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Online Submission IJCP Group of Publications A Multispecialty Journal Dr Sanjiv Chopra Volume 30, Number 2, July 2019 Group Consultant Editor From the desk of THE group editor-in-chief

Dr Deepak Chopra 105 Bihar Children Deaths: Could Refeeding Syndrome Chief Editorial Advisor Precipitated by Litchis have Triggered the Deaths? KK Aggarwal

Dr KK Aggarwal Original research Group Editor-in-Chief 107 Ambulance Services in Delhi Need an Ambulance Care Dr Veena Aggarwal KK Aggarwal, Ira Gupta Group Executive Editor ORIGINAL STUDY

Mr Nilesh Aggarwal 110 Prevalence of Thyroid Dysfunction in Pregnancy CEO Ruchika Garg, Prabhat Agrawal, Vishy Agrawal, Urvashi, Saroj Singh

Ms Naina Ahuja Review Article COO 114 Management of Diabetic End-stage Renal Disease: Role of Hemodialysis Dr Anoop Misra H Sudarshan Ballal Group Advisor 120 Evaluation of the Infertile Female Garima Kachhawa, Anju Singh

Editorial Advisors Clinical Study

Obstetrics and Gynaecology 125 A Study of Corneal Thickness and Endothelial Dr Alka Kriplani Morphology in Type 2 Diabetes Mellitus Rajender Singh Chauhan, Ashok Rathi, Jp Chugh, P Sharma, R Rajput, R Kumar Cardiology Dr Sameer Srivastava 130 Effect of Adjuvant Atorvastatin Therapy on Disease Activity in Active Rheumatoid Arthritis: A Tertiary Care Paediatrics Center Study in India Dr Swati Y Bhave H Singh, Rekha Mathur, A Singhania, Kiran B ENT Case Report Dr Chanchal Pal 136 Gastroenterology Unusual Temporary Treatment for Mastoid Fistula Dr Ajay Kumar and Dr Rajiv Khosla Subramaniam Vinayak Easweran, Sarvesh Nayak, Arpana Hegde

Dermatology 138 The Wide Clinical Spectrum of Raised Fetal Dr Anil Ganjoo Hemoglobin in Adults Pratik Vora, Sakshi Singh, Jemima Bhaskar, Manish Mehta, Ami Trivedi Oncology Dr PK Julka 141 Bilateral Single System Ectopic Ureters with Secondary Calculi in an Adult Anand Gopal Bhatnagar Editorial Anchor Gopi Kishore M, Suhasini G, Prasad Pvgs, Sainadh Av

Advisory Bodies Public Health Heart Care Foundation of India 146 Non-Resident Indians Chamber of Commerce & Industry 2013-2014 Investigation Findings of Unexplained Acute World Fellowship of Religions Neurologic Illness Outbreak, Muzaffarpur, Bihar – Brief Note This journal is indexed in IndMED (http://indmed.nic.in) HCFI Consensus Statement and full-text of articles are included in medIND databases (http://mednic.in) hosted by National 154 Patient-Doctor Relationship Informatics Centre, New Delhi. KK Aggarwal, Amarinder Singh Malhi, Ankit Om, Girish Tyagi… 156 HCFI Round Table on Health and Wellness on the Published, Printed and Edited by Interpretation of the Word “Supplied By” in Clause 23 Dr KK Aggarwal, on behalf of of Schedule K of Drugs and Cosmetics Act/Rules IJCP Publications Ltd. and Published at KK Aggarwal, Anil Khaitan, Balbir Verma, Bejon Kumar Misra, BR Sikri… E - 219, Greater Kailash Part - 1 New Delhi - 110 048 158 HCFI Expert Round Table on Off-label Use of Drugs, E-mail: [email protected] Disposables and Devices

Printed at KK Aggarwal, Manju Mani, Chander Prakash, Ahmed Quraishi, AK Grover… New Edge Communications Pvt. Ltd., New Delhi E-mail: [email protected] RTI Analysis

Copyright 2019 IJCP Publications Ltd. 164 Lack of Coordination Amongst Various Departments of All rights reserved. Ministry of Health: Diseases are Notifiable but there is no The copyright for all the editorial material contained Vaccination Policy for Them in this journal, in the form of layout, content including images and design, is held by IJCP KK Aggarwal, Ira Gupta Publications Ltd. No part of this publication may be published in any form whatsoever without the prior EXPERT’s VIEW written permission of the publisher. 168 How can One Reduce Cardiovascular Mortality in Editorial Policies Patients with Hypertension? Nandini Mukherjee The purpose of IJCP Academy of CME is to serve the medical profession and provide MediFinance print continuing medical education as a part of their social commitment. The information and 170 Budget 2019-20 Highlights opinions presented in IJCP group publications reflect the views of the authors, not those of Arun Kishore the journal, unless so stated. Advertising is accepted only if judged to be in harmony with MEDICAL VOICE FOR POLICY CHANGE the purpose of the journal; however, IJCP group reserves the right to reject any advertising at its 172 Medtalks with Dr KK Aggarwal sole discretion. Neither acceptance nor rejection constitutes an endorsement by IJCP group of Conference Proceedings a particular policy, product or procedure. We believe that readers need to be aware of any 178 INDIA LIVE 2019 affiliation or financial relationship (employment, consultancies, stock ownership, honoraria, etc.) Around the globe between an author and any organization or entity that has a direct financial interest in the 182 News and Views subject matter or materials the author is writing about. We inform the reader of any pertinent Spiritual Update relationships disclosed. A disclosure statement, 191 What is Charity? where appropriate, is published at the end of the relevant article. KK Aggarwal

Note: Indian Journal of Clinical Practice does INSPIRATIONAL Story not guarantee, directly or indirectly, the quality or efficacy of any product or service described 192 The Mango Tree in the advertisements or other material which is commercial in nature in this issue. Lighter reading 194 Lighter Side of Medicine

