metronidazole.

COMMUNITY MEDICINE Enterococci were originally classified as enteric Gram-positive cocci and later included in the genus Streptococcus. In the 1930s, with the establishment of the Lancefield serological typing system enterococci were classified as Group D streptococci and were differentiated from the nonenterococcal Group D streptococci such as Streptococcus bovis by distinctive biochemical characteristics.

Enterococcus faecalis is the most common isolate, being associated with 80-90% of human enterococcal infections. Enterococcus faecium ranks second and is isolated from 10% to 15% of infections.

HABITAT AND CLINICAL INFECTIONS These organisms are normal residents of the gastrointestinal and biliary tracts and in lower number in vagina and male urethra. Enterococcus species cause complicated UTIs, bacteremia, endocarditis, intraabdominal and pelvic infections, wound and soft tissue infections, neonatal sepsis and, rarely, meningitis.

Enterococci are second most common cause of nosocomial urinary tract and wound infections and the third most common cause of nosocomial bacteremias.6 DRUG RESISTANCE One of the major reason why these organisms have survived in the hospital environment is their intrinsic resistance to several commonly used antibiotics and perhaps more important, their ability to acquire resistance to all currently available antibiotics, either by mutation or by receipt of foreign genetic material through the transfer of plasmids and transposons (Table 1).7 Therapeutic difficulties presented by enterococci were well-recognized as early as the 1950s, when response rates of enterococcal endocarditis to penicillin used alone were found to be markedly lower than those of streptococcal endocarditis.8 Because more enterococci are tolerant to the bactericidal activity of β-lactam and glycopeptide antibiotics, bactericidal synergy between one of these antibiotics and an aminoglycoside is needed to treat most serious enterococcal infections such as endocarditis and meningitis. Since, the duration of therapy is longer and the toxicity of the combination regimens is increased compared to those used for streptococcal endocarditis, enterococci are considered problem organisms with respect to antimicrobial therapy.9 The synergistic bactericidal effect between aminoglycosides and β-lactam or glycopeptide antibiotics is lost if there is high-level resistance to either class of drug.

VANCOMYCIN RESISTANCE In 1988, the first reports of vancomycin-resistant strains surfaced. Vancomycin-resistant enterococci (VRE) infections are especially aggressive and have been associated with mortality rates approaching 60-70%.

Approximately 90% of VRE infections are attributable to E. faecium; in contrast, the majority of nonresistant infections are due to E. faecalis.10 Six phenotypes of vancomycin resistance, termed Van A, Van B, Van C, Van D, Van E and Van G are described. The Van A and Van B phenotypes are clinically significant and mediated by 1-2 acquired transferable operons that consists of 7 genes in 2 clusters termed Van A and Van B operons (Fig. 1).11 Table 1. Intrinsic and Acquired Antimicrobial Drug Resistance in Enterococci Intrinsic resistance yy β-lactams (particularly cephalosporins and penicillinaseresistant penicillins) yy Low concentrations of aminoglycosides yy Clindamycin yy Fluoroquinolones yy Trimethoprim-sulfamethoxazole Acquired resistance yy High concentrations of β-lactams, through alteration of penicillin-binding proteins or production of β-lactamases yy High concentration of aminoglycoside yy Glycopeptides (vancomycin, teicoplanin) yy Tetracycline yy Erythromycin yy Fluoroquinolones yy Rifampin yy Chloramphenicol yy Fusidic acid yy Nitrofurantion

6625 bp

Van A operon

Van Van S R

Van Van H A

Regulation Van B operon

Van Van Van Van SB RB YB W

Van X

Van Y

Van Z

Essential Van HB

Van B

Van XB

Figure 1. Comparison of arrangements of the Van A and Van B glycopeptide resistance operons. Essential genes and those involved in regulation of expression of the resistance determinant are marked.

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COMMUNITY MEDICINE ACTION OF VANCOMYCIN ON PEPTIDOGLYCAN SYNTHESIS Under normal conditions of peptidoglycan synthesis in enterococci, two molecules of D-alanine are joined by a ligase enzyme to form D-Ala-D-Ala, which is then added to UDP-N-acetylmuramyl-tripeptide to form the UDP-N-acetylmuramyl-pentapeptide. The UDP-Nacetylmuramyl-pentapeptide, when incorporated into the nascent peptidoglycan (transglycosylation), permits the formation of cross-bridges (transpeptidation) and contributes to the strength of the peptidoglycan layer.

Vancomycin binds with high affinity to the D-Ala-D-Ala termini of the pentapeptide precursor units, blocking their addition to the growing peptidoglycan chain and preventing subsequent cross-linking. Resistance to glycopeptide in enterococci is summarized in Table 2.12

Van A Glycopeptide Resistance Van A-resistant strains possess inducible, highlevel resistance to vancomycin (minimal inhibitory concentrations [MICs] ≥64 µg/mL) and teicoplanin

(MICs ≥16 µg/mL). Resistance can be induced by glycopeptides (vancomycin, teicoplanin, avoparcin and ristocetin) and by nonglycopeptide agents such as bacitracin, polymyxin B and ropendine, a drug used to treat coccidial infections in poultry. The Van A gene and other genes involved in the regulation and expression of vancomycin resistance (Van R, Van S, Van H, Van X and Van Z) are located on 10, 581-bp transposon (Tn1546) of E. faecium, which often resides on a plasmid. Expression of these genes results in the synthesis of abnormal peptidoglycan precursors terminating in D-Ala-D-Lac with markedly lower affinity than it does to the normal dipeptide product.

Van R and Van S proteins constitute a two-component regulatory system that regulates the transcription of the Van HAX gene cluster. Van S apparently functions as a sensor to detect the presence of vancomycin or more likely some early effect of vancomycin on cell wall synthesis. Van S then signals Van R, the response regulator, which results in activation or turning on, of the synthesis of some other proteins (Van H, Van A and Van X) involved in resistance.

Table 2. Resistance to Glycopeptide in Enterococci12 Phenotype Genotype (resistance operon present)

Vancomycin MIC (µg/mL)

Teicoplanin MIC (µg/mL)

Expression

Ability to transfer Species resistance

Van A

64->1,000

16-512

Inducible

Yes

Van A

E. faecium E. faecalis E. avium E. gallinarum E. durans E. mundtii E. casseliflavus E. raffinosus E. hirae

Van B

Van B

4-1,000

0.25-2

Inducible

Yes

E. faecium E. faecalis E. gallinarum E. durans

Van C

Van C-1

2-32

0.12-2

Van C

Van C-2

2-32

0.12-2

Van C

Van C-3

2-32

Van D*

Van D

16-256

Constitutive

No

E. gallinarum

Constitutive

No

E. casseliflavus

0.12-2

Constitutive

No

E. flavescens

2-64

Constitutive

No

E. faecium

Inducible

E. faecalis Van E*

Van E

16

0.5

Inducible

No

E. faecalis

Van G*

Van G

16

0.5

Inducible

No

E. faecalis

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COMMUNITY MEDICINE Van B Glycopeptide Resistance

VANCOMYCIN-DEPENDENT ENTEROCOCCI

These isolates were initially believed to be induciblyresistant to more modest levels of vancomycin (MICs, 32-64 µg/mL), but are susceptible to teicoplanin.

It is now known that levels of vancomycin resistance among Van B isolates may range from 4 to ≥1,000 µg/mL, whereas susceptibility to teicoplanin is retained. Van B resistance determinants also reside on large mobile elements that can be transferred from one strain of Enterococcus to another Van B glycopeptide resistance in enterococci is mediated by an abnormal ligase (Van B) that is structurally related to Van A ligase (76% amino acid identity). Van B protein also favors the production of pentadepsipeptide terminating in D-Ala-D-Lac.

An interesting phenomenon that has developed in some strains of Van A- and Van B-type VRE is that of vancomycin dependence. These enterococci are not just resistant to vancomycin but now require it for growth. Vancomycin-dependent enterococci have been recovered from apparently culture-negative clinical samples by plating them onto vancomycincontaining agar, such as that used for isolation of Campylobacter or gonococci. A likely explanation for the phenomenon of vancomycin dependence is that these enterococci turn off their normal production of D-Ala-D-Ala and then can grow only if a substitute dipeptide-like structure is made. With most Van A- and Van B-type enterococci, this occurs only in the presence of vancomycin, which induces the synthesis of associated dehydrogenase (Van H) and ligase (Van A or Van B) that make D-Ala-D-Lac. The reason for the cell turning off the synthesis of D-Ala-D-Ala is that as long as vancomycin is present, D-Ala-D-Ala is not necessary for cell wall synthesis by VRE (186).

Van C Glycopeptide Resistance The phenotype was described in E. casseliflavus and E. gallinarum, which demonstrate intrinsic, low level resistance to vancomycin (MICs, 4-32 µg/mL) and susceptible to teicoplanin. Low-level resistance to vancomycin is typical of E. gallinarum, E. casseliflavus, and E. flavescens. The nucleotide sequences of Van C-1 gene in E. gallinarum, the Van C-2 gene in E. casseliflavus and the van C-3 gene in E. flavescens has been reported.

Van C ligase of E. gallinarum favors the production of a pentapeptide terminating in D-ala-D-ser. Substitution of D-ser for D-ala is presumed to weaken the binding of vancomycin to novel pentapeptide.

Van D Glycopeptide Resistance A novel vancomycin resistance gene designated Van D was first described in a New York Hospital in 1991. The strain carrying this resistance trait was an E. faecium strain that was inhibited by vancomycin at 64 µg/mL and teicoplanin at 4 µg/mL. Partial sequencing of the ligase gene showed that it was distinct from but similar to the Van A and Van B ligase genes. Van D appears to be located on the chromosome and is not transferable to other enterococci.

Van E Glycopeptide resistance The Van E vancomycin resistance gene has recently been described in E. faecalis BM 4405, which is resistant to low levels of vancomycin (MIC, 16 µg/mL) and susceptible to teicoplanin (MIC, 0.5 µg/mL) (94).

This new resistance phenotype has similarities to the intrinsic Van C type of resistance. The deduced amino acid sequence has a greater identity to Van C (55%) than to Van A (45%) Van B (43%) or Van D (44%).

Indeed, it is being destroyed by the action of Van X. Once the vancomycin is removed, D-Ala-D-Ala Lac is no longer synthesized, and without either D-Ala-D-Ala or D-Ala-D-Lac, the cell cannot continue to grow or replicate. Reversion to vancomycin independence has been observed; it probably occurs by either a mutation that leads to constitutive production of D-Ala-D-Lac or one that restores the synthesis of D-Ala-D-Ala.6 MOBILITY OF ELEMENTS CONTAINING GENES FOR VANCOMYCIN RESISTANCE Enterococci have various systems of bacterial mating (conjugation) that can spread genes for resistance to other bacteria. These systems include plasmids that can replicate in several other Gram-positive species (e.g., staphylococci and streptococci), pheromone responsive plasmids that can transfer between E. faecalis strains at frequencies sometimes approaching 100%, and a specialized type of transposon (an element that can jump from one DNA site to another intracellularly) that is conjugative (that is, it can transfer intercellularly between a broad range of bacterial genera and can then become integrated into the genome of the new host bacterium).

The findings of genes for vancomycin resistance on these conjugative as well as transposable elements heightens concern about the possible transfer of such resistance to other, perhaps more pathogenic, organisms.

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COMMUNITY MEDICINE RISK FACTORS Early studies dealing with the emergence of VRE in the United States revealed that most patients with VRE were in intensive care units (ICUs). However, VRE are now being seen with increasing frequency among patients with chronic renal failure or cancer, organ transplant recipients and patients who experience prolonged hospitalization. Risk factors that have emerged are longer duration of hospitalization, longer lengths of stay in ICU, the need for intrahospital transfer to another ward, the need for surgical reexloration following liver transplantations, and the use of enteral tube feedings or sucralfate.

Risk factors specifically associated with VRE infections such as bacteremia include malignancy, increased Acute Physiologic Assessment and Chronic Health Evaluation (APACHE) II score, neutropenia, prolonged hospital stay, antibiotic therapy and preceding therapy with agents active against anaerobes, mean number of days on antibiotic therapy, renal insufficiency and hospitalization on a hematologic malignancy/bonemarrow transplantation service. Parenteral vancomycin use and receipt of third-generation cephalosporins have been cited by others as risk factors for colonization or infection with VRE. Oral vancomycin use may also be a risk factor for VRE colonization, and this has led to recommendations discouraging the use of this agent for the primary treatment of antibiotic-associated diarrhea. However, there is also recent evidence that metronidazole may not be a microbiologically innocuous alternative to oral vancomycin for the treatment of antibiotic-associated diarrhea. The use of oral or parenteral metronidazole (or other agents with significant anti-anaerobic activity) was noted as a risk factor for VRE bacteremia in one study, while others have suggested that metronidazole or clindamycin exposure is a risk factor for VRE acquisition.

COLONIZATION AND INFECTION The emergence of vancomycin resistance in enterococci in addition to the increasing incidence of high-level enterococcal resistance to penicillin and aminoglycosides presents a serious challenge for physicians treating patients with infections due to these microorganisms. Resistance to cephalosporins and clindamycin occurs almost without exception.

Infections caused by VRE often involve intra-abdominal sites, the urinary tract, the bloodstream, surgical sites and vascular catheter sites.

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VRE infections tend to occur in more debilitated or seriously ill-hospitalized patients. Mortality rates in patients with VRE bacteremia may reach 60-70%.

Approximately half of these deaths may be attributable directly to the infection.13 RESERVOIRS At present, hospitalized patients with gastrointestinal carriage of VRE appear to be the major reservoir of the organism in the United States. Because most colonized patients are asymptomatic, this reservoir can easily go unnoticed unless surveillance culture specimens are obtained from patients at risk.

Environmental surfaces and medical equipment items in the patient’s room frequently become contaminated with VRE and may also serve as a reservoir for the organism in the hospital. Widespread environmental contamination by VRE is especially likely to occur in the rooms of patients who have diarrhea.13 MODES OF TRANSMISSION Transmission of VRE by healthcare workers whose hands become transiently contaminated with the organism, while caring for affected patients is probably the most common mode of nosocomial transmission.

Transmission of VRE may also occur by way of contaminated medical equipment. Since, enterococci may remain viable for several days to weeks on dry surfaces, it seems plausible that contaminated surfaces may act as a source from which personnel may contaminate their hands or clothing. Disposable cover gowns worn by personnel who care for VRE patients have also been shown to be contaminated with the patient’s organism.13 CONTROL MEASURES In response to the dramatic increase in vancomycin resistance in enterococci, the Subcommittee on Prevention and Control of Antimicrobial-resistant Microorganisms in Hospitals of the CDC Hospital Infection Control Practices Advisory Committee (HICPAC) published recommendations.

These recommendations mainly focused on: i) prudent use of vancomycin; ii) education of hospital staff; iii) effective use of the microbiology laboratory and iv) implementation of infection control measures (including the use of gloves and gowns and isolation or cohorting of patients, as appropriate to specific conditions.

COMMUNITY MEDICINE Prudent Use of Vancomycin Efforts to control antibiotic-resistant organisms generally focus on decreasing the use of antibiotics and decreasing the opportunities for the spread of organisms between individuals. The logic behind efforts to decrease antibiotic use is that the presence of an antibiotic provides a tremendous advantage to a resistant organism and can increase the number of resistant bacteria manifold. The greater the number of resistant bacteria in a given clinical sample, the easier it is for that resistant organism to be transmitted to another person. This makes efforts at decreasing transmission more important but at the same time more difficult.14

by clinical cultures has often proved useful during outbreaks and should be considered an essential component of successful VRE control programs.

Surveillance cultures of stool, rectal or perirectal specimens should be inoculated onto selective mediacontaining vancomycin. Although brain heart infusion agar plates containing vancomycin are useful for confirming vancomycin resistance when testing isolated colonies of enterococci, they are not appropriate for screening stool specimens for VRE, because they support the growth of many other organisms.13 TREATMENT11 ÂÂ

Prior to any treatment of infections, all suspected intravenous lines, intra-arterial catheters and urinary catheters should be removed and abscesses drained. Infections that do not require bactericidal therapy are usually treated with a single antibiotic directed toward enterococci; these infections include urinary tract, intra-abdominal and uncomplicated wound infections. Some studies find that monotherapy is adequate treatment for many patients with enterococcal bacteremia when no evidence of endocarditis exists. In clinical practice, combination therapy with a cell wall-active agent and an aminoglycoside should be considered for treating serious enterococcal infections in critically ill patients and in those with evidence of sepsis, as well as in patients with endocarditis, meningitis, osteomyelitis or joint infections.

ÂÂ

For monotherapy of susceptible E. faecalis, ampicillin is the drug of choice. Ampicillin MICs are 2- to 4-fold lower compared with penicillin MICs for most isolates. For rare strains that are resistant to ampicillin because of β-lactamase production, ampicillin plus sulbactam may be used. For patients with a penicillin allergy or strains with high-level penicillin resistance due to altered penicillin-binding proteins, vancomycin should be administered. Nitrofurantoin is effective for the treatment of enterococcal UTIs, including many caused by VRE strains. As more experience is gained with the use of linezolid, daptomycin and tigecycline, these drugs may be used more commonly when VRE infections are encountered.

ÂÂ

Combination therapy with a cell wall-active agent (e.g., ampicillin, vancomycin) and an aminoglycoside (e.g., gentamicin or streptomycin) is necessary to adequately treat patients with enterococcal endocarditis. This combination results in synergistic bactericidal activity against susceptible enterococcal strains. At least 4 weeks

Implementation of Infection Control Measures The current isolation precautions recommended by HICPAC to prevent patient-to-patient transmission of VRE are as follows:12,15 ÂÂ

Place VRE-infected or colonized patients in single rooms or in the same room as other patients with VRE.

ÂÂ

Wear clean nonsterile gloves when entering the room of a VRE-infected or colonized patient.

During the course of caring for a patient, a change of gloves may be necessary after contact with material that may contain high concentrations of VRE (e.g., stool).

ÂÂ

Wear a clean nonsterile gown when entering the room of a VRE-infected or colonized patient if substantial contact with the patient or environmental surfaces in the patient’s room is anticipated or if the patient is incontinent or has diarrhea, an ileostomy, a colostomy or wound drainage not contained by a dressing.

ÂÂ

Remove gloves and gowns before leaving the patient’s room, and wash hands immediately with an antiseptic soap or use a waterless antiseptic agent. Hands can be contaminated via glove leaks or during glove removal, and bland soap is relatively ineffective in removing VRE from the hands.

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Ensure that after glove and gown removal and hand washing, clothing and hands do not contact environmental surfaces potentially contaminated with VRE (e.g., door knob or curtain) in the patient’s room.

SURVEILLANCE CULTURES Performing special surveillance cultures of patients to detect gastrointestinal colonization not identified

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COMMUNITY MEDICINE of combination therapy is recommended for the treatment of enterococcal endocarditis. Six weeks of combination therapy is recommended for patients with symptoms for more than 3 months before starting therapy, for patients who relapsed after shorter courses of therapy, and for patients with prosthetic valves. ÂÂ

If vancomycin is used in the course of treatment for endocarditis, a 6-week rather than 4-week course of therapy is recommended. Combination therapy is also recommended for the treatment of enterococcal meningitis, and treatment is usually administered for at least 2-3 weeks. Intravenous linezolid or intravenous plus intraventricular quinupistin-dalfopristin have also been used successfully for meningitis.

REFERENCES 1. Klevens RM, Edwards JR, Richards CL Jr, Horan TC, Gaynes RP, Pollock DA, et al. Estimating health careassociated infections and deaths in U.S. hospitals, 2002.

Public Health Rep. 2007;122(2):160-6.

2. Kung HC, Hoyert DL, Xu J, Murphy SL. Deaths: final data for 2005. Natl Vital Stat Rep. 2008;56(10):1-120.

3. Marothi YA, Agnihotri H, Dubey D. Enterococcal resistance - an overview. Indian J Med Microbiol.

2005;23(4):214-9.

4. Gold HS, Moellering RC Jr. Antimicrobial-drug resistance.

N Engl J Med. 1996;335(19):1445-53.

6. Cetinkaya Y, Falk P, Mayhall CG. Vancomycin-resistant enterococci. Clin Microbiol Rev. 2000;13(4):686-707.

7. Gram-positive cocci: part II. Koneman’s Color Atlas and Textbook of Diagnostic Microbiology. In: Winn W, Allen S, Janda W, Kaneman E, Procop G, Schreckenkerger P, Woods G (Eds.), 6th Edition. Baltimore, USA: Lippincott William & Wilkins. A Wolter Kluwer Company; 2006. pp. 700-1.

8. Fraser SL. Enterococcal infections. Available at: http:// www.emedicine-com/med/topic680.htm.

9. Clewell DB. Movable genetic elements and antibiotic resistance in enterococci. Eur J Clin Microbiol Infect Dis. 1990;9(2):90-102.

10. Murray BE. Vancomycin-resistant enterococci. Am J Med. 1997;102(3):284-93.

11. Grayson ML, Eliopoulos GM, Wennersten CB, Ruoff KL, De Girolami PC, Ferraro MJ, et al. Increasing resistance to beta-lactam antibiotics among clinical isolates of Enterococcus faecium: a 22-year review at one institution.

Antimicrob Agents Chemother. 1991;35(11):2180-4.

12. Zirakzadeh A, Patel R. Vancomycin-resistant enterococci: colonization, infection, detection, and treatment. Mayo Clin Proc. 2006;81(4):529-36.

13. Ang JY, Ezike E, Asmar BI. Antibacterial resistance. Indian J Pediatr. 2004;71(3):229-39.

14. Noskin GA. Vancomycin-resistant enterococci: clinical, microbiologic, and epidemiologic features. J Lab Clin Med. 1997;130(1):14-20.

5. Uttley AH, Collins CH, Naidoo J, George RC. Vancomycinresistant enterococci. Lancet. 1988;1(8575-6):57-8.

15. Rice LB. Emergence of vancomycin-resistant enterococci.

Emerg Infect Dis. 2001;7(2):183-7.

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The bulk of the evidence does not support guidelines that recommend a minimum calcium intake, including those from the Institute of Medicine. Most people don’t need to worry about their calcium at all as per Mark Bolland, MBChB, PhD, an associate professor of medicine at the University of Auckland in New Zealand. Randomized controlled trials show calcium supplementation provides only a modest reduction in the risk for fractures, and the benefit may be outweighed by adverse reactions, he said. Yet fractures are the primary reason cited for minimum calcium intake. In the two meta-analyses, both published in the September 29 issue of BMJ, Dr Bolland and colleagues found that neither calcium supplements nor dietary calcium significantly reduced the risk of fractures or improved bone mineral density. (Medscape)

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In his message on World Habitat Day, on 5 October, the UN Secretary-General Ban Ki-moon’s said, “Each year on World Habitat Day, we reflect on the state of human settlements and on what we want the cities of the future to look like. This year’s observance follows the adoption of the 2030 Agenda for Sustainable Development—an inspiring new framework that will guide our efforts to end poverty and ensure prosperity for all on a healthy planet. The new Sustainable Development Goals—which include SDG 11 to “make cities and human settlements inclusive, safe, resilient and sustainable”—represent a broad international consensus that recognizes sustainable urban development as a transformational approach. As part of an integrated agenda, cities and human settlements have an important role to play across the entire spectrum of the 2030 Agenda. The theme of World Habitat Day 2015 is “Public Spaces for All”. Frequently overlooked and undervalued, public spaces are increasingly being recognized as the vibrant, beating hearts of the world’s towns and cities, which are today home to half of humanity….(Source: http://www.un.org/press/en/2015/ sgsm17182.doc.htm/)

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COMMUNITY MEDICINE

Evaluation of Hand Hygiene Practice: Role in Prevention of Infection DEEPAK ARORA*, MK MAHAJANâ€

ABSTRACT Nosocomial infections due to poor hand hygiene are a major cause of increasing morbidity, mortality and healthcare costs among hospitalized patients worldwide. Hand hygiene is considered the single most cost-effective public health measure for preventing healthcare-associated infection. The World Health Organization has issued guidelines for procedural hand washing in order to reduce the prevalence of hospital-associated infections. Improvements in adherence to hand hygiene recommendations and proper hand washing technique among section healthcare workers are uncommon, even after educational efforts. In some hospitals, there is not even proper training of the employees regarding hand hygiene practices. The present study was undertaken to assess the level of knowledge and attitude among residents and staff nurses of Advanced Cancer Research Center, Bathinda regarding hand hygiene practices and also to identify gaps in knowledge and poor attitudes regarding hand hygiene practices among residents and staff nurses.

Keywords: Hand hygiene, healthcare-associated infection, recommended practices, compliance, high-risk procedures

I

nfection caused due to hospital-acquired microbes is an evolving problem worldwide, and horizontal transmission of bacterial organisms continues to cause a high nosocomial infection rate in healthcare settings. Nosocomial infections due to poor hand hygiene are a major cause of increasing morbidity, mortality and healthcare costs among hospitalized patients worldwide.1 The high prevalence of these infections, as high as 19%, in developing countries poses a challenge to healthcare providers.2

Transmission of healthcare-associated pathogens generally occurs via the contaminated hands of healthcare workers often transmitting virulent and multidrug-resistant strains. Though preventable with a simple hand washing, healthcare workers are reluctant to adopt recommended practices to curb these infections.3 Hand hygiene is considered the

*Associate Professor Dept. of Microbiology Guru Gobind Singh Medical College, Faridkot, Punjab †Director, Advanced Cancer Institute, Bathinda, Punjab Address for correspondence Dr Deepak Arora Associate Professor Dept. of Microbiology Guru Gobind Singh Medical College, Faridkot - 151 203, Punjab E-mail: drdeepakarora78@gmail.com

single most cost-effective public health measure for preventing healthcare-associated infection (HCAI).4 The significance of hand washing in patient care was conceptualized in the early 19th century.5-7 Labarraque5 provided the first evidence that hand decontamination can markedly reduce the incidence of puerperal fever and maternal mortality.

