IJCP July 2019

ISSN 0971-0876 RNI 50798/1990 University Grants Commission 20737/15554

Indexed with IndMED Indexed with MedIND Indian Citation Index (ICI)

www.ijcpgroup.com

A Multispecialty Journal Volume 30, Number 2

July 2019, Pages 101–200

Single Copy Rs. 300/-

Peer Reviewed Journal yy Original Research yy Original Study yy Review Article yy Clinical Study yy Case Report yy Public Health yy HCFI Consensus Statement yy RTI Analysis yy Expert’s View yy Medifinance yy Medical Voice for Policy Change yy Conference Proceedings yy Around the Globe yy Spiritual Update yy Inspirational Story yy Lighter Reading

Full text online: http://ebook.ijcpgroup.com/ijcp/ IJCP Publications | https://goo.gl/j2nXQQ

www.emedinexus.com

Online Submission

IJCP Group of Publications

A Multispecialty Journal Volume 30, Number 2, July 2019

Dr Sanjiv Chopra Group Consultant Editor Dr Deepak Chopra Chief Editorial Advisor

From the desk of THE group editor-in-chief

105 Bihar Children Deaths: Could Refeeding Syndrome Precipitated by Litchis have Triggered the Deaths?

Dr KK Aggarwal Group Editor-in-Chief Dr Veena Aggarwal Group Executive Editor Mr Nilesh Aggarwal CEO Ms Naina Ahuja COO Dr Anoop Misra Group Advisor

Editorial Advisors Obstetrics and Gynaecology Dr Alka Kriplani Cardiology Dr Sameer Srivastava Paediatrics Dr Swati Y Bhave

Original research

107 Ambulance Services in Delhi Need an Ambulance Care

KK Aggarwal, Ira Gupta

ORIGINAL STUDY

110 Prevalence of Thyroid Dysfunction in Pregnancy

Ruchika Garg, Prabhat Agrawal, Vishy Agrawal, Urvashi, Saroj Singh

Review Article

114 Management of Diabetic End-stage Renal Disease: Role of Hemodialysis

H Sudarshan Ballal

120 Evaluation of the Infertile Female

Garima Kachhawa, Anju Singh

Clinical Study

125 A Study of Corneal Thickness and Endothelial Morphology in Type 2 Diabetes Mellitus

Rajender Singh Chauhan, Ashok Rathi, Jp Chugh, P Sharma, R Rajput, R Kumar

130 Effect of Adjuvant Atorvastatin Therapy on Disease Activity in Active Rheumatoid Arthritis: A Tertiary Care Center Study in India

ENT Dr Chanchal Pal Gastroenterology Dr Ajay Kumar and Dr Rajiv Khosla

KK Aggarwal

H Singh, Rekha Mathur, A Singhania, Kiran B

Case Report

136 Unusual Temporary Treatment for Mastoid Fistula

Subramaniam Vinayak Easweran, Sarvesh Nayak, Arpana Hegde

138 The Wide Clinical Spectrum of Raised Fetal Hemoglobin in Adults

Dermatology Dr Anil Ganjoo

Oncology Dr PK Julka

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

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

Pratik Vora, Sakshi Singh, Jemima Bhaskar, Manish Mehta, Ami Trivedi

141 Bilateral Single System Ectopic Ureters with Secondary Calculi in an Adult

Gopi Kishore M, Suhasini G, Prasad Pvgs, Sainadh Av

Public Health

146 2013-2014 Investigation Findings of Unexplained Acute Neurologic Illness Outbreak, Muzaffarpur, Bihar – Brief Note HCFI Consensus Statement

154 Patient-Doctor Relationship

KK Aggarwal, Amarinder Singh Malhi, Ankit Om, Girish Tyagi…

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 Printed at New Edge Communications Pvt. Ltd., New Delhi E-mail: edgecommunication@gmail.com Copyright 2019 IJCP Publications Ltd. All rights reserved.

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

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.

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.

156 HCFI Round Table on Health and Wellness on the Interpretation of the Word “Supplied By” in Clause 23 of Schedule K of Drugs and Cosmetics Act/Rules

KK Aggarwal, Anil Khaitan, Balbir Verma, Bejon Kumar Misra, BR Sikri…

158 HCFI Expert Round Table on Off-label Use of Drugs, Disposables and Devices

KK Aggarwal, Manju Mani, Chander Prakash, Ahmed Quraishi, AK Grover…

RTI Analysis

164 Lack of Coordination Amongst Various Departments of Ministry of Health: Diseases are Notifiable but there is no Vaccination Policy for Them

KK Aggarwal, Ira Gupta

EXPERT’s VIEW

168 How can One Reduce Cardiovascular Mortality in Patients with Hypertension?

Nandini Mukherjee

MediFinance

170 Budget 2019-20 Highlights

Arun Kishore

MEDICAL VOICE FOR POLICY CHANGE

172 Medtalks with Dr KK Aggarwal Conference Proceedings

178 INDIA LIVE 2019 Around the globe

182 News and Views Spiritual Update

191 What is Charity?

KK Aggarwal INSPIRATIONAL Story

192 The Mango Tree Lighter reading

194 Lighter Side of Medicine

IJCP’s Editorial & Business Offices Delhi

Mumbai

Bangalore

Chennai

Hyderabad

Dr Veena Aggarwal 9811036687 E - 219, Greater Kailash, Part - I, New Delhi - 110 048 Cont.: 011-40587513 editorial@ijcp.com drveenaijcp@gmail.com Subscription Dinesh: 9891272006 subscribe@ijcp.com

Mr Nilesh Aggarwal 9818421222

H Chandrashekar GM Sales & Marketing 9845232974

Chitra Mohan GM Sales & Marketing 9841213823 40A, Ganapathypuram Main Road Radhanagar, Chromepet Chennai - 600 044 Cont.: 22650144 chitra@ijcp.com

Venugopal GM Sales & Marketing 9849083558

GM: General Manager

Unit No: 210, 2nd Floor, Shreepal Complex Suren Road, Near Cine Magic Cinema Andheri (East) Mumbai - 400 093 nilesh.ijcp@gmail.com

11, 2nd Cross, Nanjappa Garden Doddaiah Layout Babusapalya Kalyananagar Post Bangalore - 560 043 chandra@ijcp.com

H. No. 16-2-751/A/70 First Floor Karan Bagh Gaddiannaram Dil Sukh Nagar Hyderabad 500 059 venu@ijcp.com

From the desk of THE group editor-in-chief

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

Dr KK Aggarwal

Group Editor-in-Chief, IJCP Group

Bihar Children Deaths: Could Refeeding Syndrome Precipitated by Litchis have Triggered the Deaths?

T

he recent mortality among children in Bihar due to acute encephalopathy syndrome (AES) has generated speculations abound and raised many eyebrows. The illness has claimed more than 100 lives.

From blaming the government to identifying litchi as the cause of the condition, the hypotheses have been many. However, it is imperative at this juncture to understand that litchi may not be the underlying cause of the symptoms and subsequent deaths, but only a triggering factor.

Most malnourished children below 10 years of age experienced convulsions early in the morning without fever. Despite the fact that all of them had low sugar, mortality still remained high even after infusing sugar.

This suggests that apart from sugar, there was some other metabolic factor in play.

Understanding the reaction In significantly malnourished children, who have not consumed food in the last 24 hours, rapid carbohydrate intake (in the form of litchi in this case, which has 10% sugar) may have led to electrolyte and fluid shifts.

This may have in turn precipitated disabling or fatal medical complications. This is also called the refeeding syndrome and is marked by hypophosphatemia (this is the hallmark feature), hypokalemia, congestive heart failure, peripheral edema, rhabdomyolysis, seizures, fever and hemolysis.

We have always been taught to never overfeed a malnourished child as the outcome may be an electrolyte imbalance. Even the World Health Organization (WHO) says that acute or severe malnutrition should be treated slowly over 10 days. Rapid treatment with large intake of litchi may have precipitated fatal electrolyte imbalance.

Rapidly treating hypoglycemia with litchi, without managing phosphate levels, may be harmful. The best food in such a situation could have been sugarcane juice and not litchi. One must remember here that all those who break a long-term fast, do so with sugarcane juice.

The risk of hypophosphatemia during refeeding appears to be greater in patients who are more severely malnourished and at lower percent of ideal body weight. During episodes of starvation, the phosphate stores in the body get depleted. When nutritional replenishment starts and patients are fed carbohydrates, glucose causes release of insulin, which triggers cellular uptake of phosphate (and potassium and magnesium) and a decrease in serum phosphorous levels. Insulin also causes the cells to produce a variety of depleted molecules that require phosphate (adenosine triphosphate and 2,3-diphosphoglycerate), which further depletes the body’s stores of the latter.

The subsequent lack of phosphorylated intermediates causes tissue hypoxia, myocardial dysfunction and

IJCP Sutra: "Lower your blood pressure (BP) levels as a high BP is one of the leading causes for stroke."

105

from the desk of THE group editor-in-chief

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

respiratory failure due to an inability of the diaphragm to contract, hemolysis, rhabdomyolysis and seizures.

Some risk factors for the refeeding syndrome include low baseline levels of phosphate, potassium or magnesium prior to refeeding the patient; and little or no nutritional intake for the previous 5-10 days.

negative health outcomes. In the case of children in Bihar perhaps, many of them did not eat for a whole day knowing they will get to eat a generous supply of litchi fruit next morning.

Patients are at the highest risk in the first 1-2 weeks of nutritional replenishment and weight gain. Generally, the risk progressively dissipates over the next few weeks if there has been consistent forced intake and weight gain.

In conclusion, there is a need to raise countrywide awareness, particularly in Bihar, on the fact that children should not be allowed to sleep on an empty stomach.

More than anything else, it is the lack of awareness that can magnify any issue, and this was true in the case of these recent deaths as well. A grey area that remains is the disappearance of this disease in the wake of onset of rains, a phenomenon that must be investigated.

It is also important to note that in cases of acute malnutrition, akin to a prolonged fasting, children should be given only juices upfront. They must not be fed to a full stomach but rather the intake must be increased gradually over a period of time to avoid any

A concerted plan of action that takes into account this and other triggers must be formulated. It is time that all stakeholders come together in addressing this health issue, which raises its head every year, causing several deaths.

■■■■

Hands-only CPR: A Lifesaving Technique Within Your Reach A large Swedish study has confirmed that just like standard CPR, hands-only CPR doubles the chances of survival for a person at least 30 days after cardiac arrest. Researchers analyzed data from more than 30,000 cases of out-of-hospital cardiac arrest from 2000 to 2017, when hands-only CPR was gradually adopted into Sweden’s CPR guidelines. The use of hands-only CPR increased sixfold over the course of the study.

Overcoming barriers ÂÂ

Hands-only CPR eliminates the fear of communicable diseases, one of the main reasons people say they would hesitate to perform CPR.

ÂÂ

Another barrier people cite is fear of injuring the person, especially by doing compression incorrectly or on someone who does not actually require CPR. It’s true that even correctly done CPR can crack a person’s ribs but this can be corrected.

ÂÂ

CPR keeps the blood circulating until the heart can be shocked back into a normal rhythm with an automated external defibrillator (AED). Although emergency personnel will bring and use this device, bystanders must be trained to obtain and use public access AEDs, if we want to have the most favorable outcomes.

Basic hands-only CPR instructions ÂÂ

Place the person on the floor.

ÂÂ

Kneel beside the person.

ÂÂ

Place the heel of one hand on the center of the person’s chest. Place the heel of the other hand on top of the first hand and lace your fingers together.

ÂÂ

Position your body so that your shoulders are directly over your hands. Keeping your arms straight, push down with your arms and hands, using your body weight to compress the person’s chest.

ÂÂ

Push hard enough to press the chest down at least two inches.

ÂÂ

Continue pressing the chest at a rate of 100-120 compressions per minute.

ÂÂ

Continue hands-only CPR until emergency medical service (EMS) personnel arrive.

ÂÂ

If possible, enlist another person to take over for you after a few minutes, because doing the compressions can be tiring.

106

IJCP Sutra: "Losing weight can help prevent other associated complications such as osteoarthritis, sleep apnea."

Original research

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

Ambulance Services in Delhi Need an Ambulance Care KK aggarwal*, IRA Gupta†

Any city needs one basic ambulance for 50,000 people and one advanced ambulance for 1 lakh population. Delhi, therefore, should have a minimum of 190 advanced life support (ALS) ambulances and 380 basic life support (BLS) ambulances.

Fortunately, Delhi has two big trauma hospitals, Sushruta Trauma Centre in North Delhi and Jai Prakash Narayan Apex Trauma Center at AIIMS, New Delhi.

But shortage of ambulances will not cover the golden hour and lives will be wasted.

As Delhi has a population of over 1.9 crore, Heart Care Foundation of India (HCFI) vide Right to Information (RTI) application dated 26.09.2018 had asked as to how many BLS ambulances and how many ALS ambulances are available in Delhi.

Importance of ambulances

Vide reply dated 02.11.2018, Centralized Ambulance Trauma Services (CATS), which is an autonomous body of Government of National Capital Territory of Delhi (GNCTD) had stated that CATS have only 108 BLS ambulances and only 31 ALS ambulances.

In view of this shortage, Delhi Government should use the Essential Commodities Act. Under the Essential Commodities Act, 1955, the schedule to Section 2(a)drugs (as the meaning assigned to it in clause (b) of Section 3 of the Drugs and Cosmetics Act, 1940) is included as essential commodity. Also, under the section, the state government has powers to control production, supply, distribution, etc., of essential commodities.

An ambulance (which provides essential drugs) being an essential service, the Delhi Government can link all the private ambulances with CATS under one loop.

In cases of life-threatening emergencies one can call 100; PCR personnel have been trained in life support CPR. It is indeed pitiable that the Delhi Government’s CATS department does not even want to publicly display the information as to where the CATS ambulances are physically located. For this, they want Rs. 12/- to be deposited to get the information. Is this not a public information, which should be displayed all over for public convenience?

*Group Editor-in-Chief, IJCP Group †Advocate and Legal Advisor, HCFI

The term ambulance comes from the Latin word “ambulare” as meaning “to walk or move about”, which is a reference to early medical care where patients were moved by lifting or wheeling. The word originally meant a moving hospital, which follows an army in its movements.

An ambulance is a medically equipped vehicle which transports patients to treatment facilities, such as hospitals. In some instances, out-of-hospital medical care is provided to the patient in an ambulance.

Ambulances are used to respond to medical emergencies by emergency medical services. For this purpose, they are generally equipped with flashing warning lights and sirens. They can rapidly transport paramedics and other first responders to the scene, carry equipment for administering emergency care and transport patients to hospital or other definitive care facilities. Most ambulances use a design based on vans or pick-up trucks. Others take the form of motorcycles, cars, buses, aircraft and boats.

Following are few examples, which illustrate the importance of ambulances. ÂÂ

Rajesh Pilot died on June 11, 2000 in a car accident in Dausa 45-90 km from Jaipur. His Maruti Gypsy collided head-on with a Rajasthan Roadways Bus. He was shifted to Sawai Man Singh Hospital, Jaipur.

He was in a coma when admitted at 5:15 pm. If he was carried in an advanced cardiac life support (ACLS) ambulance, would the situation have been different? Obviously, the golden hour was lost.

ÂÂ

Giani Zail Singh, 78, the former Indian President, died in Chandigarh on December 25, 1994 after receiving multiple injuries from an accident on November 29. The accident happened near

IJCP Sutra: "Do about 30 minutes of physical activity every day."

107

original research

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

Road roundabout. Later, he was brought to the hospital by his driver and assistant. Doctors at AIIMS said that Munde was not breathing when he was brought in. Had the ACLS ambulance reached the spot….?

Kiratpur Sahib in Ropar district. He was shifted to Chandigarh 45 km away. Was he shifted in ACLS ambulance or provided a golden hour first aid in Ropar? ÂÂ

ÂÂ

Sahib Singh Varma died on June 30, 2007, when his car collided with a truck near Jonaicha khurd, on the Jaipur-Delhi Highway (NH-8). He was taken to nearby Shahjanpur Civil Hospital 13 km away.

Obviously no ACLS care was available for 13 km.

Gopinath Munde: At 6 am on June 3, 2014, his car met with an accident at Prithviraj Road-Tughlak

ÂÂ

Amitabh Bachchan was saved because of ambulance: On August 2, 1982, he had a nearfatal accident on the sets of his film Coolie. He was shifted to nearby hospital and ONLY LATER shifted to Mumbai. The early treatment did help to save him.

Analysis of Ambulance RTI Sr. No.

RTI application dated 26.09.2018

Reply by CATS (an autonomous body of GNCTD) dated 02.11.2018

1

Is it mandatory for all hospitals both private and government hospitals to have BLS and ALS ambulance for 24 hours?

Information does not pertain to CATS

2.

If answer to query No. 1 is “no”, then please provide the details of the hospitals for whom it is mandatory to have ambulance for 24 hours?

Information does not pertain to CATS

3.

How many BLS ambulances are there in Delhi?

CATS have 108 basic life support ambulances. Information about whole of Delhi is not pertaining to CATS.

4.

How many ALS ambulances are there in Delhi?

CATS have 31 ALS ambulances. Information about whole of Delhi is not pertaining to CATS.

5.

How many hospitals have BLS ambulance available for 24 hours in Delhi?

Information does not pertain to CATS

6.

Provide the list of hospitals having BLS ambulance available for 24 hours in Delhi.

Information does not pertain to CATS

7.

How many hospitals have ALS ambulance available for 24 hours?

Information does not pertain to CATS

8.

Provide the list of hospitals having ALS ambulance available for 24 hours in Delhi.

Information does not pertain to CATS

Analysis of Ambulance RTI Sr. No.

RTI application dated 28.11.2018

Reply by CATS (an autonomous body of GNCTD) dated 11.12.2018

1.

Provide the details of all the hospitals, both private as well as government, which are attached with CATS for BLS ambulances.

For operational purpose, CATS ambulances are deployed at a few Govt hospitals but they are not attached with the hospitals.

2.

Provide the details of all the hospitals, both private as well as government, which are attached with CATS for ALS ambulances.

Answer same as Sr. No. 1

3.

Provide the details of all the public places in Delhi where CATS ambulance is stationed for that particular public place.

Please deposit Rs. 12/- @ Rs. 02/- per page for 06 pages of the required information.

4.

Provide the details of all the public places in Delhi where CATS ambulances are stationed but the same are also available for any patient in emergency outside that particular public place.

List of CATS ambulances deployed is as per Sr. No. 03 above. These ambulances can attend any assigned call in Delhi.

108

IJCP Sutra: "Quit smoking and drink in moderation if you must."

ORIGINAL STUDY

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

Prevalence of Thyroid Dysfunction in Pregnancy RUCHIKA GARG*, PRABHAT AGRAWAL†, VISHY AGRAWAL‡, URVASHI*, SAROJ SINGH#

Abstract There are a few reports of prevalence of hypothyroidism during pregnancy from India with prevalence rates ranging from 4.8% to 11%. Subclinical thyroid dysfunction has adverse outcome on the mother and fetus such as miscarriage, preterm delivery, preeclampsia, eclampsia and placental abruption and can also impair the neurocognitive development of the fetus. We conducted a cross-sectional study to find out the prevalence of thyroid disorder in pregnancy in North India. The study was conducted in the antenatal OPD of the Dept. of Obstetrics and Gynecology and Dept. of Medicine, SN Medical College, Agra and antenatal clinic of District Hospital, Agra from July to December 2017. Overall, 1,020 women with uncomplicated intrauterine singleton pregnancy were included. Thyroid-stimulating hormone (TSH), free T4 (fT4) and free T3 (fT3) were measured by high sensitive radioimmunoassay. Out of 1,020 pregnant women, 109 were found as having thyroid disorders. The prevalence of thyroid disorder among women in the age groups 20-25 years, 26-30 years and 31-35 years was 8.7%, 1.8% and 0.19%, respectively.

The prevalence of subclinical hypothyroidism, overt hypothyroidism, subclinical hyperthyroidism and overt hyperthyroidism was 6.67%, 1.27%, 1.86% and 0.88%, respectively. The mean TSH level among women with subclinical hypothyroidism, overt hypothyroidism, subclinical hyperthyroidism and overt hyperthyroidism was 3.50, 7.92, 0.05 and 0.014 mIU/L, respectively.

The prevalence of thyroid disorder in the first, second and third trimester was 68.80%, 23.85% and 7.33%, respectively. This study has shown high prevalence of thyroid dysfunction, especially subclinical and overt hypothyroidism, in India.

Keywords: Thyroid disorder, pregnancy, subclinical hypothyroidism, overt hypothyroidism, subclinical hyperthyroidism, overt hyperthyroidism.

P

regnancy is a state in which the combination of events modifies the function of thyroid. There is a change in the level of thyroxine-binding globulin (TBG), total T3 and T4 and thyroid-stimulating hormone (TSH) during normal pregnancy.1

thyroid hormones and iodine requirement are increased by approximately 50% during pregnancy. In addition, pregnancy is a stressful condition for the thyroid gland, resulting in hypothyroidism in women with limited thyroid reserve or iodine deficiency.

The prevalence of hypothyroidism in pregnancy is around 2.5% according to the Western literature and prevalence of hyperthyroidism in pregnancy is 0.1-0.4%.2,3 There are a few reports of prevalence of hypothyroidism during pregnancy from India with prevalence rates ranging from 4.8% to 11%.4,5 During pregnancy, the thyroid gland may increase in size by 10% in iodine-sufficient countries and to a greater extent in iodine-deficient countries. Production of

Data from published studies have underscored the association between miscarriage and preterm delivery in women with normal thyroid function who test positive for thyroid peroxidase (TPO) antibodies.6 The prevalence of Grave’s disease is around 0.1-0.4% and that of thyroid autoimmunity (TAI) is around 5-10%.

*Associate Professor, Dept. of Obstetrics and Gynecology †Professor, Dept. of Medicine ‡Senior Resident #Professor and Head Dept. of Obstetrics and Gynecology SN Medical College, Agra, Uttar Pradesh Address for correspondence Dr Ruchika Garg Associate Professor Dept. of Obstetrics and Gynecology, SN Medical College, Agra, Uttar Pradesh E-mail: ruchikagargagra@gmail.com

110

Studies have shown that the subclinical thyroid dysfunction has adverse outcome on the mother and fetus such as miscarriage, preterm delivery, pre-eclampsia, eclampsia and placental abruption. It may also impair the neurocognitive development of the fetus.7 That’s why we conducted this study to find the prevalence of thyroid disorder in pregnancy in North India.

Material and Methods It is a cross-sectional study conducted in the antenatal OPD of the Dept. of Obstetrics and Gynecology and Dept. of Medicine, SN Medical College, Agra and

IJCP Sutra: "Keep your blood sugar levels under control."

ORIGINAL STUDY

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

antenatal clinic of District Hospital, Agra from July 2017 to December 2017.

We included 1,020 women with uncomplicated intrauterine singleton pregnancy. We excluded women who had history of thyroid disease or intake of thyroid drugs, multifetal gestation, known chronic disorders (diabetes and hypertension) or patients with bad obstetrics history due to some other cause. After enrolling the patients, a written informed consent was taken, and detailed history and examination was done.

Blood samples were collected after obtaining the consent and were sent for thyroid hormone profile testing.

TSH, free T4 (fT4), free T3 (fT3) were measured by high sensitive radioimmunoassay.

Subclinical hypothyroidism means increase in TSH with normal fT3 and fT4. Overt hypothyroidism means increase in TSH with decrease in fT3 and fT4.

Subclinical hyperthyroidism was defined as serum TSH concentration below the lower limit of reference range with fT3 and fT4 concentration within normal range.

Overt hyperthyroidism was defined as serum TSH concentration below the lower limit of reference range with increase in fT3 and fT4 concentration. Reference ranges of antithyroid antibodies were: ÂÂ

Thyroid peroxidase antibody (TPOAb) <35 IU/mL

ÂÂ

Thyroglobulin antibody (TgAb) <20 IU/mL.

American Thyroid Association (2007) recommends cutoff values for TSH as: ÂÂ

First trimester <2.5 mIU/L

ÂÂ

Second and third trimester <3 mIU/L

ÂÂ

Lower limit of normal TSH 0.04 mIU/L.

Table 3 shows that out of 1,020 women; 109 were found as having thyroid disorder and the prevalence of thyroid disorder in the study was 10.68%.

Table 4 shows that the mean TSH level among women with subclinical hypothyroidism, overt hypothyroidism, subclinical hyperthyroidism and overt hyperthyroidism was 3.50, 7.92, 0.05 and 0.014 mIU/L, respectively.

Table 5 shows that the prevalence of thyroid disorder in the first, second and third trimester was 68.80%, 23.85% and 7.33%, respectively.

Table 2. Distribution of Patients According to Different Types of Thyroid Disorders Type of disorder

No. of cases

Percentage (%)

Subclinical hypothyroidism

68

6.67

Overt hypothyroidism

13

1.27

Subclinical hyperthyroidism

19

1.86

Overt hyperthyroidism

09

0.88

Total

109

10.68

Table 3. Prevalence of Thyroid Disorders Sample No. of cases with thyroid disorder Percentage (%) 1,020

109

10.68%

Table 4. Mean TSH levels in Different Types of Thyroid Disorders

Results In the present study, a total of 1,020 pregnant women were screened and 109 females were found as having thyroid disorders.

Table 1 shows that the prevalence of thyroid disorder among women in the age groups 20-25 years, Table 1. Distribution of Patients According to Age Groups Age Group

26-30 years and 31-35 years was 8.7%, 1.8% and 0.19%, respectively. Table 2 shows that the prevalence of subclinical hypothyroidism, overt hypothyroidism, subclinical hyperthyroidism and overt hyperthyroidism was 6.67%, 1.27%, 1.86% and 0.88%, respectively.

Types

No. of cases

Mean TSH level

Subclinical hypothyroidism

68

3.50

Overt hypothyroidism

13

7.92

Subclinical hyperthyroidism

19

0.05

Overt hyperthyroidism

09

0.014

Table 5. Distribution of Patients with Thyroid Disorders According to Trimesters

No. of patients with thyroid dysfunction

Percentage (%)

20-25

89

8.7

First trimester

75 (68.80)

26-30

19

1.8

Second trimester

26 (23.85)

31-35

02

0.19

Third trimester

08 (7.33)

Trimesters

IJCP Sutra: "Reduce stress through activities such as meditation and yoga."

No. of patients (%)

111

ORIGINAL STUDY

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

Discussion The main aim of the study was to know the prevalence of thyroid disorders in pregnancy. The prevalence of thyroid disorders in our study was 10.68% and it was consistent with the study by Sahu et al5 in which the prevalence of thyroid disorders was 12.7%. It was also comparable to the study conducted by Wang et al8 (10.2%), Taghavi et al9 (14.6%) and Ajmani et al10 in which the prevalence of thyroid disorder was 13.25%.

In the study conducted by Thanuja et al,11 the prevalence of thyroid disorder was less (about 5%) and in the study conducted by Rajput et al,12 the prevalence of the thyroid disorder was high (26.5%).

The prevalence of subclinical hypothyroidism in our study was 6.67% and it was consistent with the study

by Sahu et al in which it was 6.47%. Prevalence of subclinical hypothyroidism in pregnancy according to the study conducted by Thanuja et al in Mangalore was less (0.7%), while it was 2.3% according to the study conducted by Casey et al.13 It was high in the study conducted by Dhanwal et al (13.5%),14 Murty et al (16.11%),15 and Singh et al (18%).16 The prevalence of overt hypothyroidism in the study was 1.27% and it was comparable to the studies conducted by Taghavi et al, Bandela et al17 and by Ajmani et al in which the prevalence was 2.4%, 2.87% and 3%, respectively.

Prevalence of overt hypothyroidism in pregnancy in the studies conducted by Wang et al (0.3%) and Dhanwal et al (0.7%) was less compared to the present study.

In this study, the prevalence of thyroid disorder in first, second and third trimester was 68.80%, 23.85% and 7.33%, respectively and this is in accordance with the study by Rao and Patibandla.18 In India, the most common cause of hypothyroidism in pregnancy is iodine deficiency. Hashimoto thyroiditis is the most common cause of hypothyroidism in iodine-sufficient areas. Presence of goitrogens19 in diet, micronutrient deficiency such as selenium and iron deficiency may cause hypothyroidism and goiter.20 Poverty, insufficient iodine supplementation and fluorinated water may be the cause of thyroid disorder among pregnant women. Serum TSH and fT4 are the best screen and diagnose hypothyroidism during pregnancy.

The prevalence of overt or subclinical hypothyroidism depends on the upper TSH cut-off level used. There is strong evidence that the reference range for serum TSH is lower throughout the pregnancy compared with the non-pregnant state. The lowest serum TSH levels are

112

observed during the first trimester of pregnancy and are apparently related to human chorionic gonadotropin (hCG) stimulation of the thyroid gland as serum hCG levels are highest early in gestation.

Conclusion Thyroid disease is prevalent in women of childbearing age group and for this reason it is common in pregnancy and puerperium. Women with thyroid disorder, both overt and subclinical, are at increased risks of pregnancy-related complications, such as spontaneous abortion, pre-eclampsia, preterm labor and abruption placentae and fetal complications such as low birth weight babies, preterm delivery, intrauterine growth retardation and stillbirth.

At present, there are no recommendations available for detection or screening of thyroid dysfunction among Indian pregnant women. Recent consensus guidelines recommend testing only in cases of highrisk women having personal history of thyroid or other autoimmune disorders or with a family history of thyroid disorders.

This study has shown the high prevalence of thyroid dysfunction, especially subclinical and overt hypothyroidism, in India and thus emphasizes the need to include thyroid function test in the routine screening in the antenatal clinic and the patients to be potentially aware of associated maternal and fetal complications.

References 1. Thyroid and other endocrine disorders.

In: Cunningham FG, Williams JW (Eds.). Williams Obstetrics.

23rd Edition, New York, NY: McGraw-Hill Education LLC; 2010. pp. 1126-44.

2. Studd J. Thyroid Hormones in Pregnancy and Foetus. 15th Edition; 75-102.

3. LeBeau SO, Mandel SJ. Thyroid disorders during pregnancy. Endocrinol Metab Clin North Am. 2006;35(1):117-36, vii.

4. Nambiar V, Jagtap VS, Sarathi V, Lila AR, Kamalanathan S, Bandgar TR, et al. Prevalence and impact of thyroid disorders on maternal outcome in Asian-Indian pregnant women. J Thyroid Res. 2011;2011:429097.

5. Sahu MT, Das V, Mittal S, Agarwal A, Sahu M. Overt and subclinical thyroid dysfunction among Indian pregnant women and its effect on maternal and fetal outcome. Arch Gynecol Obstet. 2010;281(2):215-20.

6. Stagnaro-Green A. Thyroid antibodies and miscarriage: where are we at a generation later? J Thyroid Res. 2011;2011:841949.

IJCP Sutra: "Get to and stay at a healthy weight."

ORIGINAL STUDY

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019 7. Gaberšček S, Zaletel K. Thyroid physiology and autoimmunity in pregnancy and after delivery. Expert Rev Clin Immunol. 2011;7(5):697-706; quiz 707.

8. Wang W, Teng W, Shan Z, Wang S, Li J, Zhu L, et al.

The prevalence of thyroid disorders during early pregnancy in China: the benefits of universal screening in the first trimester of pregnancy. Eur J Endocrinol.

2011;164(2):263-8.

14. Dhanwal DK, Prasad S, Agarwal AK, Dixit V, Banerjee AK. High prevalence of subclinical hypothyroidism during first trimester of pregnancy in North India. Indian J Endocrinol Metab. 2013;17(2):281-4.

15. Murty NVR, Uma B, Rao JM, Sampurna K, Vasantha K, Vijayalakshmi G. High prevalence of subclinical hypothyroidism in pregnant women in South India.

IJRCOG. 2015;4(2):453 -6.

9. Taghavi M, Saghafi N, Shirin S. Outcome of thyroid dysfunction in pregnancy in Mashhad, Iran. Int J Endocrinol Metab. 2009;7(2):82-5.

16. Singh KP, Singh HA, Kamei H, Devi LM. Prevalence of hypothyroidism among pregnant women in the sub mountain state of Manipur. Int J Sci Study. 2015;3(5):143-6.

10. Ajmani SN, Aggarwal D, Bhatia P, Sharma M, Sarabhai V, Paul M. Prevalence of overt and subclinical thyroid dysfunction among pregnant women and its effect on maternal and fetal outcome. J Obstet Gynaecol India.

2014;64(2):105-10.

17. Bandela PV, Havilah P, Durgaprasad K. Antenatal thyroid dysfunction in Rayalaseema region: A preliminary cross sectional study based on circulating serum thyrotropin levels. Int J Appl Biol Pharm Technol. 2013;4(4) :74-8.

11. Thanuja PM, Rajgopal K, Sadiqunnisa. Thyroid dysfunction in pregnancy and its maternal outcome.

IOSR-JDMS. 2014;13(1Ver X):11-5.

12. Rajput R, Goel V, Nanda S, Rajput M, Seth S. Prevalence of thyroid dysfunction among women during the first trimester of pregnancy at a tertiary care hospital in Haryana. Indian J Endocrinol Metab. 2015; 19(3):416-9.

13. Casey BM, Dashe JS, Wells CE, McIntire DD, Byrd W, Leveno KJ, et al. Subclinical hypothyroidism and pregnancy outcomes. Obstet Gynecol. 2005;105(2):239-45.

18. Rao S, Patibandla A. A Study to find out the prevalence of hypothyroidism among pregnant women visiting ESI Hospital, Sanathnagar, Hyderabad. Gynecol Obstet (Sunnyvale). 2016;6:363.

19. Marwaha RK, Tandon N, Gupta N, Karak AK, Verma K, Kochupillai N. Residual goitre in the postiodization phase: iodine status, thiocyanate exposure and autoimmunity.

Clin Endocrinol (Oxf). 2003;59(6):672-81.

20. Das S, Bhansali A, Dutta P, Aggarwal A, Bansal MP, Garg D, et al. Persistence of goitre in the post-iodization phase: micronutrient deficiency or thyroid autoimmunity?

Indian J Med Res. 2011;133:103-9.

■■■■

LS Passes Indian Medical Council (Amendment) Bill The government will soon come with a National Medical Commission (NMC) Bill to usher in comprehensive reforms in the medical education sector, Health Minister Harsh Vardhan said in the Lok Sabha.

He said this while replying to a debate on Indian Medical Council (Amendment) Bill, 2019, which was later passed by the House by voice vote.

This Bill provides for supersession of the Medical Council of India (MCI) for a period of 2 years with effect from September 26, 2018. It will replace an Ordinance promulgated on February 21.

The Minister said the government is working on the NMC Bill and "will soon take it to Union Cabinet and then in Parliament". He said the NMC Bill, which was introduced in December, 2017, lapsed with the dissolution of the 16th Lok Sabha.

On the Medical Council (Amendment) Bill, the Minister said that the Board of Governors (BoG) which had replaced the MCI has worked well and taken a series of steps to improve medical education in the country.

The BoG has granted accreditation to more number of medical colleges, increased number of seats and reduced procedural hurdles, he said, adding it is manned by doctors of great repute. "This is just a beginning of our work and you will see radical reforms in the medical education of the country," he said.

The Indian Medical Council or the MCI was set up under the Medical Council Act, 1956, for setting standards for medical professionals, new medical colleges and revision of curriculum, among others.

IJCP Sutra: "Limit your intake of high-calorie foods and drinks."

113

Review Article

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

Management of Diabetic End-stage Renal Disease: Role of Hemodialysis H SUDARSHAN BALLAL

Abstract Diabetes mellitus is now the most common cause of end-stage renal disease (ESRD) all across the globe, including India.

In view of the alarming rise in numbers, renal failure due to type 2 diabetes has been termed a “medical catastrophe of worldwide dimensions.” When a patient develops uremic symptoms he needs renal replacement therapy. The renal replacement therapies available for all patients with ESRD are: hemodialysis, chronic ambulatory peritoneal dialysis (CAPD) and renal transplantation. Kidney transplantation is the best option for patients with diabetic ESRD. The 5-year survival of transplant patients of 75-85% is far superior to the 5-year survival rate of around 25% on dialysis.

Keywords: Diabetes mellitus, end-stage renal disease, renal replacement therapies, hemodialysis, CAPD, renal transplantation

D

iabetes mellitus is now the most common cause of end-stage renal disease (ESRD) all across the globe, including India. It is estimated that 30-50% of patients being initiated on renal replacement therapy (RRT) have diabetes as the cause of their ESRD1 and most of these patients have type 2 diabetes. In view of the alarming rise in numbers, renal failure due to type 2 diabetes has been termed a “medical catastrophe of worldwide dimensions”.2 This article will discuss the management of diabetic ESRD specifically related to type 2 diabetes.

Renal Replacement Therapy When a patient’s kidney function, as measured by the calculated glomerular filtration rate, has reached <10 mL/min (ESRD) or the patient develops uremic symptoms they need RRT. The RRTs available for all patients with ESRD are: ÂÂ

Hemodialysis

ÂÂ

Chronic ambulatory peritoneal dialysis (CAPD)

ÂÂ

Renal transplantation.

Though these modalities are available for all patients with ESRD, there are significant differences in the

Professor of Clinical Medicine St. Louis University School of Medicine, USA Manipal Academy of Higher Education, Manipal, India

114

morbidity and mortality of any given modality between the diabetic and nondiabetic ESRD population. We will discuss some of these issues, specifically the modality of hemodialysis.

Hemodialysis for Diabetic ESRD Although hemodialysis prevents death from uremia, the patient survival on hemodialysis is poor, especially for patients with diabetes, being approximately 20-25% at 5 years as compared to 40-50% for other causes of ESRD.3 This is worse than many cancers.

The survival of patients on maintenance hemodialysis in India seems dismal for both, diabetic and nondiabetic populations.4 The important contributors for mortality in the diabetic dialysis population are: Cardiovascular disease, adequacy of dialysis and nutritional status. ÂÂ

Cardiovascular disease (CVD): CVD is the most common cause of death accounting for more than one-half of the cases.5 The main reason for such a high mortality rate, which is of cardiovascular origin in the majority of cases is that the cardiovascular conditions of patients with diabetes are already severely impaired when they start RRT, as demonstrated by the high prevalence of coronary artery disease, stroke, peripheral occlusive disease and amputations.

This also explains why patients who have diabetes and are on RRTs are at higher risk of developing de novo CVD, particularly ischemic heart disease,

IJCP Sutra: "Choose whole grains instead of refined grain products. Limit the intake of processed meat and red meat."

Review Article

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

which not only is more frequent but also has a more aggressive course than in nondiabetic patients. In view of this, aggressive measures to manage CVD need to be adopted in all diabetic patients even before they reach the stage of dialysis. ÂÂ

Adequacy of dialysis: Adequacy of dialysis, which also plays an important role in CVD and nutrition (MIA or malnutrition inflammation atherosclerosis syndrome), is also a contributor to the poor outcome and diabetics, in particular, seem to be more sensitive than nondiabetics to inadequate dialysis.6 The increase in mortality of these patients largely disappears if there is an improvement in the nutritional status as reflected by an increase in serum albumin and creatinine.7 This is a major problem in India where for various reasons like financial constraints, lack of access and availability of good dialysis units causes most patients to have inadequate dialysis.8 Whenever possible, it is very essential to monitor the adequacy of dialysis by using biochemical measures like urea reduction rates, Kt/V and clinical well-being of patients and to take measures to improve the adequacy of dialysis.

ÂÂ

Nutrition in dialysis: Nutrition in dialysis patients is closely linked to inadequate dialysis, which leads to anorexia and poor calorie and protein intake. This is reflected by poor serum albumin and creatinine levels, which are indicators for mortality in dialysis patients. The problems of diabetic gastroparesis and diabetic enteropathy compound the nutritional problems.