IJCP’s Editorial & Business Offices Delhi Mumbai Bangalore Chennai Hyderabad Dr Veena Aggarwal Mr Nilesh Aggarwal H Chandrashekar Chitra Mohan Venugopal 9811036687 9818421222 GM Sales & GM Sales & GM Sales & E - 219, Greater Unit No: 210, 2nd Floor, Marketing Marketing Marketing Kailash, Part - I, Shreepal Complex 9845232974 9841213823 9849083558 New Delhi - 110 048 Suren Road, Near Cine 11, 2nd Cross, 40A, Ganapathypuram H. No. Cont.: 011-40587513 Magic Cinema Nanjappa Garden Main Road 16-2-751/A/70 Radhanagar, Chromepet [email protected] Doddaiah Layout First Floor [email protected] Andheri (East) Chennai - 600 044 Babusapalya Karan Bagh Mumbai - 400 093 Cont.: 22650144 Subscription Kalyananagar Post Gaddiannaram [email protected] Dinesh: 9891272006 Bangalore - 560 043 [email protected] Dil Sukh Nagar [email protected] [email protected] Hyderabad - 500 059 [email protected] GM: General Manager 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?

he recent mortality among children in Bihar due We have always been taught to never overfeed a to acute encephalopathy syndrome (AES) has malnourished child as the outcome may be an electrolyte Tgenerated speculations abound and raised many imbalance. Even the World Health Organization eyebrows. The illness has claimed more than 100 lives. (WHO) says that acute or severe malnutrition should be From blaming the government to identifying litchi as treated slowly over 10 days. Rapid treatment with large the cause of the condition, the hypotheses have been intake of litchi may have precipitated fatal electrolyte many. However, it is imperative at this juncture to imbalance. understand that litchi may not be the underlying cause Rapidly treating hypoglycemia with litchi, without of the symptoms and subsequent deaths, but only a managing phosphate levels, may be harmful. The best triggering factor. food in such a situation could have been sugarcane Most malnourished children below 10 years of age juice and not litchi. One must remember here that all experienced convulsions early in the morning without those who break a long-term fast, do so with sugarcane fever. Despite the fact that all of them had low sugar, juice. mortality still remained high even after infusing sugar. The risk of hypophosphatemia during refeeding This suggests that apart from sugar, there was some appears to be greater in patients who are more other metabolic factor in play. severely malnourished and at lower percent of ideal body weight. During episodes of starvation, the Understanding the reaction phosphate stores in the body get depleted. When In significantly malnourished children, who have not nutritional replenishment starts and patients are fed consumed food in the last 24 hours, rapid carbohydrate carbohydrates, glucose causes release of insulin, which intake (in the form of litchi in this case, which has 10% triggers cellular uptake of phosphate (and potassium sugar) may have led to electrolyte and fluid shifts. and magnesium) and a decrease in serum phosphorous This may have in turn precipitated disabling or fatal levels. Insulin also causes the cells to produce a medical complications. This is also called the refeeding variety of depleted molecules that require phosphate syndrome and is marked by hypophosphatemia (this (adenosine triphosphate and 2,3-diphosphoglycerate), is the hallmark feature), hypokalemia, congestive heart which further depletes the body’s stores of the latter. failure, peripheral edema, rhabdomyolysis, seizures, The subsequent lack of phosphorylated intermediates fever and hemolysis. 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 negative health outcomes. In the case of children in to contract, hemolysis, rhabdomyolysis and seizures. Bihar perhaps, many of them did not eat for a whole day knowing they will get to eat a generous supply of Some risk factors for the refeeding syndrome include litchi fruit next morning. low baseline levels of phosphate, potassium or magnesium prior to refeeding the patient; and little or In conclusion, there is a need to raise countrywide no nutritional intake for the previous 5-10 days. awareness, particularly in Bihar, on the fact that children should not be allowed to sleep on an empty stomach. Patients are at the highest risk in the first 1-2 weeks of More than anything else, it is the lack of awareness that nutritional replenishment and weight gain. Generally, can magnify any issue, and this was true in the case of the risk progressively dissipates over the next few these recent deaths as well. A grey area that remains is weeks if there has been consistent forced intake and the disappearance of this disease in the wake of onset weight gain. of rains, a phenomenon that must be investigated. It is also important to note that in cases of acute A concerted plan of action that takes into account this malnutrition, akin to a prolonged fasting, children and other triggers must be formulated. It is time that should be given only juices upfront. They must not all stakeholders come together in addressing this health be fed to a full stomach but rather the intake must be issue, which raises its head every year, causing several increased gradually over a period of time to avoid any 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 Fortunately, Delhi has two big trauma hospitals, people and one advanced ambulance for 1 lakh Sushruta Trauma Centre in North Delhi and Jai Prakash population. Delhi, therefore, should have a minimum Narayan Apex Trauma Center at AIIMS, New Delhi. of 190 advanced life support (ALS) ambulances and 380 But shortage of ambulances will not cover the golden basic life support (BLS) ambulances. hour and lives will be wasted.

As Delhi has a population of over 1.9 crore, Heart Care Importance of ambulances Foundation of India (HCFI) vide Right to Information (RTI) application dated 26.09.2018 had asked as to how The term ambulance comes from the Latin word many BLS ambulances and how many ALS ambulances “ambulare” as meaning “to walk or move about”, which are available in Delhi. is a reference to early medical care where patients were moved by lifting or wheeling. The word originally Vide reply dated 02.11.2018, Centralized Ambulance meant a moving hospital, which follows an army in its Trauma Services (CATS), which is an autonomous body movements. of Government of National Capital Territory of Delhi (GNCTD) had stated that CATS have only 108 BLS An ambulance is a medically equipped vehicle which ambulances and only 31 ALS ambulances. transports patients to treatment facilities, such as hospitals. In some instances, out-of-hospital medical In view of this shortage, Delhi Government should care is provided to the patient in an ambulance. use the Essential Commodities Act. Under the Essential Ambulances are used to respond to medical emergencies Commodities Act, 1955, the schedule to Section 2(a)drugs by emergency medical services. For this purpose, they (as the meaning assigned to it in clause (b) of Section 3 are generally equipped with flashing warning lights of the Drugs and Cosmetics Act, 1940) is included as and sirens. They can rapidly transport paramedics and essential commodity. Also, under the section, the state other first responders to the scene, carry equipment for government has powers to control production, supply, administering emergency care and transport patients distribution, etc., of essential commodities. to hospital or other definitive care facilities. Most An ambulance (which provides essential drugs) being ambulances use a design based on vans or pick-up an essential service, the Delhi Government can link all trucks. Others take the form of motorcycles, cars, buses, the private ambulances with CATS under one loop. aircraft and boats. In cases of life-threatening emergencies one can call 100; Following are few examples, which illustrate the PCR personnel have been trained in life support CPR. importance of ambulances.