In 1975 and 1985, the Centers for Disease Control and Prevention (CDC) published guidelines on hand washing practices in hospitals, primarily advocating hand washing with nonantimicrobial soaps; washing with antimicrobial soap was advised before and after performing invasive procedures or during care for high-risk patients. Alcohol-based solutions were recommended only in situations where sinks were not available.8,9 In 1995, the Hospital Infection Control Practices Advisory Committee (HICPAC) advocated the use of antimicrobial soap or a waterless antiseptic agent for cleaning hands upon leaving the rooms of patients infected with multidrug-resistant pathogens.10 In 2002, the CDC published revised guidelines for hand hygiene.11 The World Health Organization (WHO) has issued guidelines for procedural hand washing in order to reduce the prevalence of hospital-associated infections but lack of knowledge amongst healthcare workers is associated with poor compliance.12 An alarming revelation was that compliance was found to be worst before high-risk procedures.13,14

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COMMUNITY MEDICINE Despite evidence and expert opinion that hand hygiene reduces transmission of potential pathogens or antimicrobial-resistant organisms, sustained improvements in adherence to hand hygiene recommendations and proper hand washing technique among section healthcare workers are uncommon,15 even after educational efforts. At the same time, in some hospitals, there is not even proper training of the employees regarding hand hygiene practices. This is shown by the lack of even basic awareness about hand washing guidelines among the hospital personnel. With this background, the present study was undertaken to assess the level of knowledge and attitude among residents and staff nurses of Advanced Cancer Research Center, Bathinda regarding hand hygiene practices and also to identify gaps in knowledge and poor attitudes regarding hand hygiene practices among residents and staff nurses to enhance good practices and working ethics in future.

INDIAN SCENARIO In India, the quality of healthcare is governed by various factors, the principal amongst these being whether the healthcare organization is government or private-sector run. There is also an economic and regional disparity throughout the country. About 75% of health infrastructure, medical manpower and other health resources are concentrated in urban areas, where 27% of the population lives.16 Like in other developing countries, the priority given to prevention and control of HCAI is minimal. This is primarily due to lack of infrastructure, trained manpower, surveillance systems, poor sanitation, overcrowding and understaffing of hospitals, unfavorable social background of population, lack of legislations mandating accreditation of hospitals and a general attitude of noncompliance amongst healthcare providers towards even basic procedures of infection control. In India, although hand hygiene is imbibed as a custom and promoted at school and community levels to reduce the burden of diarrhea, there is a paucity of information on activities to promote hand hygiene in healthcare facilities. Sporadic reports document the role of hands in spreading infection and isolated efforts at improving hand hygiene across the country.17-20 MATERIAL AND METHODS The study was carried out for a period of 6 months from January to June 2015 to assess the knowledge and attitude regarding hand hygiene amongst residents and staff nurses and class 4 employees (including sweepers)

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of a tertiary care hospital in Bathinda, Punjab, India after obtaining clearance from the ethical committee of the institution. Verbal consent was obtained from those who volunteered to participate. A prevalidated questionnaire was administered to respondents initially and their record and data analysis and management was done using Microsoft Excel software. A total of 50 respondents were included in the study and their level of knowledge was assessed on the basis of Questionnaire for Healthcare Workers. Then a sensitizing program regarding WHO recommendations for the hand washing hygiene and knowledge about most appropriate timing for performing hand hygiene actions that prevent transmission of germs to the patient was given to the healthcare workers. A Knowledge Questionnaire was again given to them and the record was maintained.

It was then compared with the previous questionnaire given before the sensitization.

For scoring, 1 point was given for each correct response to good level of knowledge and positive attitude and 0 point was given for poor level of knowledge and negative attitude, and they were categorized in category 1, category 2, category 3 depending on percentage they scored 75% and above was considered good, a score between 50% and 74% was moderate/average/fair and below 50% was considered poor. Data analysis and management was done using Microsoft Excel 2010 software.

RESULTS No significant difference between response and level of knowledge before and after the sensitization program was observed in first study group (residents). Out of the 10 residents, only 4 (40%) could score 75% (good) and 4 (40%) scored between 50% and 75% (moderate/ average) and 2 (20%) scored 50% and less (poor) and after the sensitization program was given 5 (50%) instead of 4 (40%) could score between 50% and 75%. As such out of 10 residents, 8 (80%) residents had a good knowledge about routes of transmission of infection and attitude regarding correct hand hygiene practices.

In second group, that included 10 (staff nurses), the attitude regarding correct hand hygiene practices was casual. Before the sensitization program, 1/10 (10%) scored 75% and 1/10 (10%) was in 50-74% category and 8/10 (80%) scored less than 50% and after the sensitization program, 4 instead of 1 entered in 50-74% category. As such out of 10 staff nurses, only 2 (20%) had a good knowledge about routes of transmission of infection and attitude regarding correct hand hygiene practices.

COMMUNITY MEDICINE In third group of 30 class 4 employees, the attitude regarding correct hand hygiene practices was also casual. Before the sensitization program was only 2 (6%) scored 75% and 5 (16%) was in 50-74% category and 23 (77%) scored less than 50% but after the sensitization program, the approach was drastically good and their level of education really improved and 4 (6%) scored 75% and 14 (47%) was in 50-74% category and 12 (40%) scored less than 50%.

DISCUSSION India is one of the prominent member countries of the World Alliance for Patient Safety. The present study highlights the importance of training sessions regarding hand hygiene practices among the residents and staff nurses to provide the current and updated knowledge in the area of nosocomial infections and prevention of infections. It would also translate in a behavioral change of attitudes and practices that would help in reducing the incidence of nosocomial infections.

In our study, residents had good knowledge on hand hygiene. Out of the total 50 participants, 30 (60%) respondents answered correctly when asked about the main route of transmission of potentially harmful germs between patients. Our results are comparable with other studies,9 which reported that 72% of participants knew that unhygienic hands of healthcare workers were the main route of transmission.

However, only 45% of residents and 27% of nurses and 14% of the class 4 knew that the most frequent source of germs responsible for HCAI’s were the germs already present on or within the patient, with residents having significantly better knowledge in this aspect.

About the minimum time needed for effective hand hygiene only residents and nurses (35% and 25%, respectively) were aware about the minimum time needed for effective hand hygiene as mentioned in WHO guidelines. Our findings were similar to a study carried out by Abd Elaziz et al21 at Ain Shams University, Cairo, wherein 23.2% of observed candidates showed inappropriate hand washing due to both short contact time (less than 30 sec) and improper drying after hand washing.

About the hand hygiene methods, both groups had answered below satisfaction level regarding the hand hygiene method required before palpation of abdomen (33%), before giving an injection (27%) and after making a patient’s bed (21%). Comparative values given in study of Ariyaratne in Sri Lanka22 are 31%, 26% and 25%, respectively. However, overall knowledge

regarding the hand hygiene method needed in the required clinical situation was unsatisfactory and this study identified gaps in their knowledge and areas needed for improvement.

The best way to improve hand washing compliance based on the finding of this study was motivation, training and education of healthcare workers. Nurses showed more positive attitudes towards hand hygiene.

In a study conducted by Suchitra19 at Dept. of Microbiology, Mysore University, it was revealed that compliance for hand washing was maximum among nurses, intermediate for technicians and the least for doctors. Barriers to practice hand hygiene was attributed to lack of education, high work load, understaffing, working in critical care units, lack of encouragement, lack of role model among senior staff and lack of knowledge of guidelines set by the institution.

CONCLUSION The results of this study should be interpreted in light of a limitation that the findings cannot be generalized to other tertiary care hospitals as ACDRC, is an autonomous institute directly funded by the Government of Punjab and similar resources may not be available to other tertiary care hospitals. However, the present study highlights the importance of training sessions regarding hand hygiene practices among the residents and staff nurses to provide the current and updated knowledge in the area of nosocomial infections and prevention of infections. It would also translate in a behavioral change of attitudes and practices that would help in reducing the incidence of nosocomial infections.

REFERENCES 1. Trampuz A, Widmer AF. Hand hygiene: a frequently missed lifesaving opportunity during patient care. Mayo Clin Proc. 2004;79(1):109-16.

2. World Health Organization. The Burden of health careassociated infection worldwide. A Summary. [Cited 2010 Apr 30]. Available from: http://www.who.int/gpsc/ country_work/summary_20100430_en.pdf.

3. Meengs MR, Giles BK, Chisholm CD, Cordell WH, Nelson DR. Hand washing frequency in an emergency department. J Emerg Nurs. 1994;20(3):183-8.

4. Pittet D, Allegranzi B, Sax H, Dharan S, Pessoa-Silva CL, Donaldson L, et al; WHO Global Patient Safety Challenge, World Alliance for Patient Safety. Evidence-based model for hand transmission during patient care and the role of improved practices. Lancet Infect Dis. 2006;6(10):641-52.

5. Labarraque AG. Instructions and observations regarding the use of the chlorides of soda and lime. In: Porter J (Ed.).

New Haven, CT: Baldwin and Treadway; 1829.

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COMMUNITY MEDICINE 6. Semmelweis I. Etiology, concept, and prophylaxis of childbed fever. In: Carter KC (Ed.). 1st Edition, Madison, WI: The University of Wisconsin Press; 1983.

14. Creedon SA. Hand hygiene compliance: exploring variations in practice between hospitals. Nurs Times.

2008;104(49):32-5.

7. Rotter ML. 150 years of hand disinfection - Semmelweis’ heritage. Hyg Med. 1997;22:332-9.

15. Trick WE, Vernon MO, Hayes RA, Nathan C, Rice TW, Peterson BJ, et al. Impact of ring wearing on hand contamination and comparison of hand hygiene agents in a hospital. Clin Infect Dis. 2003;36(11):1383-90.

8. Steere AC, Mallison GF. Handwashing practices for the prevention of nosocomial infections. Ann Intern Med. 1975;83(5):683-90.

9. Garner JS, Favero MS. CDC Guideline for Handwashing and Hospital Environmental Control, 1985. Infect Control.

1986;7(4):231-43.

10. Hospital Infection Control Practices Advisory Committee (HICPAC). Recommendations for preventing the spread of vancomycin resistance. Infect Control Hosp Epidemiol.

1995;16(2):105-13.

11. Boyce JM, Pittet D; Healthcare Infection Control Practices Advisory Committee; HICPAC/SHEA/APIC/ IDSA Hand Hygiene Task Force. Guideline for Hand Hygiene in Health-Care Settings. Recommendations of the Healthcare Infection Control Practices Advisory Committee and the HICPAC/SHEA/APIC/IDSA Hand Hygiene Task Force. Society for Healthcare Epidemiology of America/Association for Professionals in Infection Control/Infectious Diseases Society of America. MMWR Recomm Rep. 2002;51(RR-16):1-45, quiz CE1-4.

12. WHO Guidelines on Hand Hygiene in Health Care First Global Patient Safety Challenge Clean Care is Safer Care. 2009. Available from: http://whqlibdoc.who.int/ publications/2009/9789241597906_eng.pdf.

16. Mani A, Shubangi AM, Saini R. Hand hygiene among health care workers. Indian J Dent Res. 2010;21(1):115-8.

17. Mathai E, Allegranzi B, Kilpatrick C, Pittet D. Prevention and control of health care-associated infections through improved hand hygiene. Indian J Med Microbiol.

2010;28(2):100-6.

18. Chandra PN, Milind K. Lapses in measures recommended for preventing hospital-acquired infection. J Hosp Infect.

2001;47(3):218-22.

19. Suchitra JB, Lakshmi Devi N. Impact of education on knowledge, attitudes and practices among various categories of health care workers on nosocomial infections.

Indian J Med Microbiol. 2007;25(3):181-7.

20. Taneja N, Das A, Raman Rao DS, Jain N, Singh M, Sharma M. Nosocomial outbreak of diarrhoea by enterotoxigenic Escherichia coli among preterm neonates in a tertiary care hospital in India: pitfalls in healthcare. J Hosp Infect.

2003;53(3):193-7.

21. Abd Elaziz KM, Bakr IM. Assessment of knowledge, attitude and practice of hand washing among health care workers in Ain Shams University hospitals in Cairo.

Egypt J Commun Med. 2008;26(2):1-12.

22. Ariyaratne MHJD, Gunasekara TDCP, Weerasekara MM, Kottahachchi J, Kudavidanage BPJ, Fernando SSN. 13. Rumbaua R, Yu C, Pena A. A point-in-time observational Knowledge, attitudes and practices of hand hygiene study of hand washing practices of healthcare workers in among final year medical and nursing students at the the Intensive Care Unit of St. Luke’s Medical Center. Phil J University of Sri Jayewardenepura. Sri Lankan J Infect Microbiol Infect Dis. 2001;30:3-7.

Dis. 2013;3(1):15-25.

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The use of nuclear myocardial perfusion imaging (MPI) declined substantially in a large integrated healthcare system during a recent 5-year period. Following an increase in use from 2000 to 2006 at Kaiser Permanente Northern California, MPI use dropped by a relative 51% through 2011 according to Edward McNulty, MD, of Kaiser Permanente Medical Center in San Francisco. Replacement by cardiac CT and stress echocardiography did not explain the pullback from using MPI, the researchers reported March 26 issue of JAMA. The fact that we observed greater declines amongst lower-risk subsets (outpatients and younger persons) suggests MPI use became more discriminating (used preferentially in higher-risk persons), as per the authors. Other reasons may be “more recently, factors potentially discouraging use, such as appropriate use criteria, declining reimbursement, radiology benefits managers, and more publicized concerns about the health effects of radiation have emerged.”

(Source: Medpage Today)

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DENTISTRY

Desquamative Gingivitis: A Clinician’s Nightmare SWAPAN KUMAR PURKAIT*, UTPAL MUKHOPADHYAY†, SUMANTA KUMAR KOLEY‡, MAITREYI GUHA#

ABSTRACT Desquamative gingivitis refers to a pathological condition characterized by desquamation or shedding of the epithelial cells on the surface of the gingiva; often leading to erythema, sloughing or ulceration and severe discomfort to the patient. Because of its multifactorial and multidimensional onset, this disease often poses a serious challenge while providing an effective treatment.

Histopathological examination and direct immunofluorescence testing are often required to establish the final diagnosis. Proper counseling of the patient is absolutely necessary as most of such treatments need long therapeutic regimens and patients should understand that no miraculous results could possible over-night.

Keywords: Desquamative gingivitis, histopathological, histochemistry, immunohistochemistry

D

esquamative gingivitis is a clinical term, which refers to a pathological condition characterized by desquamation or shedding of the epithelial cells on the surface of the gingiva; often leading to erythema, sloughing or ulceration and severe discomfort to the patient.

Desquamative gingivitis is not a single disease entity; rather it is a manifestation of several disease conditions; many of which are dermatological in origin. Because of its multifactorial and multidimensional onset, this disease often poses a serious challenge while providing an effective treatment. Making the correct diagnosis of desquamative gingivitis is often difficult and it cannot be done with the help of clinical observation alone; rather it requires in depth investigations (e.g. histopathology, histochemistry and immunohistochemistry, etc.).

Unfortunately in most of the cases in this disease, treatments are done simply on the basis of clinical symptoms and for obvious reason, treatment outcomes are often far from satisfactory. With no satisfactory remission, patients often get confused and become more

*Professor, Dept. of Oral and Maxillofacial Pathology Buddha Institute of Dental Sciences and Hospital, Patna, Bihar †Professor and Head, Dept. of Conservative Dentistry and Endodontics Dr BR Ambedkar College of Dental Sciences, Patna, Bihar ‡Senior Lecturer, Dept. of Oral and Maxillofacial Pathology Sarjug Dental College and Mata R Devi Hospital, Darbhanga, Bihar #All India Institute of Hygiene and Public Health Urban Health Centre, Kolkata, West Bengal Address for correspondence Dr Swapan Kumar Purkait Professor, Dept. of Oral and Maxillofacial Pathology Buddha Institute of Dental Sciences and Hospital, Patna, Bihar

frightened about the disease, suspecting something extremely serious (may be malignancy, etc.) and keep on consulting one doctor after another.

Desquamative gingivitis may be caused by several diseases, which include the following: ÂÂ

Oral lichen planus

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Cicatricial pemphigoid

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Bullous pemphigoid

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Pemphigus vulgaris

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Linear IgA disease

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Dermatitis herpetiformis

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Lupus erythematosus

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Chronic ulcerative stomatitis

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Chronic bacterial, fungal and viral infections

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Hypersensitivity reactions to medications and chewing gum

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Crohn’s disease

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Sarcoidosis

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Leukemia

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Factitious (self-inflicted) injury

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Early stage of squamous cell carcinoma.

Although any of the above diseases can precipitate desquamative gingivitis; but mucocutaneous disorders such as oral lichen planus, cicatricial pemphigoid and pemphigus vulgaris are the most predominant diseases often leading to this. It is generally believed that desquamative gingivitis can be produced by oral lichen planus in about 70% cases; followed by benign mucous membrane pemphigoid in 14% cases and the

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DENTISTRY Table 1. Comparative Evaluation of Some Very Important Diseases Causing Desquamative Gingivitis Name

Clinical features

Histopathology

Immunohistochemistry Treatment

Lichen planus (Chronic inflammatory mucocutaneous disease caused by an unknown etiology)

Numerous interlacing white keratotic lines, often producing a typical ‘lacelike’ pattern against an erythematous base.

It is characterized by Liquefaction degeneration of basal cells with bandlike lymphocyte infiltration in the subepithelial region.

Linear deposition of fibrin or fibrinogen in the basement membrane zone; however, such findings are often nonspecific.

yy Oral corticosteroids such as prednisolone yy Metronidazole yy Immunosuppressive agents

Mucous membrane pemphigoid (an autoimmune, vesiculobullous disease with antibodies forming against the basement membrane of epithelium)

Gingival erythema with vesicle or bullae formation; occasionally localized blood-filled bulla also found on the gingiva.

Skin, conjunctiva, larynx, esophagus, genitourinary tract can also be affected.

Mucous membrane pemphigoid is histologically characterized by subepithelial bulla formation.

Deposition of autoantibodies in the basement membrane zone.

yy Corticosteroids yy Immunosuppressive drug yy Cyclophosphamide

Pemphigus vulgaris (It is an autoimmune disease with antibodies forming against the intercellular cement substance)

Formation of vesicle or bullae in the gingiva; which rupture rapidly to produce ulcer. Nikolsky’s sign is positive.

It is characterized by acantholysis with intraepithelial vesicle formation.

Deposition of IgG and C3 is often found between the epithelial cells and is characterized by a fishnet pattern.

yy Corticosteroids yy Immunosuppressive drug yy Cyclophosphamide yy Antibiotics

Hypersensitivity reaction (Occurs due to reactions to medications, food, mouth washes and dental restorative materials)

Localized or generalized epithelial desquamation, erythema, ulceration and/or vesiculobullous lesions of the gingiva.

Nonspecific histopathologic findings with submucosal perivascular inflammatory cell infiltration.

Patchy areas of deposition of immunoglobulins.

yy Withdrawal of offending agent if any yy Antihistaminic yy Corticosteroid

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DENTISTRY pemphigus vulgaris in about 13% cases. Clinically, desquamative gingivitis affects both the marginal as well as the attached gingiva and the lesion often extends to the alveolar mucosa. This disease is mostly seen in adult females; the affected part of the gingiva appears dusky red in color; the gingival surface is eroded or ulcerated, extremely painful with occasional development of vesiculations. Patients feel severe soreness or burning sensation especially during taking hot or spicy foods and Nikolsky’s sign is positive in many cases (the epithelium could be peeled away easily by slightly scratching the surface of the gingiva).

In some patients of desquamative gingivitis, there may be simultaneous occurrence of erosive lesions in the skin as well as in the genitalia.

As we see in the Table 1, desquamative gingivitis may have similar clinical symptoms, but the underlying disease producing this condition varies greatly; that’s why it is extremely difficult to treat such lesions.

To provide effective treatment of desquamative gingivitis a definitive diagnosis of the specific disease or disorder causing the condition must be understood first; and it is almost impossible to do so based solely on clinical manifestations. Therefore, histopathological examination and direct immunofluorescence testing are often required to establish the final diagnosis. Moreover, proper counseling of the patient is absolutely necessary as most of such treatments need long therapeutic regimens and patients should understand that no miraculous results could possible over-night.

SUGGESTED READING 1. Mobio S, Badran Z, Tessier MH, Giumelli B, Soueidan A. Desquamative gingivitis. Rev Belge Med Dent (1984).

2007;62(3):130-40.

histopathologic, and immunologic study. Quintessence Int. 1996;27(11):763-7.

3. Soukos N, Spyropoulos M. Chronic desquamative gingivitis. Etiology, clinical and histological features, immunopathological studies, diagnosis and treatment.

Odontostomatol Proodos. 1990;44(3):151-8.

4. Lozada-Nur F, Miranda C. Oral lichen planus: topical and systemic therapy. Semin Cutan Med Surg. 1997;16(4): 295-300.

5. Mollaoglu N. Oral lichen planus: a review. Br J Oral Maxillofac Surg. 2000;38(4):370-7.

6. Scully C, Beyli M, Ferreiro MC, Ficarra G, Gill Y, Griffiths M, et al. Update on oral lichen planus: etiopathogenesis and management. Crit Rev Oral Biol Med. 1998;9(1):86-122.

7. Nisengard RJ, Rogers RS 3rd. The treatment of desquamative gingival lesions.

J Periodontol.

1987;58(3):167-72.

8. Lorenzana ER, Rees TD, Hallmon WW. Esthetic management of multiple recession defects in a patient with cicatricial pemphigoid. J Periodontol. 2001;72(2):230-7.

9. Chaikin BS. A treatment of desquamative gingivitis by the use of free gingival grafts. Quintessence Int. 1980;11(9):105-11.

10. Tamizi M, Moayedi M. Treatment of gingival lichen planus with a free gingival graft: a case report. Quintessence Int. 1992;23(4):249-51.

11. Okuda K, Momose M, Murata M, Saito Y, lnoie M, Shinohara C, et al. Treatment of chronic desquamative gingivitis using tissue-engineered human cultured gingival epithelial sheets: a case report. Int J Periodontics Restorative Dent. 2004;24(2):119-25.

12. Katz J, Goultschin J, Benoliel R, Rotstein I, Pisanty S. Lichen planus evoked by periodontal surgery. J Clin Periodontol. 1988;15(4):263-5.

13. Engel MB, Ray HG, Orban B. The pathogenesis of desquamative gingivitis: a disturbance of the connective 2. Markopoulos AK, Antoniades D, Papanayotou P, tissue ground substance. J Dent Res. 1950;29(4):410-8.

Trigonidis G. Desquamative gingivitis: a clinical, ■■■■

A study led by Dr Bing Hu at Plymouth University Peninsula Schools of Medicine and Dentistry and involving other researchers from China and Switzerland, suggests for the first time that the use of local anaesthetic may affect tooth cell growth and the development of children’s teeth. The study was published in Monday 7th September 2015, in Cell Death Discovery, a new leading translational medical research journal from Nature Publishing Group, and comes at a time when more children than ever before are subjected to dental surgery and local anesthetic - because of tooth decay or other orthodontic conditions.

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DERMATOLOGY

Study of the Clinico-Epidemiological Pattern and the Precipitating Factors in 100 Melasma Patients in an Urban Town PRADIP KUMAR DAS*, DEBJIT PANJA†

ABSTRACT Melasma is a common acquired hyperpigmentation disorder that occurs primarily on the sun-exposed areas of the face and neck and, occasionally, the forearms. Melasma is the most common pigmentary disorder seen in Indians. It is much more common in women during their reproductive years but approximately 10% (in this study group 16%) men are also affected. The etiology of melasma has been attributed to multiple factors which include ultraviolet radiation exposure, pregnancy, contraceptive pills, hormonal replacement therapy and cosmetics, phototoxic and antiseizure medications, though the pathogenesis remains poorly understood. Pigmentation may also occur due to endocrine pathology and interaction of light and hormonal effects.

According to the distribution of lesions, three clinical patterns of melasma are recognized. The centrofacial pattern is the most common pattern and involves the forehead, cheeks, upper lip, nose and chin. The malar pattern involves the cheeks and nose.

The mandibular pattern involves the ramus of the mandible. Melasma can causes emotional upset, hinders normal functioning at work and is associated with anxiety and depression leading to affection on our quality-of-life. Our present research aims to study the clinico-epidemiological pattern and the precipitating or provocation factors in melasma.

Keywords: Melasma, hyperpigmentation, centrifacial, malar and mandibular pattern

T

he color of the skin is dependent on a number of factors like hemoglobin, carotenoids and melanin. The most important factor that imparts skin color is melanin pigment. It is seen that two types of melanin pigmentation occur in humans. Melasma (a term derived from the Greek word “melas” meaning black) is a common acquired hypermelanosis that occurs primarily on the sun-exposed areas of the face and neck and, occasionally, the forearms. It occurs in all skin types but is most common in Fitzpatrick skin types IV and VI, with increased susceptibility in dark-haired women. The term, “chloasma” (from the Greek word “chloazein” meaning “to be green”) is often used to describe melasma developing during pregnancy; but the

*Secretary, Swasthya Bhabna Welfare Society, Principal Investigator, Consultant Physician and Dermatologist, Master Trainers and Supportive Supervisor in GFATM-Project-7 †Consultant Physiotherapist Konnagar, Hooghly, West Bengal Address for correspondence Dr Pradip Kumar Das 15/C, Raja KL Goswami Street Serampore, Hooghly - 712 201, West Bengal E-mail: pradipdr2@gmail.com

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pigmentation never appears to be green, therefore the term, “melasma” is preferred. In South-East Asia, melasma accounts for 0.25-4% of patients seen in dermatology institutes, with peak incidence in those aged 30-44 years. One simple survey suggests that the prevalence of melasma is as high as 40% in females and 20% in males. Melasma is the most common pigmentary disorder seen in Indians. It is much more common in women during their reproductive years, but approximately 10% (in this study group 16%) men are also affected. It is rarely reported before puberty.