The help of a good dietician and measures to treat diabetic gastroparesis and enteropathy by motility agents, frequent small foods and appropriate use of broad-spectrum antibiotics to treat bacterial infections in diabetic enteropathy are needed to maintain adequate nutrition. It is to be noted that cisapride is best avoided in this population because of the risk of fatal arrhythmias.9 Diet in diabetic patients on dialysis The general recommendation for diet in dialysis patients is given in Table 1. The iron requirement of dialysis patients varies and will need to be addressed on a patient to patient basis. In general, water-soluble vitamins are routinely prescribed and calcitriol may be needed in some patients.

Table 1. Daily Dietary Recommendations for Dialysis Patients versus Nonuremicsa Factor

Nonuremic

HD

PD

0.8

1.2

1.2-1.5

30

30b

30-40b,c

15-20

15

15

Carbohydrate (%)

55-60

55-60d

55-60c,d

Fat (%)

20-30

Balance

Balance

Cholesterol (mg)

300-400

300-400

300-400

Polyunsaturated/Saturated fat ratio

2.0:1.0

2.0:1.0

2.0:1.0

25

25

25

2-6 g

2 g + 1 g/LUO

2-4 g + 1 g/LUO

Ad lib 1 L/LUO

1 L + 1 L/LUO

1.0-2.5L + 1 L/LUO

2-6 g

2 g + 1 g/LUO

4 g + 1 g/LUO

Calcium (g)

0.8-1.2

Diet +1.2

Diet + 1.2

Phosphorus (g)

1.0-1.8

0.6-1.2

0.6-1.2

Magnesium (g)

0.35

0.2-0.3

0.2-0.3

Protein (g/kg) Calories (sedentary; kcal/kg) Protein (%)

Crude fiber (g) Sodium (1 g = 43 mEq) Fluids (L) Potassium (1 g = 25 mEq)

aAll intakes calculated on the basis of normalized body weight (i.e., the average body weight of normal persons of the same age, height and sex as the patient). bThese

levels of caloric intake are rarely attained in practice.

Includes glucose absorbed from dialysis solutions. d Carbohydrate intake should be decreased in patients with hypertriglyceridemia.

HD = Hemodialysis; PD = Peritoneal dialysis; LUO = Liters of urine output per day. c

IJCP Sutra: "Reduce intake of dairy foods and diets rich in calcium."

115

Review Article

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

Blood sugar control in diabetic dialysis patients There are certain special problems about blood sugar control in dialysis patients.

Altered Insulin Metabolism In uremic patients (both diabetic and nondiabetic), insulin secretion by the β-cells of the pancreas is reduced and the responsiveness of peripheral tissues (e.g., muscle) to insulin is depressed. On the other hand, the rate of insulin catabolism (renal and extrarenal) is decreased, and therefore, the half-life of any insulin present in the circulation is prolonged.

All of these abnormalities are only partially corrected after institution of maintenance dialysis therapy.

Increased Sensitivity to Insulin In diabetic dialysis patients treated with exogenous insulin, the importance of reduced insulin catabolism overrides the impact of insulin resistance; when exogenous insulin is administered, its effect may be intensified and prolonged. Thus, smaller than usual doses should be given.

Insulin Therapy Tight control of sugars is sometimes difficult to achieve in diabetic dialysis patients. Nevertheless, good glucose control is worthwhile with split doses of insulin preferably. The "amount of insulin" per day required for patients receiving maintenance hemodialysis is usually small; optimum control of glycemia is achieved by administration of long-acting insulin at two separate times during the day (split dosing) and by supplementing with regular insulin for meals as needed. The proportions of long-acting and regular insulin, as well as the total insulin doses vary widely among different patients. Hypoglycemia is quite common in diabetic dialysis patients usually due to reduced insulin catabolism and reduced intake or food and/or poor absorption.

A fasting serum glucose of <140 mg/dL and a postprandial value <200 mg/dL is a reasonable goal to achieve.

Oral Hypoglycemic Agents Lack of clinical studies on use of oral hypoglycemic agents (OHAs) in dialysis patients restricts the use of these agents.

Nevertheless, these agents are useful adjuncts in the treatment of diabetics and are used by many

116

nephrologists. The safety of sulfonylureas depends on their mode of metabolism and their half-life. Use of short-acting agents primarily metabolized by the liver is, in general, safer in dialysis patients. Acetohexamide, chlorpropamide and tolazamide are excreted to a large extent in the urine. These drugs should not be used in dialysis patients because their half-lives will be greatly prolonged in the absence of renal function, possibly resulting in severe and prolonged hypoglycemia.

The excretion of glyburide is 50% hepatic, and prolonged hypoglycemia has been reported using this drug in dialysis patients. Metabolism of glipizide, tolbutamide and gliclazide is almost completely hepatic. Consequently, the last three drugs should be considered if an OHA is desired. Many drugs frequently used in dialysis patients either antagonize (phenytoin, nicotinic acid, diuretics) or enhance (sulfonamides, salicylates, warfarin, ethanol) the hypoglycemic action of sulfonylureas.

Metformin, a biguanide, is associated with increased incidence of lactic acidosis in dialysis patients and should not be used. Acarbose inhibits α-glucosidase in the enteric mucosa and moderates postprandial hyperglycemia. It may prove to be a useful adjunct to other diabetic medications in diabetic patients.

Troglitazone and other thiazolidinediones sensitize the target tissues to insulin and may be of help in obese, type 2 diabetics with insulin resistance. However, the use of this class of drugs may be associated with the risk of severe hepatotoxicity.

In general, insulin use is preferable in diabetic dialysis patients but judicious use of appropriate OHAs can be done.

Specific problems of hemodialysis in diabetic patients: ÂÂ

Difficulty in creating and maintaining a vascular access because of severe peripheral vascular disease (PVD) in older diabetic patients.

ÂÂ

Inability to tolerate volume shifts giving rise to hypotension during hemodialysis because of autonomic neuropathy and CVD.

ÂÂ

Risk of infection.

ÂÂ

Progression of diabetic retinopathy.

In view of all these problems, meticulous planning and appropriate management should start in the predialysis period well before dialysis is anticipated and would involve a special diabetic team consisting of an Ophthalmologist, Vascular Surgeon, Podiatrist, Endocrinologist, Cardiologist, Neurologist and Dietician to help the nephrology team in keeping

IJCP Sutra: "High BP, blood sugar and blood cholesterol can remain silent for up to a decade."

Review Article

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

the patient as fit as possible even before they reach dialysis.

Timing of dialysis in diabetic ESRD In general, most nondiabetic patients are initiated on dialysis when the creatinine clearance is <10 mL/min.

In diabetic patients, dialysis may have to be initiated at creatinine clearance even >15 mL/min.9 The reasons for this being: ÂÂ

Renal functions deteriorate rapidly in this group

ÂÂ

Hypertension is very difficult to control with severe renal failure

ÂÂ

Most patients have CVD with volume overload

ÂÂ

Uremic symptoms may manifest earlier than nondiabetic patients.

In spite of these recommendations, dialysis is usually started as an emergency in most Indian patients because of uremia, pulmonary edema or severe hyperkalemia because of poor awareness, financial constraints and lack of facilities for dialysis.4,8

Role of CAPD CAPD is another modality of treatment in diabetic ESRD. Though it has its advantages and disadvantages, the following factors decide the modality of dialysis: ÂÂ

Comorbid conditions

ÂÂ

Family and home support

ÂÂ

Financial support

ÂÂ

CVD and PVD leading to poor vascular access for dialysis

ÂÂ

Hemodynamic stability

ÂÂ

Availability of hemodialysis centers.

CAPD is 30-50% more expensive than hemodialysis in India and is generally used for patients who do not have access to hemodialysis, have severe chronic heart failure (CHF), hemodynamic instability, poor vascular access and are not candidates for transplantation. The patient and the family should be motivated and have adequate financial support. Table 2 gives the comparison between the two modalities of dialysis.

Table 2. Dialysis Modalities for Diabetics Modality

Advantages

Disadvantages

Hemodialysis

Very efficient

Risky for patients with advanced cardiac disease

Frequent medical follow-up (in center)

Multiple arteriovenous access surgeries often required; risk of severe hand ischemia

No protein loss to dialysate

High incidence of hypotension during dialysis session Predialysis hyperkalemia Prone to hypoglycemia

CAPD

CCPD

Good cardiovascular tolerance

Peritonitis, exit site and tunnel infection risks similar to those in nondiabetic dialysis patients

No need for arteriovenous access

Protein loss to dialysate

Good control of serum potassium

Increased intra-abdominal pressure effects (hernias, fluid leaks, etc.)

Good glucose control, particularly with use of intraperitoneal insulin; less severe hypoglycemia

Schedule not convenient for helper if one is required (e.g., for a patient with physical disability like blindness, stroke, etc.)

Good cardiovascular tolerance

Protein loss to dialysate

No need for arteriovenous access Good control of serum potassium Good glucose control with use of intraperitoneal insulin

Very very expensive

Good for patients with disability Peritonitis risk slightly less than for CAPD CAPD = Continuous ambulatory peritoneal dialysis; CCPD = Continuous cycling peritoneal dialysis.

IJCP Sutra: "A pulse rate of less than 60 or more than 100 is abnormal."

117

Review Article

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

Survival on hemodialysis and peritoneal dialysis There have been conflicting data about the survival of patients on CAPD compared to hemodialysis. Initial data from Michigan suggested an advantage for CAPD.10 However, most studies after adjustment for comorbid condition, have not found a statistically significant survival difference between the two modalities.11 Transplantation Kidney transplantation is the best option for patients with diabetic ESRD. The 5-year survival of transplant patients of 75-85%, though less than that of nondiabetic ESRD, is still far superior to the 5-year survival rate of around 25% on dialysis.3,12 Though in general healthier patients go on to transplant and sicker patients remain on dialysis the survival rates are better, even when these are factored in. Transplantation is also associated with a better quality-of-life and high degree of rehabilitation.

The pre- and post-transplant care of diabetic patients is generally similar to that of nondiabetics. However, in view of the high prevalence of CVD in this population, meticulous attention has to be paid to screen these patients for CVD prior to the transplantation.13 Recommendations for treatment of diabetic ESRD patients Kidney transplant remains the best option of RRT for patients with diabetic ESRD in all suitable candidates. Recommendations for those not suitable for transplantation CAPD is recommended for patients with: ÂÂ

Poor vascular access because of PVD

ÂÂ

Severe CVD with hemodynamic instability during hemodialysis

ÂÂ

Nonavailability of hemodialysis centers

ÂÂ

Good family and financial support

ÂÂ

Motivated patients.

Hemodialysis is the treatment for all the rest which is the treatment available for the vast majority of patients with diabetic ESRD in India who are not candidates for transplantation. In view of the multiple associated comorbid conditions, a multidisciplinary approach

is needed to prevent and manage the complications of vascular diseases, malnutrition and retinopathy in diabetic dialysis patients.

References 1. Ballal HS. Diabetic Nephropathy: Indian Scene, Scientific Proceedings, 1st National Conference in Prevention of Chronic Kidney Disease in India. February 2005.

2. Ritz E, Rychlík I, Locatelli F, Halimi S. End-stage renal failure in type 2 diabetes: A medical catastrophe of worldwide dimensions. Am J Kidney Dis. 1999;34(5): 795-808.

3. United States Renal Data System. Excerpts from the USRDS 2003 annual data report: Atlas of end stage renal disease in the United States. Am J Kidney Dis. 2004;42(Suppl 5): S1-S226.

4. Rao M, Juneja R, Shirly RB, Jacob CK. Haemodialysis for end-stage renal disease in Southern India - a perspective from a tertiary referral care centre. Nephrol Dial Transplant. 1998;13(10):2494-500.

5. Brunner FP, Selwood NH. Profile of patients on RRT in Europe and death rates due to major causes of death groups. The EDTA Registration Committee. Kidney Int Suppl. 1992;38:S4-15.

6. Collins AJ. How can the mortality rate of chronic dialysis patients be reduced? Semin Dial. 1993;6:102.

7. Lowrie EG, Lew NL, Huang WH. Race and diabetes as death risk predictors in hemodialysis patients. Kidney Int Suppl. 1992;38:S22-31.

8. Kher V. End-stage renal disease in developing countries.

Kidney Int. 2002;62(1):350-62.

9. Tzamaloukas AH, Friedman EA. Diabetes. In: Daugirdas JT, Blake PG, Ing TS (Eds.). Handbook of Dialysis. 3rd Edition, Philadelphia: Lippincott, Williams & Wilkins; 2001. p. 453.

10. Nelson CB, Port FK, Wolfe RA, Guire KE. Comparison of continuous ambulatory peritoneal dialysis and hemodialysis patient survival with evaluation of trends during the 1980s. J Am Soc Nephrol. 1992;3(5):1147-55.

11. Jaar BG, Coresh J, Plantinga LC, Fink NE, Klag MJ, Levey AS, et al. Comparing the risk for death with peritoneal dialysis and hemodialysis in a national cohort of patients with chronic kidney disease. Ann Intern Med. 2005;143(3):174-83.

12. Locatelli F, Pozzoni P, Del Vecchio L. Renal replacement therapy in patients with diabetes and end-stage renal disease. J Am Soc Nephrol. 2004;15 Suppl 1:S25-9.

13. Scandling JD. Kidney transplant candidate evaluation.

Semin Dial. 2005;18(6):487-94.

■■■■

118

IJCP Sutra: "Weight loss of 10 kg can reduce upper systolic BP by 5-20 mmHg."

Review Article

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

Evaluation of the Infertile Female GARIMA KACHHAWA*, ANJU SINGH*

Abstract Infertility is defined as failure to conceive after 1 year of regular unprotected intercourse and is estimated to affect 10-15% of couples worldwide. Evaluation of the female partner is started if she fails to achieve pregnancy after 12 months or more of regular unprotected intercourse. This article provides a comprehensive review of the evaluation of a woman with infertility.

We discuss the history and physical examination, evaluation of ovulatory function, tubal and peritoneal factors, uterine factors, cervical factors and ovarian reserve testing in detail.

Keywords: Female infertility, ovulatory dysfunction, uterine factors, tubal and peritoneal factors, cervical factors, ovarian reserve test, basal body temperature.

I

nfertility is defined as failure to conceive after 1 year of regular unprotected intercourse. It affects 10-15% of couples worldwide. Female factor is responsible for infertility in 35-40% of couples. Among females, the major causes of infertility include ovulatory dysfunction (30-40%), tubal and peritoneal pathology (30-40%), cervical factor (3%), uterine factor (rare) and unexplained (10%) (Fig. 1).

Usually, we start evaluation of female partner if she fails to achieve pregnancy after 12 months or more of regular unprotected intercourse. But in certain conditions earlier evaluation is warranted, which include:

History and Examination Both the partners should be made aware of underlying causes of infertility, components of basic evaluation and encouraged for simultaneous testing.

Diagnostic evaluation should begin with thorough history and physical examination. History taking of infertile partner must include the following: ÂÂ

Duration of infertility and results of any previous evaluation/treatment

ÂÂ

Coital frequency and sexual dysfunction

ÂÂ

After 6 months of unsuccessful efforts in women over age of 35 years

ÂÂ

Menstrual history (age at menarche, cycle length and characteristics, onset/severity of dysmenorrhea)

ÂÂ

History of irregular menstrual cycles

ÂÂ

ÂÂ

Known or suspected uterine/tubal or peritoneal disease

Outcome of previous pregnancy, if any, and use of contraception

ÂÂ

Past or current medical and surgical illness (particularly any history of pelvic infection,

ÂÂ

History of pelvic infection

ÂÂ

Endometriosis, particularly Stage III-IV

ÂÂ

Known or suspected male subfertility.

10% Tubal and pelvic pathology

10% 40%

Ovulatory dysfunction Unexplained infertility

*Senior Resident Dept. of Obstetrics and Gynecology All India Institute of Medical Sciences (AIIMS), New Delhi Address for correspondence Dr Anju Singh Senior Resident Dept. of Obstetrics and Gynecology All India Institute of Medical Sciences (AIIMS), New Delhi E-mail: docanju.singh691@gmail.com

120

Unusual problem

40%

Figure 1. Cause of infertility: Women.

IJCP Sutra: "Restricting salt intake to <6 g daily can reduce upper systolic BP by 2.8 mmHg."

Review Article

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

exposure to sexually transmitted infections, septic abortion, ectopic pregnancy, abdominal myomectomy, adnexal surgery) ÂÂ

Family history of birth defects, mental retardation, early menopause or reproductive failure

ÂÂ

Symptoms of thyroid hirsutism or acne

ÂÂ

Pelvic or abdominal pain or dyspareunia

ÂÂ

Occupation and addiction history.

disease,

galactorrhea,

Physical examination should document: ÂÂ

Body mass index (BMI)

ÂÂ

Thyroid nodule or tenderness

ÂÂ

Breast secretions and their character

ÂÂ

Signs of androgen excess

ÂÂ

Abdominal or pelvic mass or tenderness

ÂÂ

Vaginal or cervical abnormality or discharge

ÂÂ

Any mass, tenderness or nodularity in adnexa or cul-de-sac.

Subsequent evaluation should be carried out in a systematic and cost-effective manner to identify underlying cause.

Ovulatory function Ovulatory dysfunction, presenting as menstrual irregularity, is the underlying cause of infertility in approximately 15% of infertile couples and accounts for up to 40% of infertility in women. Diagnosis of ovulatory dysfunction can be made by menstrual history. Further investigations should be aimed to document ovulation and find the pathology of anovulation, if present.

Document Ovulation A history of regular menstrual cycles occurring at interval of 25-35 days with consistent flow characteristics strongly suggests normal ovulatory function but still objective documentation in infertile women is needed.

There are a number of methods to measure normal ovulatory function.

Methods to document ovulation ÂÂ

Basal body temperature charts

ÂÂ

Urinary luteinizing hormone (LH) Kits

ÂÂ

Mid-luteal serum progesterone level

ÂÂ

Endometrial biopsy

properties of progesterone. Ovulatory cycles have typical “biphasic” BBT recording, whereas anovulatory cycles have monophasic pattern. It is not the preferred method for infertile women because there can be few women who menstruate regularly but do not exhibit biphasic BBT. Urinary LH determination is based on identification of mid-cycle LH surge and provides indirect evidence of ovulation. Since LH has a short half-life and is rapidly cleared of the urine, testing should be done on a daily basis starting 2-3 days before the surge is expected based on the cycle length. It is done using various commercially available “ovulation prediction kits” like i-know, i-can, PregaPlan, etc., which are easy to use but can have false positive and false negative results.

Serum progesterone measurement is simplest, reliable and preferred test of ovulatory function as long as it is appropriately timed. The best time to test is Day 21 of a 28-day cycle or approximately 1 week before the expected onset of next menses. A progesterone concentration of >3 ng/mL provides reliable evidence of recent ovulation, whereas value >10 ng/mL is suggestive of normal “in phase” endometrial histology.

Endometrial biopsy identifies ovulation based on characteristic secretory endometrial changes on histology induced by progesterone. Historically, it was considered “gold standard” for diagnosis of luteal phase deficiency (LPD) but not anymore. Since endometrial biopsy is an invasive test and provides not much added information over other noninvasive methods, it is no longer recommended to evaluate ovulatory or luteal function in infertile women. Its clinical use is limited to identify or exclude endometrial hyperplasia in women with chronic anovulation and to diagnose chronic endometritis. But in our Indian population where tuberculosis is an important cause of infertility, it becomes a part of routine investigations to rule out tubercular endometritis.

Serial transvaginal ultrasonography (TVUS) can be used to monitor number and size of developing follicles. It provides most accurate estimate of ovulation identified by sudden collapse of follicle, loss of clearly defined follicular margins, appearance of internal echoes and increase in cul-de-sac fluid volume. Because of associated cost and logistic demands, it is mainly used to monitor follicle growth in women receiving ovulation induction drugs.

Establish Cause for Anovulation

Serial basal body temperature (BBT) measurement is a simple and inexpensive method based on thermogenic

Patients with irregular or infrequent menses and amenorrhea have ovulatory dysfunction and do

IJCP Sutra: "An 1% increase in cholesterol increases chances of heart attack by 2%."

121

Review Article

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

not require any specific test to establish a diagnosis of anovulation. The ovulatory disorders have been classified by World Health Organization (WHO) into three groups (Table 1).

Therefore, in women with irregular cycles, basal (Day 2-4) serum follicle-stimulating hormone (FSH), LH, serum estradiol and prolactin levels should be done to find the cause of anovulation and to treat accordingly.

Before that, pregnancy must be excluded by a urine pregnancy test. Serum thyroid-stimulating hormone (TSH) levels should be done if signs and symptoms are suggestive of it.

Tubal and Peritoneal Factors Tubal pathology is the most common cause (30-35%) of infertility among both young as well as older women.

Tubal damage should be strongly suspected in women with history of tuberculosis, pelvic inflammatory disease (PID), septic abortion, ectopic pregnancy or tubal surgery. Other important causes of tubal and peritoneal factor infertility include inflammation and adhesions related to endometriosis, inflammatory bowel disease or surgical trauma.

Hysterosalpingography (HSG) is the traditional and standard method for evaluation of tubal patency. It is a procedure which directly visualizes uterotubal anatomy as well as tubal patency with fluoroscopic screen after injecting radio-opaque dye through cervix.

It is done as an office procedure in the preovulatory phase of menstrual cycle. It is approximately 65% sensitive, 83% specific with a positive (PPV) and negative predictive value (NPV) of 38% and 94%,

respectively. It’s low PPV implies that when HSG reveals obstruction, it can be because of mucus plug or cornual spasm and there is high probability (approx.

60%) that tube is open but when it demonstrates patency, there is only 5% chance that tube is actually occluded.

Saline infusion sonography (SIS) involves TVUS after injecting saline into uterine cavity. Apart from delineating intrauterine pathology, it can also be used to determine tubal patency by appearance of fluid in cul-de-sac with saline infusion on TVUS. It does not differentiate between unilateral or bilateral patency.

Laparoscopy and chromotubation is the definitive test for evaluation of tubal factors. It provides both a panoramic view of pelvic reproductive anatomy as well as magnified view of uterine, ovarian, tubal and peritoneal surfaces. Apart from evaluation of tubal patency, it can also identify distal tubal occlusive disease (fimbrial agglutination, phimosis), pelvic or adnexal adhesions and endometriosis that adversely affect fertility but escape detection by HSG. It also provides advantage of treating the pathology at time of diagnosis.

The detection of antibodies to Chlamydia trachomatis has also been associated with tubal pathology, including tubal occlusion, hydrosalpinx and pelvic adhesions but its clinical utility has not been proved yet.

Uterine Factors Anatomic and functional abnormalities of uterus are an uncommon cause but should always be excluded as a part of infertility evaluation. The anatomic abnormalities

Table 1. WHO Classification of Ovulatory Disorders and Serum Concentration of Hormones Hormone

Normal values

Hypogonadotropic hypogonadal anovulation (WHO Class I) 5-10%

Eugonadotropic eu-estrogenic anovulation (WHO Class II) 75-85%

Hypergonadotropic Hyperanovulation prolactinemia (WHO Class III) 10-20%

Day 2/3 FSH

<10 IU/L

Decreased

Normal

Increased

Normal

Day 2/3 LH

<10 IU/L

Decreased

Normal or increased

Increased

Normal

LH:FSH ratio

ABOUT 1:2

Normal

Reversed

Normal

Normal

DAY 2/3 estradiol

<50 pmol/L

Decreased

Normal

Decreased

Decreased

Serum prolactin

15-20 ng/L

Normal

Normal or increased

Normal

Increased

Kallmann’s syndrome

Polycystic ovary syndrome Premature ovarian failure

Example

Excessive exercise Anorexia nervosa

122

IJCP Sutra: "An 1% increase in good HDL cholesterol decreases chances of heart attack by 3%."

Pituitary micro- or macroadenoma

Review Article

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

which adversely affect fertility include congenital malformations, leiomyomas, intrauterine adhesions and endometrial polyp. Chronic endometritis is the only functional uterine abnormality. Three basic methods for evaluation of uterine cavity are HSG, pelvic ultrasound or saline sonohysterography and hysteroscopy with each having its own advantage and disadvantages. ÂÂ

Ultrasound is a noninvasive method which permits visualization of position and size of uterus, fallopian tubes and ovaries. Modern 3-D ultrasonography extends the diagnostic capabilities of ultrasonography and can generate reconstructed images in the coronal plane. It is more useful in diagnosing important uterine pathologies particularly congenital anomalies, to measure endometrial volume, locate fibroids and also defines their relationship to endometrial canal. It has diagnostic accuracy comparable to magnetic resonance imaging.

ÂÂ

SIS can be used for better identification of intrauterine adhesions and endometrial polyps.

ÂÂ

HSG accurately defines size and shape of uterine cavity. It may help in delineating any developmental uterine anomaly (unicornuate, bicornuate, septate, didelphys, etc.) and acquired abnormalities (intrauterine adhesions, endometrial polyps, submucous myomas). It has relatively low sensitivity (50%) and PPV (30%) for diagnosis of endometrial polyp and submucous myomas in asymptomatic infertile women.

ÂÂ

Hysteroscopy is the definitive method for evaluation and treatment of intrauterine pathology.

Being more costly and an invasive method, its use is reserved for further evaluation and treatment of abnormalities detected on TVUS, SIS or HSG.

Cervical Factors It includes abnormalities of cervical mucus production or sperm/mucus interaction which are rarely the sole cause of infertility. Traditionally, post-coital test (PCT) was considered a basic element of infertility evaluation.

It is inconvenient to patient, does not predict inability to conceive and rarely changes clinical management.

Therefore, PCT is no longer recommended for evaluation of infertile female.

Ovarian reserve tests

Biochemical tests

yy Antral follicle count (AFC) yy Ovarian follicle Basal (Day 2/3) measurements of yy S. FSH yy S. estradiol yy S. inhibin B

Provocative test

Clomiphene citrate challenge (CCC) test

yy S. antimullerian hormone (AMH)

Figure 2. Ovarian reserve tests.

infertility but is best justified for women with any of the following characteristics: ÂÂ

Age over 35 years

ÂÂ

Family history of early menopause

ÂÂ

Previous ovarian surgery (ovarian cystectomy/ drilling, unilateral oophorectomy), chemotherapy, radiation

ÂÂ

Unexplained infertility

ÂÂ

Chronic smoking

ÂÂ

Demonstrated poor response gonadotropin stimulation.

to

exogenous

It includes a number of biochemical tests and ultrasonographic measures with each test having its own sensitivity and specificity (Fig. 2 and Table 2).

Therefore, ovarian reserve tests should always be interpreted with caution as none of the tests available at present can be recommended as a sole criteria of diminished ovarian reserve (DOR). They should only be used to obtain prognostic information and to choose the best treatment available.

Key Recommendations: NICE Guidelines ÂÂ

A careful history and physical examination can identify a specific cause of infertility and help to focus the diagnostic evaluation on the most likely cause.

ÂÂ

A blood test to measure serum progesterone in the mid-luteal phase (Day 21 of a 28-day cycle) is the preferred method to confirm ovulation even if women having regular menstrual cycle.

ÂÂ

Women with irregular menstrual cycle should be offered a blood test to measure serum gonadotropins.

Role of Ovarian Reserve Testing Ovarian reserve describes the size and quality of the remaining ovarian follicular pool. This has become a routine element of the diagnostic evaluation of

Ultrasonographic measures

IJCP Sutra: "Any chest pain, which lasts for less than 30 minutes duration is not a heart pain."

123

Review Article

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

Table 2. Summary of Different Ovarian Reserve Tests Ovarian reserve test

Cut-off range

Sensitivity (%)

10-20 IU/L

10-30

83-100

Most widely used; good reliability

S. Inhibin B

40-45 pg/mL

40-80

64-90

High inter- and intracycle variability; not used routinely

S. AMH

0.2-0.7 ng/mL

40-97

78-92

Good reliability

10-22 IU/L

35-98

68-98

Higher sensitivity than basal FSH but needs drug administration

3-10

40-97

78-92

Good reliability; widespread use

>3 mL

11-80

80-90

Limited clinical use

S. FSH (Day2/3)

CCC test (Day 10 FSH) AFC (No) Ovarian volume

Specificity Comment (%)

ÂÂ

Serum prolactin should only be offered to women who have an ovulatory disorder, galactorrhea or a pituitary tumor.

ÂÂ

Thyroid function test should not be offered routinely; rather should be estimated only in women with symptoms of thyroid disease.

ÂÂ

The routine use of endometrial biopsy and PCT of cervical mucus is no longer recommended as a part of evaluation of infertile female.

ÂÂ

HSG to screen for tubal patency is a reliable test, less invasive and makes more efficient use of resources than laparoscopy.

ÂÂ

Ovarian reserve testing should be best limited to the women at increased risk of DOR and should be interpreted with caution.

Suggested Reading 1. Practice Committee of American Society for Reproductive Medicine. Definitions of infertility and recurrent pregnancy loss. Fertil Steril. 2008;90(5 Suppl):S60.

2. Speroff L, Fritz MA. Clinical Gynecologic Endocrinology and Infertility. 8th Edition, Philadelphia, PA, USA: Lippincott Williams & Wilkins.

3. Practice Committee of American Society for Reproductive Medicine. Diagnostic evaluation of the infertile female: a committee opinion. Fertil Steril. 2012;98(2):302-7.

4. National Collaborating Centre for Women’s and Children’s Health. Fertility: assessment and treatment for people with fertility problems. London, United Kingdom: National Institute for Health and Clinical Excellence (NICE); February 2013:1-63. (Clinical Guideline No. 156).

5. Wathen NC, Perry L, Lilford RJ, Chard T. Interpretation of single progesterone measurement in diagnosis of anovulation and defective luteal phase: observations on analysis of the normal range. Br Med J (Clin Res Ed).

1984;288(6410):7-9.

6. Jordan J, Craig K, Clifton DK, Soules MR. Luteal phase defect: the sensitivity and specificity of diagnostic methods in common clinical use. Fertil Steril.

1994;62(1):54-62.

7. Soares SR, Barbosa dos Reis MM, Camargos AF. Diagnostic accuracy of sonohysterography, transvaginal sonography, and hysterosalpingography in patients with uterine cavity diseases. Fertil Steril.

2000;73(2):406-11.

8. Practice Committee of the American Society for Reproductive Medicine. Testing and interpreting measures of ovarian reserve: a committee opinion. Fertil Steril. 2015;103(3):e9-e17.

■■■■

WHO Celebrates Big Step Forward in Improving Health Security in the African Region The World Health Organization (WHO) reached an important milestone globally with the completion of the 100th Joint External Evaluation (JEE)—a voluntary assessment of a country’s ability to prevent, detect and respond to public health threats. Forty-two of these 100 countries are in the WHO African region.

“Africa has more than 150 acute public health events a year, including infectious disease outbreaks and humanitarian crises. This is more than in any other region of the world,” said Dr Matshidiso Moeti, WHO Regional Director for Africa. “The JEE is critical for identifying priority interventions in developing preparedness capacity and improving health security in the region.” (WHO)

124

IJCP Sutra: "Keep air pollution (particulate matter [PM] 2.5 and PM 10 levels) below 80 µg/mm3."

Clinical Study

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

A Study of Corneal Thickness and Endothelial Morphology in Type 2 Diabetes Mellitus RAJENDER SINGH CHAUHAN*, ASHOK RATHI*, JP CHUGH*, P SHARMA†, R RAJPUT‡, R KUMAR†

Abstract Ocular complications of diabetes mainly include diabetic retinopathy, glaucoma, cataract and ocular surface disorders.

Besides diabetic retinopathy, patients with diabetes are prone to develop corneal endothelial damage, keratoepitheliopathy in the form of recurrent corneal erosions, persistent epithelial defects and superficial keratitis. This study was conducted to assess the corneal thickness and endothelial morphology in type 2 diabetes mellitus patients and to compare these parameters with nondiabetics. The study group included 100 type 2 diabetes patients and 100 nondiabetic patients formed the control group. Specular microscopy was performed using a noncontact TOPCON SP-3000P specular microscope and SP-3000P endothelial cell analysis software (image net) on both eyes or one eye. Fasting mean blood sugar was 143.96 ± 30.83 mg/dL in study group and 77.53 ± 8.44 mg/dL in control group. Postprandial blood sugar level was also very high in study group as compared to the control group. The difference in blood sugar levels, both fasting and postprandial, between the two groups was found to be statistically significant (p < 0.001). About, 70% patients suffered from microvascular complications while both macro- and microvascular complications were observed in 35% patients in study group. Mean CCT of study group (520.09 ± 25.37 µm) was higher than mean CCT of control group (514.99 ± 21.80 µm). Statistical comparison of both the groups was found to be significant (p < 0.05). There was statistically significant lower mean hexagonality of endothelial cells, i.e., 56.69 ± 6.86% in study group, as compared to 60.79 ± 5.46% in the control group (p < 0.001). Mean ECD was slightly lower in study group (2467.27 ± 260.37 cells/mm2) as compared to control group (2498.23 ± 235.31 cells/mm2), but difference in both groups was insignificant. Difference in coefficient of variation (CV) and mean cell area was found to be insignificant in both the groups. The study concluded that the corneal health of patients with uncontrolled and long-standing diabetes is poor and can lead to loss of transparency.

Keywords: Diabetes mellitus, corneal thickness, endothelial morphology

D

iabetes mellitus is a widely spread and one amongst the most common noncommunicable disease. As of 2017, 72.9 million Indians were affected by type 2 diabetes. Ocular complications of diabetes mainly include diabetic retinopathy, glaucoma, cataract and ocular surface disorders.

In addition to diabetic retinopathy, diabetes patients can likely develop corneal endothelial damage, keratoepitheliopathy as recurrent corneal erosions, persistent epithelial defects and superficial keratitis.

*Professor †Junior Resident Regional Institute of Ophthalmology ‡Professor Dept. of Endocrinology Pt BD Sharma PGIMS, Rohtak, Haryana Address for correspondence Dr Rajender Singh Chauhan 15/8FM, Medical Enclave, Rohtak - 124 001, Haryana E-mail: drrschauhan@yahoo.co.in

Therefore, in the presence of diabetes, it is important to weigh keratopathy as a potential sight-threatening condition and appropriate clinical attention and increased research interest should be addressed towards this condition. In the developed world and increasingly elsewhere, type 2 diabetes is the major cause of nontraumatic blindness and renal failure.

Cornea has 6 layers which are epithelium, Bowman’s layer, stroma, Dua’s layer, Descemet’s membrane and endothelium. Endothelium is a monolayer of hexagonal cells which is rich in mitochondria. There are 5,00,000 endothelial cells per cornea and the adult density is 2500 cells/mm2 approximately. Functions of corneal endothelium include regular fluid and solute transport and maintenance of corneal optical transparency via active Na/K ATPase pump. Thickness of cornea reaches adult size by 3 years of age.

Damage or insult to corneal endothelium leads to increase in central corneal thickness and loss of transparency.

Diabetic keratopathy can cause alterations in all layers

IJCP Sutra: "Eat foods high in vitamin C, such as citrus fruits and fresh, raw vegetables."

125

Clinical Study

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

of cornea especially the endothelium, like decrease in endothelial cell density (ED) and hexagonality, as well as increased polymegathism, pleomorphism and central corneal thickness. Reduced corneal ECD and swelling of the cornea are indicators of corneal dysfunction.

Corneal endothelial morphology can be measured using different instruments, including contact specular microscopes, noncontact specular microscopes (NCSM) and confocal microscopes while central corneal thickness can be assessed by various techniques such as ultrasound pachymeter (USP), Orbscan, contact specular microscopy, NCSM and Pentacam. The availability of quick, accurate, noninvasive methods of central corneal thickness (CCT) assessment is essential for the effective monitoring of corneal endothelial health. One such technique widely used is the new automated NCSM Topcon SP-3000P (Topcon Corporation, Tokyo, Japan), which captures an image of the corneal endothelium and assesses corneal thickness simultaneously.

Aims and Objectives To study the corneal thickness and endothelial morphology in type 2 diabetes mellitus patients and to compare these parameters with nondiabetics.

Material and Methods

ÂÂ

Glaucoma.

ÂÂ

Previous retinal photocoagulation.

ÂÂ

Contact lens wear.

ÂÂ

Corneal disease due to chronic conjunctival or eyelid abnormality.

ÂÂ

Regular use of any eye drops.

Patient Evaluation Informed and written consent was taken from all patients. Detailed history regarding age, gender, any previous history of ocular trauma, surgery, usage of eye drops if any, was taken. Complete ocular examination was performed, including best corrected visual acuity, using Snellen acuity chart, anterior and posterior segment examination by slit-lamp, intraocular pressure measurement, fundus examination and specular microscopy.

Methodology Specular microscopy was performed using a noncontact TOPCON SP-3000P specular microscope and SP-3000P endothelial cell analysis software (image net) on both eyes or one eye, considering the exclusion criteria. This instrument takes a picture of the corneal endothelium by slit light projected diagonally.

Statistical Analysis

The present study was conducted at the Regional Institute of Ophthalmology and Dept. of Endocrinology, Pt. BD Sharma PGIMS, Rohtak, Haryana. It was a casecontrol study in which the study group included 100 type 2 diabetes patients and 100 nondiabetic patients formed the control group. The study was conducted to detect the effect of type 2 diabetes mellitus on corneal thickness and endothelial morphology.

The data was entered in Microsoft excel spreadsheet and it was analyzed using SPSS version 20.0. Student’s t-test was applied for comparison between the study group and controls. The comparison among the diabetes group was made by performing analysis of variance (ANOVA) test. Pearson correlation test was also applied. Point of statistical significance was considered if p < 0.05.

Inclusion Criteria

Results and Observations

ÂÂ

Individuals of either gender, age more than 18 years, who were diagnosed to have type 2 diabetes mellitus as per American Diabetes Association (ADA) criteria, blood glucose levels ≥126 mg/dL (fasting) or blood glucose levels ≥200 mg/dL (postprandial), were included as the study population.

Control group included age- and gender-matched nondiabetic individuals.

Exclusion Criteria ÂÂ

Previous history of ocular surgery or trauma.

ÂÂ

Active or previous eye infection or inflammation.

126

Fasting mean blood sugar was 143.96 ± 30.83 mg/dL in study group as compared to 77.53 ± 8.44 mg/dL in control group. Similarly, postprandial blood sugar level was also very high in study group patients, i.e., 238.48 ± 40.21 mg/dL as compared to 112.38 ± 8.17 mg/dL in the control group. The difference in blood sugar levels, both fasting and postprandial, between the two groups was found to be statistically significant (p < 0.001). Mean glycated hemoglobin (HbA1c) in study patients was 8.07 ± 1.24 % (Table 1).

A total of 70% of the patients were taking oral hypoglycemic agents (OHAs). Out of insulin

IJCP Sutra: "Cook in cast iron pots as this can add up to 80% more iron to your food."

Clinical Study

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

dependents, 12% were only receiving insulin while the rest 18% were on both insulin and OHA. In our study, 70% patients suffered from microvascular complications while both macro- and microvascular complications were observed in 35% patients in the study group.

Mean CCT of study group (520.09 ± 25.37 µm) was higher than mean CCT of control group (514.99 ± 21.80 µm). Statistical comparison of both the groups, i.e., study versus control group, was found to be significant (p < 0.05) (Table 2).

Table 3 and Figures 1-3 show comparison of endothelial parameters between both the groups.

We observed a statistically significant lower mean hexagonality of endothelial cells, i.e., 56.69 ± 6.86% in the study group as compared to 60.79 ± 5.46% in the control group (p < 0.001). Mean ECD was found

to be slightly lower in the study group (2467.27 ± 260.37 cells/mm2) as compared to control group (2498.23 ± 235.31 cells/mm2), but the difference in both the groups was insignificant. Difference in coefficient of variation (CV) and mean cell area was found to be insignificant in both the groups.