It is indeed pitiable that the Delhi Government’s CATS ÂÂ Rajesh Pilot died on June 11, 2000 in a car accident department does not even want to publicly display in Dausa 45-90 km from Jaipur. His Maruti Gypsy the information as to where the CATS ambulances collided head-on with a Rajasthan Roadways Bus. are physically located. For this, they want Rs. 12/- to He was shifted to Sawai Man Singh Hospital, Jaipur. be deposited to get the information. Is this not a public He was in a coma when admitted at 5:15 pm. If he information, which should be displayed all over for was carried in an advanced cardiac life support public convenience? (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 *Group Editor-in-Chief, IJCP Group receiving multiple injuries from an accident †Advocate and Legal Advisor, HCFI 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

Kiratpur Sahib in Ropar district. He was shifted to Road roundabout. Later, he was brought to the Chandigarh 45 km away. Was he shifted in ACLS hospital by his driver and assistant. Doctors at ambulance or provided a golden hour first aid in AIIMS said that Munde was not breathing when he Ropar? was brought in. Had the ACLS ambulance reached ÂÂ Sahib Singh Varma died on June 30, 2007, when the spot….? his car collided with a truck near Jonaicha khurd, ÂÂ Amitabh Bachchan was saved because of on the Jaipur-Delhi Highway (NH-8). He was taken ambulance: On August 2, 1982, he had a near- to nearby Shahjanpur Civil Hospital 13 km away. fatal accident on the sets of his film Coolie. He Obviously no ACLS care was available for 13 km. was shifted to nearby hospital and ONLY LATER ÂÂ Gopinath Munde: At 6 am on June 3, 2014, his car shifted to Mumbai. The early treatment did help met with an accident at Prithviraj Road-Tughlak 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 Information does not pertain to CATS government hospitals to have BLS and ALS ambulance for 24 hours? 2. If answer to query No. 1 is “no”, then please provide the Information does not pertain to CATS details of the hospitals for whom it is mandatory to have ambulance for 24 hours? 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 Information does not pertain to CATS 24 hours in Delhi? 6. Provide the list of hospitals having BLS ambulance Information does not pertain to CATS available for 24 hours in Delhi. 7. How many hospitals have ALS ambulance available Information does not pertain to CATS for 24 hours? 8. Provide the list of hospitals having ALS ambulance Information does not pertain to CATS available for 24 hours in Delhi.

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 For operational purpose, CATS ambulances are deployed government, which are attached with CATS for BLS ambulances. 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 Answer same as Sr. No. 1 government, which are attached with CATS for ALS ambulances. 3. Provide the details of all the public places in Delhi where CATS Please deposit Rs. 12/- @ Rs. 02/- per page for ambulance is stationed for that particular public place. 06 pages of the required information. 4. Provide the details of all the public places in Delhi where CATS List of CATS ambulances deployed is as per Sr. No. 03 ambulances are stationed but the same are also available for any above. These ambulances can attend any assigned patient in emergency outside that particular public place. 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, pre- eclampsia, 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.

regnancy is a state in which the combination of thyroid hormones and iodine requirement are increased events modifies the function of thyroid. There is a by approximately 50% during pregnancy. In addition, Pchange in the level of thyroxine-binding globulin pregnancy is a stressful condition for the thyroid gland, (TBG), total T3 and T4 and thyroid-stimulating hormone resulting in hypothyroidism in women with limited (TSH) during normal pregnancy.1 thyroid reserve or iodine deficiency. The prevalence of hypothyroidism in pregnancy Data from published studies have underscored the is around 2.5% according to the Western literature association between miscarriage and preterm delivery and prevalence of hyperthyroidism in pregnancy is in women with normal thyroid function who test 0.1-0.4%.2,3 There are a few reports of prevalence of positive for thyroid peroxidase (TPO) antibodies.6 The hypothyroidism during pregnancy from India with prevalence of Grave’s disease is around 0.1-0.4% and prevalence rates ranging from 4.8% to 11%.4,5 During that of thyroid autoimmunity (TAI) is around 5-10%. pregnancy, the thyroid gland may increase in size Studies have shown that the subclinical thyroid by 10% in iodine-sufficient countries and to a greater dysfunction has adverse outcome on the mother and fetus extent in iodine-deficient countries. Production of 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 *Associate Professor, Dept. of Obstetrics and Gynecology †Professor, Dept. of Medicine prevalence of thyroid disorder in pregnancy in ‡Senior Resident North India. #Professor and Head Dept. of Obstetrics and Gynecology SN Medical College, Agra, Uttar Pradesh Material and Methods Address for correspondence Dr Ruchika Garg It is a cross-sectional study conducted in the antenatal Associate Professor Dept. of Obstetrics and Gynecology, SN Medical College, Agra, Uttar Pradesh OPD of the Dept. of Obstetrics and Gynecology and E-mail: [email protected] Dept. of Medicine, SN Medical College, Agra and