The clinical picture and histological appearance of melasma in both the sexes are same. Cutaneous melasma is a relatively common dermatologic disease, occurring most commonly in Asian and Hispanic women of childbearing years. Exposure to solar ultraviolet radiation is the most important environmental factor in the pathogenesis of melasma. Besides these, excessive pigmentation may also occur due to endocrine pathology and interaction of light and hormonal effects. The etiology of melasma has been attributed to multiple factors which include ultraviolet radiation exposure, pregnancy, contraceptive pills, hormonal replacement therapy and cosmetics, phototoxic and

DERMATOLOGY antiseizure medications, though the pathogenesis remains poorly understood. Although the condition is found primarily in women, it also occurs in men.

According to the distribution of lesions, three clinical patterns of melasma are recognized. The centrofacial pattern is the most common pattern and involves the forehead, cheeks, upper lip, nose and chin. The malar pattern involves the cheeks and nose. The mandibular pattern involves the ramus of the mandible and all the three types are common in individuals with skin type IV and VI. In all patients with melasma, the condition can have a serious adverse effect on quality-of-life by undermining social functioning and emotional wellbeing. Our present research aims to study the clinicoepidemiological pattern and the precipitating or provocation factors in melasma.

(27%) were in the age group between 31 and 40 years and only 11 patients (11%) were in the age group between 41 and 50 years and above. It was revealed that out of 100 patients studied mostly 84% were female and 16% were male who showed hyperpigmentation in their faces. It has been shown that melasma was distributed over malar bones in 21% cases, whereas the maximum areas of face where melanin pigmentation was deposited mainly over cheek, forehead and tip of the nose was 64% (centrofacial), and over mandibular Table 1. Distribution of Melasma According to Age 20-30 years

31-40 years

62 62%

41-50 years and above

27

11

27%

11%

MATERIAL AND METHODS Hundred patients were enrolled for the study. Majority of the patients were females (84%) and they belonged to 20-50 years age group and above. Patient’s consent was obtained for this study, wherein patients attending the private clinic, Serampore, Hooghly, West Bengal were included in this study, who had an average duration of symptoms for 1 year and more. A complete clinical examination was performed for evaluating the characteristic features and extension of the pigmentary disorder.

RESULTS The study comprised of 100 patients of melasma; the demographic features of which are given in Tables 1-7 and Figures 1-7.

Out of studied 100 patients suffering from melasma, their age distribution was that 62 patients (62%) were in the age group between 20 and 30 years, 27 patients

Percentage (%)

60

62

50 40 27

30 20

11

10 0

20-30

31-40

41-50 and above

Age in years

Figure 1. Distribution of melasma according to age of patients.

Table 2. Distribution of Melasma According to Sex Female

Male

84

16

84%

16%

100 90

84

80 Percentage (%)

The present study was carried out on the clinicoepidemiology of melasma patients between July 2011 and June 2013. One hundred patients with a clinical diagnosis of melasma were enrolled for the study. The demographic data regarding age at present, age of onset of melasma, sex, duration of the illness, family history, history of taking oral contraceptive pills (OCPs) were noted. The data of different predisposing factors like sun-exposure, pregnancy, cosmetics, ovarian tumor and other endocrinal diseases specially thyroid dysfunction were included, and relevant investigations were carried out to rule out the same. Clinical evaluation was done and depending upon the distributions of lesions, they were divided into centrofacial, malar or mandibular.

70

70 60 50 40 30 20

16

10 0

Female

Male Sex

Figure 2. Distribution of melasma according to sex.

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DERMATOLOGY Table 3. Site of Distribution of Melasma Over cheek

21 21%

Over forehead

100

Over tip of nose

Over mandible

23

16

25

15

23%

16%

25%

15%

90 Percentage (%)

Over malar bone

80 68

70 60 50 40

32

30 20 10 Over malar bone

Over cheek

Over tip of nose

Over mandible

0

Over forehead

Taking OCP

Not taking OCP

Figure 5. Taking OCP as probable cause of melasma.

15%

21%

25%

23%

16%

Table 6. History of Affection of Other Family Members Affection (present)

Affection (absent)

24

76

24%

76%

Figure 3. Site of distribution of melasma.

100 90

Table 4. History of Sun-exposure as Probable Cause of Melasma

Percentage (%)

Sun-exposure (present)

Sun-exposure (absent)

66

34

66%

76

80

34%

70 60 50 40 30

24

20 10 0

100

Present

Figure 6. Affection of other family members.

Percentage (%)

80 70

Absent Affection

90

66

60

Table 7. Duration of Illness of Melasma

50 40

34

30

0-3 years

4-6 years

60 60%

20

7-10 years and more

25

15

25%

15%

10 0

Present

Absent

70

Sun-exposure

Figure 4. Sun-exposure as probable cause of melasma.

Table 5. History of Taking OCP as Probable Cause of Melasma Taking OCP 32 32%

456

Not taking OCP 68 68%

Indian Journal of Clinical Practice, Vol. 26, No. 5, October 2015

Percentage (%)

60

60

50 40 30

25 15

20 10 0

0-3

4-6 7-10 and more Duration in years

Figure 7. Duration of illness of melasma.

DERMATOLOGY area it was 15% was noted. Distribution was considered not in composite manner rather it was completely in solitary distribution. It was found that one of the cause for creating melasma over the face was sun-exposure which was evident in this study in 66 cases (66%), whereas in 34 cases of melasma no evidence of sunexposure was found, could be other causes like using OCP or hereditary, use of cosmetics, etc. In our study, 32 patients gave history of taking OCP during the course of illness, whereas 68 patients did not give the history of using OCP. It was seen that out of 100 patients suffering from hyperpigmentation in different areas of face and the adjoining areas, 24 patients revealed the history of such type of developing pigmentation in their family members, whereas 76 patients gave no such history of affection in their family members. Regarding the duration of illness, it was observed that 60 patients had of melasma for 3 years, 25 patients for 4-6 years and 15 patients for 7-10 years. Some patients gave the history of taking antithyroid drugs for their thyroid dysfunction but no history of sufferings of ovarian disease was recorded from any patients suffering from melasma in our study groups.

Few other studies have also reported a minimum relation with either pregnancy or oral contraceptives.

It appears that oral contraceptives may be a significant contributing factor in melasma. We could not find any association with ovarian tumor, but we noticed 4% of our patients having thyroid dysfunction. Twenty-three patients confirmed the association of cosmetics and melasma. Previously also, this association was found

by Grime et al, in 1995. According to the distribution of the lesions, we recognized three clinical patterns and among these, centrofacial was the most common (64%), like other studies from India and abroad.

DISCUSSION

CONCLUSION

Melasma is an acquired increased pigmentation of the skin. It is a commonly seen entity in clinical practice.

Few studies show that melasma accounts for 4-10% of the new cases in the dermatology hospital, as a referral.

Similarly, it is found to be the third most common pigmentary disorder of the skin, confirmed in a survey of 2000 black people, at a private clinic in Washington DC. The average age of melasma patients was 27 years in our study, compared to 42.3 years, reported in a study from Singapore.

Melasma is a hyperpigmentation disorder affecting commonly the females having dark skin types in the reproductive age group. Sun-exposure and hormonal changes are the important factors causing melasma.

Melasma was more common in females than in males in our study. Sun-exposure is a prime factor in the pathogenesis of developing melasma, but as on date now, exact pathogenesis of melasma is still unknown.

Melasma is more common in women. We found about 16% involvement of men in our study compared to 10% in a different study. A positive family history was observed in 24% patients, in the present study, which was similar to an earlier reported study, in which it varied from 20% to 70%. Multiple causative factors have been implicated in the etiology of melasma, including, ultraviolet light (sunlight), hormones (oral contraceptives) and pregnancy.

We have noticed that about 66% of our patients had sun-exposure, which they felt was an aggravating factor. It is in great contrast to Pathak’s report, which suggests that sunlight exacerbates melasma in all patients. In this study, 32% of them were taking oral contraceptives during their disease process. These figures are corroborative to those reported earlier.

However, studies from Singapore and South India observed that malar distribution was the most common, here in our study it is 21%. This variation of results might be due to environmental or regional differences. In our study, it was also found that some of the patient’s relatives also had melasma and some of the patient’s disease was associated with autoimmune disease, mainly thyroid dysfunction. These findings suggest some genetic implication in the development of melasma.

Current research revealed that the interaction of stem cell factor, c-kit and vascular endothelial growth factor in the dermal fibroblasts can affect melanocyte function and this needs to be further studied to determine what actually triggers the hypermelanosis. Melasma is obviously a disfiguring condition that causes emotional upset, creates a barrier to social interactions, hinders normal functioning at work and is associated with negative fear of evaluation, anxiety and depression leading to social isolation and loneliness.

SUGGESTED READING 1. Achar A, Rathi SK. Melasma: a clinico-epidemiological study of 312 cases. Indian J Dermatol. 2011;56(4):380-2.

2. Balkrishnan R, McMichael AJ, Camacho FT, Saltzberg F, Housman TS, Grummer S, et al. Development and validation of a health-related quality of life instrument for women with melasma. Br J Dermatol. 2003;149(3):572-7.

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DERMATOLOGY 3. Balkrishnan R, Kelly AP, McMichael A, Torok H. Improved quality of life with effective treatment of facial melasma: the pigment trial. J Drugs Dermatol. 2004;3(4):377-81.

4. Barankin B, Silver SG, Carruthers A. The skin in pregnancy.

J Cutan Med Surg. 2002;6(3):236-40.

5. Baumann L. Cosmetic dermatology-Principles and Practice. New York: Tata McGraw-Hill Ltd. 2003. pp. 65-9.

6. Burns T, Breathnach S, Cox N, et al. Griffiths, Rook’s Textbook of Dermatology, 7th Edition, Chapter 39, UK: Blackwell Science Ltd.; 39.1-39,16.

7. Damoa AS, Lambert WC, Schwartz RA. Melasma: insight into a distressing dyschromia. Aesthetic Dermatol.

2006;8(1):1-6.

8. Estrada-Castanon R, Torres-Bibiano B, AlarconHernandez H. Epidemiologia cutanea en dos sectores de atencion medica en Guerrero, Mexico. Dermatologia Rev Mex. 1992;36:29-34.

9. Failmezger C. Incidence of skin disease in Cuzco, Peru.

Int J Dermatol. 1992;31(8):560-1.

10. Goh CL, Dlova CN. A retrospective study on the clinical presentation and treatment outcome of melasma in a tertiary dermatological referral centre in Singapore.

Singapore Med J. 1999;40(7):455-8.

11. Grimes PE. Melasma. Etiologic and therapeutic considerations. Arch Dermatol. 1995;131(12):1453-7.

12. Halder RM, Grimes PE, McLaurin CI, Kress MA, Kenney JA Jr. Incidence of common dermatoses in a predominantly black dermatologic practice. Cutis. 1983;32(4):388, 390.

13. Hann SK, Im S, Chung WS, Kim do Y. Pigmentary disorders in the South East. Dermatol Clin. 2007;25(3):431-8.

14. Jang YH, Sim JH, Kang HY, Kim YC, Lee ES. The histopathological characteristics of male melasma: comparison with female melasma and lentigo. J Am Acad Dermatol. 2012;66(4):642-9.

16. Kauh YC, Zachian TF. Melasma. Adv Exp Med Biol.

1999;455:491-9.

17. Kligman AM, Willis I. A new formula for depigmenting human skin. Arch Dermatol. 1975;111(1):40-8.

18. Lapeere H, Boone B, Schepper SD. Hypomelanosis and hypermelanosis. In: Wolff K, Goldsmith LA, Katz SI (Eds.). Dermatology in General Medicine, 7th Edition.

New York: McGraw-Hill; 2008. p. 635.

19. Mosher DB, Fitzpatrick TB, Ortonne JP, et al.

Hypomelanoses and hypermelanoses. In: Freedberg IM, Eisen AZ, Wolff K, et al. (Eds.), Fitzpatrick’s Dermatology in General Medicine, Vol 1. New York, NY: McGraw-Hill; 1999. pp. 945-1017.

20. Sober AF, Fitzpatrick TB. Disturbances of pigmentation.

Section I. Mechanisms of pigmentation in man. In: Moschella SL, Pillsbury DM, Hurley HJ Jr (Eds.), Dermatology, Vol 2. Philadelphia, Pa: WB Saunders Co; 1975. p.1085.

21. Nicolaidou E, Antoniou C, Katsambas AD. Origin, clinical presentation, and diagnosis of facial hypermelanoses.

Dermatol Clin. 2007;25(3):321-6.

22. Pasricha JS, Khaitan BK, Dash S. Pigmentary disorders in India. Dermatol Clin. 2007;25(3):343-52.

23. Pathak MA. Clinical and therapeutic aspects of melasma: an overview. In: Fitz Patrick TB, Wick MM, Toda K (Eds.). Brown Melanoderma. Tokyo: University of Tokyo Press; 1986. pp. 161-72.

24. Pathak MA, Riley FC, FitzPatrick TB. Melanogenesis in human skin following exposure to long-wave ultraviolet and visible light. J Invest Dermatol. 1962;39:435-43.

25. Resnik S. Melasma induced by oral contraceptive drugs.

JAMA. 1967;199(9):601-5.

26. Sarvjot V, Sharma S, Mishra S, Singh A. Melasma: a clinicopathological study of 43 cases. Indian J Pathol Microbiol. 2009;52(3):357-9.

15. Jadotte YT, Schwartz RA. Melasma: insights and 27. Vázquez M, Maldonado H, Benmamán C, Sánchez JL. perspectives. Acta Dermatovenerol Croat. 2010;18(2): Melasma in men. A clinical and histologic study. Int J Dermatol. 1988;27(1):25-7.

124-9.

■■■■

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Psoriasis and psoriatic arthritis are associated with an increased risk of migraine, suggests new research published online in the Journal of the American Academy of Dermatology.

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An interleukin 17 (IL-17) receptor antagonist, brodalumab, achieved a 100% reduction in plaque psoriasis symptoms in twice as many patients as the commonly used antibody ustekinumab, suggested a phase 3 multicenter trial published in the October 1 issue of the New England Journal of Medicine.

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ENT

Tonsil Schwannoma Presenting as a Tonsillar Cyst: A Rare Case SAURABH VARSHNEY*, RAVI MEHERâ€

ABSTRACT Schwannomas can originate in any peripheral, autonomic or cranial nerve except the olfactory and optic nerves. Between 25% and 48% of all schwannomas have been reported to arise in the head and neck, with the acoustic nerve being the most common site of origin. Schwannomas arising in the tonsil are extremely uncommon, till now, only 10 such cases have been previously reported in the literature. We report a case of schwannoma of the tonsil, which first appeared to be a tonsillar cyst arising from one of the crypts of tonsil. It was diagnosed on histopathological examination, which showed characteristic Antoni A and B areas with areas of nuclear palisading and verocay bodies.

Keywords: Schwannoma, tonsil, cyst

S

chwannoma is usually solitary, benign, wellencapsulated, slow-growing tumor derived from Schwann cells of the sheaths of peripheral, cranial or autonomic nerves. In the head and neck region, it occurs most commonly in association with acoustic nerve within the skull and is rarely found in the oral cavity. In oral cavity, the most common site is tongue and tonsil is one of the rare site.

CASE REPORT

in head and neck region. All routine laboratory tests were also within normal limits. A provisional diagnosis of tonsillar cyst was made. The swelling was seen to arise from upper pole of left tonsillar fossa with a pedicle (Fig. 2). It was removed intact using sharp dissection over the cyst pedicle, with bipolar cautery and scissors.

Histopathological examination of the swelling showed it to be schwannoma. It was a globular soft to firm grey-white swelling with smooth outer surface (Fig. 3).

A 24-year-old male presented to ENT outpatient department with complaints of foreign body sensation in throat for 3 months. There was no history of dysphagia or odynophagia. On examination of the throat a smooth, globular, firm swelling of approximate 3 x 2 cm size was seen in left upper pole of tonsillar fossa (Fig. 1).

The cut surface was grey-white with no cyst. Microscopic examination showed a tumor that was circumscribed with fibrous capsule of variable thickness. One area outside the capsule showed a nerve. The tissue was composed of cells with oval to elongated nuclei, which were arranged in parallel bundles showing the characteristic Verocay bodies.

Rest of the ear, nose and throat and neurological examination was normal. There were no other swellings

*Professor and Head Dept. of ENT All India Institute of Medical Sciences, Rishikesh, Uttarakhand †Dept. of ENT & Head and Neck Surgery Maulana Azad Medical College, New Delhi Address for correspondence Dr Saurabh Varshney Professor and Head, Dept. of ENT All India Institute of Medical Sciences Rishikesh - 249 201, Uttarakhand E-mail: drsaurabh68@gmail.com

Figure 1 and 2. Clinical photograph of the patient showing lesion in left tonsillar fossa.

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ENT is probably due to trauma during mastication. This was not present in the above case probably because of the small size of the tumor. When there is pain and ulceration along with rapid increase in size, one should keep a possibility of malignancy though malignant transformation in untreated schwannoma has been rarely reported.10

Figure 3. Excised specimen.

DISCUSSION Schwannoma was first reported by Jose Verocay in 1910.1 The term “schwannoma” is used to describe tumors originating from Schwann cells. Various names, such as perineural fibroblastoma, neurilemmoma (sometimes spelled neurilemoma), neurolemoma and peripheral glioma, have also been used since Verocay initially reported this benign neurogenic tumor as “neurinoma”.

In all the soft tissue locations, schwannoma have been only occasionally associated with oral structures.

Extracranially, they are found in 25% of cases (head and neck) but only 1% have an intraoral origin.2 When present in the oral cavity, tongue is reported to be the favored site followed by the buccal mucosa, floor of mouth, palate, lip and gingiva.2-4 All cranial nerves in the head and neck region can give rise to schwannoma, except the optic and olfactory nerves, which are not considered true cranial nerves because of the absence of Schwann cells. However, nerve origin remains unidentified in approximately 10-40% of schwannomas.5,6 Most schwannomas identified intraoperatively in the oral region appear to originate in the hypoglossal and vagal nerve.7-9 In the above case, it was probably originating from glossopharyngeal nerve, which supplies the tonsillar fossa. The patient did not complain of any pain or tenderness. Pain, tenderness and paresthesia may occur in 50% of schwannoma cases, but will be characteristically absent in cases of tonsillar cyst.

The tumor varies from a few millimeters to several centimeters when it may interfere with speech or swallowing. Tonsillar cyst can also have a similar picture and may feel firm like a schwannoma when the cyst is tense. Ulceration is seen occasionally and

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In the above case, the excised swelling was wellcircumscribed covered with keratinizing stratified squamous epithelium. The bulk of the lesion was made up of Antoni A tissue in which numerous Verocay bodies typical of schwannoma were readily identified. The surgical margins were free of tumor.

The histological picture resembled classical appearance of a schwannoma.

Thus, the diagnosis of schwannoma is based on classic histologic appearance with presence of Antoni A and B areas with areas of nuclear palisading and Verocay bodies. A positive staining with S-100 using immunohistochemical techniques is for differentiation from other tumors.11 The presence of a well-defined mass lesion with heterogeneous density on computed tomography (CT) may aid in differentiation from other tonsillar tumors.12 The schwannoma is treated by conservative surgical excision, with minimal risk of recurrence. Patients with multiple neural tumors should be evaluated for von Recklinghausen neurofibromatosis or multiple endocrine neoplasia (MEN) syndrome.

CONCLUSION Schwannoma of the tonsil is a extremely rare tumor.

They usually have a history of slow-growing tonsillar swelling without much symptoms and mimic a tonsillar cyst. Large tumors may present with dysphagia and ulceration over the swelling, which might give them a malignant look. Diagnosis of schwannoma can be made easily on histological appearance and complete surgical excision is the treatment of choice with minimal risk of recurrence.

REFERENCES 1. Wakoh M, Yonezu H, Otonari T, Sano T, Matsuzaka K, Inoue T, et al. Two cases of schwannoma with marked cystic changes. Dentomaxillofac Radiol. 2005;34(1):44-50.

2. Pfeifle R, Baur DA, Paulino A, Helman J. Schwannoma of the tongue: report of 2 cases. J Oral Maxillofac Surg.

2001;59(7):802-4.

3. Cherrick HM, Eversole LR. Benign neural sheath neoplasm of the oral cavity. Report of thirty-seven cases.

Oral Surg Oral Med Oral Pathol. 1971;32(6):900-9.

Cont’d on page 472...

GASTROENTEROLOGY

Spectrum of Lesions of Liver in Autopsy in India: One Year Study AMAR RANJAN*, DIVYA SETHI†

ABSTRACT Introduction: Lesions of liver cause significant morbidity and mortality without causing significant signs and symptoms. Liver biopsy may not give the exact picture. Autopsy study may be a better choice. Aims and objectives: To find the types of lesions of liver in autopsy in India and its correlation with liver biopsy in children and adult and to establish the usefulness of autopsy pathology in clinical practice, teaching medical students and for research purposes. Material and methods: Retrospective analysis of specimens of liver was done. Out of total 116 specimens, 64 showed significant lesions and were analyzed. Males were 52 in number and females were 12 with the ratio 4.3:1. The age group was between 15 and 85 years. Result: Most cases were of hepatic steatosis mixed type (macronodular and micronodular) 26.6%. This was followed by macronodular type (15.6%) and micronodular type (3.1%). Next prominent group of diseases in descending order were cirrhosis (12.5%), various types of necrosis (10.9%), chronic hepatitis (3.2%), granuloma (1.6%) , hepatocellular carcinoma (1.6%) and cholestasis (1.6%). In females, mixed steatosis (33.3%), hemorrhagic necrosis (8.3%), centrilobular necrosis (8.3%), chronic venous congestion (25%), cirrhosis (8.3%), granuloma (8.3%) and hepatocellular carcinoma (8.3%). Discussion and summary: The pattern of liver diseases are different in the different ethnic groups. In our country, no such study is available. Autopsy study of liver diseases are different than seen in liver biopsy. For academic purposes, autopsy study plays a significant role. Histopathological examination of postmortem specimens or even liver biopsy are conducted at limited places in our country. This diminishes opportunity of medical professionals to learn about liver pathology.

Keywords: Liver biopsy, liver diseases, autopsy

L

esions of liver cause significant morbidity and mortality. Even in advanced stages, it may cause no signs and symptoms. So, it goes unnoticed or are found incidentally. Liver biopsy may not give the exact picture. Autopsy specimen gives sufficient material, but without having sufficient clinical findings.

Autopsy is done for medicolegal purposes in India.

Autopsies for research purposes are not in practice in our country.

AIMS AND OBJECTIVES ÂÂ

To find the types of lesions of liver in autopsy in India.

ÂÂ

Its correlation with liver biopsy in children and adult.

*Assistant Professor, Lab Oncology Dr BRA Institute Rotary Cancer Hospital, AIIMS, New Delhi †Senior Resident, Dept. of Pathology, VMMC and Safdarjung Hospital, New Delhi Address for correspondence Dr Divya Sethi Senior Resident, Dept. of Pathology VMMC and Safdarjung Hospital, New Delhi E-mail: dr.divyasethi@gmail.com

ÂÂ

To establish the usefulness of autopsy pathology in clinical practice, teaching medical students and for research purposes.

MATERIAL AND METHODS Cases included in this study were those who died of causes other than liver disease (medicolegal cases).

Different causes of death were suicide, homicide, etc.

Postmortem of all the cases were done by doctors of the Dept. of Forensic Medicine. Different specimens were sent by them to the Dept. of Pathology for histopathological examination. Retrospective analysis of specimens of liver was done from June 2010 to May 2011. Different specimens of 200 autopsy cases were sent to the laboratory. These included heart, pieces of lungs, liver, spleen, kidney and brain in most of the cases. Specimen of liver alone or with other specimens was received in 116 cases. In most of the cases, a piece of liver was received. Out of 116 specimens, 64 (55.17%) showed significant lesions and were analyzed. Males were 52 in number and females were 12 with the ratio 4.3:1. The age group was between 15 and 85 years (average 50 years). After routine gross examination,

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GASTROENTEROLOGY Table 1. Different Types of Liver Diseases Found at Autopsy Disease

A

B

C

D

Figure 1. A and B: Histopathological examination section of liver showing steatosis (100X, 200X); C and D: histopathological examination section of liver showing autolysis (100X, 200X).

B

A

C

D

Figure 2. A and B: Histopathological examination section of liver showing acute congestion (100X, 200X); C and D: histopathological examination section of liver showing chronic venous congestion (100X, 400X).

sections were taken and stained with routine hematoxylin and eosin (H&E) stain. Special stains like reticulin, acid-fast bacillus (AFB) stain, etc. were done wherever needed. Clinical details was not available in any case. Report of inquest as cause of death was present in all cases.

RESULT Most cases were of steatosis mostly of mixed pattern (macronodular as well as micronodular) (17/64; 26.6%).