Discussion In our study, mean CCT of 100 diabetes patients of study group was 520.09 ± 25.37 µm and that of 100 age- and gender-matched nondiabetics as controls was 514.99 ± 21.80 µm. The mean CCT was higher in diabetes patients when compared with the nondiabetics. It is well-known that diabetes reduces the activity of Na+/K+ ATPase of the corneal endothelium and thus, causes morphological and functional changes of diabetic cornea. The difference between the two groups was statistically significant (p < 0.05). This

Table 1. Blood Sugar Levels in Study and Control Groups Blood sugar (mg/dL)

Study group

Control group

Statistical significance

Mean ± SD

Mean ± SD

P

Fasting

143.96 ± 30.83

77.53 ± 8.44

0.000 (<0.001 VHS)

Postprandial

238.48 ± 40.21

112.38 ± 8.17

0.000 (<0.001 VHS)

8.07 ± 1.24

-

-

HbA1c (%)

SD = Standard deviation; VHS = Very highly significant.

Table 2. Central Corneal Thickness in Study and Control Groups Central corneal thickness CCT (µm)

Study group (n = 100)

Control group (n = 100)

Mean ± SD

Mean ± SD

520.09 ± 25.37

514.99 ± 21.80

Statistical significance P < 0.05 S

S = Significant.

Table 3. Endothelial Parameters in Study and Control Groups Endothelial parameters

Study group (n = 100)

Control group (n = 100)

Mean ± SD

Mean ± SD

Minimum cell area (µm2)

183.29 ± 35.91

183.01 ± 29.24

0.933 NS

Mean cell area (µm2)

402.65 ± 43.83

414.03 ± 43.40

0.009 NS

Coefficient of variation

0.33 ± 0.04

0.32 ± 0.05

0.201 NS

ECD (cells/mm2)

2467.27 ± 260.37

2498.23 ± 235.31

0.212 NS

Hexagonality (%)

56.69 ± 6.86

60.79 ± 5.46

<0.001 VHS

134.29 ± 23.81

139.61 ± 21.83

<0.01 HS

SD

Statistical significance

NS = Nonsignificant; ECD = Endothelial cell density; VHS = Very highly significant; HS = Highly significant.

IJCP Sutra: "Breastfeed your infant. This will increase immunity and help ward off potential complications."

127

Clinical Study

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

Hexagonality (%)

80 60

60.79

56.69

40 20 0

Study Group

Control Group

Figure 1. Comparison of mean hexagonality in patients of both groups (200 eyes each).

2500

2498.23

2467.27

Conclusion The study concluded that the corneal health of patients with uncontrolled and long-standing diabetes is poor and can lead to loss of transparency. Hence, it is recommended to have strict glycemic control of type 2 diabetes mellitus for better corneal health.

2000 ECD (cells/mm2)

accordance with other reports. In our study, percentage of hexagonal cells was observed as 56.69 ± 6.86% in the study group and 60.79 ± 5.46% in the control group.

The hexagonal shape of endothelial cells was found to be lower in type 2 diabetes patients. This difference was statistically significant as compared to the controls (p < 0.001). Similar decrease in percentage of hexagonal cells was observed in various studies done by Schultz et al and Lee et al. In our study, mean CV in diabetes study group was 0.33 ± 0.04 as compared to 0.32 ± 0.05 of the control group. This increase in the cell size variation coefficient in type 2 diabetes patients was not significant (p > 0.05). Similar nonsignificant CV changes were observed between diabetes patients and controls in others studies.

1500 1000 500 0

Suggested Reading Study Group

Control Group

Figure 2. Comparison of mean ECD in patients of both groups (200 eyes each).

Study group

Control group

402.65 414.03

450 400 Area (µm sq.)

350 300 250 200 100 50 Minimum cell area

Mean cell area

Figure 3. Comparison of mean of minimum cell area and mean cell area of in patients of both groups (200 eyes each).

was in accordance with the results from other studies.

In our study, we found out that mean ECD in patients of the study group was 2467.27 ± 260.37 cells/mm2 and 2498.23 ± 235.31 cells/mm2 in the control group. The ECD was lower in the study group when compared with the age- and gender-matched nondiabetic controls. The difference in cell loss was not statistically significant in our study (p > 0.05). This was in

128

2. Schultz RO, Matsuda M, Yee RW, Edelhauser HF, Schultz KJ. Corneal endothelial changes in type I and type II diabetes mellitus. Am J Ophthalmol. 1984; 98(4):401-10.

3. Schultz RO, Van Horn DL, Peters MA, Klewin KM, Schutten WH. Diabetic keratopathy. Trans Am Ophthalmol Soc. 1981;79:180-99.

4. Herse PR. A review of manifestations of diabetes mellitus in the anterior eye and cornea. Am J Optom Physiol Opt. 1988;65(3):224-30.

183.29 183.01

150

0

1. International Diabetes Federation. IDF Diabetes Atlas, 8th Edition, Brussels, Belgium: International Diabetes Federation; 2017.

5. Ripsin CM, Kang H, Urban RJ. Management of blood glucose in type 2 diabetes mellitus. Am Fam Physician.

2009;79(1):29-36.

6. Tuft SJ, Coster DJ. The corneal endothelium. Eye (Lond).

1990;4 (Pt 3):389-424.

7. Murphy C, Alvarado J, Juster R, Maglio M. Prenatal and postnatal cellularity of the human corneal endothelium.

A quantitative histologic study. Invest Ophthalmol Vis Sci. 1984;25(3):312-22.

8. Inoue K, Kato S, Inoue Y, Amano S, Oshika T. The corneal endothelium and thickness in type II diabetes mellitus. Jpn J Ophthalmol. 2002;46(1):65-9.

9. Siribunkum J, Kosrirukvongs P, Singalavanija A. Corneal abnormalities in diabetes. J Med Assoc Thai.

2001;84(8):1075-83.

IJCP Sutra: "It is important to get enough vitamin D as it helps in the absorption of calcium."

Clinical Study

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019 10. Martin R, de Juan V, Rodriguez G, Fonseca S, Martin S. Contact lens-induced corneal peripheral swelling differences with extended wear. Cornea. 2008;27(9):976-9.

11. Martin R, de Juan V, Rodriguez G, Fonseca S, Martin S. Contact lens-induced corneal peripheral swelling: Orbscan repeatability. Optom Vis Sci. 2009;86(4):340-9.

12. Lee JS, Oum BS, Choi HY, Lee JE, Cho BM. Differences in corneal thickness and corneal endothelium related to duration in diabetes. Eye (Lond). 2006;20(3):315-8.

13. Storr-Paulsen A, Singh A, Jeppesen H, Norregaard JC, Thulesen J. Corneal endothelial morphology and central thickness in patients with type II diabetes mellitus. Acta Ophthalmol. 2014;92(2):158-60 14. Roszkowska AM, Tringali CG, Colosi P, Squeri CA, Ferreri G. Corneal endothelium evaluation in type I

and type II diabetes mellitus. Ophthalmologica. 1999; 213(4):258-61.

15. Shenoy R, Khandekar R, Bialasiewicz A, Al Muniri A. Corneal endothelium in patients with diabetes mellitus: a historical cohort study. Eur J Ophthalmol. 2009;19(3):369-75.

16. Matsuda M, Ohguro N, Ishimoto I, Fukuda M. Relationship of corneal endothelial morphology to diabetic retinopathy, duration of diabetes and glycemic control. Jpn J Ophthalmol. 1990;34(1):53-6.

17. Sudhir RR, Raman R, Sharma T. Changes in the corneal endothelial cell density and morphology in patients with type 2 diabetes mellitus: a population-based study, Sankara Nethralaya Diabetic Retinopathy and Molecular Genetics Study (SN-DREAMS, Report 23).

Cornea. 2012;31(10):1119-22.

■■■■

Cholera Vaccination Drive in High-risk Districts in Somalia Somalia launched one of Africa’s largest immunization campaigns using oral cholera vaccines (OCV). The campaign, which ran from 22 to 28 June, 2019 in high-risk areas of Somalia, sought to vaccinate more than 6,50,000 people aged 1 year and above to eliminate the risk of the disease among vulnerable populations and to prevent recurring cholera outbreaks in the country.

Somali health authorities and the WHO conducted the campaign with the support of the UNICEF, Gavi, the Vaccine Alliance (GAVI) and the Global Task Force for Cholera Control (GTFCC)…(WHO)

Lower Incidence of Type 1 Diabetes Seen after Complete Rotavirus Vaccine Series Receipt of the complete rotavirus vaccine series in infancy is associated with a significant reduction in the incidence of type 1 diabetes in childhood, according to a database study.

Researchers noted that among children who received the complete rotavirus vaccination series, the incidence of type 1 diabetes per 1,00,000 person-years was 12.2 (12.4 for girls, 12.0 for boys), compared to 20.5 among children who were partially vaccinated and 20.6 among those who did not receive the vaccine. The findings are published in Scientific Reports.

MMF Stoppage Carries Risk in Systemic Sclerosis Mycophenolate mofetil (MMF) was effective in halting rapidly progressive diffuse cutaneous systemic sclerosis (SSc), but a substantial percentage of patients experienced recurrences when the treatment was stopped, a small open-label study found.

Five out of 19 patients (26.3%) who discontinued or decreased the dose of mycophenolate after almost 23 months of treatment had recurrences of the skin manifestations, with a 35.9% increase in their modified Rodnan skin scores from 7.8 to 10.6, according to Fabian A. Mendoza, MD, and colleagues from Thomas Jefferson University in Philadelphia. Two of those patients also had new-onset respiratory symptoms, the researchers reported online in Seminars in Arthritis & Rheumatism.

FDA Panel Against Cutting PAD Device Access The late mortality signal of paclitaxel-coated devices used in peripheral artery disease (PAD) shouldn’t force these balloons and stents off the market, a panel concluded at an FDA advisory committee meeting.

Citing a totality of evidence that still weighs heavily in favor of benefits from these devices - improved qualityof-life and reduced need for repeat revascularization for PAD - none of the panelists suggested restricting or eliminating access…(MedPage Today)

IJCP Sutra: "Some sources of vitamin D are milk, fortified orange juice, mushrooms, fatty fish and egg yolk."

129

Clinical Study

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

Effect of Adjuvant Atorvastatin Therapy on Disease Activity in Active Rheumatoid Arthritis: A Tertiary Care Center Study in India H SINGH*, REKHA MATHUR*, A SINGHANIA*, KIRAN B*

Abstract Introduction: In current practice, rheumatoid arthritis (RA) patients are being treated with combinations of different diseasemodifying antirheumatic drugs (DMARDs). This early aggressive approach halts the progression of disease. Among different drugs being used for treatment of RA, statins provide cardiovascular safety but their role as immunomodulatory drugs in RA is still being studied. In our study, we studied the effect of atorvastatin on disease activity in RA patients. Material and methods: An open-label, prospective, comparative clinical study was conducted with 100 patients. After baseline evaluation, subjects selected for the study were categorized into two groups of 50 each. Subjects in Group I received tablet atorvastatin (20 mg/day) along with their pre-existing DMARD therapy. Group II were those subjects who continued their pre-existing DMARDs, but didn’t receive atorvastatin so was considered as control group. Results: The study results showed that Group I had higher level (6.20 ± 1.2) of Disease Activity Score-28 (DAS28) at baseline than Group II (5.50 ± 1.24), which was statistically insignificant (p = 0.06). At 4 weeks, DAS28 was improved significantly from baseline in both groups. There was significant improvement in DAS28 by 2.52 and 1.53 from baseline to 12 weeks in Group I and Group II, respectively (p < 0.001). Similarly, the Clinical Disease Activity Index (CDAI) was higher in Group I (35.48 ± 16.72) than in Group II (27.56 ± 14.45). At 4 weeks, CDAI was improved significantly from baseline in both groups. There was significant reduction in CDAI by 23.32 and 12.84 from baseline to 12 weeks in both groups (p < 0.001). Conclusion: In our study, the results showed that atorvastatin, when used as adjuvant therapy with DMARDs, had beneficial effects on parameters of disease activity in RA patients and also was well-tolerated when given in combination with DMARDs.

Keywords: Atorvastatin, CDAI, DAS28, rheumatoid arthritis

R

heumatoid arthritis (RA) is associated with increased cardiovascular mortality and morbidity.1 In well-established RA, the median life expectancy is less than in control populations.2,3 Infection, renal disease and respiratory failure traditionally have been the primary factors contributing to excess mortality in RA patients, although it has been belatedly recognized that congestive heart failure, ischemic heart disease and peripheral atherosclerosis deserve the appellation as the prime killers of rheumatoid patients.4 It may be that chronic systemic inflammation in RA contributes

*Dept. of Medicine and Rheumatology PGIMS, Rohtak, Haryana Address for correspondence Dr Rekha Mathur Dept. of Medicine and Rheumatology PGIMS, Rohtak - 124 001, Haryana E-mail: drrekhamathur04@gmail.com

130

to excess cardiovascular disease (CVD) in this population either by potentiating and/or accelerating atherosclerosis or by other mechanisms such as diffuse subclinical vasculitis.5 Parallels between the inflammatory and immunological mechanisms operating in atherosclerotic plaque and rheumatoid synovitis have been highlighted and atherosclerosis is widely considered to be an inflammatory disease.6 Arterial stiffness is a marker of vascular dysfunction and an independent risk factor for CVD.7 Hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have demonstrated benefit in the primary and secondary prevention of CVD.8 The protective effect of statins appears to be greater than can be explained by their cholesterol reduction property9 and the benefit of statins appears to be even greater in the presence of higher C-reactive protein (CRP) levels.10 Statins are known to have a number of immunomodulatory effects, which may affect vascular function, plaque stability and thrombosis.11 These

IJCP Sutra: "Avoid exposure to smoke: Expectant mothers should quit smoking altogether as this is one of the major risk factors for development of asthma in children."

Clinical Study

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

immunomodulatory effects of statins may be especially important in patients with RA who have systemic immune activation. Statins have been demonstrated to reduce disease activity and inflammatory responses in a murine model of inflammatory arthritis and in patients with RA. Many data indicate effects for statins in innate immune response including effects on endothelial function,12 macrophage, natural killer cell and neutrophil effect or functions.13 Similar effects on acquired immune responses via suppression of antigen presentation14 and T-cell polarization have been shown in vitro and in vivo. Synovial inflammation in RA is characterized by activated components of both innate and acquired immune responses. Thus, postulated effects for statins might reasonably operate within the synovial membrane. Findings of an in vitro study15 showed suppression of synovial T-cell and fibroblastlike synoviocyte cytokine release, which tends to support to this notion.

Data suggest that modulation of inflammation can be achieved by atorvastatin in a proportion of patients with RA, suggesting that some of the above pathways may indeed be tractable to HMG-CoA reductase inhibition.16 Moreover, in vitro cytokine release by RA synovial mononuclear cells and by synovial fibroblasts was also reduced by statins.15 Statins have a satisfactory safety profile and relatively few adverse effects. In the absence of side effects and contraindications, it may be reasonable to consider statin use in selected cases particularly in patients with a long history of active RA that are at increased cardiovascular risk.

A previous study “Trial of Atorvastatin in Rheumatoid Arthritis16 (TARA)” showed significant improvement in Disease Activity Score-28 (DAS28) (-0.5, 95% confidence interval [CI] - 0.75 to -0.25) compared with placebo (0.03, -0.23 to 0.28; difference between groups -0.52, 95% CI -0.87 to -0.17, p = 0.004). CRP and erythrocyte sedimentation rate (ESR) declined, swollen joint counts also fell (-2.69 vs. -0.53; mean difference -2.16, 95% CI -3.67 to -0.64, p = 0.0058). Although, authors found only modest change but the significant reduction in DAS28 provides proof of concept that pathways targeted by atorvastatin offer therapeutic opportunity in inflammatory disease.

A double-blind trial studied the effect of either increased dose of methotrexate (MTX) from 7.5 mg to 15 mg (Group A) or 7.5 mg MTX plus 40 mg atorvastatin (Group B). This study showed a significant reduction in DAS28, CRP, ESR and swollen joint count in

atorvastatin group compared to placebo in patients with RA presenting with active disease despite undergoing disease-modifying antirheumatic drug (DMARD) therapy.

Although not indicative for first-line use, this effect of atorvastatin could prove beneficial in the context of DMARD combination design, in which a statin offers both vascular protective and adjunctive immunomodulatory potential. Based on the above literature, we planned to study the effect of atorvastatin on disease activity of RA as there is scant Indian data available in this regard.

Material and Methods Patients with diseases like (known or detected on baseline investigations) hepatic, renal diseases, heart failure, endocrinological disorders, hematological disorders, uncontrolled hypertension, coronary heart disease, pregnant or lactating mothers, those belonging to reproductive age group, not willing to practice contraception and who were taking lipid-lowering therapy (statin or fibrate), had hypersensitivity to statin, were excluded from the study. The study was approved by Ethical Committee. After obtaining the informed consent, we recruited 100 patients, meeting the 1987 American College of Rheumatology criteria, with high activity disease (DAS28 >5.5 and Clinical Disease Activity Index [CDAI] >22) despite ongoing DMARD therapy. All participants were informed about all possible side effects of drugs. A detailed history and clinical examination was done in all subjects included in the study. They underwent routine laboratory investigations like serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), blood urea, ESR and baseline radiograph of hands.

After baseline evaluation, subjects selected for the study were categorized into two groups of 50 each

by Random No. Table. Subjects in Group I received tablet atorvastatin (20 mg/day) along with their preexisting DMARD therapy. Group II were those subjects who continued their pre-existing DMARDs but didn’t receive atorvastatin, who were considered as control group.

Disease activity using DAS28 and CDAI in each of the subjects of either group was evaluated at baseline and every 4 weeks for 3 months by the same observer at each visit. Patients were also observed for adverse effects in both the groups. All data collected in the study were analyzed statistically at the end of study

IJCP Sutra: "Limit the intake of caffeine as this can decrease the absorption of calcium."

131

Clinical Study

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

using Independent t-test, Paired t-test and Chi-square test. Improvement in disease activity was measured by subtraction from baseline value.

Results Baseline variables were comparable in both groups (Table 1). There was statistically significant improvement in DAS28 in both groups with DMARD therapy including adjuvant atorvastatin in Group I at 4, 8 and 12 weeks (Table 2). The DAS28 score was comparable (i.e., statistically insignificant) in both groups at 4, 8 and 12 weeks (Table 3). When both groups were analyzed by CDAI, significant improvement in disease activity was observed at 4, 8 and 12 weeks (Table 4). The comparison of CDAI between groups was Table 1. Baseline Variables in Both Groups Variables

Group I

Group II

P value

42.56 ± 13.3

43.12 ± 9.96

0.237

Male

10

10

1.00

Female

40

40

1.00

2.08 years ± 1.3

2.00 years ± 1.2

60.45%

ESR (mm 1st hour) CDAI

Age (years)

comparable (i.e., statistically insignificant) at baseline, 4, 8 and 12 weeks (Table 5). Both DAS28 and CDAI showed gradual and significant improvement from high disease activity to moderate disease activity in both groups (Figs. 1 and 2). No clinical, hematological adverse events were noted. Atorvastatin when given as adjuvant therapy in active RA patients was well-tolerated.

Table 3. Analysis and Comparative Assessment of DAS28 Between Two Groups Duration

Group I

Group II

P value

Baseline

6.20 ± 1.2

5.50 ± 1.2

0.00

4 weeks

4.74 ± 1.3

4.67 ± 1.1

0.77

8 weeks

4.49 ± 1.2

4.34 ± 1.4

0.59

12 weeks

3.68 ± 1.0

3.97 ± 1.3

0.24

Table 4. Analysis and Improvement in CDAI Over 12 Weeks Duration

Group I

Group II

4 weeks

15.24

7.64

8 weeks

17.36

9.68

12 weeks

23.32

12.84

0.590

P value

<0.001

<0.001

61.33%

0.745

44.2 ± 19.4

31.92 ± 11.87

0.001

Table 5. Analysis and Comparative Assessment of CDAI Between Two Groups

35.48 ± 16.7

27.56 ± 14.4

0.01

6.20 ± 1.2

5.50 ± 1.2

0.06

TJC

10.88 ± 8.96

11.48 ± 8.41

0.730

SJC

3.2 ± 3.07

2.08 ± 2.13

0.037

PGA

3.2 ± 1.51

3.24 ± 1.22

0.884

EGA

2.96 ± 1.44

3.12 ± 1.28

0.559

GH

32 ± 15.11

32 ± 12.45

1

RF

DAS28

CDAI = Clinical Disease Activity Index; DAS28 = Disease Activity Score-28; ESR = Erythrocyte sedimentation rate; EGA = Evaluator global assessment; PGA = Patient global assessment; RF = Rheumatoid factor; TJC = Tender joint counts; SJC = Swollen joint counts; GH = Patient’s general health; P = P value (<0.05 = significant).

Table 2. Analysis and Improvement in DAS28 Over 12 Weeks in Both Groups Duration

Group I

Group II

4 weeks

1.46

0.83

8 weeks

1.71

1.16

12 weeks

2.52

1.53

<0.001

<0.001

P value

132

Duration

Group I

Group II

P value

Baseline

35.48 ± 16.7

27.56 ± 14.45

0.012

4 weeks

20.24 ± 12.9

19.92 ± 10.59

0.892

8 weeks

18.12 ± 11.9

17.88 ± 14.30

0.927

12 weeks

12.16 ± 10.3

14.72 ± 10.27

0.217

7 6

Group I (Atorvastatin) Group II (Control)

6.2 5.5

5

Mean DAS28

Disease (mean) Duration

4.74

4.67

4.49

4.34

4

3.68

3.97

3 2 1 0

Baseline

4 weeks 8 weeks Duration

12 weeks

Figure 1. Comparative assessment of DAS28 between two groups from baseline to 12 weeks.

IJCP Sutra: "If you smoke or drink, it is a good idea to quit both these habits."

Clinical Study

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

40 35 30

Mean CDAI

Group I (Atorvastatin) Group II (Control)

35.48

27.56

25 20.24

20

19.92

18.12 17.88

15

14.72 12.16

10 5 0

Baseline

4 weeks

8 weeks

12 weeks

Duration

Figure 2. Comparative assessment of CDAI between two groups from baseline to 12 weeks.

No significant liver function or muscle abnormality was detected in those given atorvastatin.

Discussion RA is a chronic disease with more predispositions to atherosclerosis owing to its inflammatory state. This increased prevalence of atherosclerosis in RA has made ischemic heart disease, the most common cause of death, followed by infection in RA, thus increasing its mortality two times greater than the general population.

Also in RA, the median life expectancy is shortened by an average of 7 years for men and 3 years for women compared to control populations. In the studies, DMARDs to some extent reduced the cardiovascular mortality in RA. Statins have been demonstrated to reduce disease activity and inflammatory responses in a murine model of inflammatory arthritis and in patients with RA.15,16 In present study, Group I had higher level (6.20 ± 1.2) of DAS28 at baseline than Group II (5.50 ± 1.24), which was insignificant (p = 0.06). At 4 weeks, DAS28 was improved significantly from baseline in both groups but the improvement in DAS28 score in Group I (1.46) was more than the Group II (0.83) (Table 2). There was significant improvement in DAS28 by 2.52 and 1.53 from baseline to 12 weeks in Group I and Group II, respectively (p < 0.001) (Table 2). Similarly, CDAI was higher in Group I (35.48 ± 16.72) than in Group II (27.56 ± 14.45) (Table 5). At 4 weeks, CDAI was improved significantly from baseline in both groups but the

improvement in CDAI score in Group I (15.24) was more than the Group II (7.64) (Table 4). There was significant reduction in CDAI by 23.32 and 12.84 from baseline to 12 weeks in the two groups (p < 0.001) (Table 4).

This study showed a significant reduction in various variables of disease activity of RA-like tender joint count (TJC), swollen joint count (SJC), patient global assessment (PGA), evaluator global assessment (EGA), ESR, patient’s general health (GH) over a period of 12 weeks in both groups (atorvastatin and control); similar finding was observed for 40 mg atorvastatin in TARA study.16 In our study, the results showed that atorvastatin when used as adjuvant therapy with DMARDs had beneficial effects on parameters of disease activity and also, was well-tolerated when given in combination with DMARDs. Since, the improvement in disease activity was numerically higher in the atorvastatin adjuvant therapy group when compared with DMARD alone group, but this was statistically insignificant; hence, it is suggested that larger and longer trails are needed so as to evaluate the modest but beneficial effect of welltolerated atorvastatin therapy in patients of RA. But thanks to good safety profile, easy administration and the existence of a broad experience regarding their use in clinical practice, statins are particularly attractive therapeutic agents, so even a modest efficacy in the treatment of RA in association with the reduction of cardiovascular risk can lead to a beneficial therapeutic ratio. This can make statins particularly useful as adjuvant therapy associated with other conventional therapeutic methods used in RA, especially in patients with dyslipidemia, where they should be the first choice of treatment.

References 1. Van Doornum S, McColl G, Wicks IP. Accelerated atherosclerosis: an extraarticular feature of rheumatoid arthritis? Arthritis Rheum. 2002;46(4):862-73.

2. Pinals RS. Survival in rheumatoid arthritis. Arthritis Rheum. 1987;30(4):473-5.

3. Vandenbroucke JP, Hazevoet HM, Cats A. Survival and cause of death in rheumatoid arthritis: a 25-year prospective follow-up. J Rheumatol. 1984;11(2):158-61.

4. Reilly PA, Cosh JA, Maddison PJ, Rasker JJ, Silman AJ. Mortality and survival in rheumatoid arthritis: a 25year prospective study of 100 patients. Ann Rheum Dis. 1990;49(6):363-9.

5. Bacon PA, Raza K, Banks MJ, Townend J, Kitas GD. The role of endothelial cell dysfunction in the cardiovascular mortality of RA. Int Rev Immunol. 2002;21(1):1-17.

IJCP Sutra: "Cut down on food or drinks rich in caffeine including coffee, tea, cola, energy drinks and chocolate.

Caffeine is a mood-altering drug, and it may worsen symptoms of anxiety disorders."

133

Clinical Study

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019 Arterioscler 1712-9.

6. Pasceri V, Yeh ET. A tale of two diseases: atherosclerosis and rheumatoid arthritis. Circulation. 1999;100(21):2124-6.

Thromb

Vasc

Biol.

2001;21(11):

7. Arnett DK, Evans GW, Riley WA. Arterial stiffness: a new cardiovascular risk factor? Am J Epidemiol.

1994;140(8):669-82.

12. Palinski W, Napoli C. Unraveling pleiotropic effects of statins on plaque rupture. Arterioscler Thromb Vasc Biol.

2002;22(11):1745-50.

8. Shepherd J, Cobbe SM, Ford I, Isles CG, Lorimer AR, MacFarlane PW, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. N Engl J Med. 1995;333(20):1301-7.

13. Choi M, Rolle S, Rane M, Haller H, Luft FC, Kettritz R. Extracellular signal-regulated kinase inhibition by statins inhibits neutrophil activation by ANCA. Kidney Int. 2003;63(1):96-106.

9. Vaughan CJ, Murphy MB, Buckley BM. Statins do more than just lower cholesterol. Lancet. 1996;348(9034):1079-82.

10. Ridker PM, Rifai N, Clearfield M, Downs JR, Weis SE, Miles JS, et al; Air Force/Texas Coronary Atherosclerosis Prevention Study Investigators. Measurement of C-reactive protein for the targeting of statin therapy in the primary prevention of acute coronary events. N Engl J Med. 2001;344(26):1959-65.

11. Takemoto M, Liao JK. Pleiotropic effects of 3-hydroxy3-methylglutaryl coenzyme a reductase inhibitors.

14. Kwak B, Mulhaupt F, Myit S, Mach F. Statins as a newly recognized type of immunomodulator. Nat Med. 2000;6(12):1399-402.

15. Leung BP, Sattar N, Crilly A, Prach M, McCarey DW, Payne H, et al. A novel anti-inflammatory role for simvastatin in inflammatory arthritis. J Immunol.

2003;170(3):1524-30.

16. McCarey DW, McInnes IB, Madhok R, Hampson R, Scherbakov O, Ford I, et al. Trial of Atorvastatin in Rheumatoid Arthritis (TARA): double-blind, randomised placebo-controlled trial. Lancet. 2004;363(9426):2015-21.

■■■■

American Academy of Pediatrics Urges All Families to Learn to Swim The American Academy of Pediatrics (AAP) has urged all communities to make water safety a No. 1 priority, which includes making swim lessons accessible for everyone.

"This is an essential life skill for children, teens and adults. It's an important part of the 'layers of protection' that families and communities can put in place to protect children and teens around water", says AAP President Kyle Yasuda, MD, FAAP. The AAP published updated recommendations on drowning prevention in March 2019. It recommends 'layers of protection' including: ÂÂ

All children and adults should learn to swim. Most children will be developmentally ready for formal swim lessons between ages 1 and 4. Talk with your pediatrician about when your child will be ready.

ÂÂ

Not all swimming lessons are created equal. Choose a program that meets your family and child's needs and skills and one that will ensure they have basic water safety skills.

ÂÂ

Close, constant, attentive supervision around water is important. Assign an adult 'water watcher,' who should not be distracted by a cell phone, socializing, chores, or drinking alcohol. With young children or poor swimmers, the adult should be within an arm's length, providing constant 'touch supervision'.

ÂÂ

Empty wading pools immediately after use.

ÂÂ

Pools should be surrounded by a four-sided fence, with a self-closing and self-latching gate. Research shows pool fencing can reduce drowning risk by 50%.

ÂÂ

Adults and older children should learn CPR.

ÂÂ

Everyone, children and adults, should wear US Coast Guard-approved life jackets whenever they are in open water, or on watercraft. Small children and non-swimmers should wear life jackets when they are near water and when swimming. Inflatable 'floaties' can't be relied upon to protect kids.

ÂÂ

Parents and teens should understand how using alcohol and drugs increases the risk of drowning while swimming or boating.

134

IJCP Sutra: "Eat right, exercise and get better sleep. Brisk aerobic exercises can help release brain chemicals, which can further cut out stress."

Case Report

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

Unusual Temporary Treatment for Mastoid Fistula SUBRAMANIAM VINAYAK EASWERAN*, SARVESH NAYAK†, ARPANA HEGDE‡

Abstract Postauricular mastoid fistula is a rare complication of chronic suppurative otitis media. It could also occur after ear surgery as a complication and at times as a complication of congenital cholesteatoma. Usual treatment suggested in literature is surgery by closing the defect by using temporalis muscle rotation flap. This article is an out of the box thinking to temporarily treat a patient having mastoid fistula by using a prosthesis made in the dental department using acrylic in order to snugly fit in the postauricular defect area. Such a prosthesis could be made use of when a patient experiences giddiness if and when water enters the fistula tract while bathing, or if the patient wants to postpone the surgery due to some reason.

Keywords: Postauricular mastoid fistula, complication, acrylic prosthesis

P

ostauricular cutaneous mastoid fistula is a rare condition, as rare as only about 6 cases were reported in literature.1 Mastoid fistula is a rare complication of chronic suppurative otitis media. This complication could be secondary to ear surgery, or a complication of congenital cholesteatoma.2 Usual treatment in all referred literature is surgery using:

ÂÂ

Temporalis muscle rotational flap for closure of the defect.1

ÂÂ

Fascio-cutaneo-periosteal advancement flap with Burow’s triangles.2

However, simple closure is often unsuccessful because of the necrotic skin edges.

This article is written as an out of the box thinking in the treatment of a postauricular mastoid fistula, which presented to us a case of complication of chronic suppurative otitis media.

*Dept. of ENT, Pandit General Hospital, Church Road, Sirsi, Uttara Kannada, Karnataka †Venkatesh Dental Clinic, Near Narashimha Temple, Pramankatta, Keni Road Mandi Bazar, Ankola, Karwar Dist, Karnataka ‡Dental Care Center, 1st floor, GP Center, Court Road, Sirsi, Karnataka Address for correspondence Dr Subramaniam Vinayak Easweran Dept. of ENT Pandit General Hospital Church Road, Sirsi, Uttara Kannada - 581401, Karnataka E-mail: vinoo121071@gmail.com

136

Case Report A 65-year-old lady presented to us in the ENT OPD with a complication of chronic suppurative otitis media in the form of a postauricular mastoid fistula.

She had uncontrolled diabetes and experienced giddiness while having bath as water was stimulating her labyrinth. Because of her comorbid condition and her debilitating giddiness, we tried helping her to buy time till she became fit for her surgery (which is the ideal treatment for a condition like this) by making a prosthesis that snugly fits in the fistula area and thus could help her overcome her giddiness, while having bath and preventing water entering the labyrinth.

The dentists initially approximated the depth of the sinus by measuring it using a match stick. Semi hot impression compound cake was molded over the match stick, which was inserted into the sinus. The impression was taken out and put into the bowl-containing wet dental stone (gypsum). Impression compound was removed after setting of dental stone by heating on to that impression cavity. Acrylic polymer and monomer were mixed and poured on a thin plate of acrylic over which water was poured and let to set.

After setting, the acrylic was taken out from the bowl by splitting of the set dental stone and checked for trying on the patient’s sinus cavity. Figure 1 a and b show the prosthesis mold and Figure 1c shows the prosthesis in situ.

IJCP Sutra: "Sleep problems and anxiety disorder often go hand in hand. It is important to get adequate rest. Follow a relaxing bedtime routine."

Case Report

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

Figure 1 a and b. Prosthesis mold and c. Prosthesis in situ.

Discussion We present here an unusual and temporary treatment of mastoid fistula. What makes this case a special one is that it has never been published in literature, and moreover it could be thought of as an ideal treatment for the patient who wants to buy time for surgery owing to the patient’s comorbid conditions. At the same time, it can help the patient get rid of the debilitating giddiness, which is a consequence of the complication of chronic suppurative otitis media. However, surgery to close the fistula is the mainstay treatment of such a case.

Conclusion We can keep this as a treatment option, though surgery is the main treatment. Such a treatment

could be given a thought for patients who have comorbid conditions making them unfit for surgery and have other associated symptoms with regards to the disease condition per say, giving a choice to the patient to buy time till the patient could be made fit for surgery.

References 1. Choo JC, Shaw CL, Chong Y C S. Postauricular cutaneous mastoid fistula. J Laryngol Otol. 2004;118(11): 893-4.

2. Olusesi AD, Opaluwah E. Postauricular advancement fascio-cutaneo-periosteal flap for closure of mastoid cutaneous fistula.

Otolaryngol Pol. 2014;68(5): 276-80.

■■■■

Zika Transmission Low, But WHO Warns Travelers to be Vigilant Pregnant women and couples intending to have a baby after traveling to places where Zika virus has been found should “consider the risks and possible consequences” of infection, the WHO said.

In a generally positive update on the spread of the mosquito-borne virus, which was linked to an unprecedented rise in the number of children born with unusually small heads in Brazil, the UN health agency said that Zika “persists”, but global transmission has been low since 2018.

In addition to its advice to pregnant women or those wanting to become pregnant after traveling to destinations where Zika has been identified, WHO says that male travelers should take precautions up to 3 months after they have traveled to potential areas of transmission... (UN)

Restrictive Approach to Blood Cell Transfusions Safe for Heart Surgery Patients In a recent clinical trial of higher risk patients undergoing cardiopulmonary bypass surgery, a restrictive approach to blood cell transfusions resulted in fewer transfusions without putting patients at increased risk of acute kidney injury. The results were consistent in patients with and without chronic kidney disease before surgery. The study is published online June 20, 2019 in the Journal of the American Society of Nephrology.

IJCP Sutra: "Ask your doctor or pharmacist before taking any over-the-counter medicines or herbal remedies."

137

Case Report

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

The Wide Clinical Spectrum of Raised Fetal Hemoglobin in Adults PRATIK VORA*, SAKSHI SINGH†, JEMIMA BHASKAR‡, MANISH MEHTA#, AMI TRIVEDI¥

Abstract Fetal hemoglobin (HbF) is found in infants up to 6 months. It is a normal physiological phenomenon. However in adults, in the absence of hemoglobin A (HbA) in thalassemic syndromes, HbF is raised even to 98%. However, presence of HbF does not always prevent symptoms. There is a wide clinical spectrum of disease. Some patients are asymptomatic as in delta-beta-thalassemia and hereditary persistence of fetal hemoglobin (HPFH) and some have severe symptomatic disease as in beta-thalassemia.

Keywords: Beta-thalassemia, delta-beta-thalassemia, HPFH, HbF, HbA, red cell indices

T

he thalassemic syndromes are inherited disorders of globin synthesis and present as hemolytic anemia. The reduced supply of globin causes hypochromia and microcytosis. In beta-thalassemia, there is unbalanced accumulation of alpha-chain and reduction of beta-chain. This is to some extent corrected by gamma-chain (fetal hemoglobin [HbF]). However, the clinical severity varies widely even though HbF replaces the hemoglobin A (HbA).

We are presenting two cases of raised HbF with widely varying clinical picture.

Case Reports

Case 1 A 13-year-old boy presented with history of fever for 3-4 days, associated with abdominal pain, along with anorexia, nausea and generalized fatigue since a week.

Patient’s parents also noticed icterus and yellowish discoloration of urine since 3-4 days. On examination, patient was anemic, icteric with splenomegaly.

*Second Year Resident †Third Year Resident ‡Senior Resident #HOD and Professor ¥Associate Professor Dept. of Medicine MP Shah Govt. Medical College, Jamnagar, Gujarat Address for correspondence Dr Jemima Bhaskar 404, Kings Palace, Mehul Nagar Opp. BSNL Telephone Exchange, Jamnagar - 361 006, Gujarat

138

Investigations Hemoglobin (Hb) - 10.1 g/dL, mean corpuscular volume (MCV) - 69.6 fl, platelet - 2.83 lakhs, erythrocyte sedimentation rate (ESR) - 40 mm/hr; Mentzer index 15.13, reticulocyte count - 0.6%.

Peripheral smear - microcytic hypochromic picture along with many target cells and few elliptocytes.

Hyperbilirubinemia was mainly indirect (total 5.2 mg/dL); serum glutamic pyruvic transaminase (SGPT) - 133 IU/L. USG abdomen - Splenomegaly, minimal ascites, distended gallbladder with sludge.

Viral markers - negative; Coombs test - negative; NESTROFT - positive; Hb electrophoresis - 98.7% HbF, 1.3% HbA2.

Past History Patient had blood transfusion three times in the last 6 years and his lowest Hb was 5 g/dL in 2009 when he took treatment for the first time. He was given 2 pints of packed cells on first occasion. Later on, after 1-2 years interval, he was again transfused when minimum Hb was 7 g/dL. Every time patient had indirect hyperbilirubinemia and predominance of HbF on Hb electrophoresis. Coombs and glucose-6-phosphate dehydrogenase (G6PD) was negative. Reticulocyte count was 3-6%. On further follow-up, Hb was 8-11 g/dL. On further analysis of patient’s parents: Father was diagnosed as thalassemia minor and mother was diagnosed as hereditary persistence of fetal hemoglobin (HPFH). Parents never required transfusion and since last 2 years patient had not required transfusion.

IJCP Sutra: "Eat a variety of foods from each food category, like fruits, vegetables and lean meats.

If you think you need vitamin supplements, check with your doctor first."

Case Report

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

Case 2 A 33-year-old male patient presented to OPD with chief complaint of abdominal pain in left hypochondrium, low intensity in nature, nonradiating since 12 days.

There was no complaint of nausea or vomiting or any previous blood transfusion. Patient was conscious, oriented, hemodynamically stable, nonicteric and nonanemic. On abdominal examination, mild splenomegaly without tenderness was noted.