110 IJCP Sutra: "Keep your blood sugar levels under control." Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019 ORIGINAL STUDY antenatal clinic of District Hospital, Agra from July 2017 26-30 years and 31-35 years was 8.7%, 1.8% and 0.19%, to December 2017. respectively. Table 2 shows that the prevalence of We included 1,020 women with uncomplicated subclinical hypothyroidism, overt hypothyroidism, intrauterine singleton pregnancy. We excluded subclinical hyperthyroidism and overt hyperthyroidism women who had history of thyroid disease or intake was 6.67%, 1.27%, 1.86% and 0.88%, respectively. of thyroid drugs, multifetal gestation, known chronic Table 3 shows that out of 1,020 women; 109 were disorders (diabetes and hypertension) or patients with found as having thyroid disorder and the prevalence of bad obstetrics history due to some other cause. After thyroid disorder in the study was 10.68%. enrolling the patients, a written informed consent was Table 4 shows that the mean TSH level among women taken, and detailed history and examination was done. with subclinical hypothyroidism, overt hypothyroidism, Blood samples were collected after obtaining the consent subclinical hyperthyroidism and overt hyperthyroidism and were sent for thyroid hormone profile testing. was 3.50, 7.92, 0.05 and 0.014 mIU/L, respectively. TSH, free T4 (fT4), free T3 (fT3) were measured by high Table 5 shows that the prevalence of thyroid disorder in sensitive radioimmunoassay. the first, second and third trimester was 68.80%, 23.85% and 7.33%, respectively. Subclinical hypothyroidism means increase in TSH with normal fT3 and fT4. Overt hypothyroidism means Table 2. Distribution of Patients According to Different increase in TSH with decrease in fT3 and fT4. Types of Thyroid Disorders Subclinical hyperthyroidism was defined as serum TSH Type of disorder No. of cases Percentage (%) concentration below the lower limit of reference range with fT3 and fT4 concentration within normal range. Subclinical hypothyroidism 68 6.67 Overt hyperthyroidism was defined as serum TSH Overt hypothyroidism 13 1.27 concentration below the lower limit of reference range Subclinical hyperthyroidism 19 1.86 with increase in fT3 and fT4 concentration. Reference Overt hyperthyroidism 09 0.88 ranges of antithyroid antibodies were: Total 109 10.68 ÂÂ Thyroid peroxidase antibody (TPOAb) <35 IU/mL

ÂÂ Thyroglobulin antibody (TgAb) <20 IU/mL. Table 3. Prevalence of Thyroid Disorders American Thyroid Association (2007) recommends cut- off values for TSH as: Sample No. of cases with thyroid disorder Percentage (%) ÂÂ First trimester <2.5 mIU/L 1,020 109 10.68% ÂÂ Second and third trimester <3 mIU/L

ÂÂ Lower limit of normal TSH 0.04 mIU/L. Table 4. Mean TSH levels in Different Types of Thyroid Disorders Results Types No. of cases Mean TSH level In the present study, a total of 1,020 pregnant women Subclinical hypothyroidism 68 3.50 were screened and 109 females were found as having thyroid disorders. Overt hypothyroidism 13 7.92 Subclinical hyperthyroidism 19 0.05 Table 1 shows that the prevalence of thyroid disorder among women in the age groups 20-25 years, Overt hyperthyroidism 09 0.014

Table 1. Distribution of Patients According to Age Groups Table 5. Distribution of Patients with Thyroid Disorders Age Group No. of patients with Percentage (%) According to Trimesters thyroid dysfunction Trimesters No. of patients (%) 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)

IJCP Sutra: "Reduce stress through activities such as meditation and yoga." 111 ORIGINAL STUDY Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

Discussion observed during the first trimester of pregnancy and are apparently related to human chorionic gonadotropin The main aim of the study was to know the prevalence (hCG) stimulation of the thyroid gland as serum hCG of thyroid disorders in pregnancy. The prevalence of levels are highest early in gestation. thyroid disorders in our study was 10.68% and it was consistent with the study by Sahu et al5 in which the Conclusion prevalence of thyroid disorders was 12.7%. It was also comparable to the study conducted by Wang et al8 Thyroid disease is prevalent in women of childbearing (10.2%), Taghavi et al9 (14.6%) and Ajmani et al10 in age group and for this reason it is common in pregnancy which the prevalence of thyroid disorder was 13.25%. and puerperium. Women with thyroid disorder, both overt and subclinical, are at increased risks of In the study conducted by Thanuja et al,11 the prevalence pregnancy-related complications, such as spontaneous of thyroid disorder was less (about 5%) and in the abortion, pre-eclampsia, preterm labor and abruption study conducted by Rajput et al,12 the prevalence of the placentae and fetal complications such as low birth thyroid disorder was high (26.5%). weight babies, preterm delivery, intrauterine growth The prevalence of subclinical hypothyroidism in our retardation and stillbirth. study was 6.67% and it was consistent with the study At present, there are no recommendations available by Sahu et al in which it was 6.47%. Prevalence of for detection or screening of thyroid dysfunction subclinical hypothyroidism in pregnancy according to among Indian pregnant women. Recent consensus the study conducted by Thanuja et al in Mangalore was guidelines recommend testing only in cases of high- less (0.7%), while it was 2.3% according to the study risk women having personal history of thyroid or 13 conducted by Casey et al. It was high in the study other autoimmune disorders or with a family history 14 conducted by Dhanwal et al (13.5%), Murty et al of thyroid disorders. (16.11%),15 and Singh et al (18%).16 This study has shown the high prevalence of The prevalence of overt hypothyroidism in the study thyroid dysfunction, especially subclinical and overt was 1.27% and it was comparable to the studies hypothyroidism, in India and thus emphasizes the 17 conducted by Taghavi et al, Bandela et al and by need to include thyroid function test in the routine Ajmani et al in which the prevalence was 2.4%, 2.87% screening in the antenatal clinic and the patients to and 3%, respectively. be potentially aware of associated maternal and fetal Prevalence of overt hypothyroidism in pregnancy in the complications. studies conducted by Wang et al (0.3%) and Dhanwal et al (0.7%) was less compared to the present study. References In this study, the prevalence of thyroid disorder in first, 1. Thyroid and other endocrine disorders. In: second and third trimester was 68.80%, 23.85% and Cunningham FG, Williams JW (Eds.). Williams Obstetrics. 7.33%, respectively and this is in accordance with the 23rd Edition, New York, NY: McGraw-Hill Education study by Rao and Patibandla.18 LLC; 2010. pp. 1126-44. In India, the most common cause of hypothyroidism in 2. Studd J. Thyroid Hormones in Pregnancy and Foetus. 15th Edition; 75-102. pregnancy is iodine deficiency. Hashimoto thyroiditis is the most common cause of hypothyroidism in 3. LeBeau SO, Mandel SJ. Thyroid disorders during iodine-sufficient areas. Presence of goitrogens19 in diet, pregnancy. Endocrinol Metab Clin North Am. 2006;35(1):117-36, vii. micronutrient deficiency such as selenium and iron deficiency may cause hypothyroidism and goiter.20 4. Nambiar V, Jagtap VS, Sarathi V, Lila AR, Kamalanathan S, Bandgar TR, et al. Prevalence and impact of thyroid Poverty, insufficient iodine supplementation and disorders on maternal outcome in Asian-Indian pregnant fluorinated water may be the cause of thyroid disorder women. J Thyroid Res. 2011;2011:429097. among pregnant women. Serum TSH and fT4 are the best 5. Sahu MT, Das V, Mittal S, Agarwal A, Sahu M. Overt and screen and diagnose hypothyroidism during pregnancy. subclinical thyroid dysfunction among Indian pregnant The prevalence of overt or subclinical hypothyroidism women and its effect on maternal and fetal outcome. Arch depends on the upper TSH cut-off level used. There is Gynecol Obstet. 2010;281(2):215-20. strong evidence that the reference range for serum TSH 6. Stagnaro-Green A. Thyroid antibodies and miscarriage: is lower throughout the pregnancy compared with the where are we at a generation later? J Thyroid Res. non-pregnant state. The lowest serum TSH levels are 2011;2011:841949.