This was followed predominantly by macronodular type 10/64 (15.6%). Predominantly micronodular type was present in two cases (3.1%). Next prominent

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Indian Journal of Clinical Practice, Vol. 26, No. 5, October 2015

Both macronodular and micronodular

No. of cases 17

Percentage (%) (n = 64) 26.6

Macronodular steatosis

10

15.6

Micronodular steatosis

02

3.1

Autolysis

03

4.7

Precirrhotic fibrosis

08

12.5

Cirrhosis

08

12.5

Chronic venous congestion

08

12.5

Acute congestion

01

1.5

Necrosis

07

10.9

Centrilobular

03

4.7

Massive

01

1.5

Hemorrhagic

01

1.5

Submassive

01

1.5

Periportal

01

1.5

Chronic hepatitis

02

3.1

Granuloma

01

1.5

Cholestasis

01

1.5

Carcinoma

01

1.5

Total

64

group was cirrhosis. Cases seen were cirrhosis 8 (12.5%), precirrhotic fibrosis 8 (12.5%), chronic venous congestion (CVC) of liver 8 (12.5%) and acute congestion 1 (1.6%). The next category of disease was various types of necroses 7 cases (10.9%). It included centrilobular type 3 (4.7%), massive type 1 (1.6%), submassive type 1 (1.6%), hemorrhagic type 1 (1.6%) and periportal type 1 (1.6%) (Table 1). Chronic hepatitis was noted in 2 (3.2%), granuloma 1 (1.6%) and carcinoma 1 (1.6%), cholestasis 1 (1.6%). In female (12) mixed steatosis 4 (33.3%), hemorrhagic necrosis 1 (8.3%), centrilobular necrosis 1 (8.3%), CVC 3 (25%), cirrhosis 1 (8.3%), granuloma 1 (8.3%) and hepatocellular carcinoma 1 (8.3%).

DISCUSSION It is important to differentiate between fatty change and autolytic changes in liver. This is possible only by adequate training. Both the conditions have clear hepatocytes and broken up cell membrane. The pattern of liver diseases are different in the different ethnic groups.1 In our country, no such study is available.

GASTROENTEROLOGY The study conducted by Sotoudehmanesh et al2 in 2006, on 896 patients showed steatosis in 31.6%, steatohepatitis in 2.1%, chronic hepatitis in 2.6% and cirrhosis in 0.8% cases. This study showed approximately similar percentage of diseases as the current one except cirrhosis, which is higher in the present study. This may be due to racial variation, as this study was from Tehran. Lee1 conducted an analysis of 1,839 consecutive necropsies. The difference in the pattern of liver diseases were seen among the different ethnic groups. Indians are found to have more alcoholic hepatitis and cirrhosis which are often of the micronodular type, while the Chinese have significantly more macronodular cirrhosis and hepatocellular carcinoma. Contrary to the study of Lee, our study shows alcoholic hepatitis predominantly macronodular type. Berry3 who examined liver in 1,500 consecutive autopsies in South-East London, revealed that 5% of livers contained solitary lesions. Clinically, nonevident lesions included cirrhosis, adenomas and metastatic carcinoma. Hamartomas were relatively common. His study also showed different pattern of liver diseases, which also may be due to racial variation.1 Geo-cultural factors influence the prevalence of liver disease of public health importance in any country. Liver disease may vary from country to country and in the same country in different cultural groups and at different periods of time.4 Alcohol accounts for 80% of cirrhosis in the United States,5 while the predominant cause of cirrhosis in China, South-East Asia and Africa is hepatitis B.6,7 In Japan in last 25 years, the hepatitis B related liver cancer cases have remained steady, but the incidence of hepatitis C related liver cancer have rapidly increasedmaking it now a major health problem.8 The liver biopsy study conducted by Fashir et al in 19969 in Saudi Arabia in the age group 15-85 years showed cirrhosis in 22.3%, chronic active hepatitis (CAH) 16.6%, hepatocellular carcinoma in 7.2%, fatty changes in 12% of patients. Less common diag­noses included cholestasis, hemochromatosis periportal fibrosis, Wilson’s disease, alcoholic hepatitis and lymphoma.

The common causes of liver cirrhosis were hepatitis C virus in 73.3% of patients tested for it and hepatitis B virus in 23.2%. This is clearly different from our autopsy study. Our study shows maximum number of steatosis, probably the commonest cause being alcoholism. This is a reversible condition in contrast to study of Fisher et al study, which showed maximum cases of cirrhosis and the commonest cause being hepatitis C virus infection.

Ramakrishna et al10 studied 134 liver biopsies obtained from 128 infants and children below the age of 16 years. The most common histological diagnoses were

neonatal hepatitis syndrome in 23, storage disorders in 11 and cirrhosis in 26 children. Less common diagnoses included Reye’s syndrome in four, fatty liver in seven, granulomas in four and chronic active hepatitis, fulminant hepatitis, congenital hepatic fibrosis and neoplasms in two children each. In our study, all the cases were of above 15 years, so we couldn’t get any outcome in children.

SUMMARY Autopsy study of liver diseases are different as seen in liver biopsy. For academic purposes, autopsy study plays a significant role. Histopathological examination of postmortem specimens are conducted at limited places in our country. In clinical practice, liver biopsy is also conducted at limited centers. This diminishes opportunity of medical professionals to learn about liver pathology. This study is focused on pattern of liver diseases in our country, most common being steatosis caused by alcoholism. However, pattern of liver diseases varies with different ethnic groups.

REFERENCES 1. Lee YS. The pattern of liver diseases in Singapore. An autopsy study. Trop Geogr Med. 1979;31(1):69-74.

2. Sotoudehmanesh R, Sotoudeh M, Ali-Asgari A, AbediArdakani B, Tavangar SM, Khakinejad A, et al. Silent liver diseases in autopsies from Forensic Medicine of Tehran.

Arch Iran Med. 2006;9(4):324-8.

3. Berry CL. Liver lesions in an autopsy population. Hum Toxicol. 1987;6(3):209-14.

4. Shrestha SM. Liver diseases in Nepal. Kathmandu Univ Med J (KUMJ). 2005;3(2):178-80.

5. Runyon BA. Ascites in liver disease. In: Haubrich WS, Schaffner F, Berk JE (Eds.). Bokus: Gastroenterology.

Philadelphia: WB Saunders Co; 1995.

6. Dong J, Zhou MH, Ye YL. Relationship between viral hepatitis B and liver cirrhosis and carcinoma. Chin Med J (Engl). 1980;93(10):712-6.

7. Lok AS. Natural history and control of perinatally acquired hepatitis B virus infection. Dig Dis. 1992;10(1):46-52.

8. Yoshizawa H. Hepatocellular carcinoma associated with hepatitis C virus infection in Japan: projection to other countries in the foreseeable future. Oncology. 2002;62 Suppl 1:8-17.

9. Fashir B, Sivasubramaniam V, Al Momen S, Assaf H. Pattern of liver disease in a Saudi patient population: a decade of experience at security forces hospital, Riyadh, KSA. Saudi J Gastroenterol. 1996;2(1):50-2.

10. Ramakrishna B, Date A, Kirubakaran C, Raghupathy P. The pattern of liver disease in Indian children: a review of 128 biopsied cases. Ann Trop Paediatr. 1993;13(2):159-63.

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Dengue Myopericarditis: A Rare Complication of Dengue Fever POOJA SHASHIDHARAN*, MANISH PANGI†

ABSTRACT Dengue is a major public health problem in tropical countries and probably the most important arthropod-borne disease worldwide. Dengue hemorrhagic fever and dengue shock syndrome are severe and dreaded forms of this disease. Cardiac complications in dengue are not common. Myopericarditis due to dengue infection is a rarity and only a few cases have been reported in world literature. Here we report a case of acute myopericarditis due to dengue in a 50-year-old woman who recovered with prompt and appropriate treatment.

Keywords: Dengue fever, dengue myopericarditis

D

engue is an acute febrile arboviral disease caused by the dengue virus, which belongs to the family Flaviviridae. There are four serotypes of dengue virus designated DENV-1, DENV-2, DENV-3 and DENV-4. Dengue virus is transmitted to humans through the bite of an infected Aedes aegypti mosquito.

An estimated 50 million dengue infections occur worldwide annually and about 2.5% of those affected die. Epidemics of dengue are increasing in frequency.1

Dengue virus infection may be asymptomatic or may cause an undifferentiated febrile illness, dengue fever (DF), dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). After an incubation period averaging 4-7 days, DF presents with sudden onset of fever, frontal headache, retro-orbital pain and back pain along with severe myalgias. Leukopenia and thrombocytopenia may be observed. Cardiac complications in dengue are not common.2 Myocarditis in dengue is rare and might not be fatal if diagnosed early and treated.3 Dengue pericarditis can occur rarely in association with myocarditis.

*Assistant Professor, Dept. of General Medicine, Sree RajaRajeshwari Medical College and Hospital, Bangalore, Karnataka †Assistant Professor, Dept. of Cardiothoracic Surgery, Sri Jayadeva Institute of Cardiology, Bangalore, Karnataka Address for correspondence Dr Pooja Shashidharan Dept. of General Medicine, Sree RajaRajeshwari Medical College and Hospital Kambipura, Bangalore - 560 074, Karnataka E-mail: poojashashidharan@gmail.com

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CASE REPORT A 50-year-old female was admitted with fever, headache and myalgia of 4 days duration. She did not have any comorbidity. Her vitals at the time of admission were as follows: pulse rate - 98 beats/min, blood pressure (BP) - 114/70 mmHg; respiratory rate - 28 cycles/min, oral temperature - 1000F. Systemic examination was normal. She did not have any subjective or objective evidence of bleeding. Blood investigations obtained on the day of admission revealed a platelet count of 60,000 cells/mm3 (normal: 1.5-4 lakhs cells/mm3), a total white blood cells of 3,230 cells/mm3 (normal: 4,000-11,000 cells/mm3) and hemoglobin of 11.6 gm% (normal: 12-14 gm%). Hematocrit was 40% and liver enzymes were mildly elevated: aspartate transaminase (AST) 81 IU/mL and alanine transaminase (ALT) - 77 IU/mL (normal: ≤40 IU/mL). Her renal function test, blood sugar and serum electrolytes were normal. Chest X-ray was normal. Ultrasound abdomen showed fatty liver and mild ascites. Electrocardiography showed sinus tachycardia and low voltage QRS complexes (Fig. 1).

2D-echocardiography showed normal chambers, normal biventricular systolic function with an ejection fraction of 61.7% and a thin trace of circumferential pericardial effusion. A provisional diagnosis of DF with possible pericarditis was made. Treatment was started with intravenous (IV) antibiotics, oral acetaminophen and IV fluids.

Patient developed progressive thrombocytopenia over the next 3 days with the lowest platelet count being 36,000 cells/mm3 on the 3rd day of admission.

INTERNAL MEDICINE However, the patient did not have any bleeding manifestations and hematocrit continued to be normal.

Dengue serology obtained on the 7th day of illness (3rd day of admission) was positive for immunoglobulin M (IgM) antibody, thus confirming the diagnosis of DF. Fever subsided and patient reported improvement in symptoms over the first 3 days of admission.

0.5 µg/L (reference range <0.01 µg/L). The possibility of acute myocardial infarction or acute myopericarditis due to dengue was considered.

On the 4th day of admission, patient developed sudden onset of breathlessness and chest pain. The pulse rate was 160 beats/min, BP was 90/60 mmHg, respiratory rate was 42 cycles/min. Oxygen saturation was 70% in room air and 84% with 10 liters of O2. Respiratory system examination revealed bilateral extensive fine crepitations. Electrocardiography showed sinus tachycardia with ST-segment elevation in V1, V2 (Fig. 2). Chest X-ray was suggestive of pulmonary edema (Fig. 3). Immediately IV furosemide 40 mg was administered to relieve pulmonary edema.

2D-echocardiography showed left ventricular anterolateral wall, septal hypokinesia with a left ventricular ejection fraction (LVEF) of 35%. A thin trace of circumferential pericardial effusion without tamponade was present. Troponin T was elevated to

The patient was started on noninvasive ventilation (NIV) and supportive treatment was given with inotropes (injection dobutamine) and IV diuretics. Tablet digoxin 0.25 mg ½-0-0 was also started. Despite the possibility of acute myocardial infarction, antithrombotics and coronary angiography were deferred in view of thrombocytopenia. However, the patient showed remarkable improvement over the next 24 hours with supportive treatment. Patient’s respiratory distress subsided and NIV was discontinued 24 hours after initiation. Repeat 2D-echocardiography obtained on the following day showed an improvement in the ejection fraction to 50% and no hypokinesia. In the subsequent day ECG, ST-segment had returned to baseline and T-wave inversions had developed in V1 and V2 (Fig. 4). Chest X-ray showed reduced pulmonary congestion, the following day and lung fields were clear after 48 hours (Fig. 5). Her BP improved to 120/80 mmHg and injection dobutamine was tapered and stopped over the next 48 hours. Furosemide was reduced to the lowest required dose and digoxin

Figure 1. ECG on admission showing sinus tachycardia and low voltage QRS complexes.

Figure 2. ECG showing ST-segment elevation in V1 and V2 with sinus tachycardia.

Figure 3. Chest X-ray showing pulmonary edema due to myocarditis.

Figure 4. ECG showing resolution of ST-segment elevation and development of T-wave inversions in V1 and V2.

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INTERNAL MEDICINE was present in 45% of patients and diastolic impairment in 42%. Dysfunction was worse among patients with severe dengue. Only one patient had borderline elevation of troponin, while biomarkers were normal in the rest of the patients. Similarly in a study conducted

by Khongphatthanayothin et al16 reduced LVEF (<50%) was found in 6.7%, 13.8% and 36% of patients with DF, DHF and DSS, respectively. Biomarker levels were normal in all 11 patients tested. The proposed mechanisms for this functional cardiac impairment include high circulating proinflammatory cytokines causing myocardial depression, altered intracellular calcium homeostasis and coronary hypoperfusion.

Figure 5. Chest X-ray showing resolution of pulmonary edema after 48 hours of supportive treatment.

was continued. The LVEF showed progressive improvement and was 61% 4 days later (8th day of admission). Digoxin was discontinued.

The patientâ&#x20AC;&#x2122;s platelet count increased to 2.7 lakhs/ mm3 and liver enzymes normalized on the 10th day of admission. Serial troponin levels were not available.

Patient was discharged on the 11th day with an ejection fraction of 61% and a thin trace of pericardial effusion. At 1 month follow-up 2D-echocardiography was normal. Coronary angiography done at this stage revealed normal coronaries. The presence of a viral prodrome along with a positive dengue serology, pericardial effusion on echocardiography, elevated cardiac biomarker, cardiac dysfunction, which resolved rapidly with supportive treatment and a normal coronary angiography - all put together confirmed the diagnosis of dengue myopericarditis.

DISCUSSION Cardiac manifestations of dengue range from asymptomatic4 to fatal myocarditis.5 Arrhythmias have been reported in dengue and include sinoatrial exit block,6 Mobitz type 1 block,7,8 complete heart block,9 atrial fibrillation,10 junctional rhythm11 and ventricular arrhythmia.12 Increased resting (diastolic) Ca2+Â in the myocardial cells, which occurs as a consequence of direct infection of the myocytes by the dengue virus may be responsible for the arrhythmias.13 Functional myocardial impairment has been reported in dengue.

Wali et al14 studied 14 dengue patients in India, out of which 70.59% patients had global hypokinesia. 99mTcpyrophosphate imaging was done in four patients and no myocardial necrosis was found. In a study conducted

by Yacoub et al15 among Vietnamese patients with different dengue severity grades, systolic impairment

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Dengue can also cause myocarditis, myopericarditis and pericarditis. Dengue myocarditis can be asymptomatic as reported by Satarasinghe et al.4 In the study conducted by Satarasinghe et al, 24% of the dengue patients studied had 2D-echocardiographic evidence of myocarditis, but none had clinical features of overt myocarditis, such as significant sinus tachycardia, raised jugular venous pressure, triple rhythm, bilateral pulmonary crepitations and peripheral edema. At the other end of the spectrum, fatal cases of dengue myocarditis have been reported.5 Dengue myocarditis can also mimic acute myocardial infarction.17,18 In the case reported by us, myocarditis masqueraded acute myocardial infarction, which was subsequently ruled out. Direct dengue viral infection of the myocardial tissues and immunologic response mediated by cytokines through complement activation may be responsible for myocarditis. Dengue pericarditis is rare and occurs as myopericarditis.19 Nagaratnam et al19 reported two cases of myocarditis due to dengue, with clinical evidence of pericarditis in both. Dengue myopericarditis was also reported by Goh.20 In the case reported by us, pleural effusion was present on echocardiography indicating pericardial involvement.

Histopathological examination of heart tissue in fatal cases has revealed multifocal areas of muscle necrosis and intense interstitial edema associated with clusters of virus particles inside the cardiomyocytes and in the interstitial space.5 CONCLUSION With the ever increasing burden of DF, it is prudent to be aware of unusual manifestations like myocarditis, since the mortality associated with it is easily avoidable through early recognition and treatment. Myocarditis can be mistaken for DSS and treated inappropriately with catastrophic outcome, if one is not aware of its possibility in dengue.

INTERNAL MEDICINE REFERENCES 1. World Health Organization. Comprehensive Guidelines for Prevention and Control of Dengue and Dengue Haemorrhagic Fever. Revised and expanded edition.

WHO; 2011.

2. Wiwanitkit V. Dengue Cardiac infection: a brief review.

Acta Cardiol Sin. 2008;24:226.

3. Wiwanitkit V. Dengue myocarditis, rare but not fatal manifestation. Int J Cardiol. 2006;112(1):122.

4. Satarasinghe RL, Arultnithy K, Amerasena NL, Bulugahapitiya U, Sahayam DV. Asymptomatic myocardial involvement in acute dengue virus infection in a cohort of adult Sri Lankans admitted to a tertiary referral centre. Br J Cardiol. 2007;14:171-3.

5. Miranda CH, Borges Mde C, Schmidt A, Pazin-Filho A, Rossi MA, Ramos SG, et al. A case presentation of a fatal dengue myocarditis showing evidence for dengue virusinduced lesion. Eur Heart J Acute Cardiovasc Care.

2013;2(2):127-30.

AA. Acute atrial fibrillation during dengue hemorrhagic fever. Braz J Infect Dis. 2003;7(6):418-22.

11. Arif SM, Ahmed H, Khokon KZ, Azad AK, Faizi MA. Dengue haemorrhagic fever with bradycardia. J Medicine.

2009;10:36-7.

12. Chuah SK. Transient ventricular arrhythmia as a cardiac manifestation in dengue haemorrhagic fever - a case report. Singapore Med J. 1987;28(6):569-72.

13. Salgado DM, Eltit JM, Mansfield K, Panqueba C, Castro D, Vega MR, et al. Heart and skeletal muscle are targets of dengue virus infection. Pediatr Infect Dis J. 2010;29(3):238-42.

14. Wali JP, Biswas A, Chandra S, Malhotra A, Aggarwal P, Handa R, et al. Cardiac involvement in dengue haemorrhagic fever. Int J Cardiol. 1998;64(1):31-6.

15. Yacoub S, Griffiths A, Chau TT, Simmons CP, Wills B, Hien TT, et al. Cardiac function in Vietnamese patients with different dengue severity grades. Crit Care Med. 2012;40(2):477-83.

6. Kaushik JS, Gupta P, Rajpal S, Bhatt S. Spontaneous resolution of sinoatrial exit block and atrioventricular dissociation in a child with dengue fever. Singapore Med J. 2010;51(9):e146-8.

16. Khongphatthanayothin A, Lertsapcharoen P, Supachokchaiwattana P, La-Orkhun V, Khumtonvong A, Boonlarptaveechoke C, et al. Myocardial depression in dengue hemorrhagic fever: prevalence and clinical description. Pediatr Crit Care Med. 2007;8(6):524-9.

7. Khongphatthallayothin A, Chotivitayatarakorn P, Somchit S, Mitprasart A, Sakolsattayadorn S, Thisyakorn C. Morbitz type I second degree AV block during recovery from dengue hemorrhagic fever. Southeast Asian J Trop Med Public Health. 2000;31(4):642-5.

17. Patra S, Bhardwaj G, Manohar JS, Srinivasa KH, Kharge J, Manjunath CN. Acute myocardial infarction being the presentation of dengue myocarditis. J Cardiovasc Dis Res. 2013;4(2):159-61.

8. Sharma JK, Zaheer S. Variable atrio-ventricular block in dengue fever. J Indian Acad Clin Med. 2014; 15(3-4):252-4.

18. Lee CH, Teo C, Low AF. Fulminant dengue myocarditis masquerading as acute myocardial infarction. Int J Cardiol. 2009;136(3):e69-71.

9. Lim SMS, Hoo FK, Sulaiman WAW. A case of dengue hemorrhagic fever with myocarditis and complete heart block. RMJ. 2014;39(1):104-6.

19. Nagaratnam N, Siripala K, de Silva N. Arbovirus (dengue type) as a cause of acute myocarditis and pericarditis. Br Heart J. 1973;35(2):204-6.

10. Horta Veloso H, Ferreira Júnior JA, Braga de Paiva JM, 20. Goh PL. Dengue perimyocarditis: a case report. Hong Kong J Emerg Med. 2010;17(1):58-60.

Faria Honório J, Junqueira Bellei NC, Vicenzo de Paola ■■■■

Findings from a Danish population-based study suggest a twofold increased relative risk for central demyelinating diseases in patients with inflammatory bowel disease (IBD) who receive tumor necrosis factor (TNF) inhibitors.

“If true, the observed association could either be attributed to the unmasking of a latent demyelinating disease or to the emergence of a de novo demyelinating disease,” write Nynne Naebo Andersen, MD, a PHD candidate in epidemiology at the Statens Serum Institut in Copenhagen, Denmark, and colleagues, in a research letter published online October 5 in JAMA Internal Medicine.

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OBSTETRICS AND GYNECOLOGY

Interstitial Brachytherapy Using Martinez Universal Perineal Interstitial Template in Locally Advanced Gynecological Malignancies MEENA J SHAH*, RAKESH K VYASâ&#x20AC;

ABSTRACT Objective: The objective of this study was to assess treatment outcome for patients with locally advanced gynecological malignancies treated with interstitial brachytherapy (ISBT) using Martinez Universal Perineal Interstitial Template (MUPIT) and to study the acute and late sequelae after treatment by this technique. Material and methods: Fifty patients with histologically confirmed carcinoma of the cervix (22 patients), vault (13 patients), vagina (10) patients and postoperative recurrence (5) were treated by a combination of external beam radiotherapy using megavoltage irradiation to the pelvis to a dose of 4,000-5,000 cGy followed by ISBT using MUPIT between June 1997 to December 2001 at Gujarat Cancer and Research Institute, Ahmedabad. Only those patients who were found unsuitable for intracavitary brachytherapy (ICBT) or in whom ICBT was found to be unlikely to encompass the tumor volume were treated with ISBT using MUPIT and were enrolled for this study. A total dose of 1,500-2,400 cGy in 3 to 6 # was delivered by ISBT on high-dose rate (HDR) microselectron (Ir-192). Results: Among the 50 patients studied, with a maximum follow-up of 2 years, local control was 74% (37/50 patients) at first follow-up and 70% (35/50 patients) at 6 months. Two patients developed bleeding per rectum (Grade I in 1 and Grrade II in other patient). Complication rate was 4% (Group 1 and Group 2) and there were no adverse effects of Grade III or higher.

Three patients (6%) developed systemic metastasis. Conclusion: Perineal ISBT using MUPIT is a technically safe and feasible procedure. It is a good alternative to ICBT/CVC (central vaginal cylinder) in patients with locally advanced gynecological malignancies where ICBT/CVC is not feasible or results in suboptimal dose distribution. Better local control can be achieved definitely with acceptable morbidity. Further investigation to identify suitable patients and beneficial procedures should be performed.

Keywords: Interstitial brachytherapy, Martinez Universal Perineal Interstitial Template, locally advanced gynecological

cancer

G

ynecologic cancer is one of the most common cancers in the female population of India.

Radiotherapy is the mainstay of treatment in management of these cancers.1,2 Radiotherapeutic management consists of external beam radiotherapy (EBRT) and intracavitary brachytherapy (ICBT). EBRT to pelvis is delivered first to shrink primary tumor, to control bleeding in exophytic tumors, to treat

*Associate Professor Government Medical College and New Civil Hospital, Surat, Gujarat â&#x20AC; Incharge Director Gujarat Cancer and Research Institute, Ahmedabad, Gujarat Address for correspondence Dr Meena J Shah B-404, Arjun Complex, Opp. Ratnadeep Society Behind Police Tenament, Bhatar-Althan Road Surat - 395 017, Gujarat E-mail: drmeena.maheshwari@gmail.com

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parametrial and nodal disease and to improve geometry for intracavitary application. Rationale of brachytherapy is: 1) increased radiation tolerance of cervix and vagina and 2) rectum and bladder are dose limiting organs.

Brachytherapy for gynecologic cancers is divided into three types, according to methods of application.

ICBT, central vaginal cylinder (CVC) application and interstitial brachytherapy (ISBT). ICBT delivers high dose to cervix and vagina with sparing of surrounding normal structures. However in some situations, ICBT is not possible technically or not enough, due to suboptimal dose distribution. Such cases are associated with high incidence of local failure and complications.

ISBT can be used to overcome problems and to get the better coverage of dose distribution in such situations.3 Therefore, this study conducted an evaluation of results of ISBT treatment using Martinez Universal Perineal Interstitial Template (MUPIT) in gynecological cancers.

OBSTETRICS AND GYNECOLOGY Two most commonly used templates for gynecological cancer are Syed-Neblett system4-7 and MUPIT8-10 to achieve proper dose distribution by ISBT. MATERIAL AND METHODS Fifty patients with histologically confirmed gynecological malignancies treated with MUPIT ISBT between June 1997 to December 2001 at Gujarat Cancer and Research Institute, Ahmedabad were selected for retrospective study. Baseline patient characteristics were as follows: cervical cancer (22 patients), vaginal cancer (10 patients), carcinoma vault (13 patients) and postoperative recurrence/carcinoma cervical stump (5 patients). Histology was epidermoid carcinoma in 43 patients, adenocarcinoma in 2 patients, adenosquamous carcinoma in 1 patient and other histology in 4 patients.