Investigations White blood cell (WBC) - 9,400 (N62,L30,M7,E0,B0), red blood cell (RBC) - 6.09 lakhs, platelet - 2.88 lakhs, Hb - 12.4 g/dL, hematocrit - 37.5%, mean corpuscular hemoglobin (MCH) - 18.7 pg/dL, MCV - 61.6 fl/dL, mean corpuscular hemoglobin concentration (MCHC) 30.4%, red blood-cell distribution width (RDW) - 45.7%, ESR - 22/hr, reticulocyte count - 1%, Mentzer index 12.3, NESTROFT - positive. Peripheral smear showed microcytic hypochromic anemia.

Serum creatinine - 0.5 mg/dL, serum urea - 19 mg/dL, random blood sugar (RBS) - 89 mg/dL, SGPT - 54 mg/dL, lactate dehydrogenase - 193.8 mg/dL. Serum bilirubin (total - 1.2, indirect - 1.0, direct 0.2 mg/dL), viral markers - negative.

USG - Hepatosplenomegaly; liver 14.5 cm and spleen 15.3 cm.

Hb electrophoresis - 100% HbF on HPLC and capillary method.

Discussion Hemoglobin A is the major normal adult Hb. It consists of heme + globin. Globin consists of two alpha chains and two beta chains. HbF is the major hemoglobin of the fetus. It consists of two alpha chains and two gamma chains. HbA2 consists of two alpha chains and two delta chains. It accounts for 1.5-3.5% of normal adult Hb. Thalassemia is an inherited disease causing impairment of globin chain production. In thalassemias, globin chains of normal structure are produced at a decreased rate. The beta-thalassemias and their associated biochemical and molecular defects are given in Table 1.

Beta-thalassemia refers to decreased production of beta chains. This is compensated by increased production of delta chains. Hence, there is an increase in HbA2.

However, it is never more than 12%. The betathalassemias are clinically classified as beta-thalassemia major, a severe and transfusion-dependent form; betathalassemia intermedia with less severe symptoms; and beta-thalassemia minor or trait without clinical symptoms but with hematological abnormalities (Table 2). With an absence (β0) or marked decrease (β+) in beta-chain production, there is an excess of

Table 1. Beta-thalassemias and their Associated Biochemical and Molecular Defects Typical DNA defect

β-chain

δ-chain

γ-chain

HbF distribution

α: Non-α-globin imbalance

β+-thalassemia

Mutation

↓

+

+

Heterocellular

+++

β0-thalassemia

Mutation

0

+

+

Heterocellular

++++

δβ-thalassemia

Deletion

0

0

+++

Heterocellular

++

HPFH

Deletion

0 or ↓

0

++++

Pancellular

+

Table 2. Major Categories of Beta-thalassemia Syndromes Syndrome

Genotype

Clinical features

Hemoglobin pattern

β+-thalassemia

β+/β+

Thalassemia major or intermedia

↓↓ HbA, ↑↑ HbF, variable HbA2

β0-thalassemia

β0/ β0

Thalassemia major

>95% HbF, rest HbA2

δβ0-thalassemia

δβ0/δβ0

Thalassemia intermedia

100% HbF

Lepore/Lepore

Thalassemia major

85% HbF, 15% Hb Lepore

β+-thalassemia

β+/β

Thalassemia minor

HbA, ↑ HbA2, ±↑ HbF

β0-thalassemia

β0/β

Thalassemia minor

HbA, ↑ HbA2, ±↑ HbF

δβ0-thalassemia

δβ0/δβ

Thalassemia minor

HbA, 5-20% HbF, ±↓ HbA2

Lepore/β

Thalassemia minor

HbA, ↑ HbF, ↓ HbA2,10% Hb Lepore

Homozygous states

Hb Lepore Heterozygous states

Hb Lepore

IJCP Sutra: "Maintain a healthy weight and encourage good eating habits. Include plenty of fruits, vegetables and whole grains in their diet."

139

Case Report alpha chains, which precipitate and cause ineffective erythropoiesis and form toxic inclusion bodies that kill erythrocytes and cause hemolytic anemia. Thalassemias are also classified as homozygous and heterozygous states.

Clinical findings include jaundice, leg ulcers, gall stones, high output cardiac failure and splenomegaly evident in early childhood. There is a prominence of frontal bones, cheek bones and jaws due to extreme bone marrow hyperplasia, presenting with characteristic chipmunk facies.

X-rays findings of thinned cortex of long and flat bones and thickening of skull with osteoporosis (hair on end appearance) are seen. Growth is stunted. Most patients require regular transfusions due to profound anemia and iron over loading occurs.

Unlike most hemolytic diseases, the anemia is microcytic and hypochromic. In b0-thalassemia (homozygous) HbA is absent, HbF is as high as 98% and HbA2 is 2%.

In β+-thalassemia (heterozygous), HbF is 60-95%, HbA is present but HbA2 ratio to HbA is always increased.

In delta-beta-thalassemia, beta and delta chains are not produced and there is a significant increase in HbF. In the homozygous state, Hb consists only of HbF. The heterozygous state is similar to mild betathalassemia trait except that HbA2 is not increased or is even reduced and HbF is increased. Clinically, homozygous delta-beta-thalassemia behaves as a mild form of beta-thalassemia intermedia with Hb level of 10-13 g/dL, mildly thalassemic red cell indices and mild hepatosplenomegaly. The mild phenotype is the result of increased production of gamma-chain, which compensate to some degree for lack of beta chains.

HPFH - In this condition, there is persistence of HbF in adults without significant hematologic abnormalities or clinical illness.

The rise in HbF in adults presents with a wide clinical spectrum. In one end of the spectrum, in β0-thalassemia, HbF may be raised to even more than 95% with the rest HbA2 and absent HbA. This presents in childhood, clinically as homozygous β0-thalassemia major, with profound anemia, microcytic hypochromic picture in peripheral smear, red cell indices of thalassemia. Target cell, poikilocytosis, Howell-Jolly bodies and anisocytosis are seen. The reticulocyte count is less elevated than expected for degree of anemia because of destruction of erythroid precursors in the marrow. Intramedullary destruction of Hb (ineffective erythropoiesis) is markedly increased. Extramedullary erythropoiesis occurs and patients die by the third decade. The raised

140

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

gamma chains do not compensate for the lack of beta chains by improving clinical outcome.

The other clinical picture is that of delta-betathalassemia (homozygous), where HbF is again very high (even 100%). HbA is absent and HbA2 may be absent or present in normal range. But unlike β0-thalassemia major, it presents clinically as a mild form of beta-thalassemia intermedia. Patients present with above 10 g/dL, mild thalassemic indices and minimal hepatosplenomegaly. The raised gamma chains compensate to high-degree for the lack of beta chains.

At the other end of the spectrum is HPFH, where HbF is raised to nearly 100%. Hb levels are normal, red cell indices are normal and patients are asymptomatic and are apparently healthy. They are usually not diagnosed as they never need treatment and may not visit a hospital.

Both our patients had raised HbF to >98%. However, 1 patient presented with severe anemia in childhood to the extent of requiring 3 blood transfusions with a clinical picture of jaundice, splenomegaly, raised reticulocyte count, Mentzer index of 15.13 and thalassemic red cell indices, HbF 98.7%, HbA2 1.3%, absent HbA and had b0-thalassemia major.

The other patient was 33 years old; clinically there was no anemia, no icterus, mild splenomegaly, with mild thalassemic red cell indices, reticulocyte count of 1%, HbF 100%, absent HbA and HbA2. He had deltabeta-thalassemia, which presented clinically with mild symptoms of beta-thalassemia intermedia.

Conclusion The carry home message of this presentation is that although HbF is elevated in the absence of HbA after birth, all is not well. The prognosis depends on the clinical picture, which can present as β0-thalassemia in childhood with early death, but it can also present as delta-beta-thalassemia and HPFH, where they are asymptomatic and lead normal lives.

Suggested Reading 1. Harrison’s Principles of Internal Medicine. 18th Edition, Vol 1. Mc-Grawhill; 2012.

2. De Gruchy’s Clinical Haematology. 5th Edition; 2011.

3. Henry’s Clinical Diagnosis and Management Laboratory Methods. 21st Edition; 2007.

by

4. Davidson’s Principles and Practice of Medicine. 21th Edition, Churchill Livingstone; 2010.

IJCP Sutra: "Load up on fiber with foods like broccoli, peas, apples, cooked split peas and beans, whole-grain breads, cereals and pasta."

CASE REPORT

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

Bilateral Single System Ectopic Ureters with Secondary Calculi in an Adult GOPI KISHORE M*, SUHASINI G*, PRASAD PVGS*, SAINADH AV*

Abstract Bilateral single system ectopic ureter (BSSEU) is a rare entity in urology presenting typically in the pediatric age group with urinary incontinence, recurrent urinary tract infection (UTI) or ureteric obstruction. It is generally agreed that these patients require ureteric reimplantation with or without bladder augmentation depending upon bladder capacity. We herein present a case of BSSEU presenting late in adulthood with secondary ureteric calculi, which is one of its kind to be reported in literature.

It was managed endoscopically with satisfactory outcome and without a need for major reconstructive surgery.

Keywords: Ectopic ureter, secondary calculi, megaureter, hydroureteronephrosis

B

y definition, an ectopic ureter is any ureter, single or duplex, that does not enter the trigonal area of the bladder. It is more common among females and is usually associated with double collecting system. About one-fifth of ectopic ureters are associated with single system kidneys and are common in males. A rare entity of bilateral single system ectopic ureters (BSSEU) occurs and may be associated with a hypoplastic bladder and bilateral renal abnormalities.

bladder (CT-KUB, Fig. 1) revealed bilateral hydroureteronephrosis with multiple calculi in right lower ureter and single calculus in left lower ureter. Intravenous pyelogram (IVP, Fig. 2) revealed bilateral single system gross hydroureteronephrosis

We are presenting a case of BSSEU in an adult male with secondary stones, which was managed endoscopically. Case Report A 50-year-old male presented with obstructive voiding symptoms, increased frequency, dysuria, hematuria and bilateral flank pain since 2 months. General examination was unremarkable. Abdominal examination was normal except mild bladder distension. External genitalia and per rectal examination was normal. All routine investigations including kidney function tests were normal.

Ultrasonography showed bilateral moderate hydroureteronephrosis with lower ureteric calculi.

Plain computed tomography-kidney, ureter and

*Dept. of Urology ESIC SSH, Sanath Nagar, Hyderabad, Telangana Address for correspondence Dr Gopi Kishore M Dept. of Urology, ESIC SSH, Sanath Nagar, Hyderabad - 500 038, Telangana E-mail: gkmeda@yahoo.com

Figure 1. Reformatted coronal image of plain CT-KUB scan showing bilateral hydroureteronephrosis with lower ureter calculi.

IJCP Sutra: "Cut down on sugar, salt and saturated fats from meat and dairy, and cholesterol."

141

CASE REPORT

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

with multiple calculi in right ureter and one calculus in left ureter. With provisional diagnosis of bilateral megaureters with secondary stones or bilateral lower ureteric calculi with megaureters, cystourethroscopy was carried out under spinal anesthesia. Cystourethroscopy (Fig. 3) showed right

ureteric orifice just distal to bladder neck and left ureteric orifice distal to right ureteric orifice and 1 cm proximal to the veru with absent trigone and good capacity bladder. Bilateral retrograde pyelography showed bilateral single system ectopic megaureters with secondary calculi.

Definitive diagnosis of BSSEU with secondary calculi was made. Bilateral ureteric meatotomy was done up to 1 cm proximal to bladder neck using a Collins knife and stones fragmented with help of nephroscope and lithotripsy. As stone burden was high, fragmented stones in bladder were removed by percutaneous cystolithotripsy and bilateral double-J (DJ) stenting done. Postoperative recovery was uneventful. In postoperative period, the patient was totally continent and able to void freely. DJ stent was removed after 1 month and follow-up ultrasound showed decrease in hydroureteronephrosis and patient is doing well without urinary tract infection (UTI) or flank pain.

Discussion

Figure 2. Post-void IVP film showing bilateral single system hydroureteronephrosis with secondary calculi.

Right ureteric orifice Left ureteric orifice

Veru

Figure 3. The cystourethroscopic picture showing both ureteric orifices in prostatic urethra.

142

Ectopic ureters are more common in females, 80% of them drain a duplicated kidney and are frequently associated with a poorly functioning renal unit. Embryologically, ectopic ureters can arise due to abnormal timing or location of the primary ureteral budding from the mesonephric ducts. That temporospatial location will determine both the character of the ureter incorporated into the emerging bladder, as well as the development of the trigone and kidney. It is believed that, as single system ectopic ureters (SSEU) are associated with dysplastic kidneys, the affected renal units do not function appreciably.

Single system ureteral ectopia is due to cranial origin of ureteric bud from mesonephric duct, which results in delay in incorporation into the urogenital sinus and prevents growth of mesenchyme, which is necessary for development of bladder neck musculature. As there is no formation of trigone and base plate, bladder neck is wide, poorly defined and incompetent.

BSSEUs are even rarer compared to SSEU. It is possible that during development, the abnormal origin of both ureteric buds results in poor mesenchymal induction of the urogenital structures, which results in failure of normal development of the bladder and bladder neck. Both the sphincter and reservoir functions of the bladder will be severely affected.

Overall, female patients are affected twice as commonly as males, although SSEU is reported to be more common in males. Usually, BSSEU presents in infants

IJCP Sutra: "Hydrate yourself well by drinking sufficient water throughout the day."

CASE REPORT

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

or children with recurrent UTIs, urinary incontinence and a poor capacity of bladder, which requires ureteric reimplantation with or without bladder augmentation.

In males, the posterior urethra is the most common site for insertion of the ectopic ureter. Evaluation is usually by ultrasonography, renal nuclear scan, micturating cystourethrography and retrograde pyelography. IVP and magnetic resonance imaging (MRI) may be used occasionally.

Male patients with BSSEU in posterior urethra proximal to external sphincter may be continent with external sphincter control and have a good capacity bladder.

Patients with good bladder capacity may require bilateral ureteric reimplantation alone.

Our patient presented with obstructive symptoms due to stone in the right distal ureter obstructing bladder neck. As the patient presented in late adulthood with secondary stones and a good capacity bladder with normal continence, endoscopic management alone was done with ureteral meatotomy, lithotripsy and DJ stenting. Surgical management consisting of transurethral endoscopic incision of the distal ureter has previously been reported by Mathews et al. Ureteric reimplantation was not preferred as reflux in late age is not a worrying factor. However, the patient is kept on close follow-up for any late symptoms.

This is one of its kind case of BSSEU with secondary ureteric calculi presenting in adulthood. As patient

presented in late adulthood with only obstructive symptoms, major reconstructive surgery was avoided and patient was managed endoscopically.

SUGGESTED READING 1. Glassberg KI, Braren V, Duckett JW, Jacobs EC, King LR, Lebowitz RL, et al. Suggested terminology for duplex systems, ectopic ureters and ureteroceles. J Urol.

1984;132(6):1153-4.

2. Peters CA, Schlussel RN, Mendelsohn C. Ectopic ureter, ureterocele, and ureteral anomalies. In: Wein AJ, Kavoussi LR, Novick AC, Partin AW, Peters CA (Eds.).

Campbell-Walsh Urology. 10th Edition, Philadelphia: Saunders Elsevier; 2011. pp. 3236-66.

3. Keating MA. Ureteral duplication anomalies: ectopic ureters and ureteral anomalies. In: Belman BA, King LR, Kramer SA (Eds.). Clinical Pediatric Urology. 4th Edition, London: Martin Dunitz; 2002. pp. 677-733.

4. Redman JF, Lightfoot ML, Reddy PP. Bilateral single ureteral ectopia in a boy. Urology. 2002;60(3):514.

5. Mathews R, Jeffs RD, Maizels M, Palmer LS, Docimo SG. Single system ureteral ectopia in boys associated with bladder outlet obstruction. J Urol. 1999;161(4):1297-300.

6. Dange AS, Sen S, Zachariah N, Chacko J, Mammen KE. Single-system ureteral ectopia - Associated malformations and management in children lacking an orthotopic ureter.

Pediatr Surg Int. 1994;9:377-80.

7. Kumar A, Goyal NK, Trivedi S, Dwivedi US, Singh PB. Bilateral single system ectopic ureters: case report with literature review. Afr J Paediatr Surg. 2008;5(2):99-101.

■■■■

Asthma Specialists Oppose Return of Primatene Mist The recent FDA decision to put the metered-dose epinephrine inhaler Primatene Mist™ back on drugstore shelves was met with alarm by asthma specialists and respiratory health groups who warned that the move will place asthma patients at risk.

Pulled from the market in 2011 along with other asthma inhalers due to environmental concerns about their ozonedepleting chlorofluorocarbon (CFC) propellants, a CFC-free version of the drug was approved last November for over-the-counter (OTC) sale, despite objections from the American Thoracic Society (ATS), American Lung Association and other health groups, that the move could lead to suboptimal treatment and poorer asthma control if patients rely solely on the OTC medication to treat symptoms.

Three asthma specialists, writing in the Annals of the American Thoracic Society, decry a lack of transparency leading up to the FDA's decision.

Blood Biomarkers Predict Concussion Recovery Blood-based inflammation markers predicted recovery time in high school and college football players who had concussions, a small prospective study showed.

Circulating levels of interleukin-6 (IL-6) and interleukin-1 receptor antagonist (IL-1RA) were elevated 6 hours after concussion, and IL-6 levels predicted the number of days concussion symptoms persisted, reported Timothy Meier, PhD, of the Medical College of Wisconsin in Milwaukee, and co-authors in Neurology.

IJCP Sutra: "Do not think you are old. Age = 100 minus years old or age 40 = age 20 plus 20 years of experience."

143

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

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

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

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

Who is Eligible?

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

Objectives Assist heart patients belonging to economically weaker sections of the society in getting affordable and quality treatment.

Raise awareness about the fundamental right of individuals to medical treatment irrespective of their religion or economical background.

Sensitize the central and state government about the need for a National Cardiovascular Disease Control Program.

Encourage and involve key stakeholders such as other NGOs, private institutions and individual to help reduce the number of deaths due to heart disease in the country.

To promote heart care research in India.

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

Important Notes The patient must be a citizen of India with valid Voter ID Card/ Aadhaar Card/Driving License.

The patient must be needy and underprivileged, to be assessed

by Fund Committee.

The HCFI Fund reserves the right to accept/reject any application for financial assistance without assigning any reasons thereof.

The review of applications may take 4-6 weeks.

All applications are judged on merit by a Medical Advisory Board who meet every Tuesday and decide on the acceptance/rejection of applications.

The HCFI Fund is not responsible for failure of treatment/death of patient during or after the treatment has been rendered to the patient at designated hospitals.

To promote and train hands-only CPR.

Activities of the Fund Financial Assistance

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

Financial assistance is given to eligible non emergent heart patients.

Apart from its own resources, the fund raises money through donations, aid from individuals, organizations, professional bodies, associations and other philanthropic organizations, etc.

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

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

Drug Subsidy

The HCFI Fund has the right to print/publish/webcast/web post details of the patient including photos, and other details. (Under taking needs to be given to the HCFI Fund to publish the medical details so that more people can be benefitted).

The HCFI Fund does not provide assistance for any emergent heart interventions.

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

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

BPL Card (If Card holder)

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

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

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

Free Diagnostic Facility

Free Education and Employment Facility

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

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

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

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

About Heart Care Foundation of India

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

Heart Care Foundation of India was founded in 1986 as a National Charitable Trust with the basic objective of creating awareness about all aspects of health for people from all walks of life incorporating all pathies using low-cost infotainment modules under one roof.

HCFI is the only NGO in the country on whose community-based health awareness events, the Government of India has released two commemorative national stamps (Rs 1 in 1991 on Run For The Heart and Rs 6.50 in 1993 on Heart Care Festival- First Perfect Health Mela). In February 2012, Government of Rajasthan also released one Cancellation stamp for organizing the first mega health camp at Ajmer.

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

Donate Now...

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

Committee Members

Chief Patron

President

Raghu Kataria

Dr KK Aggarwal

Entrepreneur

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

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

Advisors Mukul Rohtagi Ashok Chakradhar

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

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

Rishab Soni

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

http://heartcarefoundationfund.heartcarefoundation.org

Public Health

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

2013-2014 Investigation Findings of Unexplained Acute Neurologic Illness Outbreak, Muzaffarpur, Bihar â&#x20AC;&#x201C; Brief Note

O

utbreaks of an acute neurologic illness commonly described as AES (acute encephalitis syndrome) have been reported in Muzaffarpur, Bihar since 1995; there have been several subsequent outbreaks. In most outbreaks, it was found that the illness primarily affected previously healthy young children (mostly in age-group 2-5 years), and was typically characterized by acute onset seizures and altered mental status in early morning hours, quickly deteriorating to coma and associated with high mortality. Outbreaks have occurred in the dry, hot months of May and June, and coincide with Muzaffarpurâ&#x20AC;&#x2122;s litchi harvesting season.

In the years 2013 and 2014, National Centre for Disease Control (NCDC) and partner institutions, US Centers for Disease Control and Prevention (CDC), National Vector Borne Disease Control Programme and Indian Council of Medical Research (ICMR), conducted systematic investigations of this outbreak illness with the use of four key methods: examining clinical parameters, conducting descriptive and analytic epidemiologic field studies, performing detailed laboratory testing of human biologic specimens, as well as collection and laboratory analysis of environmental specimens.

Evaluation of Infectious Etiologies Clinical parameters indicated that the majority of patients presented without prodrome or fever on admission, that cerebrospinal fluid (CSF) cytology and biochemistry were unremarkable, and that the magnetic resonance imaging (MRI) brain showed no evidence of inflammation; together these findings suggested that an infectious etiology was unlikely. Pathogen-based testing of human biologic specimens at NCDC using enzyme-linked immunosorbent assay for antibodies, polymerase chain reaction (PCR) and virus isolation techniques were negative for Japanese encephalitis virus, West Nile virus, Chandipura, enteroviruses and 11 viruses tested with a multiplex PCR platform (Herpes simplex viruses 1 and 2, human herpes viruses 6 and 7, cytomegalovirus, varicella zoster virus, Epstein-Barr

146

virus, parechovirus, adenovirus, enteroviruses and parvovirus B19). In previous years, National Institute of Virology, ICMR based Nipah testing (PCR) had also been negative. Further, human biologic specimens sent to the US CDC Pathogen Discovery Laboratory were evaluated for any novel bacterial or viral etiologies using 16s ribosomal testing, pan viral PCR, and next generation metagenomic sequencing; results indicated no evidence of an infectious etiology. Additionally, entomology studies by NCDC and previously by the Centre for Research in Medical Entomology, ICMR did not suggest either adequate density of specific vectors nor presence of antigens in them to suggest any vectorborne infectious etiology. Thus, the illness diagnosis was finally concluded to be an acute encephalopathy, and not infectious encephalitis.

The next steps in the investigation involved evaluating noninfectious etiologies of pesticide toxicity and heavy metals. Clinical and epidemiologic parameters were not consistent with pesticide or heavy metal toxicity.

The National Institute of Occupational Health (NIOH), ICMR analyzed and compared acetylcholinesterase and butyrylcholinesterase levels between biologic specimens of case-patients (affected children) and controls (well children) and found no evidence to suggest organophosphate pesticide toxicity. Specimens submitted to the US CDC National Center for Environmental Health laboratories were additionally analyzed for the presence of other metabolites of herbicides (atrazine) and organophosphates (dialkylphosphate), which yielded negative results for all tests. The NIOH also tested for evidence of pesticide residues in food grains, water, local vegetation and fruits (litchi) specimens taken from case patient homes, which again tested negative. Additionally, the US CDC laboratories tested for a battery of over 25 heavy metals and found no evidence to support heavy metal toxicity in human specimens.

The clinical study findings also revealed severe levels of hypoglycemia in the majority of casepatients, suggesting that this was an outbreak of acute hypoglycemic encephalopathy, likely due to a

IJCP Sutra: "Get regular checkups for dental, vision and hearing health: Your teeth, gums, vision and hearing have the potential to last a lifetime, if cared for properly."

Public Health

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

noninfectious agent. Timely glucose assessment and correction, which was recommended after the 2013 investigation, demonstrated encouraging response and may have, in part, explained a significant reduction in mortality observed in 2014 compared to 2013. Further, the characteristic finding of an early morning illness onset in a previously healthy child and the seasonal nature of this outbreak suggested the possibility of a seasonally available exogenous toxin which somehow acted on the child’s glucose metabolism, and to which a child might be particularly vulnerable in the early morning fasting hypoglycemia state. Clinical and epidemiologic analysis indicated that the case-patients were found more likely to be malnourished than controls (well children in the same area), which again suggested that the toxin may have an increased effect on those with depleted glycogen stores.

Similar outbreaks of hypoglycemic encephalopathy have been documented in West Africa and West Indies Islands, where the illness was found to be associated with ackee fruit ingestion, due to the presence in the ackee fruit of a naturally occurring compound called hypoglycin, which causes disruptions in glucose metabolism which result in abnormal fatty acid accumulation and severe hypoglycemia. Given that litchi belongs to the same botanical family (Sapindaceae) as the ackee fruit, and also has a natural compound called methylenecyclopropylglycine (MCPG) that is a homologue of hypoglycin, which is also known to cause a similar disruption of fatty acid/ glucose metabolism as the ackee fruit in experimental animal studies, it was decided to proceed with testing for association between the Muzaffarpur outbreak illness and these naturally occurring toxins (MCPG and hypoglycin) along four lines of investigation: 1) Evaluation of an epidemiologic association between exposure to MCPG/hypoglycin-containing fruits (litchi) and illness; 2) Assessment for the presence of hypoglycin or MCPG metabolites (MCPA or MCPF) in urine specimens of affected children; 3) Assessment of biomarkers of abnormal accumulation of fatty acids (organic urinary acids and acylcarnitines) in biologic specimens of cases and 4) Assessment for the presence of hypoglycin or MCPG in litchi specimens from the affected areas.

The epidemiologic case-control studies conducted in both years 2013 and 2014 show significant associations between visit to fruit orchard in the previous 24 hours and having illness.

Furthermore, with more detailed questioning, the 2014 case-control study further shows a significant

association between consuming litchi in previous 24 hours and having illness.

The US CDC National Center for Environmental Health laboratories evaluated and confirmed the presence of both MCPG and hypoglycin metabolites in urine specimens of case-patients and also the disruption of fatty acid metabolic function by identifying biomarkers of the same (organic acids, including· dicarboxylic acid, in urine and medium and long-chain acylcarnitines in blood) in human specimens. These abnormal findings (MCPG, hypoglycin or abnormal elevations in fatty acids) were not observed on evaluation of any specimens of controls (well children). These laboratories also detected both hypoglycin and MCPG in the aril (fruit) and seeds of litchi fruits collected from Muzaffarpur in the year 2014.

It is also noted that even in some Asian countries Vietnam and Bangladesh - outbreaks of similar unexplained illness in litchi growing regions have been reported and an ecological association of illness and litchi plantation surface proportion was established in Vietnam outbreak investigations. Also, similar outbreaks are now reported from Malda district of West Bengal, another litchi growing region. Characteristically, these outbreaks from Vietnam, Bangladesh, Malda and West Africa/West Indies present as similar acute neurological illness in very young age children described as acute onset seizures and altered mental status, usually in early morning hours, quickly deteriorating to coma and with high mortality. These outbreaks have also similarly been reported to coincide with litchi/ackee fruits harvesting season.

NCDC/CDC and PARTNER AGENCIES: COLLABORATIVE INVESTIGATIONS OF MUZAFFARPUR OUTBREAKS, 2013-2014 In 2013 and 2014, NCDC/CDC conducted hospitalbased surveillance, a field-based epidemiologic study and coordinated laboratory and environmental testing in Muzaffarpur to: ÂÂ

Examine clinical features, clinical course, management and outcomes of hospitalized cases in the selected hospitals

ÂÂ

Determine the etiology of the outbreak illness

ÂÂ

Identify risk factors for illness.

The participating tertiary care hospitals in Muzaffarpur were Shri Krishna Medical College Hospital (SKMCH) and Krishnadevi Deviprasad Kejriwal Maternity Hospital (KDKMH). The case definition utilized to

IJCP Sutra: "Stay active: Make it a daily routine to undertake something that keep you fit and active.

Let it be something that promotes strength, balance and flexibility and most importantly, something that you enjoy."

147

Public Health identify affected/ill children with the suspected outbreak illness was: A child ≤15 years admitted to a participating hospital during surveillance period of late May to mid-July with– ÂÂ

Altered mental status in the last 7 days

ÂÂ

New onset seizures in the last 7 days (excluding simple febrile seizures).

Real time data were collected for all patients admitted at SKMCH or KDKMH who met the case definition.

This included clinical history, exam, neurologic evaluation, anthropometric measures, outcome, as well as routine hospital laboratory tests, and, in a selected number of patients, electroencephalograms (EEGs) and MRIs. Specimens were collected from all patients and submitted to specialized referral laboratories, including NCDC-based virology laboratory testing, CDC-based pathogen discovery, NIOH laboratory-based pesticide exposure testing and CDC National Center for Environmental Health-based toxicological testing.

Epidemiologic and environmental investigations included field entomologic survey, as well as an epidemiologic case-control study, which included detailed examination and comparison of exposures to food, water, insects, animals, agriculture, chemicals between ill children (cases) and well children (controls).

In the case-control study, for each case enrolled in surveillance, TWO AGE-MATCHED well children (CONTROLS) were enrolled: one HOSPITAL control, who was admitted to a participating hospital without any CNS symptoms, and one COMMUNITY control, who was residing in same (year 2013) or neighboring village (year 2014), without any CNS symptoms.

Home visits and collection of standardized data on epidemiologic and environmental exposures (cases and controls) were conducted.

2013 INVESTIGATION During May 17 to July 22, 2013, a total of 133 children were admitted to the two main referral hospitals in Muzaffarpur with illnesses that met the investigation case definition. Of these, 94 (71%) patients were from Muzaffarpur; other patients were from six neighboring districts. Among the 133 patients, 71% were aged 1-5 years, 94% had generalized seizures and 93% had altered mental status.

Clinical Findings, 2013 Most (61%) patients were afebrile at admission; the case fatality rate was 44%. Among 56 patients with CSF

148

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

examined, 31 (55%) had normal cytology (white blood cell [WBC] count ≤5 mm3); 48 of 59 (81%) had normal CSF protein (<45 mg/dL), and 46 of 61 (75%) had normal CSF glucose (>45 mg/dL) levels. At admission, 20 (21%) of 94 patients had hypoglycemia (blood glucose 70 mg/dL).

Laboratory: Infectious Pathogen Testing, 2013 CSF samples were tested at NCDC for selected infectious pathogens known to cause encephalitis in the region.

Of 60 CSF specimens tested for Japanese encephalitis virus by immunoglobulin M (lgM) capture enzymelinked immunosorbent assay, 33 by PCR, and 33 by virus isolation, all were negative. Sixteen convalescent serum specimens, collected 14 days after illness onset, also were negative for Japanese encephalitis virus by lgM assay. Thirty CSF specimens examined by reverse transcription-PCR for flaviviruses and 13 examined more specifically for West Nile virus also were negative, as were 23 evaluated for Chandipura virus. Fourteen CSF specimens evaluated by PCR and virus isolation for enteroviruses did not demonstrate evidence of infection.

Subsequent infectious disease testing of approximately 40 patient specimens in the US CDC Pathogen Discovery Laboratory did not reveal any evidence of an infectious etiology on evaluation by 16s ribosomal testing for bacterial pathogens, as well as pan-viral family PCR and next generation metagenomic sequencing for viral pathogens.

Laboratory: Pesticide Testing, 2013 Evaluation of case and control blood specimens at NIOH for acetylcholinesterase and butyrylcholinesterase levels to assess for the possibility of organophosphate poisoning did not indicate any evidence of poisoning by this agent. Additionally, NIOH scientists evaluated food, grains and water specimens collected from the homes of over 10 case patients for pesticide residues of over 29 agents; these test results were also negative.

Epidemiologic Findings, 2013 Analysis of risk factors for death among 94 affected children showed that low blood glucose at admission was more common among those who died (odds ratio [OR] = 2.6; 95% confidence interval [CI] = 1.0-7.2). A casecontrol study enrolled 101 case-patients and 202 agematched controls, 101 from the hospital and 101 from the community. Ill children had spent a greater amount of time in agricultural fields or orchards (matched OR = 2.6; CI = 1.2-5.2) than controls. Anthropometric

IJCP Sutra: "Stay updated with immunizations and screenings - Get a preventive screening done before various age-related disease strike."

Public Health

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

data on 24 patients suggested that younger patients (those aged <5 years) were more likely to have wasting (>2 standard deviations below the median weight for height of the reference population) than controls in the same age group (p = 0.03).

team. Among the patients, 213 (55%) were male, the median age was 4 years (range = 6 months-14 years) and 280 (72%) were aged 1-5 years. Most patients were from Muzaffarpur district (70%), although patients also were reported from six surrounding districts. As in previous years, clustering of cases was not observed; the illness of each affected child appeared to be an isolated case in various villages (approximate population per village = 1,000). The outbreak peaked in mid-June, with 147 cases reported during June 8-14, 2014. The number of cases declined significantly after the onset of monsoon rains on June 21, 2014 (Fig. 1).

2014 INVESTIGATION Building on the 2013 findings, NCDC and CDC again investigated the outbreak in 2014, using: 1) facilitybased clinical surveillance; 2) epidemiologic case-control and environmental studies to examine risk factors for illness, including toxin exposures and nutritional indices and 3) comprehensive laboratory evaluation of patient specimens and environmental samples to search for infectious pathogens as well as selected pesticides, heavy metals and naturally occurring plant or fruit toxins. Suspected patients were promptly tested for hypoglycemia on arrival at the hospital, before being given any treatment. Patients admitted with the suspected outbreak illness were recommended to receive immediate intravenous dextrose therapy.

Caregivers reported that affected children were previously healthy and experienced an acute onset of convulsions, often between 4:00 am and 8:00 am, frequently followed by a decreased level of consciousness. Of 345 patients with recorded data, 324 (94%) had seizures on admission and 267 (77%) had altered mental status. Of 357 patients with body temperature measured on admission, 219 (61%) were afebrile (≤99.5°F [≤37.5°C]). The case-fatality rate was 31%.

Clinical Investigation Findings: 2014

Of 62 patients with CSF collected for analysis, 52 (84%) had normal WBC counts, 58 (94%) had normal protein and 49 (79%) had normal glucose levels. Of 327 patients with blood glucose measurement on admission, the median blood glucose level was 48 mg/dL and

During May 26 to July 17, 2014, a total of 390 patients admitted to the two referral hospitals in Muzaffarpur with illnesses that met the same case definition used in 2013 were evaluated by the NCDC/CDC investigation 30

Case-patients Died

25

Number

20

15

10

5

17-Jul-14

15-Jul-14

13-Jul-14

11-Jul-14

9-Jul-14

7-Jul-14

5-Jul-14

3-Jul-14

1-Jul-14

29-Jun-14

27-Jun-14

25-Jun-14

23-Jun-14

21-Jun-14

19-Jun-14

17-Jun-14

15-Jun-14

13-Jun-14

11-Jun-14

9-Jun-14

7-Jun-14

5-Jun-14

3-Jun-14

1-Jun-14

30-May-14

28-May-14

26-May-14

0

Date of admission

Figure 1. Epidemic curve of patients with acute neurologic illness, Muzaffarpur (2014).

IJCP Sutra: "Eat well: A well-balanced healthy diet when combined with moderate physical activity can be the key to healthy aging."

149

Public Health

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

Cases (N = 104)

Controls (N = 208)

mOR (95% Cl)

Ate litchi*

67/103 (65%)

98/204 (48%)

2.1 (1.2-3.5)

Ate litchi from ground*

30/90 (33%)

31/136 (23%)

1.7 (0.9-3.4)

Ate rotten litchi*

23/88 (26%)

19/130 (15%)

2.4 (1.0-5.5)

Additionally, case specimens submitted to CDC National Center for Environmental Health for atrazine (herbicide) and dialkylphosphate (organophosphate) metabolites were also negative. Evaluation for food, grains, water, litchi specimens collected from the homes of case patients for pesticide residues again tested negative. Additionally, specimens of 80 patients tested at CDC did not reveal any evidence of elevated levels of >25 metals in blood and urine of 80 cases, including lead, mercury, arsenic, tin and iodine.

Visited fruit orchard*

52/100 (52%)

62/195 (32%)

2.9 (1.6-5.1)

Urinary Organic Acids and Acylcarnitines (to Assess for Abnormal Accumulation of Fatty Acids), 2014

Parent visited fruit orchard*

29/95 (31%)

39/198 (20%)

1.8 (1.0-3.1)

Emory University USA analysis of plasma from 80 cases and urine from 75 cases showed approximately 90% had abnormal profiles of urine organic acids and approximately 90% had abnormal profiles of plasma acyl carnitines. These findings indicate abnormal disruption of metabolic function and fatty acid metabolism that match well with expectations from the proposed mechanisms of hypoglycin A and MCPG. Analysis of 19 of control urine samples (2013) have been analyzed for urine organic acids with 17 being normal or essentially normal and 2 showing trace amounts of acylglycines - not elevated to the magnitude found in cases.

Epidemiologic Findings, 2014 Key risk factors

171 (52%) and 204 (62%) patients had glucose levels of ≤50 mg/dL and ≤70 mg/dL, respectively. Brain MRI of 16 patients selected at random revealed no focal abnormalities or changes suggestive of inflammation.

EEG in 30 cases demonstrated findings consistent with generalized encephalopathy.

Exposures that were examined, but not associated with illness ÂÂ

Peel litchi with mouth, bite litchi seed†, eat litchi seed†, chew litchi seed†, eat unripe litchi†, eat litchi peel†

ÂÂ

Mother or father work in litchi orchard

ÂÂ

Other seasonal fruits, vegetables, nuts, herbs

ÂÂ

Drinking water source (pump, surface, piped)

ÂÂ

Exposure to insecticides† or chemicals† sprayed in and around house or nearby fields/orchards (each asked separately)

ÂÂ

Exposure to medications†, medicines.†

†<5%

aspirin†, traditional

cases or controls reported exposure.

Laboratory: Infectious Pathogen Testing, 2014 Laboratory diagnostic testing at NCDC of 17 CSF specimens for Japanese encephalitis virus and West Nile virus by PCR was negative. Additionally, evaluation of 12 CSF specimens with a multiplex PCR platform assay with the capacity to detect 11 viruses* also was negative.

Laboratory: Pesticide, Herbicide, Heavy Metal Testing, 2014 Specimens submitted to NIOH indicated no significant difference detected in RBC acetyl and butyryl cholinesterase levels between cases and controls.

150

Laboratory: CDC Lab Analysis of Urine for Toxins (Metabolites of Hypoglycin and MCPG), 2014 The urine metabolites of hypoglycin A and MCPG were measured by isotope-dilution followed by liquid chromatographic separation and mass spectrometric detection. The assay’s analytical range was linearly proportional (R > 0.99) from the lower limit of detection (LOO) of 0.1-20 µg/mL. A set of 96 individual human urine samples were commercially obtained from Tennessee Blood Services (Memphis, TN, USA) and found to be below the assay’s LOO when analyzed.

Metabolites of both hypoglycin A and MCPG were identified in urine samples from cases. Of the 72 case samples from 2014 that had adequate volume for analysis, 65% had detectable levels of either metabolite of hypoglycin A (MCPA) or metabolite of MCPG (MCPF). Specifically, 65% had detectable levels of the metabolite of hypoglycin A (MCPA) and 46% had detectable levels of the metabolite of MCPG (MCPF).

All but one of the samples with detectable levels of the metabolite of MCPG also had detectable levels of the metabolite of hypoglycin A. All 35 control urine samples from 2013 had no detectable levels of metabolites of hypoglycin A or MCPG.