112 IJCP Sutra: "Get to and stay at a healthy weight." Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019 ORIGINAL STUDY

7. Gaberšček S, Zaletel K. Thyroid physiology and 14. Dhanwal DK, Prasad S, Agarwal AK, Dixit V, Banerjee autoimmunity in pregnancy and after delivery. Expert AK. High prevalence of subclinical hypothyroidism Rev Clin Immunol. 2011;7(5):697-706; quiz 707. during first trimester of pregnancy in North India. Indian 8. Wang W, Teng W, Shan Z, Wang S, Li J, Zhu L, et al. J Endocrinol Metab. 2013;17(2):281-4. The prevalence of thyroid disorders during early 15. Murty NVR, Uma B, Rao JM, Sampurna K, Vasantha K, pregnancy in China: the benefits of universal screening Vijayalakshmi G. High prevalence of subclinical in the first trimester of pregnancy. Eur J Endocrinol. hypothyroidism in pregnant women in South India. 2011;164(2):263-8. IJRCOG. 2015;4(2):453 -6. 9. Taghavi M, Saghafi N, Shirin S. Outcome of thyroid 16. Singh KP, Singh HA, Kamei H, Devi LM. Prevalence of dysfunction in pregnancy in Mashhad, Iran. Int J hypothyroidism among pregnant women in the sub Endocrinol Metab. 2009;7(2):82-5. mountain state of Manipur. Int J Sci Study. 2015;3(5):143-6. 10. Ajmani SN, Aggarwal D, Bhatia P, Sharma M, Sarabhai V, 17. Bandela PV, Havilah P, Durgaprasad K. Antenatal thyroid Paul M. Prevalence of overt and subclinical thyroid dysfunction in Rayalaseema region: A preliminary cross dysfunction among pregnant women and its effect on sectional study based on circulating serum thyrotropin maternal and fetal outcome. J Obstet Gynaecol India. levels. Int J Appl Biol Pharm Technol. 2013;4(4) :74-8. 2014;64(2):105-10. 18. Rao S, Patibandla A. A Study to find out the prevalence 11. Thanuja PM, Rajgopal K, Sadiqunnisa. Thyroid of hypothyroidism among pregnant women visiting dysfunction in pregnancy and its maternal outcome. ESI Hospital, Sanathnagar, Hyderabad. Gynecol Obstet IOSR-JDMS. 2014;13(1Ver X):11-5. (Sunnyvale). 2016;6:363. 12. Rajput R, Goel V, Nanda S, Rajput M, Seth S. Prevalence 19. Marwaha RK, Tandon N, Gupta N, Karak AK, Verma K, of thyroid dysfunction among women during Kochupillai N. Residual goitre in the postiodization phase: the first trimester of pregnancy at a tertiary care iodine status, thiocyanate exposure and autoimmunity. hospital in Haryana. Indian J Endocrinol Metab. 2015; Clin Endocrinol (Oxf). 2003;59(6):672-81. 19(3):416-9. 20. Das S, Bhansali A, Dutta P, Aggarwal A, Bansal MP, 13. Casey BM, Dashe JS, Wells CE, McIntire DD, Byrd W, Garg D, et al. Persistence of goitre in the post-iodization Leveno KJ, et al. Subclinical hypothyroidism and phase: micronutrient deficiency or thyroid autoimmunity? pregnancy outcomes. Obstet Gynecol. 2005;105(2):239-45. Indian J Med Res. 2011;133:103-9.

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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

iabetes mellitus is now the most common cause morbidity and mortality of any given modality between of end-stage renal disease (ESRD) all across the diabetic and nondiabetic ESRD population. We will Dthe globe, including India. It is estimated that discuss some of these issues, specifically the modality 30-50% of patients being initiated on renal replacement of hemodialysis. therapy (RRT) have diabetes as the cause of their ESRD1 and most of these patients have type 2 diabetes. In view Hemodialysis for Diabetic ESRD of the alarming rise in numbers, renal failure due to Although hemodialysis prevents death from uremia, type 2 diabetes has been termed a “medical catastrophe the patient survival on hemodialysis is poor, especially of worldwide dimensions”.2 This article will discuss the for patients with diabetes, being approximately management of diabetic ESRD specifically related to 20-25% at 5 years as compared to 40-50% for other type 2 diabetes. causes of ESRD.3 This is worse than many cancers. Renal Replacement Therapy The survival of patients on maintenance hemodialysis in India seems dismal for both, diabetic and nondiabetic When a patient’s kidney function, as measured by populations.4 the calculated glomerular filtration rate, has reached The important contributors for mortality in the diabetic <10 mL/min (ESRD) or the patient develops uremic dialysis population are: Cardiovascular disease, symptoms they need RRT. adequacy of dialysis and nutritional status.