Age range was 32-67 years. Age-wise distribution of cases is shown in Table 1. All the patients were treated by a combination of EBRT using megavoltage irradiation to the pelvis followed by ISBT using MUPIT. External radiotherapy dose schedule was 40-50 Gy/20-25 #/4-5 weeks. Response to EBRT and assessment for brachytherapy was done after 1 week. Only those patients who were found unsuitable for ICBT were treated with ISBT using MUPIT and were enrolled for this study. The indications for ISBT (MUPIT) in our study are listed in Table 2. Criteria for inclusion in this study were as follows: hemoglobin - minimum 10 gm%; performance status - 70% or more (Karnofsky scale); histopathological confirmation. Contraindications of ISBT were: 1) disease infiltrating rectovaginal septum Table 1. Age-wise Distribution of Cases Age in years

No. of cases

31-40

8

41-50

18

51-60

14

61-70

10

Table 2. Indication of ISBT in Our Study Indication

No. of patients

Non-negotiable os

8

Improper tumor geometry

10

Inadequate vaginal space

7

CVC inadequate

20

Palliation/Reirradiation

5

ISBT = Interstitial brachytherapy; OS = Overall survival; CVC = Central vaginal cylinder.

or posterior bladder wall at the time of brachytherapy; 2) very large residual tumor; 3) Frozen pelvis; 4) distant metastasis and 5) medical reasons.

The procedure was performed under epidural anesthesia with full aseptic precautions. Foleyâ&#x20AC;˛s catheterization was done with 7 mL of diatriazoate injected into its bulb to evaluate bladder dose. While inserting needles, a guide needle was inserted first mostly through the posterior vaginal wall with one finger in the rectum.

The tip of this needle was taken 1-2 cm beyond the clinically palpable disease. The total number of needles used ranged from 19 to 25 depending upon disease extension. Needles were bilaterally symmetrical in most of the cases. During implant procedure, utmost care was taken in order not to perforate bladder and rectum with needles. Thereafter, check cystoscopy was done and if any needle was found in the urinary bladder, that needle was removed. Thorough examination was done per rectally to confirm that no needle had pierced through rectal mucosa. After implantation, rectal tube (modified Malecot catheter) was inserted for evaluation of rectal dose.

TREATMENT PLANNING Orthogonal X-rays were taken on simulator. At the time of simulation radiographs, the Foley balloon was pulled down almost to the bladder neck. Five dose points were assigned to the Foley balloon, indicating dose to its center, posterior, anterior, superior and inferior points. The needles were plotted on computer by means of radiographs and planning was done according to stepping source dosimetry system (SSDS) for the treatment to be delivered on high-dose rate (HDR) microselectron (Ir-192, 10Ci).

The computer program used was PLATO TPS. Geometric and dose point optimization was used to achieve the uniform dose distribution. Isodose covering the treatment volume uniformly was selected to prescribe the dose. Depending upon the extent of disease, the active lengths of the implanted needles was up to 6-8 cm maximum. Doses to bladder and rectum were calculated by selecting points according to International Commission on Radiation Units and Measurements (ICRU) criteria. Bladder and rectal doses are shown in Figure 1.

Total dose of 1,500-2,400 cGy in 3 to 6 # was delivered on HDR microselectron with a minimum 6 hours gap between two fractions. MUPIT was removed after completion of treatment. Throughout the treatment period, adequate antibiotic coverage was given and

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OBSTETRICS AND GYNECOLOGY hydration of patient was maintained. Analgesia in the form of 60 mg of morphine was given through the epidural catheter, twice a day.

RESULTS AND COMPLICATIONS All patients were followed-up after 1 month and then every 3 months with maximum follow-up of 2 years.

Complete response was observed in 37 patients, partial response in 9 patients and 4 patients had no response (<50% response or local progression). At 6 months follow-up, 35 patients had no evidence of disease and 15 patients had residual/recurrent disease, which is shown in Table 3.

Three patients developed systemic metastasis. Two patients in computer response group developed bleeding per rectum (Grade I in 1 patient and Grade II in other) and were managed conservatively. There Bladder center

Bladder post wall

Max rectal

40 35 30 25 20 15 10 5 0

>60

40-60 <40 Percentage (%)

Figure 1. Bladder and rectal doses.

Table 3. Results of ISBT in Our Study Diagnosis No.

At first follow-up

At 6 months

CR

PR/NR

NAD

Residual/ Recurrence

Cervix

22

17

5

16

6

Vault

13

9

4

8

5

PO Rec

5

3

2

3

2

Vagina

10

8

2

8

2

Total

50

37

13

35

15

ISBT = Interstitial brachytherapy; CR = Complete response; PR = Partial response; NR = No response; NAD = No evidence in disease; PO = Per oral.

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were no adverse effects of Grade III or higher. The time gap between EBRT and ISBT also had an impact on the outcome. The local control was better for nonbulky tumors compared to bulky tumors irrespective of stage of disease and patients with good regression of disease after EBRT. The time gap between EBRT and ISBT also had an impact on the outcome.

DISCUSSION Brachytherapy is central to the successful management of gynecological cancer. ICBT is adequate for early stage cervical cancer and in those patients who have good tumor regression with EBRT. However, it does not deliver an optimal dose in those patients with bulky, locally advanced cervical cancer or in patients with distorted anatomy and poor response to EBRT. In ICBT, dose is prescribed at point A. If we deliver 100% dose to point A, point B (parametrium and pelvic lymph nodes) receives only 30%. Rectum and bladder are dose limiting structures. So, adequate dose cannot be delivered to parametrium (if significant parametrial involvement) and positive pelvic nodes with ICBT. Nowadays, treatment with ISBT is used with two intentions in gynecological cancer: 1) To boost treatment after EBRT in patients who are unsuitable for intracavitary radiotherapy and central vaginal cylinder application and 2) as a palliative procedure (reirradiation) in cases of recurrence after primary treatment.

Martinez et al constructed a multipurpose template, which could be used for a variety of perineal malignancies. It has the provision of both central tandem and central needle either of which could be used justifiably for optimal dose distribution simultaneously taking care of bladder and rectal tolerance. Martinez et al achieved the local control in 84%, with complication rate as low as 5% in a group of 78 patients with advanced gynecological malignancies. In comparison to ICBT, ISBT is the better option for giving a high dose to the target and lower dose to normal tissue.

In our study, 50 patients treated with ISBT using MUPIT were enrolled. All the patients received EBRT 40-50 Gy/20-25 #/4-5 weeks first. Only those patients, unsuitable for ICBT were taken up for ISBT using MUPIT. Brachytherapy dose/fraction ranged from 300 to 500 cGy for 3 to 6 fractions. Two fractions were delivered in 24 hours with minimum 6 hours interval between fractions. In our study, local control was achieved in 35 patients (70%) at 6 months. Three patients developed systemic metastasis. Complication

OBSTETRICS AND GYNECOLOGY Table 4. Comparison of Series Using Interstitial Brachytherapy Author’s Name

No.

Site

ISBT Details Type

Dose and dose rate

Syed et al (2002)11

185

Cx

SNT

40-50 Gy, LDR

Gupta et al (1999)12

69

Cx, vagina, endo

MUPIT

32-35 Gy, LDR

TMH

65

Cx

SNT MUPIT

Endo

Control rate (%)

Complications (%)

LC-82, DFS-65

10

LC-78,

14

Remarks

3 yr DFS-61

Martinez et al

78

Cx, vagina vulva

Eisbruch et al (2001)

22

Cx, vagina

Osaka series (2002)

15

Cx, body uterus

Monk et al (1997)13

28

Cx, body uterus

Demanes et al (1999)14

62

Cx, body uterus

SNT

Nag et al15 (1998)

39

Cx, body uterus

GCRI

50

Cx, vagina, vault, post-op rectum

24 Gy

5 yr DFS-64

7-10

LDR

LC-84

5

LDR

LC-55

20

3 yr DFS-40 MUPIT

42-48 Gy, HDR

2 yr DFS-75

30

LC-71

30

36 Gy, HDR

LC-94

6.5

SNT

30

LC-45

2.5

MUPIT

15-24 Gy, HDR

LC-70

4

CT-based customized implant

Intra-op implant

ISBT = Interstitial brachytherapy; Cx = Cervix; SNT = Syed-Neblett template; LDR = Low-dose rate; LC = Local control; DFS = Disease free survival; Endo = Endometrium; TMH = Tata Memorial Hospital; MUPIT = Martinez Universal Perineal Interstitial Template; CT = Computed tomography; HDR = High-dose rate; GCRI = Gujarat Cancer and Research Institute.

rate was 4%. Comparisons of many series of ISBT are listed in Table 4.11-15 Thus, ISBT can be used in gynecological cancer patients unsuitable for ICBT and CVC. ISBT can be used as palliative treatment, which gives promising results. However, patient selection is an important factor, which correlates with results and complications.

CONCLUSIONS Perineal ISBT using MUPIT is a technically safe and feasible procedure. It offers flexible positioning of needles ensuring adequate tumor coverage. It is good alternative to ICBT/CVC in patients with locally advanced gynecological malignancies, where ICBT/CVC is not feasible or results in suboptimal dose distribution.

Better local control can be achieved with acceptable morbidity with ISBT in patients unsuitable for ICBT/ CVC that might not have been treated with curative intent otherwise. ISBT can be an option in patients with local recurrence after previous radical irradiation, which are inoperable. The recent development of technologies in image-guided/based brachytherapy

provides definite assistance in improving the quality of ISBT. Further investigation to identify suitable patients and beneficial procedures should be performed.

REFERENCES 1. Devita VT, Hellman S, Rosenber SA. Cancer: Principles and Practice of Oncology, 6th Edition. Philadelphia (PA): Lippincott Williams and Wilkins; 2001. pp. 1542-3.

2. Rath GK, Chander S, Patel AK. Textbook of Radiation Oncology, 1st Edition, New Delhi: Churchill Livingstone; 2004. pp. 445-70.

3. Kumar PP, Taylor J, Scott JC Jr, Jacobs AJ, Rojas J. Indication for interstitial brachytherapy in carcinoma of the uterine cervix. J Natl Med Assoc. 1984;76(7):721-5.

4. Ampuero F, Doss LL, Khan M, Skipper B, Hilgers RD. The Syed-Neblett interstitial template in locally advanced gynecological malignancies. Int J Radiat Oncol Biol Phys.

1983;9(12):1897-903.

5. Perez CA, Brady LW, Halperin EC. Principles and Practice of Radiation Oncology, 4th Edition. Philadelphia (PA): Lippincott Williams and Wilkins; 2004. pp. 576-7.

6. Feder BH, Syed AM, Neblett D. Treatment of extensive carcinoma of the cervix with the “transperineal

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OBSTETRICS AND GYNECOLOGY parametrial butterfly”: a preliminary report on the revival of Waterman’s approach. Int J Radiat Oncol Biol Phys.

1978;4(7-8):735-42.

dose-rate interstitial-intracavitary brachytherapy in the treatment of carcinoma of the cervix. Int J Radiat Oncol Biol Phys. 2002;54(1):67-78.

7. Syed AM, Feder BH. Technique of after-loading interstitial implants. Radiol Clin (Basel). 1977;46(6):458-75.

12. Gupta AK, Vicini FA, Frazier AJ, Barth-Jones DC, Edmundson GK, Mele E, et al. Iridium-192 transperineal interstitial brachytherapy for locally advanced or recurrent gynecological malignancies. Int J Radiat Oncol Biol Phys. 1999;43(5):1055-60.

8. Martinez A, Cox RS, Edmundson GK. A multiple-site perineal applicator (MUPIT) for treatment of prostatic, anorectal, and gynecologic malignancies. Int J Radiat Oncol Biol Phys. 1984;10(2):297-305.

9. Martinez A, Edmundson GK, Cox RS, Gunderson LL, Howes AE. Combination of external beam irradiation and multiple-site perineal applicator (MUPIT) for treatment of locally advanced or recurrent prostatic, anorectal, and gynecologic malignancies. Int J Radiat Oncol Biol Phys.

1985;11(2):391-8.

10. Martinez A, Edmundson GK, Clarke D. The role of transperineal template implants in gynaecological malignancies. Brachyther J. 1991;5:107-13.

13. Monk BJ, Tewari K, Burger RA, Johnson MT, Montz FJ, Berman ML. A comparison of intracavitary versus interstitial irradiation in the treatment of cervical cancer.

Gynecol Oncol. 1997;67(3):241-7.

14. Demanes DJ, Rodriguez RR, Bendre DD, Ewing TL. High dose rate transperineal interstitial brachytherapy for cervical cancer: high pelvic control and low complication rates. Int J Radiat Oncol Biol Phys. 1999;45(1):105-12.

15. Nag S, Martínez-Monge R, Selman AE, Copeland LJ. Interstitial brachytherapy in the management of primary carcinoma of the cervix and vagina. Gynecol Oncol.

11. Syed AM, Puthawala AA, Abdelaziz NN, el-Naggar M, 1998;70(1):27-32.

Disaia P, Berman M, et al. Long-term results of low■■■■

...Cont’d from page 460

4. Crawford WH Jr, Korchin L, Greskovich FJ Jr. Neurilemmomas of the oral cavity: report of five cases.

J Oral Surg. 1968;26(10):651-8.

9. St Pierre S, Theriault R, Leclerc JE. Schwannomas of the vagus nerve in the head and neck. J Otolaryngol.

1985;14(3):167-70.

5. Al-Ghamdi S, Black MJ, Lafond G. Extracranial head and neck schwannomas. J Otolaryngol. 1992;21(3):186-8.

10. DiCerbo M, Sciubba JJ, Sordill WC, DeLuke DM. Malignant schwannoma of the palate: a case report and review of the literature. J Oral Maxillofac Surg. 1992;50(11):1217-21.

6. Sharaki MM, Talaat M, Hamam SM. Schwannoma of the neck. Clin Otolaryngol Allied Sci. 1982;7(4):245-51.

7. Chang KC, Leu YS. Hypoglossal schwannoma in the submandibular space. J Laryngol Otol. 2002;116(1):63-4.

11. López JI, Ballestin C. Intraoral schwannoma. A clinicopathologic and immunohistochemical study of nine cases. Arch Anat Cytol Pathol. 1993;41(1):18-23.

8. De Foer B, Hermans R, Sciot R, Fossion E, Baert AL. Hypoglossal schwannoma. Ann Otol Rhinol Laryngol.

1995;104(6):490-2.

12. Ruan LX, Zhou SH, Wang SQ. Palatine tonsil schwannoma: correlation between clinicopathology and computed tomography features. J Int Med Res. 2008;36(5):1140-7.

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New research suggests that young women who are diagnosed with ovarian cancer now have the chance to conceive later in life with the help of ovarian transplants. The findings are published in the journal Human Reproduction.

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Hormone therapy might be protective in postmenopausal women during a first myocardial infarction (MI), but could increase the risk, and severity of a second, suggests an observational Finnish study presented at the North American Menopause Society 2015 Annual Meeting.

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The Royal College of Obstetricians and Gynaecologists (RCOG) has released an updated guideline on vaginal birth after previous cesarean (VBAC) delivery. The guidelines state that planned VBAC is appropriate for majority of women with a singleton pregnancy of cephalic presentation at 37+0 weeks or beyond who have had a single previous lower segment cesarean delivery, with or without a history of previous vaginal birth.

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Indian Journal of Clinical Practice, Vol. 26, No. 5, October 2015

PEDIATRICS

Managing Iron Deficiency: New Approaches DIPANGKAR HAZARIKA

ABSTRACT In developing countries like India, nutritional anemia is a major health problem and iron deficiency anemia is by far the most common cause of nutritional anemia. The percentage of children with any anemia increased from 74.3% in NFHS-2 to 78.9% in NFHS-3. Significance of iron deficiency shifted from anemia to other aspects of children health, particularly cognitive functions, motor impairment and body’s immune response recently. Programs, which are in place for last four decade in India targeting vulnerable groups including infants, young children and pregnant women and lactating mothers fail to change the prevalence.

From various feedbacks from previous programs, Government of India has started “National Iron + Initiative” to prevent and to treat iron deficiency. Other approaches which are promising in the community level are cooking food in utensil made of iron and using iron as sprinkles. Timely supplementation with iron formulation is also important in young infants.

Keywords: Iron deficiency, iron + initiative, iron formulation

I

n developing countries like India, nutritional anemia is a major health problem and iron deficiency anemia is by far the most common cause of nutritional anemia. Despite various programs since independence the situation is same, a large number of children are still anemic. Seven out of every 10 children aged 6-59 months in India are anemic: 3% are severely, 40% moderately and 26% are mildly anemic.1 National Family Health Survey (NFHS)-3 showed 70% children under 5 years were anemic, it was 80% in under 3 years, 56% among adolescent girls (15-19 years) and 30% among adolescent boys. Prevalence of anemia among under 5 children increased from NFHS-2. The percentage of children with any anemia increased from 74.3% in NFHS-2 to 78.9% in NFHS-3. In the period between the two surveys, there was an increase in the prevalence of mild anemia (from 23% to 26%) and moderate anemia (from 46% to 49%).1 Recently, the significance of iron deficiency shifted from anemia to other aspects of children health, particularly cognitive functions, motor impairment and body’s immune response. Deficiency leads to diminished concentration, disturbed perception, impaired performances, impaired coordination of language, motor skills, equivalent to

Assistant Professor Dept. of Pediatrics Jorhat Medical College and Hospital, Jorhat, Assam Address for correspondence Dr Dipangkar Hazarika Assistant Professor, Dept. of Pediatrics Jorhat Medical College and Hospital, Jail Road, Jorhat - 785 001, Assam E-mail: dipankargmch@gmail.com

a 5-10 point deficit in intelligence quotient (IQ) and increased learning disabilities.2 Recent research has revealed that brain iron deficiency occurs even with normal levels of hemoglobin (Hb), as iron is prioritized to red blood cells (RBCs) over all other organs including brain.3,4 Most vulnerable period for this damage is between 9 and 18 months of age.1 Cognitive dysfunction in young children may not be completely reversible even after supplementation.5 In young children, iron deficiency is due to increased iron requirement during period of rapid growth, especially from 6 months to 3 years, which is almost 10 times higher per kg body weight than that of an adult male.1 Effect of childhood anemia persists in later life also. Twenty percent of maternal deaths are caused by anemia; in addition, it contributes partly to 50% of all maternal deaths. Maternal anemia also affects the fetus also leading to intrauterine growth retardation (IUGR), stillbirth, low-birth weight and neonatal death.1 The programs which are in place for last four decade in India, target vulnerable groups including infants, young children, pregnant women and lactating mothers. Failure, as evaluated in pregnant women, is largely due to poor coverage of beneficiaries. Moreover, the consumption of iron folic acid (IFA) is also poor because of belief and side effects. From various feedbacks from previous programs, Government of India has started “National Iron + Initiative” to prevent and to treat iron deficiency. It includes measures to: i) increase iron intake through food-based approaches, namely dietary diversification and food fortification with iron; ii) iron supplementation and iii) improved health services and sanitation.1

Indian Journal of Clinical Practice, Vol. 26, No. 5, October 2015

473

PEDIATRICS But, it is difficult in influencing dietary behavior, the key step in iron + initiative is supplementation part.

But, the main difference from previous program is that IFA supplementation will be “Directly Observed Therapy” with teachers in school and auxiliary nurse midwives (ANM) being instructed to ensure the actual consumption of drug under their direct supervision.1

Why this New Initiative?

Iron deficiency and infections are the most prevalent etiological factors for anemia; however, other conditions may have a contributory role. Copenhagen Consensus (2004) panel of eminent economists concluded that the returns of investing in micronutrient programs (including iron), among a list of 17 possible development investments, are second only to those fighting human immunodeficiency virus/acquired-immunodeficiency syndrome (HIV/AIDS). The benefit-to-cost ratio of iron interventions based on resource savings, improvement in cognitive development and schooling and physical productivity was estimated to be as high as 200:1.1

Apart from mass programs, other approaches can also improve the iron status. One of these approaches is cooking food in utensils made of iron. A recent study

by Kulkarni et al shows that iron content of food can be increased by 16% after cooking in iron utensils and consumption of such food resulted in increase in Hb% over 4-month period. However, for advocating such practice more studies are required.6 Using iron as sprinkles is another approach. A study by Hirve et al has demonstrated significant improvement, using 60 sachets of micronutrient powder (MNP) flexibly over a 4-month period to 17,124 children at Anganwadi centers or at home through Integrated Child Development Services (ICDS) in the age group of 6 months to 6 years.7 Such an approach of home-based fortification has earlier been shown to significantly reduce anemia.8 Advantages of this approach is low cost, ease of storage, transport and usage. Using multimicronutrient powder, it takes care of deficiency of other micronutrients, deficiency of which lead to poor hematological response to iron therapy alone. It is important to supplement multiple micronutrients for adequate hematological response.9

It is not easy to change food habits or ensure access to iron rich foods as diets in India are primarily cerealbased and bioavailability of iron from such diets is limited. In such a situation, implementation and scaling up of the IFA supplementation program through the life cycle and management of all forms of anemia seems beneficial. Supplementation is done both at community and facility based level.1

NATIONAL IRON + INITIATIVE1

Community-based Supplementation1

This new initiative brings together existing programs (IFA supplementation for pregnant and lactating women and children in age group of 6-60 months) and introduces new age groups. Targeted age groups are:

Supplementation for Children 6-60 Months

ÂÂ

Biweekly iron supplementation for pre-school children 6 months to 5 years

ÂÂ

Weekly supplementation for children from 1st to 5th grade in Govt. and Govt. Aided schools

ÂÂ

Weekly supplementation for out of school children (5-10 years) at Anganwadi centers

ÂÂ

Weekly supplementation (10-19 years)

ÂÂ

Pregnant and lactating mothers

ÂÂ

Weekly supplementation for women in reproductive age.

for

adolescents

IFA tablet has been made blue (Iron ki nili goli) to distinguish it from the red IFA tablet for pregnant and lactating women.

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Indian Journal of Clinical Practice, Vol. 26, No. 5, October 2015

What are the Interventions?

Under this initiative three components are given priorities: ÂÂ

Food-based strategies: Dietary diversification and food fortification

ÂÂ

Supplementation

ÂÂ

Improved health services.

Onset of anemia in young children is generally after 6 months, before this iron in breast milk is sufficient to meet the needs of a breastfed child. Thereafter, the incidence of anemia increases from 6 to 8 months till the child is 1 year old. In India, diets in children in the age group 6-23 months are predominantly plant-based and provide insufficient amounts of micronutrients to meet the recommended nutrient intakes.

Dose and Regime One milliliter IFA syrup containing 20 mg elemental iron and 100 µg folic acid biweekly for 100 doses in a year. Bottles have an autodispenser, so that only 1 mL of syrup is dispensed at a time. It is given under the direct supervision of an Accredited Social Health Activist (ASHA) on fixed days on a biweekly basis.

Prophylaxis with IFA syrup should be withheld in case of acute illness (fever, acute diarrhea, pneumonia, etc.),

PEDIATRICS severe acute malnutrition and known case of hemoglobinopathies/history of repeated blood transfusion. Nutritional status of children should be assessed by mid upper arm circumference (MUAC <11.5 cm) to ensure that IFA syrup is not given to children with severe acute malnutrition (SAM). Although anemia is common in severe malnutrition, iron should not be given initially due to danger of promoting free radical generation and bacterial proliferation. It should be added only after a week of therapy when the child has a good appetite and starts gaining weight.10 Iron should be given half an hour after food. Minor side effects associated with IFA such as black discoloration of stools should be explained. Apart from IFA, biannual deworming should be done. ASHA would give IFA syrup bottles to mothers for safe storage, but it will be given under her direct supervision only.

Supplementation for Children 5-10 Years and Adolescent Age Group1 Tablets containing 45 mg elemental iron and 400 µg of folic acid are given once a week throughout the 5-10 years period. Albendazole is give twice a year.

Platform of school and Anganwadi centers is utilized to provide IFA supplementation through involvement of teachers and Anganwadi workers. ASHA mobilize these children at community level.

For adolescent girls and boys (10-19 years) weekly IFA supplementation (100 mg elemental iron and 500 µg folic acid) throughout the calendar year. i.e., 52 weeks each year is done through the platform of Government/ Government aided/Municipal schools. Out of school children, in the age group 10-19 years, are reached through Anganwadi centers. It involves a “fixed dayMonday” approach for IFA distribution. Teachers and Anganwadi workers supervise the ingestion of the IFA tablets by the beneficiaries.

FACILITY-BASED MANAGEMENT1 Any child reporting to any facility (Primary Health Care [PHC] level and above) with any illness is assessed clinically by the attending Medical Officer for anemia routinely and should undergo Hb estimation if found to be anemic clinically. All children referred from field (community, outreach, sub-center) to PHC due to

Table 1. Management of Anemia on the Basis of Hb Levels in Children1 Level of Hb

Treatment

Follow-up

Referral

Mild anemia 6 months to 5 years (10-10.9 g/dL)

3 mg/kg/day for Follow-up every 14 days by ANM. Estimate Hb after 2 2 months months of treatment to document Hb >11 g/dL

If no response after 2 months of therapy refer to FRU/District hospital for further investigation and management

5-10 years (11-11.4 g/dL)

3 mg/kg/day for Follow-up every 14 days 2 months Estimate Hb after 2 months to document Hb >11.5 g/dL

-Do-

10-19 years (11-11.9 g/dL)

60 mg of iron for 3 months

Estimate Hb after 3 months to document Hb >12 g/dL

No improvement in 3 months refer

6 months to 5 years (7-9.9 g/dL)

3 mg/kg/day for Follow-up every 14 days by ANM. Estimate Hb after 2 2 months months of treatment to document Hb >11 g/dL

No improvement in 2 months refer

5-10 years (8-10.9 g/dL)

3 mg/kg/day for Follow-up every 14 days 2 months Estimate Hb after 2 months to document Hb >11.5 g/dL

-Do-

10-19 years (8-10.9 g/dL)

60 mg/day for 3 months

No improvement in 3 months refer

Follow-up every month

Moderate anemia

Investigate Follow-up every 14 days Hb estimation after 3 months to document Hb >12 g/dL

Severe anemia 6 months to 5 years (<7 g/dL)

Refer urgently to DH/FRU

5-10 years (<8 g/dL) 10-19 years (<8 g/dL) FRU = First referral unit; DH = District hospital.