IJCP Sutra: "Stay mentally active: Maintain a good amount of mental activity in old age to counter dementia and cognitive impairment that come with aging."

Public Health

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

Laboratory Testing: CDC Lab Analysis of Litchi Fruit

1 ppm and 10 ppm error, respectively, on a Thermo QExactive mass spectrometer.

Litchi fruits were collected from orchards in four blocks of Muzaffarpur, Musahari, Motipur, Bochahan and Minapur. Both Shahi and Chinese variety fruits were collected, and in each fruit variety, samples of unripe, ripe, fallen and rotten fruits were collected. Thus far, at the CDC National Center for Environmental Health laboratory, unripe litchis and ripe litchis collected from three blocks of Muzaffarpur district (Musahari, Motipur and Bochahan) have been tested.

Using high resolution mass spectrometry, the labs analyzed unripe and ripe fruit samples from the following blocks: Bochahan, Musahari and Motipur.

For hypoglycin A, in both ripe and unripe fruit, mass spectrometry analysis was consistent with the presence of hypoglycin A in seed and aril portions of fruit from each of the blocks. For MCPG, in both ripe and unripe fruit, the current mass spectrometry analysis (without isotopically labeled standards) was not sufficiently informative to detect or rule out the presence of MCPG in seed or aril portions of fruit. When isotopically labeled standards are available, labs will be able to complete these analyses and quantify the amounts of toxin(s) present. Similar qualitative work conducted on these litchis at the USDA laboratory has also identified hypoglycin A as well as suspected MCPG in the aril of the litchi fruit (unripe and ripe specimens, of both Shahi and Chinese varieties).

In each instance, homogenized extracts of litchi fruits were analyzed by liquid chromatographic separation and high-resolution mass spectrometric detection.

A readily available hypoglycin A standard was provided by colleagues at United States Department of Agriculture (USDA) and used to analyze the highresolution data obtained from the fruit. Precursor and product accurate mass spectra were obtained within

Recommendations A. Reduce Mortality Recommendations 1

Rapid assessment and correction of hypoglycemia zz Through Information Education and Communication (IEC ) and sensitization workshops - Increase awareness among community, field level health workers (ASHAs, Balwadi/Anganwadi workers, Auxiliary Nurse Midwives, Multipurpose workers, School health staff, etc.) and health staff at Primary Health Centers (PHCs)/Commercial Health Centers (CHCs) referral treatment centers on - symptoms of this illness for early detection, - about availability of free ambulatory services for early transportation, - about availability of facilities for rapid assessment and correction of glucose at nearest government health facility as well as - about availability of specialized treatment facilities at identified referral centers for early lifesaving interventions. zz Provision of adequate numbers of glucometers to all PHCs/CHCs/referral treatment centers for timely detection of low blood glucose. zz Train PHCs/CHCs/referral treatment centers staff on assessment of glucose using glucometer in children presenting with history of seizures and/or altered sensorium. zz Provide and train staff of PHCs/CHCs/referral treatment centers on protocol for correction of hypoglycemia in children with suspected outbreak illness/altered sensorium.

2.

Strengthen diagnostic and critical care capacity at all levels of health care zz As characteristically most cases report sickness in early morning hours, availability of a trained medical doctor during night in the outbreak season months of May to July at all PHCs/CHCs in the district is essential for early detection and management of cases. zz Provide and train staff of PHCs and CHCs on protocol for first-line of lifesaving health care. zz Strengthen diagnostic facilities at all identified referral treatment centers for timely and appropriate diagnosis

Strengthen laboratory facilities for electrolytes, liver function tests, CSF cytology/biochemistry and bacteriology tests

Post adequate number of trained pathologists/laboratory technicians for round the clock specimen collection, testing and reporting

Provide adequate numbers of pulse oximeters

Provide facilities of EEG and post EEG trained technicians

IJCP Sutra: "Sleep well: Many elderly people face problems with maintaining a healthy sleep cycle. Insomnia and daytime sleepiness in excess are common complaints, talk to your health care provider about such issues."

151

Public Health

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

Provide facilities of CT scans and MRI brain and post trained Radiologists/Technicians

Encourage collecting biopsy specimens and histopathology testing to confirm a tissue diagnosis of encephalopathy.

zz Strengthen specialized manpower for assessment and treatment of cases

Post adequate number of pediatricians at each of the identified referral treatment centers to handle increased case load during outbreak season

Short-term deputation of a neurologist and a critical care specialist during outbreak season

Provide treatment guidelines and train pediatricians of the identified referral treatment centres on this treatment protocol

Provide training in critical care to pediatricians of the identified referral treatment centers

Purpose: Reduce Illness Recommendations 3

Through IEC: Increase awareness among community on providing at night-time a full meal of home-made complex and low glycemic index carbohydrate (whole intact grains - such as barley and oats); this would help maintain a stable postprandial blood glucose and possibly minimize risk of early morning fasting hypoglycemia.

4

Improve general nutritional status: Undertake projects to reduce malnutrition among young children, especially the rural children of low socioeconomic status.

5.

Considering the finding of detection of hypoglycin and MCPG (natural hypoglycemic compounds known to be present in fruits of litchi family) metabolites in urine specimens of a large proportion of case-patients, it would be advisable to make efforts by IEC to minimize consumption of litchi fruits among young children in rural areas of affected district, pending further investigations in this regards.

■■■■

FDA Approves New Formulation of Tiopronin for Cystinuria The US FDA has approved an enteric-coated delayed-release formulation of tiopronin for treatment of cystinuria, a rare inherited disorder that causes an increase in cystine levels in the urine, leading to recurring cystine kidney stones. Tiopronin tablets can be taken with or without food, "an advancement over the original formulation, which has limiting food restrictions, and also provides the potential to reduce the number of tablets necessary to manage cystinuria," Eric Dube, PhD, Chief Executive Officer of Retrophin, said in a news release... (Medscape)

Low LDL Cholesterol and Hemorrhagic Stroke Lower levels of low-density lipoprotein (LDL) cholesterol were tied to a higher risk of intracerebral hemorrhage (ICH), an epidemiological study in northern China reported.

People with LDL cholesterol concentrations under 70 mg/dL had a significantly higher risk of developing hemorrhagic stroke than people with LDL levels from 70 through 99 mg/dL, reported Xiang Gao, MD, PhD, of Pennsylvania State University in University Park and co-authors. The findings are published in the journal Neurology.

Heart Defect-Cancer Link Present Already in Youth The association between congenital heart disease (CHD) and cancer is observed in young people too, and it's not just from radiation exposure, researchers found. People with CHD included in a Swedish registry showed more than double the risk of cancer compared with healthy controls when followed up to age 41 (1.9% vs 0.9%, HR 2.24, 95% CI 2.01-2.48), according to a report published online in JAMA Network Open.

"This finding suggests that particular attention should be paid to early warning signs of cancer and promotion of a healthy lifestyle," said the investigators led by Zacharias Mandalenakis, MD, PhD, of the University of Gothenburg, Sweden.

152

IJCP Sutra: " Eat less and enjoy your food by eating slowly".

2019

HCFI Consensus Statement

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

Patient-Doctor Relationship KK Aggarwal, Amarinder Singh Malhi, Ankit Om, Girish Tyagi, Ira Gupta, Sanchita Sharma, Sumedh, Vijay Kumar, Vivek Dixit

M

edicine has undergone tremendous advances, including in India. Nevertheless, there continues to be a wide gap in the availability of health care service in the country. Medial tourism is rapidly growing in India, but on the flip side of it, health care, including essential health care, is still out of reach for many in the country. India has a shortage of doctors and nurses; lack of infrastructure coupled with quality and affordable health care create further hurdles in universal health care. However, the issue which has recently hit the headlines is the deteriorating doctor-patient relationship. This erosion in trust is disheartening and needs to be urgently restored.

A Round Table was organised on the eve of Doctor’s Day, 30th June, 2019 to discuss the current scenario of health care system in India and give some suggestions and ways to improve it.

There are four types of patients: Ignorant, informed, empowered and enlightened. There has been a rapid shift from ignorance to enlightenment in the society.

More and more patients want more time from the doctor and want to be a part of shared decision making.

But this is incompatible with the present inadequate infrastructure.

Today a doctor spends less than 4 minutes per patient and most of this time is spent on explaining the deficiencies in infrastructure or non-medical counselling. The answer is posting counsellors in the establishments apart from improving the infrastructure.

The Central Government has rightly removed health services from Consumer Protection Act, but should have considered specifically excluding it.

Once a person has done MBBS, he is a qualified fullfledged doctor, then why do we call them junior doctors, trainee doctors or residents? All post-MBBS doctors up to the age of 40 should be called young doctors and not juniors for resident doctors.

One should differentiate emergent from non-emergent care.

The primary job of a doctor is to alleviate the pain and sufferings of a person without commercialising it. This is also the fundamental duty of the government under Article 21. Even in the UK, in non-emergent care, the

154

waiting time can be in years, but emergent care must be given without delay. All government hospitals in India should provide emergent care to all coming for the care and if no bed is available, they should be shifted to empanelled private sector with billing to the government under the respective Ayushman Bharat scheme.

To make emergent health care affordable, government should also come out with National lists of essential medicines, investigations, devices, reagents, disposables and equipments and they should be price capped.

One should remember that doctors are service providers and not service generators. They should not be made scapegoats for administrative errors, negligence or faulty treatment.

No antibiotic should be allowed to be prescribed by non-MBBS doctor.

There should be a transparent redressal mechanism for patients in every district.

Public Health Services should be added in the concurrent list so that there is a proper State-Centre coordination.

Medical Council of India (MCI)-Indian Medical Association (IMA) submitted Jacob Mathew guidelines, Parmanand Katara case guidelines and guidelines for MCI Ethics Regulation 8.6 should be immediately implemented by the Health Ministry.

The government and/or the police should put up a board (like the vigilance notice) in every medical establishment informing about the law against medical violence.

The time has come to debate to shift from Bolam’s consent to informed consent, including the consent for unexpected and uninformed complications and chances of sudden death in every treatment.

One should remember that quality and quantity are inversely proportional to each other. More the number of patients seen in one hour, less will be the quality of services.

The government policy of refusing to take outside delivered newborns; patient on ventilator, BiPAP (bilevel positive airway pressure) or cPAP (continuous positive airway pressure); patients on dialysis, patients for chemotherapy or patients needing terminal care should be abolished.

IJCP Sutra: "Fill half your plate with fruit and vegetables."

HCFI Consensus Statement

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

List of Authors Name

Designation

Dr KK Aggarwal

President, Heart Care Foundation of India (HCFI), New Delhi

Dr Amarinder Singh Malhi

President, RDA, AIIMS, New Delhi

Dr Ankit Om

Chairman, URDA, Delhi

Dr Girish Tyagi

President, Delhi Medical Association, New Delhi

Ms Ira Gupta

Legal Advisor, HCFI, New Delhi

Dr Sanchita Sharma

General Physician, New Delhi

Dr Sumedh

President, FORDA, New Delhi

Dr Vijay Kumar

Professor, Dept. of Orthopedics, AIIMS, New Delhi

Dr Vivek Dixit

Scientist III, AIIMS, New Delhi ■■■■

More Than a Million People to be Vaccinated in Phase 2 of Cholera Vaccination Campaign in the DRC Phase 2 of the biggest ever oral vaccination campaign against cholera took place from 3 to 8 July 2019 in 15 health districts in the four central provinces of the DRC - Kasaï, Kasaï Oriental, Lomami and Sankuru. The second dose of vaccine confers lasting immunity against cholera, and was targeted at 1,235,972 people over 1 year of age. The 5-day, door-to-door campaign involved 2,632 vaccinators recruited mainly from local communities, who administered the oral cholera vaccine, filled in vaccination cards and tally sheets and compiled a daily summary of the teams’ progress. “This cholera vaccination campaign marks the intensification of our response in the DRC,” said Dr Matshidiso Moeti, WHO Regional Director for Africa… (WHO)

FDA Approves New Treatment for Refractory Multiple Myeloma The US FDA granted accelerated approval to selinexor tablets in combination with the corticosteroid dexamethasone for the treatment of adult patients with relapsed refractory multiple myeloma (RRMM) who have received at least four prior therapies and whose disease is resistant to several other forms of treatment, including at least two proteasome inhibitors, at least two immunomodulatory agents and an anti-CD38 monoclonal antibody.

Efficacy was evaluated in 83 patients with RRMM who were treated with selinexor in combination with dexamethasone. At the end of the study, the overall response rate was measured at 25.3%, the median time to first response was 4 weeks, with a range of 1-10 weeks and the median duration of response was 3.8 months… (FDA)

Keto-like Diet may Improve Cognition in MCI, Early Alzheimer's A ketogenic diet may boost cognition in older adults who have early signs of dementia, preliminary research suggests.

Investigators at the Johns Hopkins University School of Medicine, Baltimore, Maryland, found that when older adults with mild cognitive impairment switched their diet to a low-carbohydrate, high-fat ketogenic diet, they experienced modest improvement in memory, as measured by a standardized test. The study was published in the Journal of Alzheimer's Disease.

IJCP Sutra: "Avoid oversized portions, which can cause weight gain."

155

HCFI Consensus Statement

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

HCFI Round Table on Health and Wellness on the Interpretation of the Word “Supplied By” in Clause 23 of Schedule K of Drugs and Cosmetics Act/Rules KK Aggarwal, Anil Khaitan, Balbir Verma, Bejon Kumar Misra, BR Sikri, Ganesh Mani, Girdhar J Gyani, Ira Gupta, KK Kalra, Meenakshi Datta Ghosh, NV Kamat, PP Sharma, Prachi Garg, Rajiv Nath, Saurabh Aggarwal, Prafull Sheth

Consensus Sutra: ‘Supplied’ to be read as ‘dispensed or distributed’ in Clause 23 in Schedule K of the Drugs and Cosmetics Act & Rules.

T

he Drugs and Cosmetics Act & Rules regulate the import, manufacture and distribution of the drugs in the country. Some drugs have been mentioned in Schedule E1, G, H, H1, X of the Drugs and Cosmetics Rules, 1945, which cannot be sold or purchased without proper license; they are commonly known as Scheduled Drugs. All Scheduled Drugs cannot be purchased by anybody without prescription of the registered medical practitioner. The various provisions relating to licence, sale, manufacture, etc., of the Scheduled Drugs are enumerated in Chapter IV of the Drugs and Cosmetics Rules, 1945.

However, there is an exception to the above i.e., Rule 123 of the Drugs and Cosmetics Rules, 1945 which provides that the provisions of Chapter IV of the Drugs and Cosmetics Rules, 1945 are not applicable to drugs mentioned in Schedule K to the extent specified in Schedule K of the Drugs and Cosmetics Rules, 1945.

In Schedule K of the Drugs and Cosmetics Rules, 1945 there is one Clause 23 as per which Drugs supplied

by Multipurpose Workers attached to Primary Health Centres/Sub-Centres, Community Health Volunteers under the Rural Health Scheme, Nurses, Auxiliary Nurse, Midwives and Lady Health Visitors attached to Urban Family Welfare Centres/Primary Health Centres/ Sub-Centres and Anganwadi Workers are exempted from the provisions of Chapter IV of the Act and the Rules there under which require them to be covered by a sale licence, provided the drugs are supplied under the Health or Family Welfare Programme of the Central or State Government.

Time and again there has been lot of debate as to the interpretation of Clause 23 of Schedule K of the

156

Drugs and Cosmetics Rules, 1945 as the word used in Clause 23 is ‘Supplied’ as firstly the multipurpose workers cannot supply any drugs as they are not registered medical practitioner and secondly, if they are supplying the drugs, then the patient has to pay relevant prevailing tax on the price of the drugs.

So, to understand the interpretation of the word “Supplied” in Clause 23 of the Schedule K of the Drugs and Cosmetics Act & Rules, Heart Care Foundation of India (HCFI) Round Table on Health and Wellness: Building Consensus discussed this issue in its Round Table meeting. After numerous discussions and deliberations, HCFI Round Table on Health and Wellness came out with its consensus statement, which is reproduced hereunder: ÂÂ

The HCFI Round Table on Health and Wellness: Building Consensus was held on 21st June 2019 at 4 pm, at the PHD Chambers of Commerce and Industry, PHD House, Siri Fort Institutional Area, August Kranti Marg, New Delhi - 110016 on the subject “Interpretation of the word ‘supplied by’ in Clause 23 in Schedule K of the Drugs and Cosmetics Act & Rules”.

The following consensus was made: ÂÂ

Under the Clause 23 in Schedule K, of the Drugs and Cosmetics Act, 1940, the health care workers have been empowered to give malaria drugs (by Malaria workers); gentamicin and methergine (by Asha workers), etc.

What is Clause 23?

“Drugs supplied by Multipurpose Workers attached to Primary Health Centres/Sub-Centres: (i) Community

IJCP Sutra: "Use the right healthy fats - from roasted nuts and avocados to olive, canola, soybean and other oils."

HCFI Consensus Statement

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

A physician should not run an open shop for sale of medicine or for dispensing prescriptions prescribed by doctors other than himself or for sale of medical or surgical appliances. (The word dispensing here is synonymous with prescribing and dispensing).

Health Volunteers under the Rural Health Scheme; (ii) Nurses, Auxiliary Nurse, Midwives and Lady Health Visitors attached to Urban Family Welfare Centres/Primary Health Centres/Sub-Centres and (iii) Anganwadi Workers.

Exemptions: The provisions of Chapter IV of the Act and the Rules there under which require them to be covered by a sale licence, provided the drugs are supplied under the Health or Family Welfare Programme of the Central or State Government.

ÂÂ

Clause 3.7.1 of the Indian Medical Council (Professional Conduct, Etiquettes and Ethics) Regulations, 2002 provides that: 3.7.1 “A physician shall clearly display his fees and other charges on the board of his chamber and/or the hospitals he is visiting. The prescription should also make clear if the Physician himself dispensed any medicine.

(The word dispensed here is synonymous with supplied).

ÂÂ

Non-Schedule Drugs i.e., drugs other than drugs mentioned in Schedule H, H1, X (for Modern Systems of Medicine), and Schedule E for (Indian Systems of Medicine), of the Drugs and Cosmetics Act & Rules requires no licence to sell or prescribe.

ÂÂ

Essential Commodities Act, 1955: Any State Government has the powers to control production, supply, distribution of essential commodities including drugs as specified in Clause (b) of Section 3 of the Drugs and Cosmetics Act, 1940.

What was the Consensus?

“In Clause 23 of Schedule K in the Drugs and Cosmetics Act, 1940, (i) the word ‘supplied’ should be read as synonymous with ‘dispensed’ and/or ‘distributed’.”

Basis of interpretation ÂÂ

ÂÂ

Rule 123 of Drugs and Cosmetics Rules, 1945: “The drugs specified in Schedule K shall be exempted from the provisions of Chapter IV of the Act and the Rules made there under, to the extent and subject to the conditions specified in that schedule.”

Under Medical Council of India Code of Ethics Regulations Clause 6.3: “Running an open shop (Dispensing of Drugs and Appliances by Physicians):

List of Authors Name

Designation

Dr KK Aggarwal

President, Heart Care Foundation of India (HCFI), New Delhi

Mr Anil Khaitan

Immediate Former President, PHD CCI, New Delhi

Ms Balbir Verma Mr Bejon Kumar Misra

Founder, Consumer Online Foundation, New Delhi

Mr BR Sikri

Chairman, Indian Pharmaceutical Congress (IPC)

Dr Ganesh Mani

Senior Cardiothoracic Surgeon, President-IMA, New Delhi Branch

Dr Girdhar J Gyani

Director General, Association of Healthcare Providers India (AHPI), New Delhi

Ms Ira Gupta

Legal Advisor, HCFI, New Delhi

Dr KK Kalra

Advisor, AHPI, New Delhi

Ms Meenakshi Datta Ghosh

Former Secretary, Government of India and Principal Adviser (Health), Planning Commission

Dr NV Kamat

Public Health, Former DHS, Delhi Govt.

Mr PP Sharma Dr (Maj) Prachi Garg

Secy, IMA, New Delhi Branch

Mr Rajiv Nath

Forum Coordinator, AiMeD

Mr Saurabh Aggarwal

Director, HCFI, New Delhi

Mr Prafull Sheth

IJCP Sutra: "Limit consumption of food high in trans fats and sugar."

157

HCFI Consensus Statement

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

HCFI Expert Round Table on Off-label Use of Drugs, Disposables and Devices KK Aggarwal, Manju Mani, Chander Prakash, Ahmed Quraishi, AK Grover, Anil Goyal, Anita Kant, Ashwani Dalmiya, B Jena, CM Bhagat, Ganesh Mani, Girdhar J Gyani, Girish Tyagi, Gurpreet Singh, Ira Gupta, KK Kalra, Kamal Parwal, NK Bhatia, NV Kamat, Nilesh Aggarwal, OP Yadava, Prachi Garg, Rajiv Nath, Ramesh Dutta, Sanchita Sharma, Saurabh Aggarwal, Shubnum Singh, Sonia Malik, Sundip Mishra, Veena Aggarwal, Vinod Sharma

O

ff-label use means that the particular drug is used for an indication that is not otherwise approved by the regulatory authority, which is the Drug Controller General of India (DCGI) in India, and is not included in the package insert or label carrying instructions about indications, contraindications and dosing and other instructions. Off-label use of drugs is common in clinical practice all over the world.

The US Food and Drug Administration (FDA) allows the promotion of off-label use of drugs when there is strong supporting evidence on the safety and efficacy of such use. But, the benefits and risks of such use for an individual patient must be balanced before the drug is prescribed for an off-label use and the onus of responsibility lies with the doctor. Despite the widely prevalent practice, there is no clear guideline on the offlabel use of drugs in India.

Hence, there is a need for a policy, which allows the off-label use of drugs for which there exists high quality scientific evidence.

Towards this end, an Expert Round Table on Off-label Use of Drugs, Disposables and Devices was organized

by Heart Care Foundation of India (HCFI) to build a consensus around this issue and send recommendations to the regulatory authorities to formulate a guideline on off-label use of drugs in the country.

HCFI Expert Round Table Sutra “In absence of any unethical considerations or a safety issue AND in presence of strong international or national scientific evidence; off-label use in other country; guideline or consensus statement; prevalent use in the clinical practice WITH no reported side effects under PvPI and the drug is not under RISK MAP category, THEN the use of the available DCGI approved drug (including medical devices and disposables) is justified for off-label indications under implied consent. In all other situations, one needs to take an informed consent.”

158

Definition of off-label use of drugs, disposables and devices Off-label use of drugs is the use of pharmaceutical drugs (drug, device, disposable) for an unapproved indication or in an unapproved age group, dosage or route of administration.

Marketing of pharmaceuticals for off-label use is usually prohibited. But, both prescription drugs and over-the-counter (OTC) drugs can be used in off-label ways, although most studies of off-label use focus on prescription drugs.

Off-label use is generally considered legal across the world unless it violates ethical guidelines or safety regulations.

More than 50% of all drugs are prescribed off-label based on available scientific and safety evidence and amongst psychiatrists and children, the number is even higher.

Need for the policy In the matter of Balram Prasad vs. Kunal Saha & Ors on 24 October, 2013, the Apex Court said “73. ……….. In fact punitive damages are routinely awarded in medical negligence cases in western countries for reckless and reprehensible act by the doctors or hospitals in order to send a deterrent message to other members of the medical community. In a similar case, the Court of Appeals in South Carolina in Welch Vs. Epstein [31] held that a neurosurgeon is guilty for reckless therapy after he used a drug in clear disregard to the warning given by the drug manufacturer causing the death of a patient. This Court has categorically held that the injection Depomedrol used at the rate of 80 mg twice daily by Dr Sukumar Mukherjee was in clear violation of the manufacturer’s warning and recommendation and admittedly, the instruction regarding direction for use of the medicine had not been followed in the instant case. This Court has also made it clear that the excessive use of the medicine by the doctor was out of sheer ignorance of basic hazards relating

IJCP Sutra: "Choose healthy fats. Use fat-free or low-fat milk and/or dairy products."

HCFI Consensus Statement

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

to the use of steroids as also lack of judgment. No doctor has the right to use the drug beyond the maximum recommended dose.”

Existent Government Policy As per the reply received by HCFI to a Right to Information (RTI) filed HCFI/March/2019/042 dated 18th March 2019, the Central Drugs Standard Control Organization (CDSCO) vide reply Z-28020/233/2019DC dated 3rd May 2019 replied as under “Medical devices notified under Drugs and Cosmetics Act, 1940 are regulated as per the provisions of Medical Devices Rules, 2017. As per rule 44 (k) of Medical Devices Rules, 2017, if the device is intended for single use, it should be labeled appropriately. Further there is mention in Medical Devices Rules to label the device appropriately if the device is intended for single use.

Legal implications when there is no policy In the present scenario, we need to protect ourselves from the legal risks. Even if there is scientific evidence showing the beneficial action of the off-label use of a drug, the first step should be to find an answer to counter the judgment to safeguard ourselves. All Supreme Court judgments are guidelines, till they are made into law. Once they become a law, they cannot be challenged. ÂÂ

Source of Law: The main sources of law in India are the Constitution, statutes (legislation), customary law and case law. Statutes are enacted

by Parliament, State legislatures and Union Territory legislatures. Besides, there is a vast body of laws known as subordinate legislation in the form of rules, regulations as well as byelaws made

by Central/State governments and local authorities like municipal corporations, municipalities, gram panchayats and other local bodies. This subordinate legislation is made under the authority conferred or delegated either by Parliament or State or Union Territory legislatures concerned. Judicial decisions of superior courts like Supreme Court and High Courts are important sources of law. Decisions of Supreme Court are binding on all courts within the territory of India. Local customs and conventions which are not against statute, morality, etc., are also recognized and taken into account by courts while administering justice in certain spheres (https:// archive.india.gov.in/citizen/lawnorder.php?id=6).

ÂÂ

When there is a law, rule or any policy, then any violation of the said law, rule or policy is unethical and illegal.

ÂÂ

When there is no government policy, the Court often relies on reliable authentic literature; authentic peer group consensus; published literature, guidelines and consensus statements.

ÂÂ

The admissibility of evidence in Courts in India is dependent on its relevancy as per the provisions of Indian Evidence Act. Illegality or impropriety in obtaining the evidence will not affect its admissibility, if it is otherwise relevant. Test of admissibility of evidence lies in its relevancy and not on how it was obtained. In Kuruma v The Queen [1955] AC 197, the Privy Council laid down that if the evidence is admissible, the Court is not concerned how it was obtained. The Privy Council observed: “...the test to be applied in considering whether evidence is admissible is whether it is relevant to the matters in issue. If it is, it is admissible, and

Penalty in case of violation of any provisions of Drugs and Cosmetics Act, 1940 and Medical Devices Rules, 2017 will be prescribed as per the said Act and Rules.

Refurbishing of medical devices and disposables does not come under the purview of CDSCO. However, refurbishing of medical equipment comes under the Ministry of Environment, Forest and Climate change.

Has DCGI allowed off-label use of drugs?

The government can ban off-label use of any drug as it did in the case of bevacizumab. On January 21, 2016, the DCGI took the bold step of prohibiting the use of intraocular bevacizumab as off-label treatment for various retinal diseases. Unfortunately, this decision put a large percentage of the population at risk of inaccessibility to treatment for common blinding retinal diseases. But, after 2 months, the DCGI agreed to withdraw the alert notice, enabling retinal surgeons to again use bevacizumab.

This decision may be a landmark judgment for India and other countries around the world to look at evidence-based off-label use of drugs.

Clearly, there is a need for an off-label policy.

The pharmaceuticals cannot be promoted or advertised legally. The onus therefore falls on the medical profession to “certify” the off-label use of drugs.

Time has come to formulate guidelines. We need to build a baseline document and draft suggestions to be sent to medical specialty societies cum associations and/or all medical stakeholders before sending it to the regulatory authorities.

IJCP Sutra: "Drink plenty of water. Avoid sugary drinks."

159

HCFI Consensus Statement the Court is not concerned with how the evidence was obtained.” These observations of the Privy Council were quoted with approval by the Supreme Court in Pooran Mal v Director of Inspection AIR 1974 SC 348. After quoting the above observations of the Privy Council, the Supreme Court observed as follows: “It would be thus seen that in India, as in English, where the test of admissibility of evidence lies in its relevancy, unless there is an express or necessarily implied prohibition in the Constitution or other law, evidence obtained as a result of illegal search or seizure is not liable to be shut out.”

Can a doctor be held liable for mere deviation from normal practice? ÂÂ

The Hon’ble Supreme Court of India in the matter titled as “Jacob Mathew versus State of Punjab & Anr on 5 August, 2005” has held that:

“A mere deviation from normal professional practice is not necessary evidence of negligence. Let it also be noted that a mere accident is not evidence of negligence. So also, an error of judgment on the part of a professional is not negligence per se. Higher the acuteness in emergency and higher the complication, more are the chances of error of judgment.” …..The degree of skill and care required by a medical practitioner is so stated in Halsbury’s Laws of England (Fourth Edition, Vol 30 Para 35): “…… and a person is not liable in negligence because someone else of greater skill and knowledge would have prescribed different treatment or operated in a different way; nor is he guilty of negligence if he has acted in accordance with a practice accepted as proper by a responsible body of medical men skilled in that particular art, even though a body of adverse opinion also existed among medical men.” ÂÂ

patient still does not survive or suffers a permanent ailment, it would be difficult to hold the doctor to be guilty of negligence.” ÂÂ

The opinion has to be by an authentic body. In the matter titled as “Vinitha Ashok versus Lakshmi Hospital, AIR 2001 SC 3914”, the Hon’ble Supreme Court has held that:

“[28] Thus in large majority of cases, it has been demonstrated that a doctor will be liable for negligence in respect of diagnosis and treatment in spite of a body of professional opinion approving his conduct where it has not been established to the court's satisfaction that such opinion relied on is reasonable or responsible. If it can be demonstrated that the professional opinion is not capable of withstanding the logical analysis, the court would be entitled to hold that the body of opinion is not reasonable or responsible.” ÂÂ

In the matter titled as “Kusum Sharma & Others versus Batra Hospital & Medical Research Centre, 2010 (3) SCC 480”, the Hon’ble Supreme Court of India has held that:

“In the realm of diagnosis and treatment there is scope for genuine difference of opinion and one professional doctor is clearly not negligent merely because his conclusion differs from that of other professional doctor.”

“The medical professionals are entitled to get protection so long as they perform their duties with reasonable skill and competence and in the interest of the patients. The interest and welfare of the patients have to be paramount for the medical professionals.” ÂÂ

Indian Penal Code Section 92 - Act done in good faith for benefit of a person without consent: “Nothing is an offence by reason of any harm which it may causes to a person for whose benefit it is done in good faith, even without that person’s consent, if the circumstances are such that it is impossible for that person to signify consent, or if that person is incapable of giving consent, and has no guardian or other person in lawful charge of him from whom it is possible to obtain consent in time for the thing to be done with benefit.”

ÂÂ

IPC Section 88 - Act not intended to cause death, done by consent in good faith for person’s benefit: “Nothing, which is not intended to cause death, is an offence by reason of any harm which it may cause, or be intended by the doer to cause, or be known by the doer to be likely to cause, to any person for whose benefit it is done in good faith, and who has given a consent, whether express or implied to suffer that harm, or to take the risk of that harm.”

In the matter titled as “Achutrao Haribhau Khodwa vs. State of Maharashtra, 1996 SCC (2) 634”, the Hon’ble Supreme Court has held that:

“The skill of medical practitioners differs from doctor to doctor. The very nature of the profession is such that there may be more than one course of treatment which may be advisable for treating a patient. Courts would indeed be slow in attributing negligence on the part of a doctor if he has performed his duties to the best of his ability and with due care and caution. Medical opinion may differ with regard to the course of action to be taken by a doctor treating a patient, but as long as a doctor acts in a manner which is acceptable to the medical profession, and the Court finds that he has attended on the patient with due care, skill and diligence and if the

160

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

IJCP Sutra: "Avoid foods that have high sodium levels such as snacks, processed foods."

HCFI Consensus Statement

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

Law on off-label use of drugs in the US and UK ÂÂ

In the United States, the law permits a physician or other health care practitioner to prescribe an approved medication for indications other than their specific FDA-approved indications. Pharmaceutical companies are not allowed to promote a drug for any other purpose without formal FDA approval.

However, once a drug has been approved for sale for one purpose, physicians are free to prescribe it for any other purpose that in their professional judgment is both safe and effective, and are not limited to official, FDA-approved indications.

This off-label prescribing is most commonly done with older, generic medications that have found new uses but have not had the formal (and often costly) applications and studies required by the FDA to formally approve the drug for these new indications. However, there is often extensive medical literature to support the off-label use. ÂÂ

Regulation in the United Kingdom: Physicians in the United Kingdom (UK) can prescribe medications off-label. According to General Medical Council guidance, the physician must be satisfied that there is sufficient evidence or experience of using the medicine to demonstrate safety and efficacy.

Prescribing may be necessary when no suitably licensed medicine is available to meet the patient’s need (or when the prescribing is part of approved research).

ÂÂ

HCFI Expert Round Table Sutra “In absence of any unethical considerations or a safety issue AND in presence of strong international or national scientific evidence; off-label use in other country; guideline or consensus statement; prevalent use in the clinical practice WITH no reported side effects under PvPI and the drug is not under RISK MAP category THEN the use of the available DCGI approved drug (including medical devices and disposables) is justified for off-label indications under implied consent. In all other situations, one needs to take an informed consent.”

“Anticipate and prepare ourselves” ÂÂ

To begin with, sensitize the medical profession on this issue. Most doctors are unaware of off-label use.

ÂÂ

Identify situations in which drug/s can be used offlabel; supported by strong scientific evidence; being used for the said indication for years and PvPI has not recorded any adverse effect with the drug.

ÂÂ

Seek recommendations from professional associations and societies as they understand safety issues and scientific evidences.

ÂÂ

Sensitize the ethics committees of institutions regarding this issue.

ÂÂ

National workshops: Invite specialists with scientific data; organize round tables in different zones of the country. Points to be discussed in these workshops:

Round Table consensus on off-label use of drugs

zz Safety and ethics of off-label use zz Is the drug used anywhere else in the world or in India for the off-label indication?

Few Examples of Off-label Use ÂÂ

Metformin in India is used off-label for polycystic ovarian disease (PCOD), which is used by gynecologists across the country; Federation of Obstetrics & Gynaecological Societies of India (FOGSI), Indian Menopausal Society, Endocrine Society of India recommend this use in their guidelines. No consent needs to be taken if used for this indication; but, it is not DCGI-approved for this indication. Use of metformin-myoinositol combination in PCOD is also an off-label use.

Using injection methotrexate for sarcoidosis, one may need to take an informed consent.

zz Is the drug approved for off-label indication/s in other countries? zz Are there enough international/national studies on the off-label use? ÂÂ

Invite government participation

ÂÂ

Include off-label use as part of informed consent; hospitals must have their individual “Ethics Committee guidelines” on this till a national policy is available.

ÂÂ

Amlodipine is approved for use only for mild and moderate hypertension, but it is also being used for severe hypertension, which is an off-label use.

ÂÂ

Phase 4 post-marketing trials should be regulated.

Adverse events should be reported. This will strengthen PvPI.

ÂÂ

Use of aspirin in acute myocardial infarction is not a DCGI-approved indication.

ÂÂ

Robust data including level of evidence is needed along with risk-benefit analysis.

IJCP Sutra: "Preventing mosquito bite is the best form of defense."

161

HCFI Consensus Statement

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

ÂÂ

Commercial bias and conflict of interest needs to be taken care of.

ÂÂ

Expert evidence by peer group is accepted by the Courts as “prevalent practice”, “peer group recommendations” or “society recommendations” unless there is a national existing policy. Till a law is formulated, this can be followed.

ÂÂ

Submit the draft to DCGI with copy to Health Ministry and other regulatory bodies; follow-up with RTIs; file PIL if no satisfactory reply.

Guidance on Reuse of Cardiovascular Catheters and Devices in India ÂÂ

Each medical establishment should have its own off-label, list of devices which can be reprocessed; number of times a device can be reused; Reprocess, Reuse, Re-Sterilize Committee consisting of doctors, infection control officers, microbiologists, nurses, and administrators to oversee central sterilization, re-processing, infection control, biomedical engineering and cost accounting.

ÂÂ

The above committee should have approval of the Institutional Ethics Committee.

ÂÂ

The in-house committee should take responsibility for the protocol linked to safety issues.

ÂÂ

The medical establishment should provide adequate space for reprocessing, trained personnel and other consumables that are required.

ÂÂ

Standard and validated written protocols should be followed for reprocessing for each type of single use device.

ÂÂ

Establishment should ensure a mechanism for tracking of such devices.

ÂÂ

There should be a periodic review and audit.

ÂÂ

Cardiology and other specialties reusing catheters should formulate common guidelines and standard operating procedures for reuse. These guidelines should include the list of items that can be

reused, the number of recommended reuses, the procedure for reuse and validating effectiveness of reprocessing procedures, to ensure sterility and intact functionality of these devices and ensure quality control. ÂÂ

An adverse event record should be maintained for all reused devices and there should be a periodic review and audit.

ÂÂ

Third party reprocessing units should be encouraged and need to be stringently regulated and accountable for quality control.

ÂÂ

The reused catheters/devices should not be billed on the new item rate to the patient as the reuse policy is primarily done to reduce the cost.

ÂÂ

The cost of sterilization process should be accounted for in the catheterization laboratory charges and/or should not exceed 10% of the original cost of the catheters.

ÂÂ

Reused cardiac implantable electronic devices (CIEDs) should not be charged.

ÂÂ

Made or make in India concept for these single use devices (SUDs) should be encouraged and facilitated to offset the cost, issues related to reuse and improve penetration of therapy.

ÂÂ

Engagement with the health regulatory authorities and price control for all imported medical devices should be addressed. Sealing the maximum retail price (MRP) based on the landing price with a well-defined formula for different SUDs should be established.

ÂÂ

ICMED: There is a basic policy on reprocessing of single use devices; it needs to be expanded. This assumes significance given the waste generated causing environmental hazard, an important public health problem today. Three important issues to be taken care of with regard to SUDs: Identify which SUDs can be reused safely, consent and that the benefit of cost has been passed over to the consumer.

List of Authors Name

Designation

Dr KK Aggarwal

President, Heart Care Foundation of India (HCFI), New Delhi

Dr Manju Mani

Consultant Anesthetist, New Delhi

Dr Chander Prakash Dr Ahmed Quraishi Dr AK Grover

162

Chairman, Vision Eye Centre, Siri Fort Road and West Patel Nagar, New Delhi

IJCP Sutra: "Refrain from going outdoors at dusk or dawn when the mosquitoes are highly active."

HCFI Consensus Statement

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

List of Authors Name

Designation

Dr Anil Goyal

Senior Urologist, Goyal Hospital & Urology Centre, New Delhi

Dr Anita Kant

Chairman, OBG Services, Asian Institute of Medical Sciences, Faridabad

Dr Ashwani Dalmiya

Chairman, Directory Committee, DMA

Wing Commander B Jena

Director Operations, National Heart Institute, New Delhi

Dr CM Bhagat Dr Ganesh Mani

Senior Cardiothoracic Surgeon, President-IMA, New Delhi Branch

Dr Girdhar J Gyani

Director General, Association of Healthcare Providers India (AHPI), New Delhi

Dr Girish Tyagi

President, Delhi Medical Association, New Delhi

Dr Gurpreet Singh

Ophthalmologist, Janakpuri, New Delhi

Ms Ira Gupta

Legal Advisor, HCFI, New Delhi

Dr KK Kalra

Advisor, AHPI, New Delhi

Dr Kamal Parwal

Hony. Associate Editor, DMA News Bulletin

Dr NK Bhatia

Medical Director, Mission Jan Jagriti Blood Banks (Regional Blood Transfusion Centre, South West Delhi)

Dr NV Kamat

Public Health, Former DHS, Delhi Govt.