The RRTs available for all patients with ESRD are: ÂÂ Cardiovascular disease (CVD): CVD is the ÂÂ Hemodialysis most common cause of death accounting for more than one-half of the cases.5 The main ÂÂ Chronic ambulatory peritoneal dialysis (CAPD) reason for such a high mortality rate, which is ÂÂ Renal transplantation. of cardiovascular origin in the majority of cases Though these modalities are available for all patients is that the cardiovascular conditions of patients with ESRD, there are significant differences in the 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 Professor of Clinical Medicine St. Louis University School of Medicine, USA and are on RRTs are at higher risk of developing Manipal Academy of Higher Education, Manipal, India de novo CVD, particularly ischemic heart disease,

114 IJCP Sutra: "Choose whole grains instead of refined grain products. Limit the intake of processed meat and red meat." Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019 Review Article

which not only is more frequent but also has a more ÂÂ Nutrition in dialysis: Nutrition in dialysis patients aggressive course than in nondiabetic patients. In is closely linked to inadequate dialysis, which leads view of this, aggressive measures to manage CVD to anorexia and poor calorie and protein intake. This need to be adopted in all diabetic patients even is reflected by poor serum albumin and creatinine before they reach the stage of dialysis. levels, which are indicators for mortality in dialysis patients. The problems of diabetic gastroparesis ÂÂ Adequacy of dialysis: Adequacy of dialysis, and diabetic enteropathy compound the nutritional which also plays an important role in CVD and problems. nutrition (MIA or malnutrition inflammation atherosclerosis syndrome), is also a contributor The help of a good dietician and measures to treat to the poor outcome and diabetics, in diabetic gastroparesis and enteropathy by motility particular, seem to be more sensitive than agents, frequent small foods and appropriate use of nondiabetics to inadequate dialysis.6 The increase broad-spectrum antibiotics to treat bacterial infections in mortality of these patients largely disappears if in diabetic enteropathy are needed to maintain there is an improvement in the nutritional status adequate nutrition. It is to be noted that cisapride is as reflected by an increase in serum albumin and best avoided in this population because of the risk of 9 creatinine.7 This is a major problem in India where fatal arrhythmias. for various reasons like financial constraints, lack Diet in diabetic patients on dialysis of access and availability of good dialysis units causes most patients to have inadequate dialysis.8 The general recommendation for diet in dialysis Whenever possible, it is very essential to monitor patients is given in Table 1. The iron requirement of the adequacy of dialysis by using biochemical dialysis patients varies and will need to be addressed measures like urea reduction rates, Kt/V and on a patient to patient basis. In general, water-soluble clinical well-being of patients and to take measures vitamins are routinely prescribed and calcitriol may be to improve the adequacy of dialysis. needed in some patients.

Table 1. Daily Dietary Recommendations for Dialysis Patients versus Nonuremicsa Factor Nonuremic HD PD Protein (g/kg) 0.8 1.2 1.2-1.5 Calories (sedentary; kcal/kg) 30 30b 30-40b,c Protein (%) 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 Crude fiber (g) 25 25 25 Sodium (1 g = 43 mEq) 2-6 g 2 g + 1 g/LUO 2-4 g + 1 g/LUO Fluids (L) Ad lib 1 L/LUO 1 L + 1 L/LUO 1.0-2.5L + 1 L/LUO Potassium (1 g = 25 mEq) 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 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. c 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.

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 nephrologists. The safety of sulfonylureas depends on patients their mode of metabolism and their half-life. Use of short-acting agents primarily metabolized by the liver There are certain special problems about blood sugar is, in general, safer in dialysis patients. Acetohexamide, control in dialysis patients. chlorpropamide and tolazamide are excreted to a large Altered Insulin Metabolism extent in the urine. These drugs should not be used in dialysis patients because their half-lives will be greatly In uremic patients (both diabetic and nondiabetic), prolonged in the absence of renal function, possibly insulin secretion by the β-cells of the pancreas is resulting in severe and prolonged hypoglycemia. reduced and the responsiveness of peripheral tissues The excretion of glyburide is 50% hepatic, and (e.g., muscle) to insulin is depressed. On the other prolonged hypoglycemia has been reported using hand, the rate of insulin catabolism (renal and this drug in dialysis patients. Metabolism of glipizide, extrarenal) is decreased, and therefore, the half-life tolbutamide and gliclazide is almost completely of any insulin present in the circulation is prolonged. hepatic. Consequently, the last three drugs should be All of these abnormalities are only partially corrected considered if an OHA is desired. Many drugs frequently after institution of maintenance dialysis therapy. used in dialysis patients either antagonize (phenytoin, nicotinic acid, diuretics) or enhance (sulfonamides, Increased Sensitivity to Insulin salicylates, warfarin, ethanol) the hypoglycemic action In diabetic dialysis patients treated with exogenous of sulfonylureas. insulin, the importance of reduced insulin catabolism Metformin, a biguanide, is associated with increased overrides the impact of insulin resistance; when incidence of lactic acidosis in dialysis patients and exogenous insulin is administered, its effect may be should not be used. Acarbose inhibits α-glucosidase intensified and prolonged. Thus, smaller than usual in the enteric mucosa and moderates postprandial doses should be given. hyperglycemia. It may prove to be a useful adjunct to Insulin Therapy other diabetic medications in diabetic patients. Troglitazone and other thiazolidinediones sensitize the Tight control of sugars is sometimes difficult to achieve target tissues to insulin and may be of help in obese, in diabetic dialysis patients. Nevertheless, good glucose control is worthwhile with split doses of insulin type 2 diabetics with insulin resistance. However, the use preferably. The "amount of insulin" per day required of this class of drugs may be associated with the risk of for patients receiving maintenance hemodialysis severe hepatotoxicity. is usually small; optimum control of glycemia is In general, insulin use is preferable in diabetic dialysis achieved by administration of long-acting insulin at patients but judicious use of appropriate OHAs can be two separate times during the day (split dosing) and done. by supplementing with regular insulin for meals as Specific problems of hemodialysis in diabetic patients: needed. The proportions of long-acting and regular insulin, as well as the total insulin doses vary widely ÂÂ Difficulty in creating and maintaining a vascular among different patients. Hypoglycemia is quite access because of severe peripheral vascular disease common in diabetic dialysis patients usually due to (PVD) in older diabetic patients. reduced insulin catabolism and reduced intake or food ÂÂ Inability to tolerate volume shifts giving rise to and/or poor absorption. hypotension during hemodialysis because of autonomic neuropathy and CVD. A fasting serum glucose of <140 mg/dL and a postprandial value <200 mg/dL is a reasonable goal to ÂÂ Risk of infection. achieve. ÂÂ Progression of diabetic retinopathy. Oral Hypoglycemic Agents In view of all these problems, meticulous planning and appropriate management should start in the Lack of clinical studies on use of oral hypoglycemic predialysis period well before dialysis is anticipated agents (OHAs) in dialysis patients restricts the use of and would involve a special diabetic team consisting these agents. of an Ophthalmologist, Vascular Surgeon, Podiatrist, Nevertheless, these agents are useful adjuncts in Endocrinologist, Cardiologist, Neurologist and the treatment of diabetics and are used by many Dietician to help the nephrology team in keeping