Indian Journal of Clinical Practice, Vol. 26, No. 5, October 2015

475

PEDIATRICS palmar pallor undergo Hb estimation before initiating treatment. Children are categorized as having mild, moderate and severe anemia on the basis of Hb levels and managed accordingly (Table 1).

Recommendation for Use of Iron in <6 Months of Age Preterm infants (<37 weeks) who are breastfeed should receive iron supplementation at 2 mg/kg/day starting by 1 month of age and extending through 12 months of age.11 Those who are using standard preterm formula (14.6 mg of iron per L) get 1.8-2.2 mg/kg/ day of iron, assuming a formula intake of 150 mL/kg/ day.11 Despite the use of iron containing formula, 14% preterm infants develop iron deficiency between 4 and 8 months of age. Thus, some formula fed preterm may require an additional iron supplementation,12 although there is not enough evidence to make this a general recommendation at this time. Exception to this practice is in preterm, who received multiple blood transfusions during hospitalization.13 Term breastfed infants have sufficient iron store until 4-6 months of age, assuming that small amount of iron in human milk is sufficient for exclusively breastfed infants. Exclusive breastfeeding for more than 6 months has been associated with increased risk of iron deficiency anemia at 9 months of age. It is recommended that exclusively breastfed term infants receive an iron supplementation of 1 mg/kg/day, starting at 4 months of age and continued until appropriate iron-containing complementary foods have been introduced. Early supplementation results in higher Hb concentration, higher mean corpuscular volume, better visual acuity and higher psychomotor developmental indices.13 In term partially breastfed infants, who receive more than one-half of their daily feeding as human milk and who are not receiving iron-containing complementary foods should also receive 1 mg/kg/day of supplemental iron.13 CONCLUSION Iron is the most common single nutrient deficiency worldwide and there is some evidence of cognitive and behavioral impairment because of its deficiency.

It is important to minimize iron deficiency and iron deficiency anemia in all age groups by taking timely interventions. Iron + initiative may be one such intervention, which if implemented in all the states can reduce the burden of iron deficiency in India.

REFERENCES 1. Guidelines for Control of Iron Deficiency Anemia: National Iron + Initiative. Ministry of Health and Family Welfare, Government of India, 2013. Assessed from www. pbnrhm.org/docs/iron_plus_guidelines.pdf on 12th January 2015.

2. Chandra J. Combating iron deficiency in children. Indian J Pediatr. 2013;80(12):983-4.

3. Yadav D, Chandra J. Iron deficiency: beyond anemia.

Indian J Pediatr. 2011;78(1):65-72.

4. Lozoff B. Perinatal iron deficiency and the developing brain. Pediatr Res. 2000;48(2):137-9.

5. Grantham-McGregor S, Ani C. A review of studies on the effect of iron deficiency on cognitive development in children. J Nutr. 2001;131(2S-2):649S-666S; discussion 666S-668S. 6. Kulkarni SA, Ekbote VH, Sonawane A, Jeyakumar A, Chiplonkar SA, Khadilkar AV. Beneficial effect of iron pot cooking on iron status. Indian J Pediatr. 2013;80(12): 985-9.

7. Hirve S, Martini E, Juvekar SK, Agarwal D, Bavdekar A, Sari M, et al. Delivering sprinkles plus through the Integrated Child Development Services (ICDS) to reduce anemia in pre-school children in India. Indian J Pediatr.

2013;80(12):990-5.

8. Hirve S, Bhave S, Bavdekar A, Naik S, Pandit A, Schauer C, et al. Low dose ‘Sprinkles’ - an innovative approach to treat iron deficiency anemia in infants and young children.

Indian Pediatr. 2007;44(2):91-100.

9. Allen LH, Rosado JL, Casterline JE, López P, Muñoz E, Garcia OP, et al. Lack of hemoglobin response to iron supplementation in anemic Mexican preschoolers with multiple micronutrient deficiencies. Am J Clin Nutr.

2000;71(6):1485-94.

10. Paul VK, Lodha R, Agarwala A. Nutrition. In: Paul VK, Bagga A (Eds.). Ghai Essential Pediatrics, 8th Edition.

New Delhi: CBS Publishers; 2013. pp. 88-109.

11. American Academy of Pediatrics. Committee on nutrition.

Nutritional needs of the premature infant. In: Kleinman RE (Ed.). Pediatric Nutrition Handbook, 6th Edition. Elk Grove Village, IL: American Academy of Pediatrics; 2008. pp. 79-112.

12. Griffin IJ, Cooke RJ, Reid MM, McCormick KP, Smith JS. Iron nutritional status in preterm infants fed formulas fortified with iron. Arch Dis Child Fetal Neonatal Ed. 1999;81(1):F45-9.

13. Baker RD, Greer FR; Committee on Nutrition American Academy of Pediatrics. Diagnosis and prevention of iron deficiency and iron-deficiency anemia in infants and young children (0-3 years of age). Pediatrics.

2010;126(5):1040-50.

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RESPIRATORY INFECTIONS

To Evaluate the Compliance with ICS/NCCP Guidelines in the Management of Community-acquired Pneumonia in a North Indian Tertiary Care Hospital PAYAL PREET, HARINDER SINGH, VIJAY K SEHGAL, VISHAL CHOPRA*

ABSTRACT Background: Pneumonia is a common illness having significant morbidity and mortality. Irrational use of antibiotics in the treatment of pneumonia has led to antibiotic resistance, over prescribing and increased cost of treatment. Therefore, the present study was undertaken to evaluate the trends of antimicrobial prescription in community-acquired pneumonia (CAP). Aims: To evaluate the deviation in the treatment of CAP given in the Dept. of Chest and Tuberculosis, Rajindra Hospital, Patiala from the guidelines (Guidelines for Diagnosis and Management of Community-acquired Pneumonia in Adults: Joint ICS/NCCP recommendations). Material and methods: All the antimicrobial containing prescriptions of CAP were monitored. Data from the prescriptions was entered into data entry forms. Patients of either sex, both inpatients and outpatients were included in the study. The prescriptions were analyzed and any deviation in the treatment of CAP from the Indian pneumonia guidelines given by joint ICS-NCCP Committee was evaluated. Results: In the present study, there was 100% compliance with ICS/NCCP Guidelines with respect to all the investigations. There was no compliance with ICS/NCCP Guidelines with respect to CRB-65 score for risk stratification of patients, but there was 100% compliance with guidelines with respect to clinical judgment. There was no compliance with ICS/NCCP Guidelines with respect to duration of treatment for outpatients, but there was 72.3% compliance with guidelines with respect to duration of treatment for inpatients. There was 0% compliance with ICS/NCCP Guidelines with respect to antibiotic therapy in outpatients without comorbidities and 47.05% compliance inpatients without comorbidities (i.e., 16 patients out of 34 inpatients without comorbidities), but there was 100% compliance with guidelines with respect to antibiotic therapy in outpatients having associated comorbidities and 76.9% compliance in inpatients having associated comorbidities (i.e., 10 patients out of 13 inpatients with comorbidities). According to the present study, overall percentage compliance calculated for the treatment of CAP given in the Dept. of Chest and Tuberculosis, Rajindra Hospital, Patiala with ICS/NCCP Guidelines is 54.85%.

Keywords: Community-acquired pneumonia, antimicrobials, overprescribing, antibiotic resistance, ICS/NCCP Guidelines

C

ommunity-acquired pneumonia (CAP) is pneumonia that has been acquired in a community in a patient who has not been hospitalized within 14 days prior to onset of symptoms or hospitalized less than 4 days prior to onset of symptoms.1 The mortality rate is less than 1% for persons with CAP who do not require hospitalization; however, the mortality rate averages from 12% to 14% among hospitalized patients with CAP. Among patients

*Dept. of Pharmacology and Chest and Tuberculosis Government Medical College, Patiala, Punjab Address for correspondence Dr Payal Preet Flat-206, Tower Magnolia, Mayfair Apartments Soul Space, Sector-70, Mohali - 160 071, Punjab E-mail: payal_gh20@rediffmail.com

who are admitted to the intensive care unit (ICU), or who are bacteremic or who are admitted from a nursing home, the mortality rate averages from 30% to 40%.

Therefore, it is crucial that physicians recognize and treat CAP appropriately.2 Constant exposure to contaminated air and frequent aspiration of nasopharyngeal flora make lung parenchyma susceptible to virulent microorganisms.

Most microorganisms reach lower respiratory tract as inhaled and contaminated microdroplets. Complex interactions between virulence and quantum of aspirated or inhaled microorganisms, that arrive at lower respiratory tract, integrity of defense barriers and host immunity status, decide occurrence of pneumonia.3,4 The extensive list of potential etiologic agents in CAP includes bacteria, fungi, viruses and protozoa.

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477

RESPIRATORY INFECTIONS Newly identified pathogens include hantaviruses, metapneumoviruses, the coronavirus responsible for severe acute respiratory syndrome (SARS) and community-acquired strains of methicillin-resistant Staphylococcus aureus (MRSA).

Most cases of CAP; however, are caused by relatively few pathogens. Although Streptococcus pneumoniae is most common, other organisms must also be considered in light of the patientâ&#x20AC;&#x2122;s risk factors and severity of illness.5 The American Thoracic Society (ATS) emphasizes certain modifying factors that increase the risk of infection with drug-resistant and unusual pathogens.

Risk factors for drug-resistant S. pneumoniae (DRSP) include age greater than 65 years, β-lactam therapy within the past 3 months, immunosuppression (either as the result of an illness or induced by treatment with corticosteroids), multiple medical comorbidities, alcoholism and exposure to a child in a day care center.

Risk factors for enteric Gram-negative organisms are as follows: recent antibiotic therapy, underlying cardiopulmonary disease, residence in a nursing home and multiple medical comorbidities.6 CAP can vary from indolent to fulminant in presentation and from mild to fatal in severity. The various signs and symptoms that depend on the progression and severity of the infection include both constitutional findings and manifestations limited to the lung and associated structures. The patient is frequently febrile with tachycardia or may have a history of chills and/ or sweats. Cough may be either nonproductive or productive of mucoid, purulent or blood-tinged sputum. Depending on severity, the patient may be able to speak in full sentences or may be very short of breath. If the pleura is involved, the patient may experience pleuritic chest pain.5 The presentation of pneumonia can vary from a mild, self-limiting illness to a severe, life-threatening illness with significant mortality. Thus, the most important decision facing the physician once a diagnosis of pneumonia is confirmed is the site of care. This decision affects both patient outcomes and healthcare costs.7,8 Several predictive models and scoring systems have been developed and validated to help develop uniform, guidelines based protocols.9 CURB-65 (Confusion, Urea nitrogen, Respiratory rate, Blood pressure, 65 years of age and older) is a simpler scoring system, which is easier to remember and apply.10 CURB-65 uses five variables which include confusion, urea >20 mg/dL, respiratory rate >30/min, blood pressure

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(systolic blood pressure <90 mmHg or diastolic blood pressure <60 mmHg) and age more than 65 years. Each parameter is assigned 1 point to get a severity score.

The recommendations on the basis of CURB-65 scoring are outpatient treatment for patients with a score of 0-1, hospital admission for a score of 2 and consideration for admission to ICU with a score of 3 or more. CRB-65 (Confusion, Respiratory rate, Blood pressure, 65 years of age) can be used when urea levels are not available.

CRB-65 has the benefit of using only clinical parameters and has been found to have discriminatory value similar to CURB-65.11 The first step in treatment of CAP following severity assessment and decision regarding site of care, is initiation of treatment with appropriate antibiotics as bacteria are the most common pathogen. Early initiation of antibiotics is seen to abbreviate the illness and lead to a decrease in both complications and mortality. This is usually empirical as the organism is not isolated in a large proportion of patients at the onset.9 Severe cases of CAP require immediate institution of therapy, which must be adjusted after confirming microbiological etiology. Switch from intravenous antibiotics to oral treatment is recommended in case of observed improvement in symptoms, improved respiratory rate and oxygen saturations, patient being afebrile for more than 24 hours, hemodynamic stability, reduction in white blood cell count (if elevated earlier) and absence of nausea/vomiting.9 All appropriate spectrum antibiotics are equally effective. The main purpose is to target S. pneumoniae. β-lactams and macrolides are most commonly used antibiotics. Combination therapy is recommended for severe pneumonia only.12 Pneumonia is a common illness having significant morbidity and mortality. Irrational use of antibiotics in the treatment of pneumonia has led to antibiotic resistance, over prescribing and increased cost of treatment. Therefore, the present study was undertaken to evaluate the trends of antimicrobial prescription in CAP. MATERIAL AND METHODS

Study Design This prospective, open and observational study was conducted for the duration of 1 year starting from the date of approval of protocol of study and the approximate sample size calculated for the study was 80.

The patients of CAP attending the Dept. of Chest and

RESPIRATORY INFECTIONS Tuberculosis, Rajindra Hospital, Patiala were included.

The patients fulfilling the inclusion criteria and having none of the exclusion criteria were enrolled in the study after obtaining written informed consent.

Inclusion Criteria All patients with radiological or clinical evidence of CAP. Exclusion Criteria ÂÂ

Patients less than 18 years of age.

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Immunosuppressed (human immunodeficiency virus [HIV] positive or concurrent chemotherapy or immunosuppressant therapy).

ÂÂ

Cystic fibrosis

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Bronchiectasis.

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Suspected or confirmed tuberculosis.

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Aspiration or hospital-acquired pneumonia.

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Discharged from hospital within the previous 14 days.

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Transferred from another hospital (unless transferred within 4 hours of presentation at original institution).

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Patients unwilling or unable to comply with study proceedings.

Study Sequence All the patients were informed about the study in layman language and written informed consent was taken. The patients of CAP coming to the Dept. of Chest and Tuberculosis, Rajindra Hospital, Patiala were included in the study. All the antimicrobial containing prescriptions of CAP were monitored. Data from the prescriptions was entered into data entry forms.

Patients of either sex, both inpatients and outpatients were included in the study. The prescriptions were analyzed and any deviation in the treatment of CAP from the Indian pneumonia guidelines given by joint Indian Chest Society-National College of Chest Physicians (ICS-NCCP) Committee was evaluated. The research was conducted after obtaining approval from Institutional Ethics Committee.

Statistical Analysis Descriptive statistics had been applied for the analysis of data. Data was expressed in proportion and percentage form and represented in the form of tables, charts and bar diagrams.

Formula for the calculation of percentage of compliance of the present study with ICS/NCCP Guidelines is:

Percentage Compliance =

Mean deviation

× 100

Mean

RESULTS Data from the prescriptions was entered into data entry forms. Patients of either sex, both inpatients and outpatients were included in the study. The prescriptions were analyzed and any deviation in the treatment of CAP from the Indian pneumonia guidelines given by joint ICS-NCCP Committee was evaluated.

As shown in Table 1, in present study, there was 100% compliance with ICS/NCCP Guidelines with respect to all the investigations as X-ray was done in all the 80 patients and blood culture, sputum culture and Gram stain was done in all the 47 hospitalized patients, which was in accordance with ICS/NCCP Guidelines.

As shown in Table 2, there was no compliance with ICS/NCCP Guidelines with respect to CRB-65 score for risk stratification of patients, but there was 100% compliance with guidelines with respect to clinical judgment as clinical judgment was used in all the patients for assessment of severity and site of care and CRB-65 score for risk stratification was not used in any of the patients and according to guidelines both clinical judgment and CRB-65 score should be used to assess severity and site of care for each patient.

Table 3 shows that there was no compliance with ICS/ NCCP Guidelines with respect to duration of treatment for outpatients as according to ICS/NCCP Guidelines outpatients should be given antibiotic therapy for 5 days but in present study all the outpatients were treated for Table 1. Percentage of Compliance with ICS/NCCP Guidelines with Respect to Investigations Investigations

Compliance (%)

X-ray

100

Blood culture

100

Sputum culture

100

Gram stain

100

Table 2. Percentage of Compliance with ICS/NCCP Guidelines with Respect to Risk Stratification Risk stratification criteria CRB-65 score Clinical judgment

Compliance (%) 0 100

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RESPIRATORY INFECTIONS Table 3. Percentage of Compliance with ICS/NCCP Guidelines with Respect to Duration of Therapy Duration of therapy

Compliance (%)

Mean Deviation Parameters

Individual parameter (x)

Mean (x)

|x - x|

5 days for outpatients

0

1

100

66.35

33.65

7 days for inpatients

72.3

2

100

66.35

33.65

3

100

66.35

33.65

4

100

66.35

33.65

5

0

66.35

66.35

6

100

66.35

33.65

Table 4. Percentage of Compliance with ICS/NCCP Guidelines with Respect to Antibiotic Therapy in Outpatient Setting Patient population Without comorbidities With comorbidities

Compliance (%)

7

0

66.35

66.35

0

8

72.3

66.35

5.95

100

9

0

66.35

66.35

10

100

66.35

33.65

11

47.05

66.35

19.3

12

76.9

66.35

10.55

more than 5 days, but there was 72.3% (i.e., 34 patients out of 47 inpatients) compliance with guidelines with respect to duration of treatment for inpatients as according to ICS/NCCP Guidelines inpatients should be given antibiotic therapy for 7 days but in present study out of 47 inpatients only 34 inpatients were treated in accordance with guidelines and remaining 13 inpatients were given treatment for more than 7 days, which was not in compliance with guidelines.

As shown in Table 4, in present study, there was 0% compliance with ICS/NCCP Guidelines with respect to antibiotic therapy in patients without comorbidities who were treated in outpatient setting, but there was 100% compliance with guidelines with respect to antibiotic therapy in patients having associated comorbidities treated in outpatient setting as according to ICS/NCCP Guidelines outpatients without comorbidities should be treated with monotherapy either with macrolides or β-lactams and outpatients with comorbidities should be treated with combination of β-lactam and macrolide but in present study all outpatients irrespective of the presence or absence of associated comorbidities were treated with combination of β-lactam and macrolide.

Calculation of percentage compliance of treatment of CAP with ICS/NCCP guidelines

=

Mean deviation Mean

× 100

100 + 100 + 100 + 100 + 0 + 100 + 0 + 72.3 + 0 + 100 + 47.05 + 76.9 × 66.35 Mean = 12

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MAD =

Σ| x − | x | n

= 436.75/12 = 36.39

Percentage of compliance of present study with ICS/ NCCP guidelines is: Mean deviation × 100 Percentage compliance = Mean =

66.39 66.35

× 100 = 54.85%

DISCUSSION Pneumonia refers to a syndrome caused by acute infection, usually bacteria, characterized by clinical and/or radiographic signs of consolidation of a part or parts of one or both lungs. True incidence of CAP is exactly not known.13 Diagnosis of CAP is a challenge to the evaluating physician as this condition closely mimics the common cold or flu. Appropriate medical history and physical examination are an important part of making pneumonia diagnosis.14,15 The present prospective, open and observational was conducted for the duration of 1 year to study the trend of use of antimicrobials in CAP. Eighty prescriptions were analyzed and data from the prescriptions was entered into data entry forms. Till present date, no study has been conducted in the Indian scenario to evaluate the compliance with standard guidelines in the management of CAP. The mean age of cases was 53.83 years and 61.25% of the patients were males (i.e. 49 patients out of

RESPIRATORY INFECTIONS 80 patients) and 38.75% were females (i.e., 31 patients out of 80 patients).

Associated comorbidities were present in 33.75% of patients (i.e., 27 patients out of 80 patients). Out of 27 patients with comorbidities, 14 patients were outpatients and 13 were inpatients. The two commonest comorbid illnesses were chronic heart disease (CHD) present in 11 patients out of 27 patients with comorbidities and chronic obstructive pulmonary disease (COPD) present in nine patients out of 27 patients.

Diagnosis of CAP In the present study, X-ray was done in all 80 patients whether outpatients or inpatients. According to ICS/ NCCP Guidelines wherever feasible, a chest radiograph should be obtained in all patients suspected of having CAP. In the absence of availability of chest radiograph, patients may be treated on the basis of clinical suspicion.

Chest radiograph should be repeated if the patient is not improving and also for all those patients who have persistence or worsening of symptoms/physical signs or those in whom an underlying malignancy needs to be excluded. It is not routinely necessary to repeat a chest radiograph in patients who have improved clinically.12 Percentage of compliance with ICS/NCCP Guidelines with respect to X-ray for diagnosis of CAP was 100%.

Duration of Treatment In the present study, blood culture, sputum culture and Gram stain was done in all the 47 inpatients. According to ICS/NCCP Guidelines, blood cultures should be obtained in all hospitalized patients with CAP and an initial sputum Gram’s stain and culture (or an invasive respiratory sample as appropriate) should be obtained in all hospitalized patients with CAP. Therefore, percentage of compliance with ICS/NCCP Guidelines with respect to blood culture, sputum culture and Gram stain for diagnosis of CAP was 100%.

In the present study, 67 patients received antibiotic therapy for 7 days, which included all the outpatients (33 patients) and 34 inpatients out of 47 inpatients, whereas 13 patients who were all inpatients received antibiotic therapy for 14 days.

According to ICS/NCCP Guidelines outpatients should be treated for 5 days and inpatients for 7 days.12 Percentage of compliance with ICS/NCCP Guidelines with respect to duration of therapy was 0% for outpatients as all the 33 outpatients were given antibiotic

therapy for more than 5 days and 72.3% for inpatients as only 34 inpatients out of 47 inpatients were given antibiotic therapy for 7 days, which was in accordance with guidelines, whereas remaining 13 inpatients were given antibiotic therapy for 14 days, which was not in compliance with guidelines.

Antibiotic Therapy in Outpatient Setting In the present study, outpatients were treated with combination therapy (β-lactam plus macrolide) irrespective of presence or absence of comorbidities and none of the patient without comorbidity was treated with monotherapy. All the patients were given oral therapy.

According to ICS/NCCP Guidelines therapy in outpatient setting should be targeted towards coverage of the most common organisms, namely S. pneumoniae.

Outpatients should be stratified as those with or without comorbidities. Recommended antibiotics are oral macrolides (e.g., azithromycin) or oral β-lactams (e.g., amoxicillin 500-1,000 mg thrice-daily) for outpatients without comorbidities. For outpatients with comorbidities oral combination therapy is recommended (β-lactams plus macrolides).12 Percentage of compliance with ICS/NCCP Guidelines with respect to antibiotic therapy in outpatient setting was 0% for outpatients without comorbidities as 19 patients out of 33 outpatients who were without any associated comorbidity were also treated with combination of β-lactam and macrolide, which was not in accordance with guidelines as these patients should have been treated with either β-lactams or macrolides i.e., monotherapy instead of combination therapy and 100% for outpatients with comorbidities as 14 patients out of 33 outpatients with associated comorbidities were treated with combination of β-lactam and macrolide, which was in compliance with guidelines.

Antibiotic Therapy in Inpatient Setting In inpatient setting, nine patients were treated with twodrug combination therapy (1 patient with amoxicillinazithromycin, 5 patients with azithromycin-cefotaxime, 3 patients with azithromycin-ceftriaxone) and 38 patients were treated with three drug combination therapy (18 patients with azithromycin-co-amoxiclav, 20 patients with ceftriaxone-piperacillin-tazobactam).

Forty-six patients out of 47 inpatients were given parenteral therapy. In inpatient setting out of 47 patients, 34 patients are without any associated comorbidities and 13 patients were with associated comorbidities.

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RESPIRATORY INFECTIONS According to ICS/NCCP Guidelines the recommended regimen is combination of a β-lactam plus a macrolide (preferred β-lactams include cefotaxime, ceftriaxone and amoxicillin-clavulanic acid). Route of administration (oral or parenteral) should be decided based upon the clinical condition of the patient and the treating physician’s judgment regarding tolerance and efficacy of the chosen antibiotics. Switch to oral from intravenous therapy is safe after clinical improvement in moderate-to-severe CAP.12 Percentage of compliance with ICS/NCCP Guidelines with respect to antibiotic therapy in inpatient setting was 47.05% for inpatients without associated comorbidities and 76.9% for inpatients with associated comorbidities as only 16 inpatients out of 34 inpatients without associated comorbidities and 10 inpatients out of 13 inpatients with associated comorbidities were given antibiotic combinations, which are recommended by ICS/NCCP Guidelines (i.e., combination of a β-lactam plus a macrolide and preferred β-lactams include cefotaxime, ceftriaxone and amoxicillin-clavulanic acid).

Overall Compliance According to the present study, overall percentage compliance calculated for the treatment of CAP given in the Dept. of Chest and Tuberculosis, Rajindra Hospital, Patiala with ICS/NCCP Guidelines is 54.85%.

The results were similar to 2009/2010 Adult CommunityAcquired Pneumonia Audit conducted by British Thoracic Society from 1 December 2009 and 31 January 2010. According to British Thoracic Society Community Acquired Pneumonia Audit, antibiotics were given in accordance with local CAP guidelines in only 54% of cases.16 Therefore, the results of present study conducted in the Dept. of Chest and Tuberculosis, Rajindra Hospital, Patiala to study the trends and prescription auditing of antimicrobials in CAP were similar to British Thoracic Society Community Acquired Pneumonia Audit.

14 days. Percentage of compliance with ICS/NCCP Guidelines with respect to investigations was 100% as X-ray was done in all the 80 patients and blood culture, sputum culture and Gram stain was done in all the 47 hospitalized patients, which was in accordance with ICS/NCCP Guidelines.

Percentage of compliance with ICS/NCCP Guidelines with respect to risk stratification was 100% for clinical judgment and 0% for CRB-65 score.

Percentage of compliance with ICS/NCCP Guidelines with respect to duration of therapy was 0% for outpatients and 72.3% for inpatients.

Percentage of compliance with ICS/NCCP Guidelines with respect to antibiotic therapy in outpatient setting was 0% for outpatients without comorbidities and 100% for outpatients with comorbidities.