Mr Nilesh Aggarwal

CEO, IJCP Group of Publications, New Delhi

Dr OP Yadava

Cardiothoracic Surgeon, CEO, National Heart Institute, New Delhi

Dr (Maj) Prachi Garg

Secy, IMA, New Delhi Branch

Mr Rajiv Nath

Forum Coordinator, AiMeD

Dr Ramesh Dutta

Past National President, IMA HQs., New Delhi

Dr Sanchita Sharma

General Physician, New Delhi

Mr Saurabh Aggarwal

Director, HCFI, New Delhi

Dr Shubnum Singh

Director, Medical Education & Research Advisor, Max Healthcare, New Delhi

Dr Sonia Malik

Director, Southend Fertility & IVF, New Delhi

Dr Sundip Mishra

Dept. of Cardiology, AIIMS, New Delhi

Dr Veena Aggarwal

Senior Gynecologist, New Delhi

Dr Vinod Sharma

Interventional Cardiologist, National Heart Institute, New Delhi ■■■■

No Repeat Imaging for Most Adrenal Tumors, Call to Change Guidelines Adrenal tumors found incidentally on imaging tests that are either nonfunctioning or have mild cortisol excess are highly unlikely to grow significantly or to develop into cancer or Cushing syndrome, US and UK researchers have found.

The results of this new meta-analysis therefore suggest that guidelines on the management of these tumors need to be updated to reflect the clinical reality - that is, patients do not need repeated imaging or testing over years of follow-up, say the authors. The study was published online June 25 in Annals of Internal Medicine.

IJCP Sutra: "Sleep inside an insecticide-treated mosquito net."

163

RTI Analysis

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

Lack of Coordination Amongst Various Departments of Ministry of Health: Diseases are Notifiable but there is no Vaccination Policy for Them KK aggarwal*, IRA Gupta†

I

question. Also, the answer given by the Directorate General of Health Services (DGHS) is different.

However, is there really coordination at the InterMinisterial level and even among various Departments of the same Ministry?

The PH (IH) Division of Ministry of Health and Family Welfare vide reply dated 23.10.2018 stated that: “This division deals with implementation of International Health Regulations (IHR) at Points of Entry and Public Health Emergencies of International Concern (PHEIC). This division does not have any information pertaining to notified diseases and their vaccinations in India.”

n India, the Cabinet Secretariat functions directly under the Hon’ble Prime Minister. The Cabinet Secretariat is responsible for the administration of the Government of India (Transaction of Business) Rules, 1961 and Government of India (Allocation of Business) Rules, 1961 facilitating smooth transaction of business in Ministries/Departments. The Secretariat assists in decision-making in Government by ensuring Inter-Ministerial coordination, ironing out differences amongst Ministries/Departments and evolving consensus through the instrumentality of the standing/ Ad-HoC Committees of Secretaries.

The answer is NO. The main problem in India is lack of coordination among various departments within the same ministry. Forget about Inter-Ministerial coordination.

Heart Care Foundation of India (HCFI), a national level Public Charitable Trust vide Right to Information (RTI) Application dated 27.08.2018 had asked a simple question from Ministry of Health and Family Welfare.

The question was: “Is there any notified list of communicable diseases in India?”

The Public Information Officer of Ministry of Health and Family Welfare forwarded the said RTI to its three departments and asked all the three departments to give relevant information. It is quite astonishing that all the three departments of the same Ministry of Health and Family Welfare gave different answers for same

*Group Editor-in-Chief, IJCP Group †Advocate and Legal Advisor, HCFI

164

The answers given by three departments and DGHS are: National Centre for Disease Control, Integrated Disease Surveillance Programme (IDSP) of Ministry of Health and Family Welfare vide reply stated that: “IDSP is a disease surveillance programme which is routinely collecting data of 22 communicable diseases. Health is a state subject and each State has its own list of notifiable diseases.”

Immunisation Division of Ministry of Health and Family Welfare vide reply dated 15.10.2018 has stated that: “in this regard, the matter regarding list of notifiable communicable diseases doesn’t pertain to Immunisation section hence your RTI application is being transferred under Section 6(3) of RTI Act, 2005 to DGHS for providing information directly to you. However, the list of diseases against which vaccination provided under Universal Immunisation Programme (UIP) is enclosed herewith.”

DGHS vide reply dated 17.10.2018 has stated: “in this regard, the matter regarding list of notifiable communicable diseases doesn’t pertain to Immunisation Section hence your RTI application is being transferred under Section 6(3) of RTI Act, 2005 to DGHS for providing information directly to you. However, the list of diseases against which vaccination provided under UIP is enclosed herewith.”

Vide RTI application, HCFI has also asked “Is there any policy or law or scheme under which a person can get vaccination for all notified communicable diseases?”

IJCP Sutra: "Cover yourself with long-sleeved shirts and trousers."

RTI Analysis

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

All the different departments of Ministry of Health and Family Welfare stated that there is no law, policy or data available and it is quite astonishing that there is no law/policy/scheme under which a person can get vaccination for all notified communicable diseases.

Further, it is surprising that none of the departments of Ministry of Health and Family Welfare have data of any vaccination notified for such communicable diseases in India.

Also, vide RTI application dated 27.11.2018, HCFI had asked “Is this UIP operating in all private as well as government hospitals?” The Immunisation Division of Ministry of Health and Family Welfare does not have any information relating to the same.

Vide reply dated 28.12.2018, the Immunisation Division of Ministry of Health and Family Welfare gave following answer to the question “Does government apply these vaccines to the people living on street and beggars under this UIP?”: “It is to state that, the RTI Act, 2005 and guidelines issued there under make it clear that, only

such information is required to be given which already exists and, it is not required to create information or to interpret information or to solve the problems raised by the applicant/ appellant of to furnish replies to hypothetical question.”

Instead of just giving reply in Yes or No to the query raised by HCFI, the Immunisation Division stated that it is required to give only such information which already exists.

We are talking about ONE INDIA. But from the reply given by different departments, the dream of achieving ONE INDIA is quite impossible. The Cabinet Secretariat needs to work out some stringent and effective measures for ensuring better Inter-Ministerial coordination and also among various departments of same Ministry. Till the time, the different departments of single ministries have coordination and better data availability, the Ministry as a whole will not be able to work effectively.

The new Cabinet is requested to ensure better coordination not just at the Inter-Ministerial level but also among various departments of the same ministry.

Analysis of Communicable Diseases RTI Sr. No.

RTI application dated 27.08.2018

Reply by Ministry of Health and Family Welfare, Immunisation Division dated 15.10.2018 & reply By DGHS dated 17.10.2018

Reply by PH (IH) Section of Ministry of Health and Family Welfare, dated 23.10.2018

Reply by National Centre for Disease Control, Integrated Disease Surveillance Programme (IDSP)

1.

Is there any notified list of communicable diseases in India?

Vide reply dated 15.10.2018, the Immunisation Division of Ministry of Health and Family Welfare, Government of India has stated:

The PH (IH) Division deals with implementation of International Health Regulations (IHR) at Points of Entry and Public Health Emergencies of International Concern (PHEIC). This division does not have any information pertaining to notified diseases and their vaccinations in India.

IDSP is a disease surveillance programme which is routinely collecting data of 22 communicable diseases. Health is a state subject and each State has its own list of notifiable diseases.

“in this regard, the matter regarding list of notifiable communicable diseases doesn’t pertain to Immunisation section hence your RTI application is being transferred under Section 6(3) of RTI Act, 2005 to DGHS for providing information directly to you.

However, the list of diseases against which vaccination provided under UIP is enclosed herewith.”

List of vaccines under Universal Immunisation Programme and Diseases prevented: Vaccine

Disease prevented

Bacillus CalmetteGuerin (BCG)

Severe form of childhood tuberculosis

Oral Polio vaccine (OPV)

Poliomyelitis

Hepatitis B vaccine

Hepatitis B

IJCP Sutra: "Refrain from sporting strong perfume or cologne, which can draw the attention of mosquitoes."

165

RTI Analysis

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

2.

If answer to query no. 1 is “Yes”, then please provide the said notified list of communicable diseases in India?

3.

Is there any vaccination notified for such communicable diseases in India?

4.

5.

6.

If answer to query no. 3 is Yes, then please provide the details of all vaccinations notified for all notified communicable diseases in India?

Is there any policy or law or scheme under which a person can get vaccination for all notified communicable diseases?

Pentavalent Vaccine Diphtheria, pertussis, tetanus, hepatitis B, pneumonia and meningitis caused by H. influenzae type b Rotavirus vaccine

Rotavirus diarrhea

Inactivated Polio vaccine

Poliomyelitis

Pneumococcal conjugate vaccine

Pneumococcal pneumonia

Measles vaccine

Measles

Measles & Rubella (MR) vaccine

Measles and Rubella

Japanese encephalitis (JE) vaccine

Japanese encephalitis

DPT vaccine

Diphtheria, pertussis and tetanus

Tetanus toxoid

Tetanus

‘Nil’ keeping in view of information on point one above.

List of notifiable diseases for each State may be obtained from respective State Information not available with IDSP

If answer to query no. 5 is “Yes”, then please provide the details of all policies or law or scheme under which the person can get vaccination for all notified communicable diseases?

Analysis of Communicable Diseases RTI Sr. No.

RTI application dated 27.08.2018

Reply by Immunisation Division of Ministry of Health and Family Welfare dated 28.12.2018

1.

How many states in the country have adopted the UIP?

UIP is implemented across the country State-wise details of vaccines is provided in the enclosed schedule.

2.

Are all vaccines under UIP available free of cost for the poor patients?

Yes

3.

If answer to query no. 2 is “No”, then provide the details of the vaccines which are available free of cost for the poor patients?

Question does not arise.

4.

Is this UIP operating in all private as well as government hospitals?

No such information available.

5.

Does government apply these vaccines to the people living on street and beggars under this UIP?

It is to state that, the RTI Act, 2005 and guidelines issued there under make it clear that, only such information is required to be given which already exists and, it is not required to create information or to interpret information or to solve the problems raised by the applicant/appellant of to furnish replies to hypothetical question.

6.

If answer to query no. 5 is “No”, then under which programme or policy or law, the government provides immunisation vaccine to the people living on street and beggars?

As per the reply given on point no. 5 question does not arise.

166

IJCP Sutra: "Pregnant women should be given preventive antibiotics in case of Chorioamnionitis, Group B strep colonization or a previous baby with sepsis caused by bacteria."

RTI Analysis

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

National Immunisation Schedule (Age-wise) Age

Vaccines given

Birth

Bacillus Calmette-Guerin (BCG), Oral Polio vaccine (OPV)-0 dose, Hepatitis B birth dose

6 weeks

OPV-1, Pentavalent-1, Rotavirus vaccine (RVV)-1***, Fractional dose of inactivated Polio vaccine (fIPV)-1, Pneumococcal conjugate vaccine (PCV)-1***

10 weeks

OPV-2, Pentavalent-2, RVV-2***

14 weeks

OPV-3, Pentavalent-3, fIPV-2, RVV-3***, PCV-2***

9-12 months

Measles-1 or Measles & Rubella (MR)-1***, JE-1*, PCV-Booster***

16-24 months

Measles-2 or MR-2***, JE-2*, Diphtheria, Pertussis & Tetanus (DPT)-Booster-1, OPV-Booster

5-6 years

DPT-Booster-2

10 years

Tetanus Toxoid (TT)/Tetanus & adult Diphtheria (Td)

16 years

TT/Td

Pregnant mother

TT/Td1, 2 or TT/Td Booster**

*JE in 231 endemic districts. **One dose if previously vaccinated within 3 years. ***Rotavirus vaccine: MR/Measles vaccine and PCV in selected states/districts as per details below: Rotavirus: Andhra Pradesh, Assam, Haryana, Himachal Pradesh, Jharkhand, Madhya Pradesh, Odisha, Rajasthan, Tamil Nadu, Tripura and Uttar Pradesh.

MR vaccine: Andhra Pradesh, Andaman & Nicobar Islands, Arunachal Pradesh, Chandigarh, Daman & Diu, Dadra & Nagar Haveli, Goa, Haryana, Himachal Pradesh, Karnataka, Kerala, Lakshadweep, Manipur, Mizoram, Punjab, Odisha, Puducherry, Tamil Nadu, Telangana and Uttarakhand.

PCV: Bihar, Himachal Pradesh, Madhya Pradesh, Uttar Pradesh (12 districts) and Rajasthan (9 districts).

■■■■

16 Crore People in India Consume Alcohol: Minister Alcohol is the most common psychoactive substance used by Indians followed by cannabis and opioids, the Rajya Sabha was informed recently.

Making a statement in response to a calling attention motion introduced by BJP MP RK Sinha, Social Justice and Empowerment minister Thawar Chand Gehlot said over 16 crore people in the country consume alcohol, around 3.1 crore use cannabis and about 77 lakh people take opioids. The findings were part of a national household survey conducted by the Ministry of Social Justice and Empowerment in 2018.

"The report establishes that a substantial number of people use psychoactive substances in India and the substance use exists in all the population groups with adult men bearing the brunt of substance use disorders," Gehlot said… (ET Healthworld – PTI)

Strategy Helps Identify Candidates for Supplemental Breast Imaging Breast-density notification combined with breast-cancer risk helps identify women at high risk of advanced breast cancer who might benefit from supplemental imaging, according to an analysis of Breast Cancer Surveillance Consortium (BCSC) registry data.

"Discussions of supplemental imaging in women with dense breasts should be combined with evaluating breastcancer risk, given 50% of women with dense breasts are at low breast-cancer risk," said Dr. Karla Kerlikowske of the University of California, San Francisco, and the Department of Veterans Affairs, San Francisco. Women with dense breasts accounted for 47.0% of screened women and 60.0% of advanced cancers, researchers report in JAMA Internal Medicine, online July 1.

IJCP Sutra: "It is important to prevent and treat infections in mothers, including herpes simplex virus."

167

EXPERT’s VIEW

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

How can One Reduce Cardiovascular Mortality in Patients with Hypertension?

Nandini Mukherjee, Kolkata

C

ardiovascular disease (CVD) including coronary heart disease (CHD) is the commonest cause of death in hypertensive patients. In elderly hypertensives, notably the diuretic-treated group in the Medical Research Council (MRC) elderly trial and in two trials of isolated systolic hypertension (SHEP and SYST-EUR), there was significant reduction (30%) in coronary disease events with reduction of blood pressure (BP). There is no doubt that it is essential to reduce the level of systolic and diastolic BP to prevent cardiovascular (CV) mortality, but there are many pros and cons. These are: when to intervene- at any particular level of BP or in presence of any particular clinical feature?

What Associated Risk Factors Need Special Attention?

How to intervene, when first detected? By pharmacological agents or by nonpharmacological means? Which agents are most helpful? Attempts have been made to find out the most effective drug treatment strategies. Systolic and diastolic thresholds of 160 and 100 mmHg, respectively are clear indicators of drug treatment. Systolic pressure in the range of 140159 mmHg and diastolic pressure in the range of 9099 mmHg indicate treatment under certain situations.

It is remarkable from different observational studies that international guidelines are inconsistent in their recommendations on thresholds for intervention to prevent CHD and CVD. In recent years; however, the following recommendations have been made:

notably women, may have high levels of BP or cholesterol which, when projected through their life time, would reduce life expectancy, but under current guidelines, would not warrant therapeutic intervention. ÂÂ

An estimated 10-year coronary risk of 15% (equivalent to a CVD risk of 20%).

Pharmacological Agents Used Vary in their Ability to Prevent CV Mortality Antihypertensive agents, which achieve similar reduction of level of BP, differ in their ability to prevent CV mortality, due to the differences of their mechanism of action or their effect on central or peripheral pulse pressure. It is found that central pulse pressure i.e., mean aortic pressure, which is the chief determinant of arterial wall stiffness, is the predictor of all-cause mortality including CV mortality. Very stiff arteries cause increase in circumferential arterial wall stress, and this is likely to cause breakdown of medial elastic tissue and it increases possibility of endothelial damage and development of atherosclerosis. So, antihypertensive drugs need to be effective not only in reducing brachial artery BP but also in reducing central arterial wall stiffness.

ÂÂ

When there is evidence of end-organ damage, like left ventricular hypertrophy (LVH).

ÂÂ

When coexistent clinical situation, like diabetes, may increase the risk of CV mortality.

ÂÂ

When dyslipidemia adds to the risk factor; premature mortality from hypertension among first-degree relatives.

Calcium channel blockers, though may have very little effect on large central elastic arteries, through their effect on peripheral muscular arteries, they reduce wave reflection amplitude and markedly lower systolic and pulse pressure, hence ventricular afterload. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) study failed to identify any treatment benefit attributable to a particular class of agent, but the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) study shows BP reduction with b-blockers and diuretics as the best recorded intervention for prevention of CV mortality.

ÂÂ

In elderly hypertensives: Most elderly people exceed the threshold for intervention both on BP and lipid-lowering. In contrast, younger people,

The Losartan Intervention For Endpoint reduction (LIFE) in Hypertension study and Perindopril pROtection aGainst REcurrent Stroke Study (PROGRESS) clearly

168

IJCP Sutra: "There should be a provision of a clean place for birth."

EXPERT’s VIEW

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

showed that angiotensin-converting enzyme (ACE) inhibitors prevent CV mortality more than b-blockers for a similar reduction of BP. ‘Pressure-independent’ effect of ACE inhibitors and receptor blockers may be explained by their optimal effects on arterial stiffness, augmentation of aortic pressure, left ventricular wasted energy, all of which should be reduced to lowest possible level to prevent CV mortality.

Hypertension (DASH) done to investigate the effects of diet on hypertension has recommended: ÂÂ

A diet with decreased content of dairy produce

ÂÂ

A diet with increased fruit and vegetable content

ÂÂ

A diet avoiding salty and processed food

ÂÂ

A diet rich in starchy food (which promotes weight loss by flat glycemic response, reduces BP and protects against atherosclerosis by providing phytoestrogens, helpful for raising high-density lipoprotein [HDL]: total cholesterol ratio).

Lipid-Lowering Drugs These drugs, formerly set at a higher threshold for global risk of intervention, are brought down by the joint British guidelines. With introduction of statin, the West of Scotland Coronary Prevention Study (WOSCOPS) and ASCOT-Lipid-Lowering Arm (ASCOT-LLA) studies showed that a 20% reduction in cholesterol was associated with a 30-40% reduction of the incidence of CHD. The issue relating to treatment of patients with lower levels of cholesterol becomes an economic argument rather than one demanding an evidence base.

Salt Restriction Studies on salt restriction show that a reduction in salt intake by 76 mmol/day (4.6 g/day) results in 5.0 mmHg and 2.7 mmHg falls in systolic and diastolic BP, respectively. There is evidence of additive effect of salt restriction in hypertensive patients when used in conjunction with drugs which block the reninangiotensin-aldosterone system (RAAS).

Smoking Cessation Smoking cessation may reduce CHD by about 25%.

Antioxidants In hypertensives, endothelial dependent dilatation is impaired. This dilatation is mediated largely by release of nitric oxide (NO), which plays an important role in maintaining vascular integrity by modulating vascular tone, inhibiting thrombosis and leukocyte adhesion and influencing smooth muscle proliferation. So, reduced endothelial NO may contribute to vascular injury and hence increase CV mortality. Despite the plausibility for antioxidant therapy in CVD risk reduction, there is lack of evidence of benefit in prospective placebocontrolled trials.

Lifestyle Modifications Lifestyle modifications produce important effect in lowering BP and prevention of CV mortality. In obese patients, a 10 kg loss of weight might well normalize the BP. Short-term studies of physical exercise program demonstrated a 10% fall in mean arterial pressure, a 25% fall in total peripheral resistance and a 20% rise in cardiac index. Epidemiological studies demonstrated that potassium intake, given as potassium chloride tablets, brings about a significant fall in BP. Potassium intake, as potassium chloride tablet, is not recommended but intake may be increased as fruits and vegetables.

A major American study, Dietary Approaches to Stop

Moderation of Alcohol Intake Moderation in alcohol intake shows a significant fall in both systolic and diastolic BP, though relationship of alcohol intake and CHD is more complex due to beneficial effect of alcohol on HDL cholesterol.

Therefore, preventive strategies for CV mortality in essential hypertension include: ÂÂ

Early detection

ÂÂ

Lifestyle modification

ÂÂ

Timely therapeutic intervention

ÂÂ

Appropriate choice of therapeutic agents

ÂÂ

Adoption of preventive program not only at personal and clinical level, but also at national level.

Suggested Reading 1. Hanson L, Hedner T, Lund-Johnasen P, Kjeld SE, Lindholm LH, Syvertsen Jo, et al. Lancet. 2000;356(9227):359-65.

2. Yusuf S, Sleight P, Pogue J, Bosch J, Davies K, Dagenais G. N Engl J Med. 2000;342(3):145-53.

3. du Cailar G, Ribstein J, Mimran A. Am J Hypertens.

2002;15(3):222-9.

4. Frolich ED, Varagic J. Nat Clin Pract Cardiovasc Med. 2004;1:24-30.

5. He FJ, MacGregor GA. BMJ. 2001;323(7311):497-501.

IJCP Sutra: "The baby should be delivered within 12-24 hours of when the membranes break.

In case of complications, a cesarean delivery should be done in women within 4-6 hours or sooner of membranes breaking."

169

MediFinance

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

Budget 2019-20 Highlights Arun Kishore, CA

Income-tax The threshold limit for reduced tax rate of 25% in case of domestic companies has been increased from Rs. 250 crores to Rs. 400 crores. Thus, a domestic company whose total turnover or the gross receipt in the previous year 2017-2018 does not exceed Rs. 400 crore shall be taxable at the rate of 25%.

A new Section 80EEA has been inserted to provide for deduction of up to Rs. 1.50 lakhs for interest on loan taken from any financial institution for acquisition of a residential house property whose stamp duty value does not exceed Rs. 45 lakhs.

A new Section 80EEB has been inserted to provide for a deduction of Rs. 1.5 lakhs in respect of interest on loan taken for purchase of an electric vehicle from any financial institution.

The new rate of surcharge for Individual, HUF, AOP, BOI and AJP shall be - 10% (for income of Rs. 50 lakhs to Rs. 1 crore), 15% (for income of Rs. 1 crore to Rs. 2 crores), 25% (for income of Rs. 2 crores to Rs. 5 crores) and 37% (for income exceeding 5 crores).

Any sum of money paid, or any property situated in India transferred, on or after July 5, 2019 by a person resident in India to a person outside India shall be deemed to accrue or arise in India under Section 9.

Furnishing of return of income shall be mandatory under Section 139, if an individual has deposited Rs. 1 crore or more in current account or he has incurred expenditure of Rs. 2 lakhs or more on foreign travel or he has incurred expenditure of Rs. 1 lakh or more on electricity consumption.

Income-tax return can be filed using Aadhaar Number, if a person hasn't been allotted PAN. If a person has linked his Aadhaar number with PAN, he may also furnish his Aadhaar number in place of PAN in the Income-tax return.

PAN allotted to a person shall be deemed to be invalid, if he failed to intimate the Aadhaar to the Dept.

A new Section 194N has been inserted to require deduction of tax at source at the rate of 2% if aggregate of cash withdrawn during the financial year from

170

any account maintained with a banking company or cooperative bank or post office exceeds Rs. 1 crore.

The sunset date for transfer of residential house property, for claiming exemption under Section 54GB in respect of investment made in eligible start-ups, has been extended from 31st March, 2019 to 31st March, 2021. Further, the conditions of minimum shareholding or voting rights has been relaxed from 50% to 25%.

Application under Section 195(2) and 195(7) for lower or nil deduction of tax from sum paid or payable to non-resident person can be filed electronically.

A new Section 194M has been inserted to require any individual or HUF (who is not required to deduct tax under Section 194C or 194J) to deduct tax at source from sum paid to a contractor or professional if aggregate payment during the year exceeds Rs. 50 lakh. The tax can be deposited under this provision without any requirement to obtain TAN. As per Section 194-IA, a buyer is required to deduct tax at source from the consideration paid to buy an immovable property. An explanation has been inserted that “consideration for immovable property” shall include all charges paid towards club membership fee, car parking fee, electricity and water facility fees, maintenance fee or any other charges of similar nature, which are incidental to transfer of the immovable property.

In case of failure to file an Income-tax return, the prosecution proceedings are initiated under Section 276CC if the tax payable by the assessee is Rs. 3,000 or more. This threshold limit has been increased to Rs. 10,000.

Constituent entity of an International group shall now be required to keep and maintain information and document under Section 92D and file required form even when there is no international transaction undertaken by such constituent entity.

There are various provisions in the Act which requires a person to make payment by account payee cheque/ draft or ECS. In order to encourage other electronic modes of payment, the Government has proposed to amend relevant provisions to include other electronic modes of payment.

IJCP Sutra: "Eat a balanced diet that is high in fiber and low in fat. Drink plenty of water."

MediFinance

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

Tax shall be deductible under Section 194DA at the rate of 5% only on the income component of life insurance pay-out. The existing rate of TDS was 1% on the gross amount.

Relief under Section 89 shall be considered while computing the tax liability under Section 140A, Section 143, Section 234A, Section 234B and Section 234C to avoid genuine hardships to the taxpayers who are claiming such relief.

Every person, carrying on business, shall provide facility for accepting payment through electronic modes if his turnover or gross receipts exceeds Rs. 50 crores. The Payment and Settlement Systems Act, 2007 is proposed to be amended to provide that no bank or system provider shall impose any charge upon anyone, either directly or indirectly, for using the electronic modes of payment.

A taxpayer has been allowed to withdraw 60% of total amount from NPS as tax free. Currently, the exemption is allowed only up to 40% of the total corpus amount.

Benefit of first proviso of Section 201(1) has been extended in case of failure to deduct tax at source from sum paid to non-residents. Thus, a deductor shall not be deemed to be an assessee in default even if he fails to deduct tax from sum paid to a non-resident, if such nonresident discloses such income in his return of income and pays tax due on such income and a certificate from a Chartered Accountant is furnished to this effect.

Deduction of up to 10% of salary is allowed under Section 80CCD in respect of contribution made by an employer to NPS. The limit has been proposed to be increased to 14% of salary in case of Central Government's employees.

Section 12AA has been amended to provide that at the time of granting of registration to a trust or institution, the Pr. CIT or CIT shall also satisfy himself that the applicant trust or institution also satisfy the requirements of any other law which is material for the purpose of achieving its objects.

The Pr. CIT or CIT has been empowered to cancel the registration under Section 12AA, if after granting registration it has been noticed that the trust or institution has violated requirements of any other law which was material for the purpose of achieving its objects.

Section 115QA which requires payment tax on distributed income in case of buy-back of shares has proposed to be extended to listed companies as well.

ITR filing is mandatory, if total income of assessee before claiming the benefit of capital gain exemption under sections 54, 54B, 54EC, 54F, 54G, 54GA and 54GB, doesn't exceed the maximum amount not chargeable to tax.

Goods and Services Tax A Proviso has been inserted to clarify that interest for late payment of tax shall be levied only on that portion of tax which has been paid by debiting the electronic cash ledger. Earlier there was a confusion among taxpayers on this issue whether such interest would be charged on gross tax liability or only on net tax liability. However, there is one exception to this rule wherein interest shall be levied on gross tax liability. Where returns are filed subsequent to initiation of any proceedings under GST Act, the interest shall be levied on the gross tax liability.

Every registered person shall authenticate, or furnish proof of possession of Aadhaar number. If an Aadhaar number is not assigned to the registered person, such person shall be offered an alternate and viable means of identification. In case of failure to undergo authentication or furnish proof of possession of Aadhaar number or furnish alternate and viable means of identification, registration allotted to such person shall be deemed to be invalid.

Now a registered person can transfer any amount of tax, interest, penalty, fee or any other amount available in the electronic cash ledger to the electronic cash ledger for Integrated Tax, Central Tax, State Tax, Union Territory Tax or Cess through a new form PMT-09 subject to the conditions and restrictions prescribed under GST Act. Such transfer shall be deemed to be a refund from the electronic cash ledger.

The Central Government has been authorized to pay the amount of refund towards State taxes to the taxpayers.

The Government shall constitute an Authority “National Appellate Authority for Advance Ruling (NAAAR)” for hearing appeals. It shall pass an order within 90 days from the date of filing of appeal.

The value of exempt supply of services provided by way of extending deposits, loans or advances (where consideration is received in form of interest or discount) shall not be considered for determining turnover under Composition Scheme.

Simplified return forms will be implemented soon.

Composition registered dealers are required to pay tax quarterly and file return on annual basis.

IJCP Sutra: "If our leptin is off balance, most likely the body will feel that it never gets enough food, which leads to overeating."

171

Medical Voice for Policy change

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

Medtalks with Dr KK Aggarwal Encephalitis Claims Lives of Children in Bihar’s Muzaffarpur (Inputs from Dr Vipin M. Vashishtha) Recurrent, seasonal outbreaks of acute brain disease in children with high case-fatality rates have been occurring almost every year in some regions of the country. All outbreaks need not have been due to one specific disease/ syndrome. Cases may be occurring sporadically also, but whether sporadic and epidemic cases represent one syndrome needs clarification.

Currently, there seems to be two sets of these outbreaks dominating the entire scenario; first caused by viruses like Japanese encephalitis, Chandipura, influenza, enteroviruses, etc., or bacteria such as Orientia tsutsugamushi (e.g., Scrub typhus in Gorakhpur).

Another group of these outbreaks is caused by environmental toxins like Cassia occidentalis, toxins in litchi fruits like MCPG and MCPA (hypoglycins), etc.

While former group is constituted by a true encephalitic illness, the latter is not true encephalitis but a multisystem disease in which brain is involved secondarily, i.e., the encephalopathy illness. However, often this key difference is not appreciated owing to faulty case definition that leads to unnecessary investigations.

We, a group of four health professionals, investigated fatal, recurring outbreaks of acute brain illness in many district of Western UP, Uttarakhand and Haryana during late 90s’ and early 2000, and found it was not an encephalitis but a Reye-like encephalopathy that presented in outbreak form every year during winter months. Later, we found it was caused by consumption of beans of a ubiquitous weed, C. occidentalis that lead to the genesis of acute hepatomyoencephalopathy (HME) syndrome.

The anthroquinones present in the beans were responsible for this syndrome. This was a landmark study that presented a new paradigm in outbreak investigations in India and some neighboring countries. It also brought the role of environmental toxins to the forefront. Later, a mysterious outbreak in Bangladesh was found due to consumption of ‘Ghaghra Shak’ by the natives, litchi consumption behind Muzaffarpur outbreaks, Cassia poisoning in Malkangiri, Odisha outbreaks, etc. When we retrospectively analyzed some of the unexplained outbreaks in the past like the one in Bengaluru (Benakappa DG, et al. Indian Pediatr. 1991), another near

172

Haryana, Punjab and Chandigarh (Ghosh D, et al. Indian Pediatr. 1999), etc., they were all pointing toward HME syndrome secondary to Cassia consumption.

All these illnesses were confused with encephalitis or with Reye-syndrome. In fact, now we can claim that any Reye-like illness presenting in epidemic form must be investigated for the possibility of some environmental toxin as a putative etiologic agent.

A precise case definition is necessary for any outbreak investigation. Strict case definitions were applied in only a few investigations and in all of them the disease was clinically not encephalitis.

Outbreak investigations in India are lacking on this front right from the days of ‘Jamshedpur fever’ described by late Dr Najeeb Khan in 1954 (Indian J Med Sci. 1954;8:597-9).

Similarly, the enigma of so called ‘Nagpur encephalitis’, which was earlier attributed to JE virus and later to heat hyperpyrexia (Sriramachari S, et al. Indian J Med Res. 1976), still persists.

Coming to the Muzaffarpur illness, these recurrent outbreaks are caused by some toxins involved in either the litchi fruit itself like MCPG or MCPA or some hitherto undiagnosed compound used in the litchi cultivation. The disease is not a true encephalitis but an encephalopathy that needs further elucidation. Rapid correction of hypoglycemia may prevent death in few cases.

Heart Failure Registry Underway to Create a Data Bank Thiruvananthapuram: A National Heart Failure Registry is being prepared to create a data bank on heart diseases across the country. Funded by Indian Council of Medical Research, the idea is to collate data on 10,000 patients in 1 year. Already 5,000 patients have been listed in the registry. The Sree Chitra Tirunal Institute for Medical Sciences and Technology here is among the nodal agencies that is preparing the registry. “The registry work began in January and we intend to study the impact of the heart diseases with this registry. In the first 1,000 cases ‘enrolled’ in the registry, it has been found that ischemic heart disease is the highest among various forms of heart diseases in the country. Its mortality rate is higher compared to that of cancer,’’ said Dr S Harikrishnan, National Principal Investigator and Coordinator of National Heart Failure Registry... (ET Healthworld)

IJCP Sutra: "Get enough sleep and avoid stress."

Medical Voice for Policy change

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

person in lawful charge of him from whom it is possible to obtain consent in time for the thing to be done with benefit.

Can One Use Expired Injections?

EpiPens and other autoinjectors filled with epinephrine to treat severe allergic reactions may still be potent enough to work many months past their labeled expiration date, according to a new study online in the Journal of Allergy and Clinical Immunology.

The US Food and Drug Administration (FDA) requires autoinjector expiration dates to ensure that the devices never contain less than 90% of the original dose of epinephrine. For the study, researchers tested the contents of 46 different autoinjectors to see how much epinephrine remained after the expiration dates on the labels. Half of the devices were tested at least 2 years after their labeled expiration date. At this point, 80% of the devices still retained 90% or more epinephrine, indicating they were still effective under the FDA rules.

Devices 6 months past their labeled expiration date in the study still had 100% of the original epinephrine dose. One year after the labeled expiration date, devices still had 95% of the original epinephrine dose.

And all of the autoinjectors tested that were up to 30 months beyond their labeled expiration date still had 90% of the dose remaining.

The authors also note that they did not test the expired injectors’ effectiveness in stopping an anaphylaxis episode.

Right now, the expiration date is 18 months from the time the product is manufactured, a duration that is shorter than the expiration date for most other medications.

Legal implications As per the Supreme Court of India, any violation of the manufacturer’s warning and recommendation is not to be done (Balram Prasad vs. Kunal Saha & Ors on 24 October 2013). But in life-threatening situations in absence of any other available alternative there are exceptions: ÂÂ

Section 52 in The Indian Penal Code: Good faith— Nothing is said to be done or believed in “good faith”, which is done or believed without due care and attention.

ÂÂ

Section 92: Act done in good faith for benefit of a person without consent - Nothing is an offence by reason of any harm which it may cause to a person for whose benefit it is done in good faith, even without that person’s consent, if the circumstances are such that it is impossible for that person to signify consent, or if that person is incapable of giving consent, and has no guardian or other

ÂÂ

IPC 88: Act not intended to cause death, done by consent in good faith for person’s benefit —Nothing which is not intended to cause death, is an offence by reason of any harm which it may cause, or be intended by the doer to cause, or be known by the doer to be likely to cause, to any person for whose benefit it is done in good faith, and who has given a consent, whether express or implied, to suffer that harm, or to take the risk of that harm.

Illustration A, a surgeon, knowing that a particular operation is likely to cause the death of Z, who suffers under a painful complaint, but not intending to cause Z’s death and intending in good faith, Z’s benefit performs that operation on Z, with Z’s consent. A has committed no offence.

Fecal Transplant Linked to Death, the FDA Warns As per FDA, two patients received donated stool that had not been screened for drug-resistant germs, leading it to halt clinical trials until researchers prove proper testing procedures are in place.

Fecal transplants have come into increasing use to treat severe intestinal disorders, particularly an infection caused by a bacterium called Clostridium difficile, which can be deadly and tends to occur in hospitalized patients who have been heavily treated with antibiotics.

The idea behind the transplants is to use stool from a healthy donor to restore the normal balance of bacteria and other organisms in the intestine, the microbiome.

Both transplants came from the same donor’s fecal matter. The report does not state whether the fecal material was given in liquid form as an infusion into the digestive tract or swallowed as pills. Other samples from the same donor were tested after the patients got sick.

The samples were found to harbor the same dangerous germs found in the patients, known as multidrugresistant organisms. They were Escherichia coli bacteria that produced an enzyme called extended-spectrum b-lactamase, which makes them resistant to multiple antibiotics. The stool had not been tested for the germs before being given to the patients.

The FDA issued a warning to researchers that stool from donors in studies of fecal transplantation should be screened for drug-resistant microbes, and not used if those were present. It is also warning patients that the procedure can be risky, is not approved by the agency and should be used only as a last resort when C. difficile does not respond to standard treatments.

IJCP Sutra: "Avoid using tobacco, alcohol or other drugs."

173

Medical Voice for Policy change Clinical Case Does a very low coronary artery calcium (CAC) score signify very low risk?

A 46-year-old female came with atypical chest pain with reported wall motions on echo and questionable coronary artery disease (CAD) on CT angiography.

She was put on treatment for the last 6 months and was now advised enhanced external counter pulsation (EECP) and chelation therapy. The patient came for a third opinion.

A: On reviewing the CT report it was found she had a coronary calcium score of zero. She was put of lifestyle advise.

Discussion American Heart Association: CAC score of zero (CAC = 0; i.e., no calcified plaque detected) indicates that: ÂÂ

The presence of atherosclerotic plaque, including unstable or vulnerable plaque is highly unlikely.

ÂÂ

The presence of significant luminal obstructive disease is highly unlikely (negative predictive value on the order of 95-99%).

ÂÂ

The risk of a cardiovascular event in the next 2-5 years is quite low (0.1 per 100 person-years).

ÂÂ

CAC = 0 is useful in the emergency room setting as a tool to rule out myocardial ischemia in symptomatic patients.

The presence of CAC is highly sensitive for the presence of ≥50% angiographic stenosis in moderately specific, especially in older patients. The absence of CAC, particularly in an asymptomatic patient, is highly predictive of the absence of significant coronary artery stenosis and implies a favorable prognosis.

CAC screening, especially for borderline and intermediate risk patients, can enhance the prediction of risk in asymptomatic individuals and increase the predictive value of the Framingham risk score. Among asymptomatic patients with a low Framingham risk score (<10% 10-year risk), only a small number (<15%) of those with CAC will have a cardiac event over the ensuing 5 years.

CAC screening is unlikely to benefit low- or high-risk (>20% 10-year risk) patients, and is not recommended. It has not been established that instituting or intensifying pharmacologic risk factor modification in asymptomatic patients with CAC improves outcomes.

174

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

Muzaffarpur Encephalopathy: A Multi-ministry Coordination and Comprehensive Action Plan is the Answer The outbreak of acute encephalitis syndrome (AES) in Muzaffarpur has claimed more than a hundred lives.

AES has been occurring every year for the past so many years with no solution in sight. A visit by the Chief Minister of the state, or the state or central health minister is alone not the answer.

Since this is a local outbreak in Muzaffarpur and adjoining districts, the state should declare a public health emergency and invoke the Essential Commodities Act. This would bring the entire state health services, both government and private sectors, under the gambit of the Essential Commodities Act and Essential Services Maintenance Act as ‘essential medical services’.

A multi-ministry coordination and comprehensive action plan should be drawn up and acted upon. ÂÂ

Health Ministry: Should arrange for 24x7 ICU, ventilators, ambulances; Asha workers should be provided with glucometers and thermometers so that they can monitor the temperature and blood sugar levels. They should be taught how to prevent deaths due to hypoglycemia in children. They should be advised to give 1 teaspoon of sugar sublingually (not as a drink) every 20 minutes in children <15 years of age. Make sure that the child does not clinch teeth or swallow the sugar.

All health care providers should do home-to-home survey.

ÂÂ

ICMR/DST/ all medical colleges: Should spearhead research in the illness to understand its cause, to prevent future such outbreaks.