116 IJCP Sutra: "High BP, blood sugar and blood cholesterol can remain silent for up to a decade." Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019 Review Article the patient as fit as possible even before they Role of CAPD reach dialysis. CAPD is another modality of treatment in diabetic Timing of dialysis in diabetic ESRD ESRD. Though it has its advantages and disadvantages, the following factors decide the modality of dialysis: In general, most nondiabetic patients are initiated on ÂÂ Comorbid conditions dialysis when the creatinine clearance is <10 mL/min. ÂÂ Family and home support In diabetic patients, dialysis may have to be initiated at creatinine clearance even >15 mL/min.9 The reasons for ÂÂ Financial support this being: ÂÂ CVD and PVD leading to poor vascular access for ÂÂ Renal functions deteriorate rapidly in this group dialysis ÂÂ Hypertension is very difficult to control with severe ÂÂ Hemodynamic stability

renal failure ÂÂ Availability of hemodialysis centers. ÂÂ Most patients have CVD with volume overload CAPD is 30-50% more expensive than hemodialysis in ÂÂ Uremic symptoms may manifest earlier than non- India and is generally used for patients who do not have diabetic patients. access to hemodialysis, have severe chronic heart failure In spite of these recommendations, dialysis is usually (CHF), hemodynamic instability, poor vascular access started as an emergency in most Indian patients because and are not candidates for transplantation. The patient of uremia, pulmonary edema or severe hyperkalemia and the family should be motivated and have adequate because of poor awareness, financial constraints and financial support. Table 2 gives the comparison between lack of facilities for dialysis.4,8 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 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 Schedule not convenient for helper if one is required (e.g., for intraperitoneal insulin; less severe hypoglycemia a patient with physical disability like blindness, stroke, etc.)

CCPD Good cardiovascular tolerance Protein loss to dialysate No need for arteriovenous access Good control of serum potassium Good glucose control with use of intraperitoneal Very very expensive insulin 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 is needed to prevent and manage the complications dialysis of vascular diseases, malnutrition and retinopathy in diabetic dialysis patients. There have been conflicting data about the survival of patients on CAPD compared to hemodialysis. Initial References data from Michigan suggested an advantage for CAPD.10 1. Ballal HS. Diabetic Nephropathy: Indian Scene, Scientific However, most studies after adjustment for comorbid Proceedings, 1st National Conference in Prevention of condition, have not found a statistically significant Chronic Kidney Disease in India. February 2005. survival difference between the two modalities.11 2. Ritz E, Rychlík I, Locatelli F, Halimi S. End-stage renal failure in type 2 diabetes: A medical catastrophe of Transplantation worldwide dimensions. Am J Kidney Dis. 1999;34(5): Kidney transplantation is the best option for patients 795-808. with diabetic ESRD. The 5-year survival of transplant 3. United States Renal Data System. Excerpts from the USRDS patients of 75-85%, though less than that of nondiabetic 2003 annual data report: Atlas of end stage renal disease in the United States. Am J Kidney Dis. 2004;42(Suppl 5): ESRD, is still far superior to the 5-year survival rate of S1-S226. around 25% on dialysis.3,12 Though in general healthier 4. Rao M, Juneja R, Shirly RB, Jacob CK. Haemodialysis for patients go on to transplant and sicker patients remain end-stage renal disease in Southern India - a perspective on dialysis the survival rates are better, even when these from a tertiary referral care centre. Nephrol Dial are factored in. Transplantation is also associated with a Transplant. 1998;13(10):2494-500. better quality-of-life and high degree of rehabilitation. 5. Brunner FP, Selwood NH. Profile of patients on RRT The pre- and post-transplant care of diabetic patients is in Europe and death rates due to major causes of death generally similar to that of nondiabetics. However, in groups. The EDTA Registration Committee. Kidney Int Suppl. 1992;38:S4-15. view of the high prevalence of CVD in this population, meticulous attention has to be paid to screen these 6. Collins AJ. How can the mortality rate of chronic dialysis patients be reduced? Semin Dial. 1993;6:102. patients for CVD prior to the transplantation.13 7. Lowrie EG, Lew NL, Huang WH. Race and diabetes as Recommendations for treatment of diabetic death risk predictors in hemodialysis patients. Kidney Int ESRD patients Suppl. 1992;38:S22-31. 8. Kher V. End-stage renal disease in developing countries. Kidney transplant remains the best option of RRT Kidney Int. 2002;62(1):350-62. for patients with diabetic ESRD in all suitable 9. Tzamaloukas AH, Friedman EA. Diabetes. In: Daugirdas candidates. Recommendations for those not suitable for JT, Blake PG, Ing TS (Eds.). Handbook of Dialysis. 3rd transplantation - Edition, Philadelphia: Lippincott, Williams & Wilkins; 2001. p. 453. CAPD is recommended for patients with: 10. Nelson CB, Port FK, Wolfe RA, Guire KE. Comparison ÂÂ Poor vascular access because of PVD of continuous ambulatory peritoneal dialysis and ÂÂ Severe CVD with hemodynamic instability during hemodialysis patient survival with evaluation of trends hemodialysis during the 1980s. J Am Soc Nephrol. 1992;3(5):1147-55. 11. Jaar BG, Coresh J, Plantinga LC, Fink NE, Klag MJ, ÂÂ Nonavailability of hemodialysis centers Levey AS, et al. Comparing the risk for death with ÂÂ Good family and financial support peritoneal dialysis and hemodialysis in a national cohort of patients with chronic kidney disease. Ann Intern Med. ÂÂ Motivated patients. 2005;143(3):174-83. Hemodialysis is the treatment for all the rest which is 12. Locatelli F, Pozzoni P, Del Vecchio L. Renal replacement the treatment available for the vast majority of patients therapy in patients with diabetes and end-stage renal with diabetic ESRD in India who are not candidates disease. J Am Soc Nephrol. 2004;15 Suppl 1:S25-9. for transplantation. In view of the multiple associated 13. Scandling JD. Kidney transplant candidate evaluation. comorbid conditions, a multidisciplinary approach Semin Dial. 2005;18(6):487-94.