Percentage of compliance with ICS/NCCP Guidelines with respect to antibiotic therapy in inpatient setting was 47.05% for inpatients without comorbidities (i.e., 16 patients out of 34 inpatients without comorbidities) and 76.9% for inpatients with comorbidities (i.e., 10 patients out of 13 inpatients with comorbidities).

According to the present study, overall percentage compliance of the treatment of CAP given in the Dept. of Chest and Tuberculosis, Rajindra Hospital, Patiala with ICS/NCCP Guidelines is 54.85%.

Further studies involving large number of prescriptions of CAP are required to find the compliance of treatment with guidelines in order to avoid antibiotic resistance and misuse. This study gives an interesting perspective on how patients are currently managed for CAP in the Dept. of Chest and Tuberculosis, Rajindra Hospital, Patiala. There are clearly some areas where there could be improvement which would both be of benefit to patients and to the cost of providing their care in hospital.

Acknowledgment The authors would like to thank Dr Anjleen Kaur for her kind collaboration in the preparation of this article.

CONCLUSION

REFERENCES

In the present study, it was observed that CAP was most common in the age group of 42-60 years and the disease was more prevalent in males as compared to females.

In the present study, 58.75% were inpatients (i.e., 47 patients out of 80 patients) and 41.25% were outpatients (i.e., 33 patients out of 80 patients). Study showed that 83.75% of the patients received the treatment for 7 days and 16.25% of the patients received the treatment for

1. Bartlett JG, Dowell SF, Mandell LA, File Jr TM, Musher DM, Fine MJ; Infectious Diseases Society of America. Practice guidelines for the management of community-acquired pneumonia in adults. Clin Infect Dis. 2000;31(2):347-82.

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2. Mandell LA, Bartlett JG, Dowell SF, File TM Jr, Musher DM, Whitney C; Infectious Diseases Society of America.

Update of practice guidelines for the management of community-acquired pneumonia in immunocompetent adults. Clin Infect Dis. 2003;37(11):1405-33.

RESPIRATORY INFECTIONS 3. Mason CM, Nelson S. Pulmonary host defenses.

Implications for therapy. Clin Chest Med. 1999;20(3): 475-88, vii.

4. Welsh DA, Mason CM. Host defense in respiratory infections. Med Clin North Am. 2001;85(6):1329-47.

5. Mandell LA, Wunderink R. Pneumonia. In: Longo DL, Kasper DL, Jameson JL, Fauci AS, Hauser SL, Loscalzo J (Eds.). Harrison’s Principles of Internal Medicine, 18th Edition. New York: Mc Graw-Hill; 2011. pp. 2130-41.

6. Niederman MS, Mandell LA, Anzueto A, Bass JB, Broughton WA, Campbell GD, et al; American Thoracic Society. Guidelines for the management of adults with community-acquired pneumonia. Diagnosis, assessment of severity, antimicrobial therapy, and prevention. Am J Respir Crit Care Med. 2001;163(7):1730-54.

7. Dean NC, Silver MP, Bateman KA, James B, Hadlock CJ, Hale D. Decreased mortality after implementation of a treatment guideline for community-acquired pneumonia.

Am J Med. 2001;110(6):451-7.

8. Capelastegui A, España PP, Quintana JM, Gorordo I, Ortega M, Idoiaga I, et al. Improvement of process-ofcare and outcomes after implementing a guideline for the management of community-acquired pneumonia: a controlled before-and-after design study. Clin Infect Dis. 2004;39(7):955-63.

10. Lim WS, van der Eerden MM, Laing R, Boersma WG, Karalus N, Town GI, et al. Defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study. Thorax.

2003;58(5):377-82.

11. Man SY, Lee N, Ip M, Antonio GE, Chau SS, Mak P, et al.

Prospective comparison of three predictive rules for assessing severity of community-acquired pneumonia in Hong Kong. Thorax. 2007;62(4):348-53.

12. Gupta D, Agarwal R, Aggarwal AN, Singh N, Mishra N, Khilnani GC, et al; Pneumonia Guidelines Working Group.

Guidelines for diagnosis and management of communityand hospital-acquired pneumonia in adults: Joint ICS/ NCCP(I) recommendations. Lung India. 2012;29(Suppl 2):S27-62.

13. Prasad R. Community acquired pneumonia: clinical manifestations. J Assoc Physicians India. 2012;60 Suppl:10-2.

14. Pimentel L, McPherson SJ. Community-acquired pneumonia in the emergency department: a practical approach to diagnosis and management. Emerg Med Clin North Am. 2003;21(2):395-420.

15. Andrews J, Nadjm B, Gant V, Shetty N. Communityacquired pneumonia. Curr Opin Pulm Med. 2003;9(3): 175-80.

9. Guleria R, Kumar J. Management of community acquired 16. Lim WS. 2009/10 Adult Community Acquired Pneumonia pneumonia. J Assoc Physicians India. 2012;60 Suppl:21-4 Audit. BTS National Respiratory Audits 2010;2:1-4.

■■■■

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The programmed death (PD-1) inhibitor pembrolizumab (Keytruda, Merck & Co) has been granted approval by the US Food and Drug Administration (FDA) for use in lung cancer, becoming the second immunotherapy available for this tumor type. The accelerated approval is for use in patients with advanced non–small cell lung cancer (NSCLC) across all histologies whose disease has progressed on or after platinum-containing chemotherapy, as well as a targeted agent in epidermal growth factor receptor– or anaplastic lymphoma kinase–positive patients.

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A new study, published in Science Translational Medicine, suggests that a lack of contact with certain bacteria could increase asthma risk in newborns. Researchers reported that the acquisition of four types of gut bacteria by 3 months of age may actually protect an infant from developing asthma.

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All people infected with HIV should receive antiretroviral therapy (ART) as soon as possible, and those at “substantial” risk should be offered pre-exposure prophylaxis (PrEP), according to new guidelines by the World Health Organization, published online September 30.

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The American College of Chest Physicians have updated evidence-based guideline for unexplained chronic cough providing six recommendations for appropriate treatment of patients, including the use of speech pathology based cough suppression as a treatment option. The updated guidelines are published in the journal Chest.

Indian Journal of Clinical Practice, Vol. 26, No. 5, October 2015

483

SURGERY

What Gravity, Genetics and Smoking, Together can Achieve SOMENDRA MOHAN SHARMA

ABSTRACT All women experience sagging of their breast at some age, and find it unavoidable. Various causes have been described for this essential phenomenon. Gravity also has been widely accepted as a cause, but use of a bra to alleviate the effect of gravity, and, thereby reducing sagging, is still controversial. We are discussing here a case in which, in presence of many other predisposing factors, nonavailability of the support of a bra lead to extreme ptosis of a lump-laden breast. We could single out gravity because the other breast of the same woman, which had no lump, was normal for age.

Keywords: Bra, breast ptosis, breast fibroma, neurofibromata, smoking

S

agging (Ptosis) of breast is a common problem, and is generally attributed to aging, repeated pregnancies, smoking, weight gain or sudden weight loss, malnutrition and also gravity (larger cup size).1 Breastfeeding and exercise have not been found to contribute to ptosis.1

CASE REPORT The patient, 54 years female, (Fig. 1) presented to our OPD with complaints of an elongated right breast with painful excoriating ulcers over the breast contour.

Generally, the breasts do not hang more than a few inches below the inframammary fold. Regnault has classified ptotic breast into three grades depending upon the position of the nipple in relation to the inframammary fold - Grade C being when the nipple lies at the most dependent part of the breast.2 But how low the breasts can sag if more than one causative factors combine, as they generally do? And what, amongst all is the most effective causal factor for ptosis.

We are presenting a one of its kind case of extreme (2.5 feet!!) ptosis of breast, which was caused by several factors working together, like aging, multiparity, smoking, genetic changes associated with multiple neurofibromata, and, above all, the weight of a large fibroma.

Consultant General and Minimal Access Surgeon J Watumull Global Hospital and Research Center Mount Abu, Rajasthan Address for correspondence Dr Somendra Mohan Sharma Consultant General and Minimal Access Surgeon J Watumull Global Hospital and Research Center Mount Abu - 307 501, Rajasthan E-mail: drsomendra@gmail.com

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Indian Journal of Clinical Practice, Vol. 26, No. 5, October 2015

Figure 1. Extreme ptosis of the right breast.

SURGERY On examination, the affected breast was about twohalf feet long, hanging up to the groin, with a wellcircumscribed round large fibroma about 10 × 6 × 4 cm, palpable below the nipple, but separate from it. The nipple-areola complex was slightly stretched, but was normal in color and texture. The breast skin over the mound had several excoriated ulcers which were painful, and were the cause of her seeking medical advice. The lady also had multiple dermal neurofibromata spread all over her body with no associated symptoms. The opposite breast was slightly hypotrophic, without any lump and had a Grade B ptosis.

The patient had breastfed four children about 30-35 years ago, she smoked 20-30 beedis (indigenous, stronger substitutes to cigarettes) a day for last 20 years or so, she used to wear a loose blouse and had left wearing ‘choli’ (Indian home-made bra) for about last 20-30 years. She was an average built, average nourished thin lady and, as mentioned earlier, had several neurofibromata all over her body.

Simple excision mammoplasty without nipple conservation was done on her affected breast, the histopathology report was consistent with benign fibroma, which weighed about 300 g. The diagnosis of multiple neurofibromata was clinical and no biopsy was done. The patient never returned for follow-up.

DISCUSSION Ptosis of breast is a fairly common problem. Various causes for sagging of female breast have been found and documented including aging, gravity (lack of support), multiparity, smoking, obesity, malnutrition and sudden weight loss.1 Aging and gravity are the factors upon which we have no control, and so, some amount of sagging is unavoidable, and this normal sagging is generally more in obese and heavy breasted women.1,3 But, there are other factors completely under our control like parity, nutrition, smoking, etc.

Gravity is a very important factor causing breast sagging1 and it has been found that women with a large cup size experience greater sagging because of the weight of the breast.1,3 It is therefore, logical to conclude that wearing a well-fitted bra can prevent sagging by preventing the stretching of the Cooper’s ligaments and skin. But, there are some studies, although not on breasts but on other body ligaments, to show that weight-bearing and movement are necessary for the maintenance of healthy ligaments.4 A number of website articles related to women’s health announce

that a bra has no role in preventing sagging of the breast,5 although there are not enough well-designed, published and peer reviewed studies to support or refute the claim. True, a bra alone cannot prevent sagging because gravity alone is not responsible for the sagging of breasts. It seems that because of the weak intrinsic anatomical support in the breast structure and the movement it allows, female breasts require some form of external support, if not to prevent sagging, than at least to avoid pain and discomfort it can lead to during vigorous activities including sports.6 Smoking also leads to significant loss of elasticity of skin and subcutaneous tissue, and is an independent cause of skin aging and lack of skin elasticity.7 This patient had one additional predisposing factor in the form of her genetic changes, which lead to multiple neurofibromata all over her body. It has been observed that the skin of neurofibroma patients lacks the elasticity of normal people.8 Smoking, genetics, gravity and the weight of the fibroma formed a grave combination against her. Looks like support of a bra might have definitely helped her in preventing this extreme sagging of the right breast.

REFERENCES 1. Rinker B, Veneracion M, Walsh CP. Breast ptosis: causes and cure. Ann Plast Surg. 2010;64(5):579-84.

2. Regnault P. Breast ptosis. Definition and treatment. Clin Plast Surg. 1976;3(2):193-203.

3. Ashizawa K, Sugane A, Gunji T. Breast form changes resulting from a certain brassière. J Hum Ergol (Tokyo).

1990;19(1):53-62.

4. Ho S, Luo Y, Yu W, Chung J. 6.4.3 Prevention of sagging.

In: Yu W, Fan J, Harlock SC, Ng SP (Eds.). Innovation and Technology of Women’s Intimate Apparel, 1st Edition.

USA: Woodhead Publishing Ltd; 2006. p. 138.

5. News article. Professor says bras are useless. Available at: http://www.connexionfrance.com/Brasupport-damageprofessor-Rouillon-back-pain-nipple-14626-view-article. html. [Accessed 18 March, 2015].

6. Ho S, Luo Y, Yu W, Chung J. 6.4.5 Relief of breast pain.

In: Yu W, Fan J, Harlock SC, Ng SP (Eds.). Innovation and Technology of Women’s Intimate Apparel, 1st Edition.

USA: Woodhead Publishing Ltd; 2006. p. 139.

7. Just M, Ribera M, Monsó E, Lorenzo JC, Ferrándiz C. Effect of smoking on skin elastic fibres: morphometric and immunohistochemical analysis. Br J Dermatol.

2007;156(1):85-91.

8. Mimoun N, Razzouq N, Wolkenstein P, Moreno JC, Marty JP, Lantieri L, et al. Evaluation of skin viscoelasticity in type 1 neurofibromatosis patients. Skin Pharmacol Physiol. 2006;19(1):22-7.

Indian Journal of Clinical Practice, Vol. 26, No. 5, October 2015

485

DIAGNOSTICS

Dengue Diagnostics for Clinicians

T

he objectives of dengue laboratory diagnosis are: i) to confirm the clinical diagnosis and ii) to provide information for epidemiological surveillance. Laboratory diagnosis is not necessary for clinical management except in atypical cases or when carrying out differential diagnosis with other infectious diseases.

Laboratory diagnosis of dengue is made by detecting the virus and/or any of its components (infective virus, virus genome, dengue antigen) or by investigating the serological responses present after infection (specifically immunoglobulin [Ig] M and IgG levels) (Table 1).1-4

Dengue viruses are RNA viruses belonging to the family Flaviviridae, genus Flavivirus. The four dengue viruses (DEN-[1-4]) are serologically related but antigenically and genetically distinctive.5-7 Three main aspects should be considered for an adequate dengue diagnosis: ÂÂ

Virological and serological markers in relation to the time of dengue infection

ÂÂ

Type of diagnostic method in relation to clinical illness

ÂÂ

Characteristics of the clinical samples.

VIROLOGICAL AND SEROLOGICAL MARKERS IN RELATION TO TIME OF DENGUE INFECTION (FIG. 1) An incubation period of 4-10 days occurs after the mosquito bites, resulting in an asymptomatic or symptomatic dengue infection. During this period, the virus replicates and an antibody response is developed.

In general, viremia is detectable in most dengue cases at the same time that symptoms appear, and is no longer detectable at the time of defervescence. The development of IgM antibody is coincident with the disappearance of fever and viremia.8 Virological and serological markers differ in time evolution and titer response and according to whether the infection is primary or secondary.

In a primary infection (i.e., when an individual is infected for the first time with a Flavivirus), viremia develops from 1 to 2 days before the onset of fever until 4-5 days after.

Accordingly, anti-dengue IgM-specific antibodies can be detected 3-6 days after fever onset. On average, IgM is detected in 50% of cases by Days 3-5 after the onset of illness, this figure increasing to 95-98% for Days 6-10. Low levels of IgM are still detectable around 1-3 months after fever. In addition, the primary infection is characterized by slowly increasing but low levels of

Table 1. Dengue Diagnostics and Sample Characteristics Clinical sample Virus detection and Acute serum (1-5 days of fever) and its components necropsy tissues

Serological response

Diagnostic method

Methodology

Time to results

Viral isolation

Mosquito or mosquito cell culture 1 week or more inoculation

Nucleic acid detection Antigen detection

RT-PCR and real-time RT- PCR

1 or 2 days

NS1 Ag rapid tests

Minutes

NS1 Ag ELISA

1 day

Immunohistochemistry

2-5 days

Paired sera (acute serum from1 to 5 days and second serum 15 to 21 days after)

IgM or IgG seroconversion

ELISA, HIA

1-2 days

Neutralization test

Minimum 7 days

Serum after Day 5 of fever

IgM detection (recent infection)

ELISA

1 or 2 days

Rapid tests

Minutes

IgG detection

IgG ELISA, HIA

1 or 2 days

ELISA = Enzyme-linked immunosorbent assay; HIA = Hemagglutination inhibition assay; IgG = Immunoglobulin G; IgM = Immunoglobulin M; NS1 Ag = Nonstructural protein 1 antigen; RT-PCR = Reverse transcriptase polymerase chain reaction.

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DIAGNOSTICS Critical and Convalescent Phases (After Days 4-5 of Illness) IgG

Viremia

IgM

Primary infection

Viremia Secondary infection

Figure. 1. Virological and serological markers of dengue infection according to time of illness.

dengue-specific IgG, becoming elevated at Days 9-10.

Low IgG levels persist for decades, an indication of a past dengue infection.1-4,9,10 A totally different picture is observed during a secondary infection, with a rapid and higher increase of anti-dengue specific IgG antibodies and slower and lower levels of IgM. High IgG levels remain for 30-40 days. A short-lasting but higher viremia level characterizes the secondary infection compared to the primary infection.1-4,9,10 TYPE OF DENGUE DIAGNOSTIC METHOD IN RELATION TO TIME OF CLINICAL ILLNESS The diagnostic method to confirm an acute infection depends on the time of clinical illness: the febrile phase is coincident with the presence of viremia, some viral components and replication products in blood; the critical and convalescent phases coincide with the development of antibodies, as summarized in Table 1.

Febrile Phase (Day 1 to Days 4–5 of Fever) The infective virus can be isolated in serum by inoculation in tissue culture (mosquito cell cultures) and mosquitoes. This method allows for identification of the viral serotype. Virus genome detection using reverse transcriptase polymerase chain reaction (RTPCR) and real-time RT-PCR confirms an acute dengue infection. Both methods have a high sensitivity and allow serotype identification and quantification of genome copies.1-4,11-13 Some studies suggest the presence of a higher number of copies in severe dengue cases.14-16 NS1 Ag is a marker of acute dengue infection.

Both enzyme-linked immunosorbent assay (ELISA) and rapid commercial tests are available for NS1 Ag detection. The sensitivity and specificity of commercial kits in different serotype infections and days of illness are being evaluated.17-19

Specific IgM is the best marker of a recent dengue infection. MAC-ELISA and rapid tests are the most frequent methods for IgM detection; however, a recent evaluation of four rapid tests demonstrated a low sensitivity.20,21 In addition to IgM, high levels of specific IgG in sera collected early after fever onset as detected

by ELISA and hemagglutination inhibition assay (HIA) also suggest a recent dengue infection.1-4,9 Primary infections are characterized by high levels of IgM and low levels of IgG, while low levels of IgM with high levels of IgG characterize secondary infections.

A single serum sample collected after Day 5 of fever onset is useful for IgM determination. Depending on the IgG level in the sample, classification into primary or secondary infection can also be determined using the IgM/IgG optical density ratio. Ratios greater than 1.2 (using the patient’s sera at 1/100 serum dilution) or 1.4 (using serum dilution of 1/20) suggest a primary infection.1 In addition, IgG titers higher than 1/1,280

by HIA or ELISA are also suggestive of a secondary infection.1,4,9,10 As IgM antibodies persist for almost 3 months after fever onset, the detection in samples collected late after the acute phase of illness suggests a recent infection.

In dengue endemic countries, acute clinical cases with a positive IgM are classified as probable dengue cases.

The study of paired sera (acute and convalescent serum samples with the second sample being collected 15-21 days after the first sample), allows for serological confirmation of dengue infection. The diagnosis depends upon the demonstration of rising titers of dengue antibodies between acute and convalescent sera.1,4,9,22 A broad cross-reactivity of ELISA and HIA with other flaviviruses has been observed. Neutralization test is the method of choice for determination of specific serotype.1-4,9,10,23 CHARACTERISTICS OF THE CLINICAL SAMPLE Similar to other enveloped viruses, dengue virus is labile and readily inactivated at temperatures above 30°C, so care should be taken during transportation and storage of samples. Serum samples collected during the first 4 days of fever are useful for virus, genome and dengue antigen detection, thus confirming a dengue infection. Samples should be rapidly transported at 4°C to the laboratory and be processed as soon as possible. Sterile serum without anticoagulant is useful.

If specimen delivery cannot be performed in the first

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DIAGNOSTICS 24-48 hours, freezing at –70°C is recommended. Sera for serological studies should be stored at 4°C for short time periods and at –20°C for a longer time periods. When serum collection or transportation is not possible, blood collected on filter papers represents an opportunity for IgM and IgG determination and also for RNA detection.24,25 Tissue specimens collected from fatal cases are useful for virus, genome and antigen detection. Liver, spleen and lymph nodes are the tissues of choice.26,27 Tissue samples should be collected immediately after death and be immediately frozen at –70°C, or rapidly transported at 4°C to the laboratory for sample processing. Fresh tissues are also suitable for virus isolation.26-29 Besides general patient information, a summary of clinical and

epidemiological data, such as the date of fever onset, method of sample collection and the type of sample, should accompany clinical samples.1 The usefulness of available diagnostic tests depends on the level of healthcare (Table 2). At primary-care level, rapid tests for NS1 Ag detection (suggestive of an acute dengue infection) as well as rapid tests for IgM determination (suggestive of a recent infection), are useful.

As patients access care independent of the period of infection suffered –some early, some late – a combination of both NS1 Ag and IgM markers is advisable. At district health centers, both antigen-based tests and serology can be performed using ELISA and

Table 2. Recommended Diagnostic Tools According to Laboratory Service Level Primary healthcare centers

District health centers

Reference centers

Virus isolation

Yes

Genome detection

Yes

NS1 Ag detection

Rapid tests

Yes

ELISA IgM detection

Rapid tests

Yes

ELISA IgG detection

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

ELISA

Yes

IHA

Yes

Neutralization assay

Yes

ELISA = Enzyme-linked immunosorbent assay; IgG = Immunoglobulin G; IgM = Immunoglobulin M; IHA = Indirect hemagglutination; NS1 Ag = Nonstructural protein 1 antigen.

Table 3. Confirmed and Probable Dengue Diagnosis, Interpretation of Results and Sample Characteristics Confirmed dengue infection

Method

Interpretation

Sample characteristics

Viral isolation

Virus isolated

Serum (collected at 1-5 days of fever)

Genome detection

Positive RT-PCR or positive real-time RT-PCR

Necropsy tissues

Antigen detection

Positive NS1 Ag Positive immunohistochemical

Necropsy tissues

IgM seroconversion From negative IgM to positive IgM in paired sera

Acute serum (Days 1-5) and convalescent serum (15-21 days after IgG seroconversion From negative IgG to positive IgG in paired sera or first serum) 4-fold increase IgG levels among paired sera Probable dengue infection

Positive IgM

Positive IgM

High IgG levels

High IgG levels by ELISA or HI (≥1,280)

Single serum collected after Day 5

ELISA = Enzyme-linked immunosorbent assay; IgG = Immunoglobulin G; IgM = Immunoglobulin M; NS1 Ag = Nonstructural protein 1 antigen; RT-PCR = Reverse transcriptase polymerase chain reaction.

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DIAGNOSTICS rapid tests. All diagnostic methods should be available at reference centers, including virus isolation, nucleic acid detection, diagnostics for tissues samples and all serological techniques.1-4,30 LABORATORY CONFIRMATION OF A DENGUE CASE A diagnosis of dengue infection is confirmed by the detection of the virus, the viral genome or NS1 Ag or seroconversion of IgM or IgG (from negative to positive IgM/IgG or four-fold increase in the specific antibody titer) in paired sera (Table 3). A positive IgM serology or a HIA antibody titer of 1,280 or higher (or comparable figures by ELISA in a single specimen), are all diagnostic criteria of a probable dengue infection.

Both probable and confirmed dengue cases should be notified to health authorities.1-4,9,30 REFERENCES 1. Dengue. Guidelines for diagnosis, treatment prevention and control. Geneva, TDR/WHO, 2009. WHO/HTM/NTD/ DEN/2009.

2. Guzman MG, Rosario D, Kouri G. Diagnosis of dengue virus infection. In: Kalitzky M, Borowski P (Eds.), Molecular Biology of the Flaviviruses. UK: Horizon Bioscience; 2009.

3. Buchy P, Yoksan S, Peeling RW, Hunsperger E. Laboratory tests for the diagnosis of dengue virus infection. TDR/ Scientific Working Group. TDR/SWG/08 Geneva, Switzerland, 1-5 October. 2006. pp. 74-85.

4. Guzmán MG, Kourí G. Dengue diagnosis, advances and challenges. Int J Infect Dis. 2004;8(2):69-80.

5. Burke DS, Monath TP. Flaviviruses. In: Knipe DM, Howley PM (Eds.), Fields Virology. London-New York-Tokyo: Lippincott Williams & Wilkins; 2001. pp.1043-125.

6. Lindenbach BD, Rice CM. Flaviviridae: the viruses and their replication. In: Knipe DM, Howley PM (Eds.) Fields Virology. London-New York-Tokyo: Lippincott Williams & Wilkins: 2001. pp. 991-1042.

7. Chambers TJ, Hahn CS, Galler R, Rice CM. Flavivirus genome organization, expression, and replication. Annu Rev Microbiol. 1990;44:649-88.

8. Vaughn DW, Green S, Kalayanarooj S, Innis BL, Nimmannitya S, Suntayakorn S, et al. Dengue viremia titer, antibody response pattern, and virus serotype correlate with disease severity. J Infect Dis. 2000;181(1):2-9.

11. Kumaria R, Chakravarti A. Molecular detection and serotypic characterization of dengue viruses by singletube multiplex reverse transcriptase-polymerase chain reaction. Diagn Microbiol Infect Dis. 2005;52(4):311-6.

12. Rosario D, Alvarez M, Diaz J, Contreras R, Rodrigues R, Vazques S, et al. Rapid detection and typing of dengue viruses from clinical samples using reverse transcriptase polymerase chain reaction. Pan Am J Public Health 1998;4:1-5.

13. Chien LJ, Liao TL, Shu PY, Huang JH, Gubler DJ, Chang GJ. Development of real-time reverse transcriptase PCR assays to detect and serotype dengue viruses. J Clin Microbiol. 2006;44(4):1295-304.