ÂÂ

Agriculture Ministry: To act on rotten litchis; advise farmers to destroy the rotten fruits; create awareness on harms of eating only litchis by malnourished children.

ÂÂ

Ayush Ministry: Should deliberate if their pathy has some alternative treatment to offer.

ÂÂ

Women & Child Development Ministry: Should look after the nutrition of the children in the area; an Evening Day Meal Scheme for the children can be started in addition to the Mid-day Meal Scheme already in place.

ÂÂ

Transport Ministry and Civil Aviation Ministry: To arrange for airlifting patients and shift them to other states for management, as and when required.

IJCP Sutra: "To keep the reproductive system healthy, keep the genitals clean and avoid coming into contact with body fluids, like blood or semen."

Medical Voice for Policy change

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

ÂÂ

Law Ministry: Should ensure that no law and order problems arise in such situations and the action plan is implemented smoothly.

Pediatricians should Screen their Patients for Alcohol Use, Recommends American Academy of Pediatrics

ÂÂ

Environment Ministry: Should take all measures to prevent heat stroke in the area by providing makeshift shelter homes.

ÂÂ

Military: Can be called in for house-to-house visits to identify probable cases; when Zika threatened Brazil in 2015-16, when it was preparing to host the 2016 Olympic Games, the army was called into action and asked to join the efforts to control the virus, which was made into a public movement.

In an updated policy statement “Alcohol Use by Youth”, the American Academy of Pediatrics (AAP) has urged parents to talk with their teens about the risks of alcohol and set firm rules against its use.

Its time some concrete steps are taken to prevent recurrence of this illness.

Health Care Workers Often Work While Sick Most health care workers (HCWs) with an acute respiratory illness (ARI) have worked during most episodes of ARI, putting their patients and coworkers at risk for infection, finds a recent study published online in Infection Control & Hospital Epidemiology.

HCWs from 9 Canadian hospitals were prospectively enrolled in active surveillance for ARI during the 2010-2011 to 2013-2014 influenza seasons. Daily illness diaries during ARI episodes collected information on symptoms and work attendance. ÂÂ

At least 1 ARI episode was reported by 50.4% of participants each study season.

ÂÂ

Overall, 94.6% of ill individuals reported working at least 1 day while symptomatic, resulting in an estimated 1.9 days of working while symptomatic and 0.5 days of absence during an ARI per participant season.

ÂÂ

In multivariable analysis, the adjusted relative risk of working while symptomatic was higher for physicians and lower for nurses relative to other HCWs.

ÂÂ

Participants were more likely to work if symptoms were less severe and on the illness onset date compared to subsequent days.

ÂÂ

The most cited reason for working while symptomatic was that symptoms were mild and the HCW felt well enough to work (67%).

ÂÂ

Participants were more likely to state that they could not afford to stay home if they did not have paid sick leave and were younger.

The statement is published in the July issue of Pediatrics (published online June 24). An accompanying technical report outlines the evidence for AAP recommendations and states that alcohol remains the most common substance used by teens.

“The teen years are a critical time for brain growth, when connections responsible for emotional regulation, planning and organization are being formed and finetuned,” said Joanna Quigley, MD, FAAP, lead author of the policy statement. “Alcohol paves a pathway for addiction when the brain is still maturing, affecting the area that governs decision-making. As parents, we don’t want to downplay those risks, but keep the conversations open and model healthy habits.”

“Binge drinking is especially dangerous and is known to lead to other risky behaviors, such as drinking and driving,” said Sheryl Ryan, MD, FAAP, who chairs the AAP Committee on Substance Use and Prevention and is lead author of the technical report. “Pediatricians should screen their patients for alcohol use and help them understand the impact on the brain and behaviors.”

The AAP recommends that pediatricians screen for alcohol use and provide education to teens and their families about hazards, consequences and potential interventions.

Other recommendations include: ÂÂ

Send a clear message against the use of alcohol under age 21.

ÂÂ

Support existing state laws for a minimum purchase age of 21 for alcohol and advocate for taxes on alcohol products.

ÂÂ

Support strengthening graduated driver licensing programs... The laws indirectly affect drinking and driving by restricting night-time driving and the transportation of younger passengers.

ÂÂ

Advocate for more research on the impact of alcohol use on the developing brain.

ÂÂ

Support the role of schools in screening for underage alcohol use and providing general health education and community programs.

ÂÂ

Ban the sale and distribution of powdered alcohol.

IJCP Sutra: "To check for cancer, women should perform monthly self-exams of their breasts, and men should perform monthly self-exams of their testes."

175

Medical Voice for Policy change Do These 7 Things Today, to Save Your Sight Tomorrow, Says AAO to Young Adults The American Academy of Ophthalmology (AAO) urges young adults to protect their eyes to prevent vision loss in the future. It recommends adults under age 40 have a comprehensive medical eye exam every 5-10 years.

1.

Wear sunglasses (even when it’s cloudy). Longterm exposure to the sun without proper protection can increase the risk of eye disease, including cataract, macular degeneration, growths on the eye and a rare form of eye cancer. Wear sunglasses that block 99-100% of both ultraviolet A and B radiation.

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

Addiction Terms Harvard: People sometimes confuse the words tolerance, physical dependence and withdrawal. These terms are not interchangeable, though they are related: ÂÂ

Tolerance means that, over time, a person will need larger doses to get the same effect first experienced with smaller doses. Because tolerance to some side effects does not occur, people with tolerance often face worsening side effects as they take larger and larger doses.

ÂÂ

Physical dependence means that the body gets used to having the substance or activity and “misses it” if it’s taken away. People with physical dependence who stop using their object of dependence or who decrease their dose might develop uncomfortable withdrawal symptoms.

ÂÂ

Withdrawal refers to a range of typical symptoms that vary depending on the substance or activity in question, but they often reflect the opposite of the high. How long withdrawal symptoms last and how severe they are depends on which substance (or activity) a person uses, at what dose and for how long. The fear of withdrawal symptoms sometimes makes people nervous about stopping or lowering their dose. That’s sometimes true even for people who no longer derive pleasure from their object of addiction.

2.

Exercise. Regular physical activity can protect you from serious eye diseases, such as age-related macular degeneration (ARMD) and glaucoma.

3.

Stop smoking. Smoking increases the risk for eye diseases such as cataract and ARMD. Smoking also raises the risk for cardiovascular diseases, which can indirectly influence your eye health. Tobacco smoke, including second-hand smoke, also worsens dry eye.

4. Protect your eyes at work and at play. Every year, thousands of people in the United States get a serious work-related eye injury or sports-related eye injury. Wearing protective eyewear can prevent most of these injuries. To make sure you have the right kind of protective eyewear and you’re using it correctly, talk with your eyecare professional.

5.

Be aware of eye fatigue. If you spend a lot of time at the computer or staring at your phone, you may forget to blink and that can tire out your eyes. Try using the 20-20-20 rule throughout the day: Every 20 minutes, look away from the screens and focus about 20 feet in front of you for 20 seconds. Eye fatigue won’t damage your vision, but if it persists, it can be a sign something else is wrong. You may have dry eye, presbyopia or spectacles with lenses that are not properly centered.

6.

Take proper care of contact lenses. Sleeping, showering and swimming in contact lenses increases your risk for a potentially blinding eye infection.

Learn how to properly care for contact lenses.

7.

Know your family history. Certain eye diseases can be inherited. If you have a close relative with macular degeneration, you have a 50% chance of developing this condition. A family history of glaucoma increases your glaucoma risk by 4-9 times.

Talk to family members about their eye conditions.

It can help you and your ophthalmologist evaluate your risk.

176

NIH Launches Large TB Prevention Trial for People Exposed to Multidrug-resistant TB National Institute of Health (NIH): A large phase 3 clinical trial called PHOENIx MDR-TB (Protecting Households on Exposure to Newly Diagnosed Index MultidrugResistant Tuberculosis Patients) to assess treatments for preventing people at high risk from developing multidrug-resistant tuberculosis (MDR-TB) has begun.

The study is comparing the safety and efficacy of a new MDR-TB drug, delamanid, with isoniazid, the standard anti-TB drug for preventing active MDR-TB disease in children, adolescents and adults at high risk who are exposed to adult household members with MDR-TB. Study participants are at high risk for MDR-TB because they either have latent TB infection, immune systems suppressed by HIV or other factors, or are younger than age 5 years and therefore have a weak immune system. The study investigators hypothesize that prophylactic treatment with delamanid will prove better than isoniazid at reducing the likelihood that atrisk household members of individuals with MDR-TB will develop active TB disease.

IJCP Sutra: "Be aware of the products you use in your home and on your skin.

For example, cleaning products with harsh chemicals."

Medical Voice for Policy change

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

“It is important to perform randomized, controlled clinical trials on how best to provide preventive care for people who come in close contact with individuals with MDR-TB, since this is a major gap in global public health policy,” said Anthony S Fauci, MD Director of the National Institute of Allergy and Infectious Diseases (NIAID), which is co-funding the study and is part of the NIH.

ÂÂ

Only foods that contain 20 mg gluten/kg or less can be labeled as ‘gluten-free’.

ÂÂ

The patients with celiac disease should: zz Buy foods that are labelled ‘gluten- free’. zz Check the ingredient list and confirm that there is no gluten in the food.

Study Identifies Early Warning Signs of Eating Disorders

zz Check the food package for ‘gluten free’ label in the immediate proximity of the name of the product.

New research from the Swansea University Medical School has identified early warning signs that someone may have an eating disorder such as anorexia nervosa, bulimia nervosa and binge eating disorder, which may help in earlier detection of these disorders.

zz Check FSSAI license number on the package(s).

The results, published in the British Journal of Psychiatry by the Royal College of Psychiatrists, showed that people diagnosed with a disorder had higher rates of other conditions and of prescriptions in the years before their diagnosis. The researchers examined anonymized electronic health records from general practitioners (GPs) and hospital admissions in Wales. Overall, 15,558 people in Wales were diagnosed as having eating disorders between 1990 and 2017. In the 2 years before their diagnosis, data shows that these 15,558 people had: ÂÂ

Higher levels of other mental disorders such as personality or alcohol disorders and depression.

ÂÂ

Higher levels of accidents, injuries and self-harm.

ÂÂ

Higher rate of prescription for central nervous system drugs such as antipsychotics and antidepressants.

ÂÂ

Higher rate of prescriptions for gastrointestinal drugs (e.g. for constipation and upset stomach) and for dietetic supplements (e.g. multivitamins, iron).

Therefore, looking out for one or a combination of these factors can help GPs identify eating disorders early.

FSSAI Guidance Note on Gluten-free Foods Recognizing the challenges faced by celiac patients, Food Safety and Standards Authority of India (FSSAI) has established the standard for ‘gluten free foods’ and their labeling requirements under the Food Safety and Standards Regulations, 2011. It has released a guidance note, set up standards and made easy to perform rapid tests available for the common consumer. The key takeaways from the guidance note: ÂÂ

People with celiac disease should not consume food product containing gluten (wheat, barley, etc.)

zz Should not buy flour from local mills where wheat may also be grounded for other customers and there are high chances of cross contamination. zz Always read the manufacturing/packaging date and best before date before buying food. zz Check the labels, even on foods one buys regularly, as there may be some changes in ingredients used and that may contain gluten.

(Source: FSSAI)

Long-term Increased Risk of Cancer Death Following Radioactive Iodine Treatment for Hyperthyroidism (NIH): Findings from a study of nearly 19,000 patients who received radioactive iodine (RAI) treatment for hyperthyroidism and none of whom had had cancer at study entry show an association between the dose of treatment and long-term risk of death from solid cancers, including breast cancer. The study, led by researchers at the National Cancer Institute (NCI), part of the National Institutes of Health, was published July 1, 2019 in JAMA Internal Medicine. Most of the radiation is absorbed by the thyroid gland, but other organs like the breast and stomach are also exposed during treatment.

The relationship was statistically significant for female breast cancer, for which every 100 mGy of dose led to a 12% increased relative risk of breast cancer mortality, and for all other solid tumors considered together, for which relative risk of mortality was increased by 5% per every 100 mGy. Based on these findings, the researchers estimated that for every 1,000 patients aged 40 years with hyperthyroidism who were treated with the radiation doses typical of current treatment, a lifetime excess of 19 to 32 radiation-attributable solid cancer deaths would be expected.

■■■■

IJCP Sutra: "Fresh fruits and vegetables contain fiber and substances that can help in flushing toxins out of your system."

177

Conference Proceedings

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

INDIA LIVE 2019 March 01, 2019 | Renaissance Mumbai Convention Centre Hotel, Powai, Mumbai

Pathological Insights into Mitral Valve Intervention Dr Renu Virmani, USA Mitral valve is a complex structure. The entire structure of mitral valve consists of anterior and posterior leaflets, chordae tendineae, papillary muscles, left atrium and a partial annulus which is D-shaped. The pathophysiology of mitral regurgitation is also complex, involving defect in leaflets, chordae, annulus and papillary muscle and LV wall. Surgical repair has worked but not surgical valve replacement. Therefore, repair is more likely to be a better treatment. In patients with high operative surgical risk, transcatheter valve repair is more reasonable than surgical replacement.

Aortic Dissection During Coronary Intervention Dr Ruchit Shah, Mumbai Aortic dissection is a rare complication (0.005%).

Most of the dissections occur during guide catheter manipulation. Right coronary artery is more frequently involved. JR and AL are responsible for most of the aortic dissections. It is best to prevent this complication by ensuring the correct guide size, curvature and coaxial alignment. Always look for pressure, damping or ventricularization and give gentle contrast injections. Aortic dissection during PCI is detected by aortogram, bedside echocardiography, transesophageal echocardiography and CT scan. Dissection of aorta limited to the ipsilateral cusp or <4 mm from cusp can be treated by stenting and has good prognosis. Dissections which extend >4 mm from the cusp may require surgery and have a guarded prognosis. Management of hemodynamics and life-threatening arrhythmias is of prime importance.

FFR in Special Subsets Dr CG Bahuleyan, Thiruvananthapuram ÂÂ

178

In serial lesions, the FFR of individual lesions should not be used. Measure the pressure gradients across lesions during pull back with hyperemia to decide which lesion is to be stented.

ÂÂ

In LM with LAD disease to decide which lesion is significant, place the pressure wire distal to LAD lesion; achieve adenosine hyperemia and record FFR: zz FFR >0.80: Both lesions insignificant, no stenting zz ≤0.80 and ≤0.60: Treat LAD and repeat FFR to assess LM stenosis zz ≤0.80 and >0.60: Place pressure wire in LCx to assess LM FFR zz FFR apparent: >0.80 - Stent LAD lesion; ≤0.80 Consider treating both LM and LAD lesions.

What is the Role of OCT Guidance in Calcified Lesions?

Dr Balbir Singh, Gurugram The presence of calcified and rigid lesions makes PCI challenging. Adjuvant techniques are often required to achieve satisfactory stent results. Angiography has low sensitivity (48%) for calcium detection, except for severe calcification. Optical coherence tomography (OCT) is a tool that precisely detects calcium as a signal poor heterogeneous region with sharply defined borders. OCT estimates the area of calcification more accurately than intravascular ultrasound (IVUS) as the light penetrates calcium without shadowing. OCT also helps the operator to distinguish between superficial and deep calcium with accurate measurement of the minimum distance from the lumen, the thickness of the calcium, and arc of calcium. OCT could thus be a more useful clinical tool for quantifying calcified lesions. Total calcium arc >180° and increased calcium thickness of >0.5 mm are associated with greater risk of stent underexpansion. OCT is the ideal method to capture these parameters and indicate or defer the use of atherectomy before stent implantation and guide optimization of PCI. How can we Benefit the Patients by Incor­ porating Newer Technologies into Practice?

Dr Rajesh Dave, USA Interventional technologies in the field of Cardiology have changed the way diseases are diagnosed and

IJCP Sutra: "Take steps to combat stress as this lowers your immune system function."

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

treated. Interventional Cardiologists are faced with challenging situations every day with decisionmaking in terms of whether to proceed with stenting or surgery, ascertaining the correct stent placement, especially in case of multivessel disease, calcified lesions, long blockages, edge dissection as well as need for revascularization in intermediate lesion.

Newer technologies, like OCT, are a great help in planning of interventional strategies and optimization before and after the stent deployment, particularly with complex diseases. New age imaging tools help improve patient outcomes by limiting geographic misses, stent malapposition, under-expansion, etc., thus translating into better long-term clinical results.

FFR to Guide Precision PCI of CAD Dr Ajit Mullasari, Chennai Unlike coronary angiography alone, fractional flow reserve (FFR) assists interventional cardiologists in accurately determining whether coronary atherosclerotic plaques are responsible for myocardial ischemia, and need to be revascularized.

FFR is unparalleled in diagnostic accuracy when compared to nonhyperemic indices and noninvasive techniques. It continues to be the gold standard for detection of ischemia-inducing coronary stenoses.

FFR-guided PCI has been found to be superior to angiography-guided PCI and over medical therapy alone.

FAME 2 trial investigators clearly demonstrated that in patients with stable CAD, FFR-guided PCI, as compared with medical therapy alone, improved the outcome. A meta-analysis supported current guidelines advising FFR-guided PCI strategy for CAD. FFR-guided PCI was found to be associated with lower MACE/MACCE, death, MI, repeat revascularization, and death or MI than angiography-guided PCI strategy.

Revascularization guided by FFR in patients with CAD and stenoses >50% yields better outcomes than revascularization based on a visual analysis of angiographic stenosis severity alone.

DEFER and FAME trials have shown that in patients with stable CAD, conservative management of stenoses that could be angiographically severe, but are not hemodynamically relevant, is safe.

FFR is, therefore, an ideal tool to guide treatment in CAD.

Conference Proceedings Durable Polymer DES vs. Biodegradable Polymer DES Dr Keyur Parikh, Ahmedabad Durable polymer DES (DP-DES) have been studied in a large number of patients and also in those with comorbidities like diabetes, high bleeding risk, etc., along with complex lesions like chronic total occlusion (CTO), left main, etc. Biodegradable polymer DES (BPDES) have not demonstrated superiority to DP-DES. BP-DES still have to prove superiority in terms of safety and efficacy in complex lesions. BP-DES change to BMS following drug-elution, and in clinical and pre-clinical trials, DP-DES have proven to be superior to BMS. BP-DES have still not shown superiority of safety and efficacy vs. current generation DP-DES in randomized clinical trials.

Researchers showed in ISAR-TEST (Intracoronary Stenting and Angiographic Results: Test Efficacy of 3 Limus-Eluting Stents) 4 that in head-to-head comparisons between three DES, biodegradable polymers did not make for better long-term outcomes.

BP-DES have, at best, been shown to be noninferior to the durable-polymer standard. There seems to be no real late advantage to BP-DES. DAPT Duration and Regimen Prof (Dr) Ashok Seth, New Delhi Dual antiplatelet therapy (DAPT) is the cornerstone of pharmacological treat­ ment aimed at preventing the atherothrombotic complications in patients with several coronary artery disease (CAD) manifestations.

Physicians face several challenges while prescribing DAPT that include selecting the appropriate P2Y12 inhibitor and determining the optimal duration of DAPT while minimizing the risk of ischemic and bleeding complications in light of each patient’s clinical characteristic and circumstance.

The ACC/AHA guidelines recommend that for patients with ACS treated with DAPT following BMS or DES implantation, P2Y12 inhibitor therapy (clopidogrel, prasugrel, or ticagrelor) should be given for at least 12 months. In patients treated with DAPT, a daily aspirin dose of 81 mg (range, 75 mg to 150 mg) is recommended. The guideline further recommends that in patients treated with DAPT after coronary stent implantation who subsequently undergo CABG, P2Y12 inhibitor therapy should be resumed postoperatively so that DAPT continues until the recommended duration of therapy is completed. In patients with ACS

IJCP Sutra: "Sleep well as it reduces cortisol produced by the body during stress. It also balances leptin, which determines how much food we eat."

179

Conference Proceedings (NSTE-ACS or STEMI) being treated with DAPT who undergo CABG, P2Y12 inhibitor therapy should be resumed after CABG to complete 12 months of DAPT therapy after ACS. Additionally, in patients with ACS managed with medical therapy alone (without revascularization or fibrinolytic therapy) and treated with DAPT, P2Y12 inhibitor therapy (clopidogrel or ticagrelor) should be continued for at least 12 months.

According to the ESC guidelines, for stable CAD patients treated with PCI, the duration of DAPT is 1-6 months depending on the bleeding risk. For patients in whom the ischemic risk prevails over the risk of bleeding, a longer DAPT duration may be considered. For ACS patients irrespective of the final revascularization strategy (medical therapy, PCI, or CABG), the default DAPT duration is 12 months. Sixmonth therapy duration should be considered in high bleeding risk patients, while >12-month therapy may be considered in ACS patients who have tolerated DAPT with a low bleeding risk. Clopidogrel is considered the default P2Y12 inhibitor in patients with stable CAD treated with PCI, those with an indication for concomitant oral anticoagulation, as well as in ACS patients in whom ticagrelor or prasugrel are contraindicated. Some studies have found no increased risk of stent thrombosis with shorterduration DAPT (3-6 months). A shorter duration of DAPT results in fewer bleeding complications. Shorterduration DAPT may be most reasonable in patients currently being treated with “newer-generation” (eg, everolimus-eluting) DES, which are associated with lower stent thrombosis and MI rates than those of “first-generation” DES. In line with this, the STOPDAPT trial assessed the outcome with 3-month DAPT duration after CoCr-EES implantation. The event rates beyond 3 months were very low (cardiovascular death: 0.5%, MI: 0.1%, ST: 0%, stroke: 0.7%, and TIMI major/minor bleeding: 0.8%).

Cumulative 1-year incidence of the primary endpoint (composite of cardiovascular death, MI, stroke, definite stent thrombosis (ST) and TIMI major/minor bleeding) was 2.8%, which was lower than the pre-defined performance goal of 6.6%. Using the CoCr-EES group in the RESET trial as a historical comparison group, where about 90% of patients had continued DAPT at 1 year, cumulative incidence of the primary endpoint tended to be lower in the STOPDAPT than in the RESET (2.8% versus 4.0%) and adjusted hazard ratio was 0.64.

The cumulative incidence of definite/probable ST was lower in the STOPDAPT than in the RESET [0 patient

180

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

(0%) versus 5 patients (0.3%)]. The study concluded that stopping DAPT at 3 months in selected patients after CoCr-EES implantation was at least as safe as the prolonged DAPT regimen adopted in the historical control group.

Decisions about the timing of surgery and whether to discontinue DAPT after coronary stent implantation must be individualized. Such decisions involve weighing the particular surgical procedure and the risks of delaying the procedure, the risks of ischemia and stent thrombosis, and the risk and consequences of bleeding.

Why is Stent Quality Important?

Dr MS Hiremath, Pune A stent, once implanted, stays in the patient’s body forever. Stent technologies are complex and all stents are not same. Each brand undergoes varied innovation and testing procedures.

Therefore, it is important that a good quality stent, with a proven safety and efficacy profile from long-term clinical data from various clinical trials is selected for the patients. DES brands approved by US FDA offer the most robust technology, stringent approval process and best clinical evidence.

The key expectations from a stent include - Good deliverability and flexibility; good scaffolding; high radial strength with minimum recoil; good visibility; minimal foreshortening; side branch accessibility; appropriate metal to artery ratio; biocompatibility; optimal stent delivery system; variety of size and lengths; drug and polymer.

Along with all of these factors the comorbidity of the patient and lesion should be taken into account, so it is very important to select a stent which has an indication approval such as diabetes mellitus, CTO, ACS, etc., which is suitable for the lesion and the patient.

How can OCT Help in Improving Outcomes in Bifurcations Lesions?

Dr Rajneesh Kapoor, Gurugram Optical coherence tomography (OCT) has approximately 10 times higher resolution than IVUS. It can precisely measure lumen diameters in the variable geometry of a bifurcation lesion and identify superficial lipid laden plaques and calcium, relevant to confirm the severity of the lumen obstruction prior to treatment and guide location and diameter of the stent. OCT produces fewer strut-induced artifacts and

IJCP Sutra: "Searing and sautéing foods in a pan builds flavor. Roasting brings out the natural sweetness of many vegetables and the taste of fish and chicken. If you do steam or microwave food, perk up these dishes with a finishing drizzle of flavorful oil and a squeeze of citrus."

Conference Proceedings

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

offers precise evaluation of strut apposition in a reallife clinical setting. The increase in the speed of image acquisition with the introduction of frequency domain OCT allows rapid pull-back at a speed of 36 mm/sec, minimizing the amount of contrast required to clear blood during image acquisition. This enables serial OCT acquisitions, particularly before treatment if the lesion is not very severe and flow is expected to be present around the OCT catheter, after predilatation and to assess and guide stent expansion.

Repeated OCT examinations at follow-up can help in the detection of presence and characteristics of strut coverage, which can predict late stent thrombosis.

These applications are of particular interest in the context of bifurcation lesion treatment as this condition is still associated with a higher number of malapposed stent struts and frequent impairment of stent expansion.

OCT can provide unique insights in the setting of bifurcation lesions by enabling detailed evaluation of coronary bifurcation pathology and facilitating procedural planning. OCT imaging has contributed enormously to the optimization of bifurcation stenting techniques. With its high resolution, OCT enables interventionalists to re-cross proper stent cell, which is the key procedure in both provisional stenting and 2-stent techniques. Poststenting OCT imaging provides unique information for further optimal treatment strategy.

OCT is a better tool as compared to angiography as it depicts ostial lesions in bifurcation without the misleading two-dimensional appearance of angiography such as overlap and foreshortening. OCT can help reconstruct a bifurcation in three dimensions and can assess the side branch ostium from 3D reconstruction of the main vessel pull-back, which can be applied to ensure optimal re-crossing position of the wire after main vessel stenting.

Its ability to provide unique information on the plaque at high risk for rupture, plaque composition, thickness of fibrous cap, the presence of macrophage and thrombi has assisted in simple PCI as well as in complex bifurcation lesions PCI. OCT helps provide valuable anatomic information to optimize stent implantation and adapt PCI strategy in individual patients.

OCT in CTO: Strong Clinical Evidence Dr Girish Navasundi, Bengaluru PCI of CTOs is challenging. It is associated with low success rates, increased restenosis and reocclusion.

CTOs of arteries are more challenging lesions to treat with angioplasty and stenting as compared to stenotic vessels primarily on account of the difficulty in guiding the wire across the lesion. Angiography alone cannot differentiate between the occluded lumen and the vessel wall and to characterize the content of the occlusion.

Angiography provides a two-dimensional image of contrast-filled lumen, and does not allow an accurate assessment of the plaque.

OCT is a high resolution imaging technique that can improve the understanding of the vascular response after stenting of chronically occluded vessels. OCT correctly identifies tissue composition within the CTO, such as the presence of collagen and calcium and can identify intraluminal microchannels. OCT imaging of CTO anatomy and tissue characteristics can possibly result in significant improvements in PCI interventions by providing novel guiding capabilities.

In the ACE-CTO study, OCT was performed 8-months post stenting. High rates of stent strut malapposition and incomplete stent strut coverage were observed after CTO PCI using EES. The study highlighted unique challenges associated with stent implantation in CTOs. The PRISON-IV trial showed inferior outcome in patients with CTOs treated with the ultrathin-struts (60 μm for stent diameter ≤ 3 mm, 81 μm >3 mm) hybrid-sirolimus eluting stents (SES) compared with everolimus eluting stents (EES, 81 μm). A recent study evaluated if the use of smaller stents (≤3 mm) was responsible for the inferior outcome reported in the trial. The study population was divided according to the different size of stents implanted in those receiving only stents with diameter ≤3 mm (Group-A, 178 patients), only stents >3 mm (Group-B, 59 patients), and those receiving stents of both sizes (Group-C, 93 patients). OCT was performed in 60 patients at follow-up, and documented a mild trend toward lower values of minimum in stent area in Hybrid-SES arm of Group A (4.4 ± 1.02 mm2 vs 5.0 ± 1.28 mm2, respectively, P = 0.16).

OCT can thus provide significant information in CTOs.

■■■■

IJCP Sutra: "Exercises and stretches can help maintain strength and stop joints becoming stiff in children with spinal muscular atrophy.

Although the amount of exercise will depend on the condition, it's best to try and stay as active as possible."

181

Around the Globe

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

News and Views Clinical Practice Guidelines 2019 Acute lower gastrointestinal bleeding: 10 Key Takeaways This year, the British Society of Gastroenterology released clinical practice guidelines on the diagnosis and management of acute lower gastrointestinal (GI) bleeding published online April 8, 2019 in the BMJ. Here are 10 key takeaways from the guidelines.

1. Patients who present with low GI bleeding should be first categorized as unstable (shock index >1) or stable. The Oakland score can be used to categorize stable bleeds as minor or major. Patients with minor self-terminating bleed (Oakland score ≤8) can be discharged for urgent outpatient investigation, if there are no indications for hospitalization. But patients with major bleed should be hospitalized for colonoscopy on the next available list.

2. Before planning endoscopic or radiological therapy, localize the site of bleeding quickly and least invasively via CT angiography in hemodynamically unstable patients or those who have shock index >1 after initial resuscitation and/or in whom active bleeding is suspected.

3. If no source of bleeding can be identified on initial CT angiography in hemodynamically unstable patients, an upper GI endoscopy should be performed immediately. Gastroscopy may be the first investigation when patient stabilizes after initial resuscitation.

4. If a source of bleeding is found on CT angiography, a catheter angiography with a view to embolization should be done at the earliest. Centers with a 24/7 interventional radiology service should be capable of performing catheter angiography for hemodynamically unstable patients within 60 minutes of admission.

5.

Patients should not proceed to emergency laparotomy unless an exhaustive effort has been made to localize the source of bleeding using radiologic and/or endoscopic modalities.

6.

Restrictive red blood cell (RBC) thresholds (Hemoglobin [Hb] trigger 70 g/L and Hb concentration target of 70-90 g/L post transfusion)

182

should be used in clinically stable patients who need RBC transfusion. The trigger and target should be 80 g/L and 100 g/L, respectively in patients with a history of cardiovascular disease.

7.

Interrupting warfarin therapy at presentation is recommended. In patients with low thrombotic risk, warfarin should be restarted at 7 days after hemorrhage. In patients with high thrombotic risk (i.e., prosthetic metal heart valve in mitral position, atrial fibrillation with prosthetic heart valve or mitral stenosis, <3 months after venous thromboembolism), low molecular weight heparin (LMWH) should be considered at 48 hours after the bleeding.

8.

Permanently discontinue aspirin for primary prophylaxis of cardiovascular events. But, restart aspirin for secondary prevention, if stopped, as soon as hemostasis is achieved.

9. Routine stopping of dual antiplatelet therapy with a P2Y12 receptor antagonist and aspirin is not recommended in patients with coronary stents in situ; a cardiologist should be part of the management team. Continue aspirin if P2Y12 receptor antagonist is interrupted in unstable hemorrhage; restart P2Y12 receptor antagonist within 5 days.

10.

Direct oral anticoagulant therapy should be interrupted at presentation. Treatment with inhibitors such as idarucizumab or andexanet should be considered for life-threatening hemorrhage in patients on direct oral anticoagulants.

Restart direct oral anticoagulant drug treatment at a maximum of 7 days after the bleeding.

(Source: Oakland K, Chadwick G, East JE, et al. Diagnosis and management of acute lower gastrointestinal bleeding: guidelines from the British Society of Gastroenterology.

Gut. 2019;68(5):776-89).

Evaluate Gait Speed as a ‘Vital Sign’ to Predict Prognosis in Older Adults with Blood Cancers Gait speed is an easily obtained ‘vital sign’ that accurately identifies frailty and predicts survival and unplanned hospital visits regardless of age, cancer or treatment type, or other factors among older patients with hematologic cancers, according to a new study published June 5, 2019 in the journal Blood. This

IJCP Sutra: "There are exercises that can be done to strengthen the breathing muscles and make coughing easier."

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

Around the Globe

association was found to be strongest in those with nonHodgkin lymphoma.

New Guidelines Issued on Sexually Transmitted Infections

For every 0.1 meter per second decrease in gait speed, the risk of dying, unexpectedly going to the hospital, or ending up in the emergency room increased by 22%, 33% and 34%, respectively.

Updated guidelines on sexually transmitted infections (STIs) address a number of dermatologic manifestations that are not always included in recommendations from other specialty groups, delegates heard at the World Congress of Dermatology 2019.

Every 5 kg decrease in grip strength was associated with worse survival, but not hospital or ED use.

Monitoring gait speed not only helps to recognize individuals who are frail and may fare worse, it also identifies people who are in much better shape than expected based on age alone.

Researchers suggest that gait speed should be used as a routine part of medical assessments along with other vital signs to improve patient assessment, prognostication and individualization of care.

Collaboration Between France and WHO to Realize the Vision of the WHO Academy Emmanuel Macron, President of the French Republic and Dr Tedros Adhanom Ghebreyesus, WHO DirectorGeneral met at WHO Headquarters in Geneva and signed a Declaration of Intent to establish the WHO Academy that will revolutionize lifelong learning in health.

The Academy aims to reach millions of people with innovative learning via a state-of-the-art digital learning experience platform at a campus in Lyon and embedded in the six WHO regions. The WHO Academy Lyon hub will feature high-tech learning environments, a world-class health emergencies simulation center and collaboration spaces for learning co-design, research and innovation...(WHO)

One-in-Five Suffers Mental Health Condition in Conflict Zones: UN Figures More than one-in-five people living in conflict-affected areas suffers from a mental illness, according to a new report based on UN figures, prompting the WHO to call for increased, sustained investment in mental health services in those zones.

Around 22% of those affected, suffer depression, anxiety or post-traumatic stress disorder, according to an analysis of 129 studies published in The Lancet.

The study also shows that about 9% of conflict-affected populations have a moderate to severe mental health condition; substantially higher than the global estimate for these mental health conditions in the general population...(UN)

Diagnosing and treating genital lumps and lacerations are necessary, said Marco Cusini, MD, from the Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico in Milan, who was onsite representing the International Union Against Sexually Transmitted Diseases (IUSTI), which recently issued the guidance (J Eur Acad Dermatol Venereol).

An important aspect of the updated IUSTI guidelines is that they urge doctors to be mindful of several high-risk populations. Sex workers, gay men and transgender people are all at risk for STIs. The update expands information on how to treat transgender patients.

TAVR on Bicuspid Valves may Carry Early Risks People with bicuspid aortic stenosis had an early disadvantage for stroke after getting transcatheter aortic valve replacement (TAVR) with a balloon-expandable valve, researchers found from the TVT Registry.

While post-TAVR mortality rates were similar between Sapien 3 recipients with two- and three-leaflet anatomy, early stroke was more common with bicuspid valves before reaching statistical equivalency at 1 year.

The bicuspid group also experienced significantly more procedural complications requiring open heart surgery (0.9% vs. 0.4%), according to a group led by Raj Makkar, MD, of Cedars-Sinai Medical Center in Los Angeles, in a preliminary report in JAMA.

No Link Between HIV Infection and Contraceptive Methods, Says Study A large clinical research study conducted in four African countries found no significant difference in risk of human immunodeficiency virus (HIV) infection among women using one of three highly effective, reversible contraceptive methods - depot medroxyprogesterone acetate (DMPA) intramuscular, levonorgestrel implant and a copper-bearing intrauterine device (IUD).

Published in the Lancet, the study showed that each method had high levels of safety and effectiveness in preventing pregnancy, with all methods well-accepted by the women using them.

IJCP Sutra: "It is important for children with spinal muscular atrophy to get the right nutrients for healthy growth and development.

A dietitian can offer advice about feeding and diet."

183

Around the Globe “These results support making available to women and girls a broad choice of effective contraceptive methods that empower them to make informed decisions about their own bodies - including if and when to have children,” said Dr James Kiarie, from the Dept. of Reproductive Health and Research at the WHO…(WHO)

Yemen: Maternal and Newborn Health “on the Brink of Total Collapse”, UNICEF Alerts After more than 4 years of grinding conflict in Yemen, health care for mothers and their babies is “on the brink of collapse”, the UN Children’s Fund (UNICEF) warned in a report that highlights the difficulties of childbirth and parenting in a war zone.

According to UNICEF, 1 woman and 6 newborns die every 2 hours from complications during pregnancy or childbirth. The years of intense fighting in the country have contributed to limited access to crucial health care, with only 3 out of 10 births taking place in regular health facilities.

The results are part of a series compiled by the agency, Childbirth and parenting in a war zone…(UN)

Fecal Transplants may Transmit Deadly Drugresistant Infections, FDA Warns The US Food and Drug Administration (FDA) alerted health care providers and patients that fecal microbiota for transplant (FMT) may transmit multidrug-resistant organisms, leading to serious or life-threatening infections. In a safety communication, the FDA said two immunocompromised adults who received FMT developed invasive bacterial infections caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli. One of the patients died…(Medscape)

Restless Legs Syndrome Tied to Gut Health Preliminary research suggests an association between small intestine bacterial overgrowth (SIBO) and restless legs syndrome (RLS), supporting emerging research linking gut microbial health to sleep health.

While the study is ongoing and recruitment just beginning, the researchers found SIBO in all 7 RLS patients studied to date. The study was presented at SLEEP 2019: 33rd Annual Meeting of the Associated Professional Sleep Societies.

Novel Sickle Cell Drug Improves Hemoglobin Characteristics For sickle cell disease, novel oral agent voxelotor improved hemoglobin characteristics in the phase III HOPE trial.

184

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

Levels of normal hemoglobin levels rose >1.0 g/dL from baseline at week 24 - a degree associated with significantly decreased rates of multiorgan failure and death in natural history studies, and considered a “response” - for 51% of patients randomized to the 1,500 mg of voxelotor group compared with 7% of those on placebo (p < 0.001) in the intention-to-treat analysis for the primary endpoint. The findings were published online in the New England Journal of Medicine.

Meeting of the International Health Regulations (2005) Emergency Committee for Ebola Virus Disease in DRC The meeting of the Emergency Committee convened by the WHO Director-General under the International Health Regulations (IHR) (2005) regarding Ebola virus disease in the Democratic Republic of the Congo (DRC) took place on June 14, 2019.

The Committee expressed its deep concern about the ongoing outbreak, which, despite some positive epidemiological trends, especially in the epicentres of Butembo and Katwa, shows that the extension and/or reinfection of disease in other areas like Mabalako, presents, once again, challenges around community acceptance and security.

It was the view of the Committee that the outbreak is a health emergency in DRC and the region but does not meet all the three criteria for a PHEIC under the IHR. While the outbreak is an extraordinary event, with risk of international spread, the ongoing response would not be enhanced by formal Temporary Recommendations under the IHR (2005)…(WHO)

Federal Officials Seized Adulterated Dietary Supplements from Life Rising Corporation due to Poor Manufacturing Practices At the request of the US FDA, US Marshals seized more than 3,00,000 containers of dietary supplements, including tablets, capsules and teas from Life Rising Corporation. The seized goods consisted of more than 500 products bearing brand names Life Rising, Holicare or HopeStream, and are valued at approximately $3.5 million.

The FDA inspection at Life Rising found that its dietary supplements were prepared, packed and/or held under conditions that violated Current Good Manufacturing Practice (CGMP) regulations. Among other observed deficiencies, the company failed to establish product specifications for the identity, purity, strength and composition of each finished batch of dietary supplement,

IJCP Sutra: "Wait until the afternoon to shop for shoes - your feet naturally expand with use during the day and may swell in hot weather."

Around the Globe

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

and for limits on certain types of contamination, to ensure the quality of the supplement... (FDA)

Gabapentinoids Tied to Suicidal Behavior and Unintentional Overdose Gabapentinoid prescriptions were associated with an increased risk of suicidal behavior and unintentional overdose, a population cohort study in Sweden showed.