14. Libraty DH, Young PR, Pickering D, Endy TP, Kalayanarooj S, Green S, et al. High circulating levels of the dengue virus nonstructural protein NS1 early in dengue illness correlate with the development of dengue hemorrhagic fever. J Infect Dis. 2002;186(8):1165-8.

15. Libraty DH, Endy TP, Houng HS, Green S, Kalayanarooj S, Suntayakorn S, et al. Differing influences of virus burden and immune activation on disease severity in secondary dengue-3 virus infections. J Infect Dis. 2002;185(9): 1213-21.

16. Wang WK, Chao DY, Kao CL, Wu HC, Liu YC, Li CM, et al. High levels of plasma dengue viral load during defervescence in patients with dengue hemorrhagic fever: implications for pathogenesis. Virology. 2003;305(2):330-8.

17. Dussart P, Petit L, Labeau B, Bremand L, Leduc A, Moua D, et al. Evaluation of two new commercial tests for the diagnosis of acute dengue virus infection using NS1 antigen detection in human serum. PLoS Negl Trop Dis. 2008;2(8):e280.

18. Hang VT, Nguyet NM, Trung DT, Tricou V, Yoksan S, Dung NM, et al. Diagnostic accuracy of NS1 ELISA and lateral flow rapid tests for dengue sensitivity, specificity and relationship to viraemia and antibody responses.

PLoS Negl Trop Dis. 2009;3(1):e360.

19. Kumarasamy V, Wahab AH, Chua SK, Hassan Z, Chem YK, Mohamad M, et al. Evaluation of a commercial dengue NS1 antigen-capture ELISA for laboratory diagnosis of acute dengue virus infection. J Virol Methods. 2007; 140(1-2):75-9.

20. Blacksell SD, Newton PN, Bell D, Kelley J, Mammen MP Jr, Vaughn DW, et al. The comparative accuracy of 8 commercial rapid immunochromatographic assays for the diagnosis of acute dengue virus infection. Clin Infect Dis. 2006;42(8):1127-34.

9. Pan American Health Organization. Dengue and dengue hemorrhagic fever in the Americas: Guidelines for Prevention and Control;1994;Scientific Publication No.: 548.

21. Hunsperger EA, Yoksan S, Buchy P, Nguyen VC, Sekaran SD, Enria DA, et al. Evaluation of commercially available antidengue virus immunoglobulin M tests. Emerg Infect Dis. 2009;15(3):436-40.

10. Vázquez S, Cabezas S, Pérez AB, Pupo M, Ruiz D, Calzada N, et al. Kinetics of antibodies in sera, saliva, and urine samples from adult patients with primary or secondary dengue 3 virus infections. Int J Infect Dis. 2007;11(3):256-62.

22. Vázquez S, Pérez AB, Ruiz D, Rodríguez R, Pupo M, Calzada N, et al. Serological markers during dengue 3 primary and secondary infections. J Clin Virol.

2005;33(2):132-7.

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MEDILAW

Fundamental Rights of Patients and the Consumer Protection Act KK AGGARWAL

What are the fundamental rights as defined by the Constitution of India?

of 6-14 years in such manner as the State may, by law, determine.”

Part III of the Constitution of India guarantees fundamental rights to the citizens of India provided for in Articles 14 to 35 as follows:

Right against exploitation ÂÂ

Article 23. Prohibition of traffic in human beings and forced labour.

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Article 24. Prohibition of employment of children in factories, etc.

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Right to equality

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Right to freedom

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Right against exploitation

Right to freedom of religion

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Right to freedom of religion

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Cultural and educational rights

Article 25. Freedom of conscience and free profession, practice and propagation of religion.

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Right to constitutional remedies.

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Article 26. Freedom to manage religious affairs.

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Article 27. Freedom as to payment of taxes for promotion of any particular religion.

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Article 28. Freedom as to attendance at religious instruction or religious worship in certain education institutions.

Right to equality ÂÂ

Article 14. Equality before law.

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Article 15. Prohibition of discrimination on grounds of religion, race, caste, sex or place of birth.

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Article 16. Equality of opportunity in matters of public employment.

Cultural and educational rights

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Article 17. Abolition of untouchability.

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Article 29. Protection of interests of minorities.

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Article 18. Abolition of titles.

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Article 30. Right of minorities to establish and administer educational institutions.

Right to freedom ÂÂ

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Article 19. Protection of certain rights regarding freedom of speech, etc.

Article 20. Protection in respect of conviction for offences.

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Article 21. Protection of life and personal liberty.

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Article 22. Protection against arrest and detention in certain cases.

‘Right to Education’ was made a fundamental right under Article 21A amended by The Constitution (Eighty-Sixth Amendment) Act, 2002 (brought into force on April 1, 2010), “The State shall provide free and compulsory education to all children of the age

Senior Physician and Cardiologist, Moolchand Medcity, New Delhi Group Editor-in-Chief, IJCP Group and eMedinewS

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Right to constitutional remedies ÂÂ

Article 32. Remedies for enforcement of rights conferred by this Part.

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Article 33. Power of Parliament to modify the rights conferred by this Part in their application to Forces, etc.

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Article 34. Restriction on rights conferred by this Part while martial law is in force in any area.

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Article 35. Legislation to give effect to the provisions of this Part.

What are the rights of a consumer in India?

The Consumer Guidance Society of India (CGSI), a non-profit, non-political voluntary body, has listed the following rights of the consumer (Source: www.cgsiindia. org/how-to-become-a-member-of-cgsi/).

1. The Right to the Satisfaction of Basic Needs

MEDILAW 2. The Right to Safety 3. The Right to be Informed 4. The Right to be Heard 5. The Right to Choose 6. The Right to Redress 7. The Right to Consumer Education 8. The Right to a Healthy and Sustainable

Environment

What are the consumer rights as defined in the Consumer Protection Act, 1986?

The following rights have been provided to the consumers under the Consumer Protection Act, 1986.

Chapter II Section 6 of the Act has defined the rights of the consumer as below: a) The right to be protected against the marketing of goods and services which are hazardous to life and property

1. Patients have the right to be told about their illness; to have their medical records explained.

2. Patients should be explained about whatever treatment/medicines are prescribed to them. They should be made aware of the risks and side effects, if any. They have the right to ask questions and clarify their doubts about the treatment.

3. Patients have the right to know a doctor’s qualifications.

4. Patients have the right to be handled with consideration and due regard for their modesty when being physically examined by the doctor.

5. Patients have the right to maintain confidentiality regarding their illness and can expect the same from the doctors.

6. Patients have the right to a second opinion if they are doubtful about the medicines or treatment suggested.

b) The right to be informed about the quality, quantity, potency, purity, standard and price of goods or services, as the case may be so as to protect the consumer against unfair trade practices

7. Patients have the right to know what a suggested operation/surgery is for and the possible risks involved. If he/she is unconscious or unable to make the decision due to other reasons, informed consent needs to be taken from their nearest relatives.

c) The right to be assured, wherever possible, access to a variety of goods and services at competitive prices

8. Patients have the right to get their medical records/ case papers on request from the doctor/hospital.

d) The right to be heard and to be assured that consumer’s interests will receive due consideration at appropriate forums

9. If the patient needs to be moved to another hospital, he/she has the right to know the reason for it and also has the right to make their own choice in consultation with the doctor.

e) The right to seek redressal against unfair trade practices or restrictive trade practices or unscrupulous exploitation of consumers f) The right to consumer education.

What are the rights and responsibilities of a patient?

10. Patients have the right to get details of the bills they have paid for.

Does an unconscious patient have rights?

The World Medical Association (WMA) has provisions for the rights of the unconscious patient in 2005 “WMA Declaration of Lisbon on the Rights of the Patient”. It states as follows:

The medical profession came under the purview of the Consumer Protection Act in 1995 in a landmark judgement of the Supreme Court of India, Indian Medical Association vs. VP Shantha & Ors on 13th November, 1995, 1996 AIR 550, 1995 SCC (6) 651. Consequent to this, the medical profession has also been included within the ambit of a ‘service’ as defined in the Consumer Protection Act, 1986.

a) If the patient is unconscious or otherwise unable to express his/her will, informed consent must be obtained whenever possible, from a legally entitled representative.

As per the CGSI, the patient’s rights as a consumer are the following: (Available from: www.cccindia.co/corecentre/ guest/news/news_oct_2013_9.asp)

b) If a legally entitled representative is not available, but a medical intervention is urgently needed, consent of the patient may be presumed, unless it is

4. The unconscious patient

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MEDILAW obvious and beyond any doubt on the basis of the patient’s previous firm expression or conviction that he/she would refuse consent to the intervention in that situation.

he/she has the right to forbid the disclosure of information to his/her legally entitled representative.

Do legally incompetent patients have rights?

c) If the patient’s legally entitled representative, or a person authorised by the patient, forbids treatment which is, in the opinion of the physician, in the patient’s best interest, the physician should challenge this decision in the relevant legal or other institution. In case of emergency, the physician will act in the patient’s best interest.

The WMA 2005 Declaration of Lisbon on the Rights of the Patient has defined rights of the legally incompetent patient as follows:

Does a patient have the right to choose his/her doctor?

c) However, physicians should always try to save the life of a patient unconscious due to a suicide attempt.

5. The legally incompetent patient a) If a patient is a minor or otherwise legally incompetent, the consent of a legally entitled representative is required in some jurisdictions.

Nevertheless the patient must be involved in the decision-making to the fullest extent allowed by his/ her capacity. b) If the legally incompetent patient can make rational decisions, his/her decisions must be respected and

Yes. According to the WMA 2005 Declaration of Lisbon on the Rights of the Patient, a patient has the “right to freedom of choice” and states as follows: a) The patient has the right to choose freely and change his/her physician and hospital or health service institution, regardless of whether they are based in the private or public sector. b) The patient has the right to ask for the opinion of another physician at any stage.”

■■■■

...Cont’d from page 489

23. Alvarez M, Rodriguez-Roche R, Bernardo L, Vázquez S, Morier L, Gonzalez D, et al. Dengue hemorrhagic fever caused by sequential dengue 1-3 virus infections over a long time interval: Havana epidemic, 2001-2002. Am J Trop Med Hyg. 2006;75(6):1113-7.

27. Rosen L, Drouet MT, Deubel V. Detection of dengue virus RNA by reverse transcription-polymerase chain reaction in the liver and lymphoid organs but not in the brain in fatal human infection. Am J Trop Med Hyg. 1999;61(5): 720-4.

24. Vázquez S, Sáenz E, Huelva G, González A, Kourí G, Guzmán M. Detection de IgM contra el virus del dengue en sangre entera absorbida en papel de filtro. Rev Panam Salud Publica [Pan American Journal of Public Health].

1998;3(3):174-8.

28. Hall WC, Crowell TP, Watts DM, Barros VL, Kruger H, Pinheiro F, et al. Demonstration of yellow fever and dengue antigens in formalin-fixed paraffin-embedded human liver by immunohistochemical analysis. Am J Trop Med Hyg. 1991;45(4):408-17.

25. Prado I, Rosario D, Bernardo L, Alvarez M, Rodríguez R, Vázquez S, et al. PCR detection of dengue virus using dried whole blood spotted on filter paper. J Virol Methods.

2005;125(1):75-81.

29. Limonta D, Capó V, Torres G, Pérez AB, Guzmán MG. Apoptosis in tissues from fatal dengue shock syndrome.

J Clin Virol. 2007;40(1):50-4.

26. Guzmán MG, Alvarez M, Rodríguez R, Rosario D, Vázquez S, Vald s L, et al. Fatal dengue hemorrhagic fever in Cuba, 1997. Int J Infect Dis. 1999;3(3):130-5.

30. Vorndam V, Kuno G. Laboratory diagnosis of dengue virus infections. In: Gubler DJ, Kuno G (Eds.), Dengue and Dengue Hemorrhagic Fever. New York, NY: CAB International; 1997. pp. 313-33.

Source: Handbook for Clinical Management of Dengue. World Health Organization, 2012.

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AROUND THE GLOBE

News and Views ÂÂ

ÂÂ

A new study shows that luteolin, present in vegetables such as celery, could counter the risk of breast cancer caused by the combination of natural estrogen and synthetic progestin used in hormone replacement therapy (HRT). The study is published in Springer Plus.

Marijuana use in early adulthood was associated with an increased risk for prediabetes, but not diabetes, by middle adulthood in an adjusted analysis of data from the Coronary Artery Risk Development in Young Adults (CARDIA) study, published in Diabetologia.

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A clinical trial, published in Neurology, has revealed that the compound resveratrol stabilizes a biomarker found to decline alongside the progression of the disease in people with mild-tomoderate Alzheimer’s disease.

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In contrast with widespread misperceptions, older adults with arthritis are less likely than their younger counterparts to report worse outcomes, suggested Canadian research published in BMC Musculoskeletal Disorders.

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A new study by UC Davis pathologists suggests that many patients are mistakenly diagnosed with Clostridium difficile infection and do not need antibiotic treatment. Researchers suggested that patients are likely being over diagnosed and over treated on the basis of positive results on molecular tests, adding to concerns about antibiotic resistance.

The findings are published in JAMA Internal Medicine.

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Low vitamin D levels are very common in older adults, especially African Americans and Hispanics, and are associated with accelerated decline in episodic memory and executive function, the two cognitive domains strongly associated with Alzheimer’s disease dementia, suggests a new study published online September 14 in JAMA Neurology.

A double-blind, phase 2 study of the investigational opioid TRV130 showed that it was superior to placebo in terms of reducing pain intensity in patients undergoing a bunionectomy, relieving pain within 5 minutes of administration and without causing serious adverse events. The results were presented at PAINWeek 2015.

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Brief, daily bouts of hopping or jumping can strengthen hip bones and reduce the risk of fracture following a fall, suggests a new study of older men, published in the Journal of Bone and Mineral Research.

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Nocturnal enuresis in postmenopausal women may be associated with symptoms of obstructive sleep apnea (OSA), suggests data from the Women’s Health Initiative (WHI) program, published online in Menopause.

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New research suggests that people who think they are doing the right thing by choosing a diet beverage then do the wrong thing by snacking on sodium, sugar and high-carbohydrate goodies like cookies, ice cream, fries and pastries. The findings are published in the Journal of the Academy of Nutrition and Dietetics.

ÂÂ

NIH: Students who reported using electronic cigarettes by the time they started high school were more likely to report later use of traditional tobacco products. The finding highlights the importance of learning more about how e-cigarettes can affect teen smoking patterns.

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Children who were exposed to indoor-based pesticides appear to have a higher risk of developing leukemia and lymphoma, according to a small meta-analysis on 16 observational studies examining pesticide exposure and childhood cancer.

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On September 10, the American Board of Anesthesiology (ABA) unveiled a redesign of its Maintenance of Certification in Anesthesiology (MOCA) program that replaces a dreaded 10-year exam with an online learning tool called the MOCA minute that will quiz and teach physicians on a continuous, baby-step basis at their convenience.

MOCA 2.0, as it is called, also drops a requirement for assessing an anesthesiologist’s simulated care of a dummy patient and makes it optional instead.

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Screening healthy men for prostate cancer remains controversial, but if the decision is taken to undergo such screening - after detailed discussion with the individual, then “both a blood test for prostate-specific antigen (PSA) and a digital rectal examination (DRE) should be carried out”, says David Penson, MD, MPH, chair of the Dept. of Urologic Surgery at Vanderbilt University Medical Center in Nashville, Tennessee.

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AROUND THE GLOBE ÂÂ

Organizers expect to hear guidance on which treatments work best in age-related macular degeneration, diabetic macular edema and retinal vascular occlusion at the European Society of Retina Specialists 15th EURETINA Congress.

ÂÂ

Infants who contract pertussis from a known source are now more likely to have gotten it from a sibling than from their mother. That represents a shift in the pattern of known sources of infection, although in about half of cases the source is unknown, reports an article published online September 7 in Pediatrics.

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Eating fish may protect against depression, suggests a new meta-analysis published online in the Journal of Epidemiology and Community Health.

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Cardiac-based monitoring for an impending epileptic seizure and subsequent vagus nerve stimulation (VNS) has the potential to decrease seizure severity and duration and improve overall quality-of-life, suggested a study presented at the 31st International Epilepsy Congress (IEC).

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New data on a needle-free nasal delivery system for glucagon, presented at the European Association for the Study of Diabetes (EASD) 2015 Meeting, for use in severe hypoglycemia appear promising.

Researchers noted that needle-free nasal delivery of glucagon was faster and had a much higher success rate with fewer errors than delivery of glucagon via injection.

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Clinicians can now refer to the Michigan Appropriateness Guide for Intravenous Catheters (MAGIC), a new tool to help them determine when and how to use peripherally inserted central catheters (PICCs) and related venous access devices. The guide is published as a supplement to the Annals of Internal Medicine.

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A Mediterranean diet (MeDiet) appears to protect against breast cancer, suggest results from the randomized controlled Prevención con Dieta Mediterránea (PREDIMED) trial. The findings were published online September 14 in JAMA Internal Medicine.

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In the United States, nearly 138.5 million people— almost 44% of the population—currently live in areas where levels of air pollution are deemed dangerous to heath, according to the “State of the Air 2015” report issued by the American Lung Association (ALA).

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There is an association between acute and chronic exposure to ambient air pollution and an increased

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risk for respiratory disease (asthma, chronic obstructive pulmonary disease, lung cancer) and cardiovascular disease (myocardial infarction, heart failure, stroke), diabetes, obesity, cognitive decline, and anxiety. Prenatal exposure has been associated with preterm birth. People living in areas with poor air quality have consistently been shown to be at increased risk for premature death from cardiopulmonary and other diseases. Number of preterm deaths linked to reduced air quality caused by road transportation exceeds the number of fatal accidents by up to 30%. ÂÂ

An article by Anupam B Jena, MD, PhD, from Harvard Medical School in Boston, Massachusetts, and colleagues published in the September 15 issue of JAMA reports that although women make up half of all medical school graduates; 30,464 women are medical faculty members versus 60,609 men in a cohort representing about a tenth of physicians in the United States.

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The FDA has “clarified and enhanced” prescribing information for clozapine to better explain how to monitor patients for neutropenia and manage clozapine treatment, and it approved a new, shared risk evaluation and mitigation strategy (REMS), called the Clozapine REMS Program.

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A scoring system based on five “easily and readily available” clinical and laboratory variables, called the GLOBE score, was better able than existing criteria to predict the transplant-free survival of patients with primary biliary cirrhosis (PBC) who were treated with ursodeoxycholic acid (UDCA), as reported by Willem J Lammers, MD, of the Erasmus University Medical Center in Rotterdam, the Netherlands and colleagues in Gastroenterology. These variables include: Age, bilirubin level, albumin, alkaline phosphatase and platelet count.

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Air pollution is killing 3.3 million people a year worldwide, according to a new study published Wednesday in the journal Nature, which also has a surprise observation: Farming plays a large role in smog and soot deaths in industrial nations. The study also projects that if trends don’t change, the yearly death total will double to about 6.6 million a year by 2050. With nearly 1.4 million deaths a year, China has the most air pollution fatalities, followed by India with 6,45,000 and Pakistan with 1,10,000. The United States, with 54,905 deaths in 2010 from soot and smog, ranks seventh highest for air pollution deaths.

LIGHTER READING

HUMOR

Lighter Side of Medicine A friend and I stayed at a Chicago hotel while attending a convention. Since we weren’t used to the big city, we were overly concerned about security. The first night we placed a chair against the door and stacked our luggage on it. To complete the barricade, we put the trash can on top. If an intruder tried to break in, we’d be sure to hear him.

Dr. Good and Dr. Bad SITUATION: A diabetic with A1c 6% had a BP of 130/88 mmHg.

This is very good control of diabetes

This is very good control but we also need to control BP

Around 1 a.m. there was a knock on the door.

“Who is it?” my friend asked nervously. © IJCP Academy

“Honey,” a woman on the other side yelled, “you left your key in the door.”

--A carpenter was giving evidence about an accident he had witnessed. The lawyer for the defendant was trying to discredit him and asked him how far away he was from the accident.

The carpenter replied, “Twenty-seven feet, six and one-half inches.”

LESSON: Cardiovascular morbidity can only be reduced with aggressive management of hypertension, cholesterol (LDL <100 mg/dL) and aspirin (75-150 mg/day) in patients with or at high-risk for cardiovascular disease.

A patient filed a case in the Medical Council against his treating doctor citing irregularity in the medical bills issued to him for expenses incurred on account of his treatment.

This patient has filed a complaint after 9 years of the incident.

This is a time-barred complaint. It stands dismissed.

© Dr KK Aggarwal

Proceed

Lesson: If the period of limitation lapses and no complaint has been lodged then the complaint is treated as “Time-barred.” Period of limitation is the time period within which a complaint has to be lodged. There are many Delhi Medical Council orders where complaints filed after 3 years of the incident have been rejected.

•• In a case DMC/DC/F14/562/2009 decided on 2nd September, 2009, the Council rejected a complaint alleging professional misconduct on the part of the treating doctor on the ground that as the complaint had been made after a period of 9 years, the same did not merit consideration.

•• DMC/DC/F14/567/2009: The case was dismissed as the cause of action arose 6 years back.

•• DMC/DC/F14/580/2010: The case was dismissed as the cause of action arose 4 years back.

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Information for Authors Manuscripts should be prepared in accordance with the ‘Uniform requirements for manuscripts submitted to biomedical journals’ compiled by the International Committee of Medical Journal Editors (Ann. Intern. Med. 1992;96: 766-767).

Indian Journal of Clinical Practice strongly disapproves of the submission of the same articles simultaneously to different journals for consideration as well as duplicate publication and will decline to accept fresh manuscripts submitted by authors who have done so.

The boxed checklist will help authors in preparing their manuscript according to our requirements. Improperly prepared manuscripts may be returned to the author without review. The checklist should accompany each manuscript.

Authors may provide on the checklist, the names and addresses of experts from Asia and from other parts of the World who, in the authors’ opinion, are best qualified to review the paper.

Covering letter –

– –

The covering letter should explain if there is any deviation from the standard IMRAD format (Introduction, Methods, Results and Discussion) and should outline the importance of the paper.

Principal/Senior author must sign the covering letter indicating full responsibility for the paper submitted, preferably with signatures of all the authors.

Articles must be accompanied by a declaration by all authors stating that the article has not been published in any other Journal/Book. Authors should mentioned complete designation and departments, etc. on the manuscript.

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

–

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

–

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

Note: Please keep a copy of your manuscript as we are not responsible for its loss in the mail. Manuscripts will not be returned to authors.

Title page Should contain the title, short title, names of all the authors (without degrees or diplomas), names and full location of the departments and institutions where the work was performed,

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name of the corresponding authors, acknowledgment of financial support and abbreviations used.

– The title should be of no more than 80 characters and should represent the major theme of the manuscript.

A subtitle can be added if necessary.

– A short title of not more than 50 characters (including inter-word spaces) for use as a running head should be included.

– The name, telephone and fax numbers, e-mail and postal addresses of the author to whom communications are to be sent should be typed in the lower right corner of the title page.

– A list of abbreviations used in the paper should be included. In general, the use of abbreviations is discouraged unless they are essential for improving the readability of the text.

Summary – The summary of not more than 200 words. It must convey the essential features of the paper.

– It should not contain abbreviations, footnotes or references.

Introduction – The introduction should state why the study was carried out and what were its specific aims/objectives.

Methods – These should be described in sufficient detail to permit evaluation and duplication of the work by others.

– Ethical guidelines followed by the investigations should be described.

Statistics The following information should be given: – The statistical universe i.e., the population from which the sample for the study is selected.

– Method of selecting the sample (cases, subjects, etc. from the statistical universe).

– Method of allocating the subjects into different groups.

– Statistical methods used for presentation and analysis of data i.e., in terms of mean and standard deviation values or percentages and statistical tests such as Student’s ‘t’ test, Chi-square test and analysis of variance or non-parametric tests and multivariate techniques.

–

Confidence intervals for the measurements should be provided wherever appropriate.

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

Discussion –

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

References These should conform to the Vancouver style. References should be numbered in the order in which they appear in the texts and these numbers should be inserted above the lines on each occasion the author is cited (Sinha12 confirmed other reports13,14...). References cited only in tables or in legends to figures should be numbered in the text of the particular table or illustration. Include among the references papers accepted but not yet published; designate the journal and add ‘in press’ (in parentheses). Information from manuscripts submitted but not yet accepted should be cited in the text as ‘unpublished observations’ (in parentheses).

At the end of the article the full list of references should include the names of all authors if there are fewer than seven or if there are more, the first six followed by et al., the full title of the journal article or book chapters; the title of journals abbreviated according to the style of the Index Medicus and the first and final page numbers of the article or chapter. The authors should check that the references are accurate. If they are not this may result in the rejection of an otherwise adequate contribution.

Examples of common forms of references are: Articles Paintal AS. Impulses in vagal afferent fibres from specific pulmonary deflation receptors. The response of those receptors to phenylguanide, potato S-hydroxytryptamine and their role in respiratory and cardiovascular reflexes.

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

Figures – Two complete sets of glossy prints of high quality should be submitted. The labelling must be clear and neat.

– All photomicrographs should indicate the magnification of the print.

– Special features should be indicated by arrows or letters which contrast with the background.

– The back of each illustration should bear the first author’s last name, figure number and an arrow indicating the top. This should be written lightly in pencil only. Please do not use a hard pencil, ball point or felt pen.

– Color illustrations will be accepted if they make a contribution to the understanding of the article.

–

Do not use clips/staples on photographs and artwork.

–

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

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

Books

5. Special requests _____________________________

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

6. Suggestions for reviewers (name and postal address)

Articles in Books

2.____________ 2.________________

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

3.____________ 3.________________

4.____________ 4.________________

Tables –

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

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

–

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

Indian 1.____________Foreign 1.________________

7. All authors’ signatures________________________ 8.

Corresponding author’s name, current postal and e-mail address and telephone and fax numbers __________________________________________

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

Dr KK Aggarwal

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

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

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