The risks were strongest for people who were prescribed pregabalin over gabapentin, especially among young people, reported Seena Fazel, MD, of the University of Oxford in England, and colleagues in The BMJ.

IL-17a Drug Rescues Many Refractory Psoriatic Arthritis Cases Despite having been treated with numerous regimens, including multiple attempts with biologic agents, many patients with psoriatic arthritis benefited from a 6-month course of secukinumab in a “real-world” analysis reported at the European Congress on Rheumatology.

Among 177 heavily pretreated patients, 47% achieved remission or low disease activity as measured by the DAPSA (Disease Activity in Psoriatic Arthritis) score, reported Maria Martin-Lopez, MD, of Hospital Universitario 12 de Octubre in Madrid.

Amid Measles Outbreak, New York Ended Religious Exemptions for Vaccines Amid a measles outbreak, New York required schoolchildren to be vaccinated, even if parents have religious objections.

Gov. Andrew Cuomo signed a legislation that removes nonmedical exemptions from school vaccination requirements.

The move, which came despite opposition from antivaccination activists and religious freedom advocates, put New York alongside other states that do not allow nonmedical exemptions: California, Mississippi, West Virginia and Maine…(CNN)

Leuprorelin Depot Handling Errors Prompt EMA Review Reports of handling errors with depot formulations of leuprorelin (leuprolide acetate) prompted the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) to launch a review.

The reports indicate that “handling errors during preparation and administration can cause some patients

to receive insufficient amounts of their medicine, thus reducing the benefits of treatment,” the EMA said in a news release.

The review only covered depot formulations that are given by injection under the skin or into a muscle and that release the active substance slowly over 1 to 6 months.

These products include implants as well as powders and solvents for the preparation of injections…(Medscape)

Incivility in ORs Linked to Diminished Clinical Performance Research on anesthesiology residents exposed to incivility in a simulated operating room (OR) environment indicates that rudeness in the OR has a negative impact on clinician performance.

The recent research published in BMJ Quality & Safety exposed anesthesiology residents to an impatient surgeon-actor in a simulated OR hemorrhage scenario.

Compared to a control group of residents who were not exposed to an impatient surgeon-actor, the experimental residents scored lower on all four performance metrics in the study: vigilance, diagnosis, communication and patient management.

Father’s Smoking During Pregnancy Tied to Asthma in Kids Children who are exposed to tobacco smoke from their fathers while they are in the womb may be more likely than those who are not to develop asthma by age 6, according to a study of chemical changes to DNA. While prenatal smoke exposure has long been linked to an increased risk of childhood asthma, the current study offers fresh evidence that it’s not just a pregnant mother’s smoking that can cause harm. The findings are published in Frontiers in Genetics.

FDA Approves New Treatment for Pediatric Patients with Type 2 Diabetes The US FDA approved liraglutide injection for treatment of pediatric patients 10 years or older with type 2 diabetes. Liraglutide is the first non-insulin drug approved to treat type 2 diabetes in pediatric patients since metformin was approved for pediatric use in 2000.

The drug has been approved to treat adult patients with type 2 diabetes since 2010... (FDA.)

Researchers Find Way to Convert Type A Blood to Type O Researchers have found a way to use a pair of enzymes from a human gut bacterium to convert type A to the

IJCP Sutra: "Wear the same type of socks that you intend to wear with the shoes."

185

Around the Globe universal donor type O blood, according to a report published in Nature Microbiology.

The researchers say the high activity and specificity of these enzymes “make these very promising candidates for cost-efficient implementation into the already existing automated routines of blood collection, processing and storage, with major implications for the flexibility of our blood supply and possible applications in organ transplantation.”

Necrotizing Infections Rise with Warming Oceans, Study Shows As ocean temperatures increase, serious Vibrio vulnificus infections are on the rise in previously nonendemic areas, according to a case series published online in Annals of Internal Medicine. This emerging Vibrio risk in nonendemic areas means clinicians need to be aware of the infection, especially if they have never seen a case in their practice. The bacterium typically lives in warm seawater.

WHO Offers a New Tool and Sets a Target to Accelerate Action Against Antimicrobial Resistance WHO has launched a global campaign urging governments to adopt a tool to reduce the spread of antimicrobial resistance, adverse events and costs.

The AWaRe tool was developed by the WHO Essential Medicines List to contain rising resistance and make antibiotic use safer and more effective. It classifies antibiotics into three groups – Access, Watch and Reserve – and specifies which antibiotics to use for the most common and serious infections, which ones should be available at all times in the healthcare system, and those that must be used sparingly or preserved and used only as a last resort. The new campaign aims to increase the proportion of global consumption of antibiotics in the Access group to at least 60%, and to reduce use of the antibiotics most at risk of resistance from the Watch and Reserve groups...(WHO)

UN Environment Agency Tackles Climate Change One Bite at a Time

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

aspiring chefs were challenged to share dishes that were not only delicious, but good for people and the planet, with an emphasis on reducing meat and promoting plant-based diets...(UN)

Convicted Physicians Received Message of Support from World’s Doctors On behalf of millions of physicians globally, the World Medical Association (WMA) delivered an open message of support to all Turkish doctors, and in particular to those sentenced to prison, for declaring in a press release that “war is a public health problem’. In an open letter, WMA leaders denounced ‘the pervasive obstruction campaign” by the Turkish state against doctors and declared: “We are shocked and deeply disturbed by the recent decision of the Criminal Court of Ankara which condemned TMA’s Central Council members to prison sentences for their call for peace. This is pure aberration”.

The public statement “War is a Public Health Problem” was issued as a press release on January 24, 2018 by 11 doctors as members of the Central Council of Turkish Medical Association...(WMA)

Osteoporosis Drugs may Help Oldest, Sickest Women Most Frail, very elderly women with osteoporosis may benefit the most from osteoporosis drugs, according to a study published online in JAMA Internal Medicine.

Women older than 80 years with osteoporosis and multiple medical problems or poor prognosis had more than triple the risk for hip fracture in the next 5 years, compared with women in the same age group who had increased fracture risk but no osteoporosis.

“Clinicians should consider the initiation of drug treatment to prevent fracture in late-life women with osteoporosis (bone mineral density [BMD] T-score -2.5 or below) and multiple comorbidities, as this group of women may derive the greatest absolute benefit of treatment in preventing future hip fractures,” author Kristine Ensrud, MD, MPH, University of Minnesota, Minneapolis, said.

If we all change the way we eat, we can make significant progress in the fight against climate change. This was the message from the` UN environment agency (UNEP) on Sustainable Gastronomy Day - June 18, as it launched a new campaign to encourage healthy and sustainable food choices.

Novel Agent Shows Promise as First Possible Therapy for Achondroplasia

As part of its #ActNow initiative, a global call to individual action on climate change, professional and

A phase 2, proof of concept study found that treatment with vosoritide, a recombinant C-type natriuretic peptide

186

The results are preliminary, but a novel investigative agent has shown promise in a small trial in children for the treatment of achondroplasia, the most common form of human dwarfism.

IJCP Sutra: "Have the salesperson measure both of your feet. If one foot is larger or wider than the other, buy a size that fits the larger foot."

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

analogue, demonstrated a favorable safety profile and efficacy at a dose of 15 μg/kg. The findings were published online in the New England Journal of Medicine.

WHO Flags Critical Funding Gap, Calls for Political Parties to Join Fight Against Ebola The Ebola outbreak in the DRC will only end with bipartisan political cooperation and community ownership, according to the WHO’s Director-General, Dr Tedros Adhanom Ghebreyesus. He was speaking to Member States in Geneva after returning from a visit to DRC, where he reviewed the health response and met with leaders from multiple sectors to galvanize their commitment.

WHO’s funding needs for the response are US$98 million, of which US$44 million have been received, leaving a gap of US$54 million. The funding shortfall is immediate and critical: if the funds are not received, WHO will be unable to sustain the response at the current scale…(WHO)

Cardiac MRI Safely Reduces Invasive Tx for Stable Angina A noninvasive approach to imaging for stable angina in patients with risk factors for coronary artery disease (CAD) reduces invasive treatment without greater risk of a major cardiac event, the MR-INFORM trial showed.

A strategy of myocardial-perfusion cardiovascular MRI led to revascularization for 35.7% of patients, whereas the rate was 45.0% for those who had invasive angiography and measurement of fractional flow reserve (FFR).

Only 48.2% of the MRI group ended up with invasive angiography (compared with nearly the entire FFR group), despite a pretest likelihood for CAD of 75%, Eike Nagel, MD, of Goethe University Frankfurt, Germany, and colleagues reported online in the New England Journal of Medicine.

CARMELINA: Linagliptin Safe in Diabetes Across Age, Renal Groups In patients with type 2 diabetes and either cardiovascular disease or impaired kidney function, the dipeptidyl peptidase 4 (DPP-4) inhibitor linagliptin demonstrated cardiovascular safety, no increased risk of hospitalization for heart failure and “reassuring” kidney safety including a reduction in albuminuria across renal function and age groups - over 2.2 years.

These findings, from the Cardiovascular and Renal Microvascular Outcome Study With Linagliptin (CARMELINA) outcome trial, showed that safety of the

Around the Globe agent can be extended to older patients and those with worse kidney function, researchers report.

The findings were presented at the American Diabetes Association (ADA) 2019 Scientific Sessions.

New Multi-Partner Trust Fund Launched to Combat Antimicrobial Resistance Globally Noordwijk, the Netherlands: In a major boost to combat one of the gravest risks to global health, a dedicated funding vehicle allowing partners to devote resources to accelerate global action against Antimicrobial Resistance (AMR) was unveiled at a Ministerial Conference.

The Tripartite - a joint effort by the Food and Agriculture Organization (FAO), the World Organization for Animal Health (OIE) and the WHO, launched the AMR Multi-Partner Trust Fund, which is being supported by an initial contribution of US$5 million from the Government of the Netherlands. The AMR Trust Fund has a 5-year scope, through 2024, and aims to scale up efforts to support countries to counter the immediate threat of AMR…(WHO)

FDA Expands Approval of Treatment for Cystic Fibrosis to Include Patients Ages 6 and Older The US FDA has expanded the indication for a combination of tezacaftor/ivacaftor tablets for treatment of pediatric patients ages 6 years and older with cystic fibrosis who have certain genetic mutations. Last year, the FDA approved the combination to treat patients ages 12 and older who had the same specific genetic mutations. The approval for children as young as 6 years old provides an important treatment option for younger patients, and also provides more context on the safety and dosing specific to this population…(FDA)

Expected Shortage of TB Tests Prompts New CDC Recommendations The CDC issued new recommendations for tuberculosis (TB) skin testing in response to the anticipated 3- to 10-month nationwide shortage of a purified-protein derivative (PPD) tuberculin antigen approved by the US FDA for tuberculin skin tests (TSTs).

The report was published in MMWR. The CDC’s recommendations were intended to address the potential decrease in TB testing because of the shortage.

CDSCO Issues Alert for Security Risk to Certain Medtronic Insulin Pumps Vide a notice File No: 29/Misc/03/2019-DC (100) dated July 2, 2019, the Central Drugs Standard Control

IJCP Sutra: "Stand in the shoes: Make sure you have at least a quarter-to a half-inch of space between your longest toe and the end of the shoe."

187

Around the Globe Organization (CDSCO) has issued a medical device alert for some insulin pumps manufactured by Medtronic.

The MiniMed™ Paradigm™ series insulin pumps (MMT715, MMT-712, MMT-722, MMT-754) are designed to communicate using a wireless radio frequency (RF) with other devices such as a blood glucose meter, glucose sensor transmitters and CareLink™ USB devices. Security researchers have identified potential cybersecurity vulnerabilities related to these insulin pumps.

An unauthorized person with special technical skills and equipment could potentially connect wirelessly to a nearby insulin pump to change settings and control insulin delivery.

The CDSCO has advised the following actions for Medical Directors/Health care professionals, Distributors and the Users and Staff involved in the management of patients. ÂÂ

Check to see if the model and software version of your insulin pump is affected.

ÂÂ

Talk to your health care provider about a prescription to switch to a model with more cybersecurity protection.

ÂÂ

Keep your insulin pump and the devices that are connected to your pump within your control at all times whenever possible.

ÂÂ

Do not share your pump serial number.

ÂÂ

Be attentive to pump notifications, alarms and alerts.

ÂÂ

Monitor your blood glucose levels closely and act appropriately.

ÂÂ

Immediately cancel any unintended boluses.

ÂÂ

Connect your Medtronic insulin pump to other Medtronic devices and software only.

ÂÂ

Disconnect the USB device from your computer when you are not using it to download data from your pump.

The alert comes a week after the US FDA issued a warning to patients and health care providers that certain Medtronic MiniMed insulin pumps are being recalled due to potential cybersecurity risks…

(Source: CDSCO)

Malaria to be Made Notifiable Disease Monsoons bring welcome relief from the scorching heat, but they also bring with them a host of illnesses, notably dengue, Chikungunya.

188

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

In a meeting held to review the preparedness for prevention and control of vector-borne diseases (malaria, dengue and chikungunya) in the national capital, the Union Health Minister, Dr Harsh Vardhan urged the state government and the Mayors to work towards making hospitals, schools and government buildings 'Vector-Free'.

He also suggested that Malaria should be made a notifiable disease, which was assured by the Delhi Health Minister.

In the meeting, it was also suggested that all hospitals, including the private ones, should appoint a nodal person for vector-borne diseases to ensure that the Government and private interventions and efforts to prevent/cure vector-borne diseases are in tandem. The focus should be on active case finding of cases and reduction of vectors.

What each doctor can do ÂÂ

Ask every suspected case of dengue, chikungunya or malaria to trace the mosquito breeding site in the vicinity of 50 houses.

ÂÂ

Surgical strikes on all the mosquitoes in the vicinity of identified cases can make the difference.

Low Vitamin D in Early Childhood Predicts High BP in Adolescence Deficiency or insufficient levels of vitamin D in early childhood predisposes children to greater risk of high blood pressure (BP) during later childhood and adolescence. ÂÂ

Compared to children born with adequate vitamin D levels, low vitamin D status at birth was associated with higher risk of elevated systolic BP at ages 3-18 years: OR 1.38 (95% CI, 1.01-1.87).

ÂÂ

Low vitamin D status in early childhood was associated with a 1.59-fold (95% CI, 1.02-2.46) higher risk of elevated systolic BP at age 6-18 years.

ÂÂ

Children with persistently low levels of vitamin D through early childhood was associated with higher risk of elevated systolic BP (OR, 2.04 [95% CI, 1.13-3.67]) at ages 3-18 years.

The prospective birth cohort study published in the journal Hypertension followed 775 children from birth to age 18 at the Boston Medical Center. Most lived in a low-income urban area, and about two-thirds were African American.

Based on their findings, the researchers suggest that screening and treatment of vitamin D deficiency with supplementation during pregnancy and early childhood may prevent or reduce high BP later in life.

IJCP Sutra: "Walk around in the shoes to determine how they feel. Is there enough room at the balls of the feet?

Do the heels fit snugly, or do they pinch or slip off? Find shoes that fit from the start."

Around the Globe

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

Venezuela: More Than 2.8 Million People to Gain Access to Safe Drinking Water with UNICEF Support More than 2.8 million people, including Venezuelan children, adolescents and families, will gain improved access to safe drinking water after a collaboration agreement signed between UNICEF and the Government of Venezuela.

As part of the agreement with the Ministry of Water, UNICEF will work on expanding the supply of safe drinking water through systems repair and extension, water-trucking and other alternative sources, strengthening of priority sanitation systems, and providing technical assistance and cooperation in water quality monitoring.

“Water is fundamental to families’ life and dignity.

This agreement will help children and adolescents access safe water, which is critical to their survival and healthy development,” said María Cristina Perceval, UNICEF Regional Director for Latin America and the Caribbean… (UNICEF)

Most Older Adults with “Prediabetes” don't Develop Diabetes Older adults with slightly elevated blood sugar, sometimes called “prediabetes”, usually don’t develop full-blown diabetes, a Swedish study suggests.

Researchers followed 2,575 men and women aged 60 and older without diabetes for up to 12 years. At the start of the study, 36% of the group did have higherthan-normal blood sugar levels that were still below the threshold for diabetes. Only 119 people, 13% of those who started out with elevated blood sugar, went on to develop diabetes. Another 204, or 22%, had blood sugar levels drop enough to no longer be considered prediabetic… (Reuters)

Opioids Overused in Acute Gout Opioids were commonly given to patients as a treatment for acute gout attacks, despite the availability of other effective and appropriate therapies, a retrospective study found.

Among 456 patients who were discharged from the hospital or emergency department (ED) with a primary diagnosis of gout, 28.3% received an opioid prescription, according to Deepan S. Dalal, MD, of Brown University Warren Alpert School of Medicine in East Providence, Rhode Island, and colleagues.

While the median duration of the prescription was 8 days, one-quarter of these patients had prescriptions

for 14 days or more, which exceeds gout attack’s normal expected length, the researchers reported in Arthritis Care & Research.

New Guideline for Trigeminal Neuralgia Released All patients with trigeminal neuralgia (TN) should undergo MRI, a new guideline for diagnosing and treating this condition recommends.

The guideline, developed by a task force of the European Academy of Neurology (EAN), also recommends that neurovascular contact (NVC) should not be used to confirm a diagnosis of primary TN but to determine whether surgery is warranted. In addition, the guideline recommends carbamazepine and oxcarbazepine as first-line prophylactic treatments of TN. Highlights of the guideline were presented at the Congress of the European Academy of Neurology (EAN) 2019.

A Few Pathogens Account for Most Severe Pneumonias in African, Asian Kids A short list of pathogens accounts for most cases of pneumonia requiring hospital admission in children without HIV infection from Africa and Asia, according to results from the PERCH study.

Researchers noted that pneumonia was most commonly due to viral pathogens (61.4%), with respiratory syncytial virus (RSV) causing the greatest number of cases (31.3%).

Bacterial pathogens other than Mycobacterium tuberculosis accounted for 27.3% of cases. Other pathogens accounting for 5% or more of the etiological distribution included human rhinovirus, human metapneumovirus (HMPV) A or B, human parainfluenza virus (types 1-4 combined), Streptococcus pneumoniae, M. tuberculosis and Haemophilus influenzae, the team reports in The Lancet.

Assam Doctors' Leaves Canceled as Japanese Encephalitis Claims 49 Lives Across State Assam government has canceled all leaves of doctors, paramedical staff and surveillance workers in order to deal with the outbreak of encephalitis that has claimed 49 lives across the state from January till July 5.

In an order issued by the Health and Family Welfare Department, all leaves of the government medical staff in the state were canceled in order to effectively deal with the present situation of rising acute encephalitis syndrome (AES)/Japanese encephalitis (JE) cases.

To deal with rising number of cases of AES and JE, the government has decided to involve the private hospitals. "Critical AES/JE patients, who are admitted in the ICUs of private hospitals/nursing homes... will

IJCP Sutra: "Trust your own comfort level rather than a shoe’s size or description.

Sizes vary from one manufacturer to another. You’re the real judge."

189

Around the Globe

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

be extended a monetary support of up to Rs 1 lakh," the order stated... (News 18 – PTI)

Screen All Pregnant Women for GBS Colonization to Prevent Newborn Infections The updated recommendations from the American Academy of Pediatrics (AAP) on management of infants at risk for group B streptococcal (GBS) disease support universal antenatal microbiologic-testing of pregnant women for the detection of maternal GBS colonization so that appropriate intrapartum antibiotic prophylaxis may be administered to prevent transmission of the bacteria from mother to the newborn before or during delivery as also recommended by the American College of Obstetricians and Gynecologists (ACOG).

Published online July 8, 2019 in the journal Pediatrics, the AAP recommendations for infant care include: ÂÂ

Administering antibiotic during childbirth, when indicated and as recommended by the ACOG to protect the newborn from transmission of GBS.

ÂÂ

In evaluating the risk of GBS infection in the newborn, infants born at ≥35 0/7 weeks gestation and those born at ≤34 6/7 weeks gestation should be considered separately. Infants born at 34 6/7 weeks gestation are preterm and are at highest risk for early-onset sepsis, including GBS disease.

ÂÂ

Early-onset GBS infection should be diagnosed by blood or cerebrospinal fluid culture.

ÂÂ

Evaluation for late-onset GBS disease, which is associated with preterm birth, should be based on clinical signs of illness.

ÂÂ

The preferred antibiotic for confirmed GBS disease in infants is penicillin G, followed by ampicillin.

A healthy pregnant woman might be colonized with no evident signs and symptoms of the illness. GBS infection in infants can be potentially fatal due to complications like sepsis, meningitis or pneumonia.

Heat Stress Spike Predicted to Cost Global Economy $2.4 Trillion a Year An increase in heat stress at work linked to climate change is set to have a massive impact on global productivity and economic losses, notably in agriculture and construction, UN labor experts said.

Highlighting that the world’s poorest countries will be worst affected, particularly in West Africa and SouthEast Asia, the International Labour Organization (ILO) warned that the lost output will be equivalent to 80 million full-time jobs - or 2.2% of total working hours worldwide - during 2030.

The total cost of these losses will be $2.4 trillion every year, ILO’s Working On A Warmer Planet report maintains, based on a global temperature rise of only 1.5°C by the end of this century.

“The impact of heat stress on labor productivity is a serious consequence of climate change”, said Catherine Saget, Chief of Unit in the ILO’s Research Department and one of the main authors of the report. “We can expect to see more inequality between low and highincome countries and worsening working conditions for the most vulnerable.”

In the ILO report, heat stress is defined as generally occurring at above 35°C, in places where there is high humidity. Excess heat at work is an occupational health risk and in extreme cases can lead to heatstroke, which can be fatal.

Besides agriculture and construction, other at-risk sectors include refuse collection, emergency services, transport, tourism and sports, with southern Asian and western African States suffering the biggest productivity losses, equivalent to approximately 5% of working hours by 2030… (UN)

After Bihar, Assam on Alert for Japanese Encephalitis Outbreak Following nearly 170 deaths from acute encephalitis syndrome (AES) in just 2 months in Bihar, Assam is now on alert for a Japanese encephalitis outbreak.

At least 57 people have died in the last 3 months from Japanese encephalitis and 234 positive cases have been reported in the state in this fresh outbreak.

Over the past 3 months, Assam has also seen over 50 deaths due to AES. While the state's health establishment is on the highest alert, the biggest worry is that this time, cases have been reported from 26 out of Assam's 27 districts, and many new areas have become vulnerable to the killer disease, officials said...

(NDTV.)

■■■■

190

IJCP Sutra: "Feel the inside of the shoes to see if they have any tags, seams or other material that might irritate your feet or cause blisters."

Spiritual Update

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

What is Charity?

KK aggarwal

A

fter returning from a free health check-up camp sometime back, I met a Professor of Cardiology from Lucknow and began to boast that I had seen 100 patients today free of charge. He said do not get excited. Charity is positive, but still not the absolute positive, unless it is done without any motive or done secretly. He said that you were honored on the stage, you received blessings from the patients and people talked about you in positive sense. It was an investment in the long run and not an absolute charity. When you never get honored on the stage by the people you are serving or have served, then it is like give and take. The purpose of life should be to help others without any expectations.

Understanding helping others Helping others should not harm somebody else.

Even with your unconditional help, if you end up

Group Editor-in-Chief, IJCP Group

in promoting number two by superseding another senior deserving person, it is not regarded as a help because the person you have helped will give you only one blessing but the person whom you have harmed may curse you 10 times. So, ultimately you end up with minus 9 points. Helping other means that it should give happiness to you, to the persons you have helped and also to others to whom you have not helped.

Helping always pays The difference between American and Indian models is that Indians always think of now and do not invest in future. Americans always plan for the future. When you help somebody, you want that the same person should help you when you are in need in a shorter run. But charity does not believe in that. Your job is to help others and negate your negative past karmas.

You never know, may be decades later, you get a help from a person to whom you helped decades earlier.

Help should never be linked to returns.

■■■■

European Commission Approves Fixed-dose Combination for HIV The European Commission has approved the fixed-dose combination of dolutegravir and lamivudine for HIV-1 infection.

The combination contains 50 mg dolutegravir, an integrase inhibitor and 300 mg lamivudine, a nucleoside analogue. It is indicated for treatment-naïve adults and children older than 12 years weighing at least 40 kg with no known or suspected resistance to the integrase inhibitor class or lamivudine… (Medscape)

Nerve Transfers Restore Hand, Elbow Functions in Paralyzed Patients Nerve transfers restored hand function and elbow extension in 13 young adults with traumatic spinal cord injury, a prospective case series from Australia showed.

Surgery to attach functioning nerves above the injury to paralyzed nerves below it, combined with 2 years of physical therapy, helped tetraplegic patients grasp, pinch and open and close their hands and improved their ability to propel their wheelchair and transfer into a bed or a car, reported Natasha van Zyl, MBBS, of Austin Health in Melbourne, Australia and co-authors, in The Lancet.

IJCP Sutra: “The key to weight loss is reducing how many calories you take in.“

191

INSPIRATIONAL Story

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

The Mango Tree

O

nce upon a time, there lived a big mango tree.

A little boy loved to come and play around it every day. He climbed to the tree top, ate the mangoes and took a nap under the shadow… He loved the tree and the tree loved to play with him.

Time went by… The little boy grew, and he no longer played around the tree. One day, the boy came back to the tree with a sad look on his face. “Come and play with me,” the tree asked the boy.

“I am no longer a kid, I don’t play around trees anymore.” The boy replied, “I want toys. I need money to buy them.” “Sorry, I don’t have money… but you can pick all my mangoes and sell them so you will have money.”

The boy was so excited. He picked all the mangoes on the tree and left happily. The boy didn’t come back.

The tree was sad. One day, the boy, grown into a man, returned. The tree was so excited. “Come and play with me,” the tree said.

“I don’t have time to play. I have to work for my family.

We need a house for shelter. Can you help me?” “Sorry, I don’t have a house, but you can chop off my branches to build your house.” So, the man cut all the branches off the tree and left happily. The tree was glad to see him happy but the boy didn’t come back afterward.

The tree was again lonely and sad.

One hot summer day, the man returned and the tree was delighted. “Come and play with me!” The tree said. “I am sad and getting old. I want to go sailing to relax myself. Can you give me a boat?” “Use my trunk to build your boat. You can sail far away and be happy.”

So, the man cut the tree trunk to make a boat. He went sailing and didn’t come back for a long time. Finally, the man returned after he had been gone for so many years. “Sorry, my boy, but I don’t have anything for you anymore. No more mangoes to give you.” The tree said.

“I don’t have teeth to bite,” the man replied. “No more trunk for you to climb on.” “I am too old for that now,” the man said. “I really can’t give you anything… the only thing left is my dying roots,” the tree said with sadness. “I don’t need much now, just a place to rest.

I am tired after all these years,” the man replied. “Good!

Old tree roots are the best place to lean on and rest.

Come sit down with me and rest.”

The man sat down and the tree was glad and smiled.

Moral: The tree in the story represents our parents.

When we are young, we love to play with them. When we grow up, we leave them and only come back when we need help. Parents sacrifice their lives for us.

■■■■

Risk of Stillbirth may be Higher in Prolonged Pregnancies Risk of stillbirth at term increases considerably for low-risk pregnancies continuing beyond 40 weeks, according to the results of a systematic review and meta-analysis.

Stillbirth risk steadily increased from 0.11 per 1,000 pregnancies at 37 weeks (95% confidence interval [CI] 0.070.15) to 3.18 per 1,000 at 42 weeks (95% CI 1.84-4.35), reported Shakila Thangaratinam, MBBS, of the Queens Mary University of London and colleagues.

Patients were 64% more likely (95% CI 1.51-1.77, p < 0.001) to have a stillbirth when continuing their pregnancy to 41 weeks - as currently recommended - compared to patients who delivered at 40 weeks, researchers wrote in PLOS Medicine.

192

IJCP Sutra: “Dust mites tend to live in beds, carpeting, upholstered furniture and soft toys. It is important to keep all these things dust free.“

Ind ex ISS ed N 09 with 71-0 Ind 876 MED

Volume 1, Number 1

w

w

w

om .c up ro pg jc .i

ww

Pee

rR

mber

18, Nu

Am

ch ar yM Ja nu ar 5 um ber ,N 17 Vo lu m e

is

w.ij cp

grou

p.co

Subscription Form

m

Jour

nity

Fam

ily

Med

Jan

Phys

uary

icia

n

icin

troe nte Infe rolo ctio gy us Inte Dis ease rnal s Med Obs icin tetr e ics Ped and iatr Gal yn ics garw ecol Med Ag hief ogy ilDr tor-in-C aw KK up Edi

d

an

Isch I in ial ings MR thy rd ca ee St diac pa l Myoey B Car yo ca e of diom lent Hon logi le Issu yo ro Car d Si le br ic an tip ter Em ging re Mul s af d er chem ilu Its nt Fa ing y: Em -is tie n an er al llow Pa tio Non Art rc Ren Fo etic Infa ial n te ab ch e di ial Acu rctio as Bra Bhav fa Non card — In ati Y ting en e in MyoDr Sw tor Edi es nc te lera cu a Pr n e To of A — om nsio with ar se ck yx te le A R co tta e l M er ric ck: Glu t A com tria Hyp nt rs Ve Blo ft A y — Fi Out Le onar ight ular its e of lm d R ric re vent Cas Pu A vere mbe trio m — Se lis Cha 1 A bo ble-ent 2: n Em ir Dou si tatio an yA — Tr esen er Art Pr ry na Cor —

logy

mu

T

an

dio

Com EN

ic

—

eric

Car

em

Th

wed

nal

Gas

In

evie

3

20 15

e Volum

e

Gro

Full

text

onlin

e...

mor

e: h

ttp:/

/eb

With

ook.

Bes

ijcpg

t Com

roup

plim

.com

ents

-Fe

bru

ary

201

4, P

age

Jan-Dec 2019

s1

-64

Subscribe to

All Journals /ijcp

from : Mak ers of

` 10,500/-

/

SAVE

` 500/-

Special Discount on Institutional Packages

Yes, I am interested in subscribing to the *Institutional Combo package for one year (Institutional) Yes, I am interested in subscribing to the following journal(s) for one year (Institutional)

JOURNALS

INSTITUTIONAL

ISSUES

(` Amount)

(individual)

INDIVIDUAL (` Amount)

Indexed with IndMED ISSN 0971-0876 www.ijcpgroup.com

Indian Journal of Clinical Practice

January-February 2014, Pages 1-64 Peer Reviewed Journal

American Family Physician Cardiology Community Medicine ENT Gastroenterology Infectious Diseases Internal Medicine

12

5,000/-

1,650/-

4

1,500/-

550/-

4

1,500/-

550/-

4

1,500/-

550/-

4

1,500/-

550/-

Obstetrics and Gynecology Pediatrics Medilaw

Full text online: http://ebook.ijcpgroup.com/ijcp/ With Best Compliments from: Makers of

Asian Journal of Clinical Cardiology

In This Issue —

Emerging role of Cardiac MRI in Ischemic and Non-ischemic Cardiomyopathy

—

Acute Renal Failure and Silent Myocardial Infarction Following Multiple Honey Bee Stings

— —

Asian Journal of Diabetology

Brachial Artery: Its Embryological Glucose Tolerance in Nondiabetic Patients after First Attack of Acute Myocardial Infarction and its Outcome

—

A Case of Left Atrial Myxoma Presenting as Severe Pulmonary Hypertension

—

Double-Chambered Right Ventricle with Transient 2:1 Atrioventricular Block: A Rare Presentation

—

Cornary Artery Air Embolism

Volume 17, Number 5

more...

January-March 2015

Volume 1, Number 1

Asian Journal of Obs & Gynae Practice Asian Journal of Paediatric Practice

Volume 18, Number 3

Dr Swati Y Bhave

Dr KK Aggarwal

Editor

Group Editor-in-Chief

Payment Information

Total `11,000/- for 1 year

Name: .......................................................................................................

Pay Amount: ............................................................................................

Speciality: ................................................................................................

Address: .................................................................................................. ..................................................................................................................

Country: ................................... State: .....................................................

Pincode: ...................................

Dated (dd/mm/yyyy): ...............................................................................

Cheque or DD No.: ..................................................................................

Telephone: ............................... Mobile: ..................................................

E-mail: .....................................................................................................

Drawn on Bank: .......................................................................................

Cheques/DD should be drawn in favor of “M/s IJCP Publications Ltd.” Mail this coupon to (HO):

IJCP Publications Ltd. : E - 219, Greater Kailash Part - 1, New Delhi - 110 048 Telefax: 40587513 Mob.: 9891272006 E-mail: subscribe@ijcp.com Website: www.ijcpgroup.com

Online subscription: http://subscription.ijcpgroup.com/Default.aspx

We accept payments by Cheque/DD only, Payable at New Delhi. Do not pay Cash.

lighter reading

Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

HUMOR

Lighter Side of Medicine Communication technician

Get yourself a train!

A communication technician drafted by the army was at a firing range. At the range, he was given some instructions, a rifle and 50 rounds. He fired several shots at the target. The report came from the target area that all attempts had completely missed the target. The technician looked at his weapon, and then at the target. He looked at the weapon again, and then at the target again. He then put his finger over the end of the rifle barrel and squeezed the trigger with his other hand.

The end of his finger was blown off, whereupon he yelled toward the target area: “It’s leaving here just fine, the trouble must be at your end!”

Dear Dad

New hearing aid Seems an elderly gentleman had serious hearing problems for a number of years.

He went to the doctor and the doctor was able to have him fitted for a set of hearing aids that allowed the gentleman to hear 100%.

The elderly gentleman went back in a month to the doctor and the doctor said, “Your hearing is perfect. Your family must be really pleased that you can hear again.”

To which the gentleman said, “Oh, I haven’t told my family yet. I just sit around and listen to the conversations. I’ve changed my will three times!”

Weight loss A blonde woman is terribly overweight, so her doctor puts her on a diet. “I want you to eat regularly for two days, then skip a day, and repeat this procedure for 2 weeks. The next time I see you, you’ll have lost at least 5 pounds.”

Berlin is wonderful, people are nice and I really like it here, but Dad, I am bit ashamed to arrive to my college with my Gold Mercedes, when all my Teachers travel by train.

Your Son Nasser Sometime later Nasser gets reply to his e-mail from his Dad: Loving son Twenty Million Dollars transferred to your account, please stop embarrassing us, go and get yourself a train too.

Dad Don’t thank me Looking down at the defendant, the judge said, “Mr Riley, I’ve decided to give you a suspended sentence.”

Tears pouring from his eyes, Riley cried, “Oh, thank you, Your Honor!”

“Don’t thank me,” the judge replied. “I’m sentencing you to be hanged.”

Dr. Good and Dr. Bad Situation:

A 45-year-old male with NAFLD was warned about the development of type 2 diabetes in the future.

NAFLD does not increase the risk for type 2 diabetes

The risk of developing type 2 diabetes is high

© IJCP GROUP

When the blonde returned, she shocked the doctor by losing nearly 20 pounds.

“Why, that’s amazing!” the doctor said. “Did you follow my instructions?”

The blonde nodded. “I’ll tell you though, I thought I was going to drop dead that third day.”

“From hunger, you mean?” asked the doctor.

“No, from skipping.”

194

Lesson: Several studies display a link between the presence and severity of NAFLD and increased risk of incident type 2 diabetes and hypertension. In addition, it has been reported that the presence and severity of NAFLD also act as independent predictors of fatal and nonfatal cardiovascular events.

J Hepatol. 2017;68(2):335-52.

IJCP Sutra: “To make your overall diet healthier, eat more plant-based foods, such as fruits, vegetables and whole-grain carbohydrates.“

ISSN 0971-0876 RNI 50798/1990 University Grants Commission 20737/15554

Indexed with IndMED Indexed with MedIND Indian Citation Index (ICI)

www.ijcpgroup.com

A Multispecialty Journal Volume 29, Number 11

April 2019, Pages 1001–1100

Single Copy Rs. 300/-

Peer Reviewed Journal

y

Consensus Statement

y

Original Article

y

Clinical Study

y

Case Report

y

Medicolegal

y

Medical Voice for Policy Change

y

Conference Proceedings

y

Around the Globe

y

Spiritual Update

y

Inspirational Story

y

Lighter Reading

Full text online: http://ebook.ijcpgroup.com/ijcp/ IJCP Publications | https://goo.gl/j2nXQQ

www.emedinexus.com

Indian Citation Index (ICI),

IndMed (http://indmed.nic.in/)

MedIND (http://medind.nic.in/)

University Grants Commission (20737/15554).

ISSN number 0971-0876

RNI number 50798/1990.

The Medical Council of India (UGC, ICI)

Indian Journal of Clinical Practice is published by the IJCP Group. A multispecialty journal, it provides clinicians with evidence-based updated information about a diverse range of common medical topics, including those frequently encountered by the Indian physician to make informed clinical decisions. The journal has been published regularly every month since it was first launched in June 1990 as a monthly medical journal. It now has a circulation of more than 3 lakh doctors.

IJCP is a peer-reviewed journal that publishes original research, reviews, case reports, expert viewpoints, clinical practice changing guidelines, Medilaw, Medifinance, Lighter side of medicine and latest news and updates in medicine. The journal is available online (http://ebook.ijcpgroup.com/ Indian-Journal-of-Clinical-Practice-January-2018.aspx) and also in print. IJCP can now also be accessed on a mobile phone via App on Play Store (android phones) and App Store (iphone). Sign up after you download the IJCP App and browse through the journal.

IJCP is indexed with Indian Citation Index (ICI), IndMed (http://indmed.nic.in/) and is also listed with MedIND (http://medind.nic.in/), the online database of Indian biomedical journals. The journal is recognized by the University Grants Commission (20737/15554). The Medical Council of India (MCI) approves journals recognized by UGC and ICI. Our content is often quoted by newspapers.

The journal ISSN number is 0971-0876 and the RNI number is 50798/1990.

If you have any Views, Breaking news/article/research or a rare and interesting case report that you would like to share with more than 3 lakh doctors send us your article for publication in IJCP at editorial@ijcp.com.

Dr KK Aggarwal Padma Shri Awardee Group Editor-in-Chief, IJCP Group

IJCP Sutra: “Make exercise an important part of your daily routine. Start slow and increase the duration as you go along.“

195

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,

196

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.

IJCP Sutra: “Prevent exposure to dust mites. These are tiny insects and one of the most common asthma triggers.“

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

IJCP Sutra: “Restrict the child’s contact with pets especially if he/she is allergic.“

197

One Stop for All Diagnostics

MRI

Latest MRI by Siemens

CT Scan

16- Multislice Spiral CT

Health Packages

Executive Health Check Up

Ultra Short Magnet = No Claustrophobia

Safest Scanner

Risk Categories

1st MRI in India on VC 15 Platform

Least Radiation Dose

Age Based Health Packages

Fully Automated Digital Pathology Laboratory - NABL Accredited

Immunology

Contact Us

Biochemistry

S-63 Greater Kailash Part 1 Opposite M Block Market, New Delhi 110048 Tel.: 011- 41234567

Haematology

Special Tests

Talking Point Communications -A Unit of the IJCP Group of Medical Communications

Start-Up

CEO/Leadership

E L Y T S E LIF

PHA

RM A

Management

Profiling

Outreach

Digital

Marketing

L

& Service Launches

Reputation

Media

Events

SS E N

New product

Conferences

Coordination

L WE

Profiling

Launches

Celebrity

HEALTH

Brand

IIC SUMMIT 2014

For More Information call: 9582363695, E-mail naina.a@talkingpointcommunications.com Website: http://talkingpointcommunications.com

R.N.I. No. 50798/1990 Date of Publication 13th of Same Month Date of Posting 13-14 Same Month

POSTAL REGISTRATION NO. DL (S)-01/3200/2018-2020 Posted in N.D. PSO New Delhi