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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.

nfertility is defined as failure to conceive after 1 year History and Examination of regular unprotected intercourse. It affects 10-15% of couples worldwide. Female factor is responsible Both the partners should be made aware of underlying I causes of infertility, components of basic evaluation and for infertility in 35-40% of couples. Among females, the major causes of infertility include ovulatory encouraged for simultaneous testing. dysfunction (30-40%), tubal and peritoneal pathology Diagnostic evaluation should begin with thorough (30-40%), cervical factor (3%), uterine factor (rare) and history and physical examination. History taking of unexplained (10%) (Fig. 1). infertile partner must include the following:

Usually, we start evaluation of female partner if she fails  Duration of infertility and results of any previous to achieve pregnancy after 12 months or more of regular evaluation/treatment unprotected intercourse. But in certain conditions earlier evaluation is warranted, which include:  Coital frequency and sexual dysfunction  Menstrual history (age at menarche, cycle length  After 6 months of unsuccessful efforts in women over age of 35 years and characteristics, onset/severity of dysmenorrhea)  Â History of irregular menstrual cycles  Outcome of previous pregnancy, if any, and use of contraception  Known or suspected uterine/tubal or peritoneal disease  Past or current medical and surgical illness (particularly any history of pelvic infection,  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 Unusual problem Dept. of Obstetrics and Gynecology All India Institute of Medical Sciences (AIIMS), New Delhi Address for correspondence 40% Dr Anju Singh Senior Resident Dept. of Obstetrics and Gynecology All India Institute of Medical Sciences (AIIMS), New Delhi E-mail: [email protected] Figure 1. Cause of infertility: Women.

120 IJCP Sutra: "Restricting salt intake to <6 g daily can reduce upper systolic BP by 2.8 mmHg." Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019 Review Article

exposure to sexually transmitted infections, properties of progesterone. Ovulatory cycles have septic abortion, ectopic pregnancy, abdominal typical “biphasic” BBT recording, whereas anovulatory myomectomy, adnexal surgery) cycles have monophasic pattern. It is not the preferred method for infertile women because there can be few ÂÂ Family history of birth defects, mental retardation, early menopause or reproductive failure women who menstruate regularly but do not exhibit biphasic BBT. ÂÂ Symptoms of thyroid disease, galactorrhea, hirsutism or acne Urinary LH determination is based on identification of mid-cycle LH surge and provides indirect evidence of ÂÂ Pelvic or abdominal pain or dyspareunia ovulation. Since LH has a short half-life and is rapidly ÂÂ Occupation and addiction history. cleared of the urine, testing should be done on a daily Physical examination should document: basis starting 2-3 days before the surge is expected based on the cycle length. It is done using various ÂÂ Body mass index (BMI) commercially available “ovulation prediction kits” like ÂÂ Thyroid nodule or tenderness i-know, i-can, PregaPlan, etc., which are easy to use but can have false positive and false negative results. ÂÂ Breast secretions and their character

ÂÂ Signs of androgen excess Serum progesterone measurement is simplest, reliable and preferred test of ovulatory function as long as it ÂÂ Abdominal or pelvic mass or tenderness is appropriately timed. The best time to test is Day 21 ÂÂ Vaginal or cervical abnormality or discharge of a 28-day cycle or approximately 1 week before ÂÂ Any mass, tenderness or nodularity in adnexa or the expected onset of next menses. A progesterone cul-de-sac. concentration of >3 ng/mL provides reliable evidence of recent ovulation, whereas value >10 ng/mL is suggestive Subsequent evaluation should be carried out in a of normal “in phase” endometrial histology. systematic and cost-effective manner to identify underlying cause. Endometrial biopsy identifies ovulation based on characteristic secretory endometrial changes on Ovulatory function histology induced by progesterone. Historically, it was considered “gold standard” for diagnosis of luteal phase Ovulatory dysfunction, presenting as menstrual deficiency (LPD) but not anymore. Since endometrial irregularity, is the underlying cause of infertility in biopsy is an invasive test and provides not much approximately 15% of infertile couples and accounts for added information over other noninvasive methods, up to 40% of infertility in women. Diagnosis of ovulatory it is no longer recommended to evaluate ovulatory or dysfunction can be made by menstrual history. Further luteal function in infertile women. Its clinical use is investigations should be aimed to document ovulation limited to identify or exclude endometrial hyperplasia and find the pathology of anovulation, if present. in women with chronic anovulation and to diagnose chronic endometritis. But in our Indian population Document Ovulation where tuberculosis is an important cause of infertility, A history of regular menstrual cycles occurring at it becomes a part of routine investigations to rule out interval of 25-35 days with consistent flow characteristics tubercular endometritis. strongly suggests normal ovulatory function but still Serial transvaginal ultrasonography (TVUS) can be used objective documentation in infertile women is needed. to monitor number and size of developing follicles. It There are a number of methods to measure normal provides most accurate estimate of ovulation identified ovulatory function. by sudden collapse of follicle, loss of clearly defined follicular margins, appearance of internal echoes Methods to document ovulation and increase in cul-de-sac fluid volume. Because of ÂÂ Basal body temperature charts associated cost and logistic demands, it is mainly used ÂÂ Urinary luteinizing hormone (LH) Kits to monitor follicle growth in women receiving ovulation induction drugs. ÂÂ Mid-luteal serum progesterone level

ÂÂ Endometrial biopsy Establish Cause for Anovulation Serial basal body temperature (BBT) measurement is a Patients with irregular or infrequent menses and simple and inexpensive method based on thermogenic 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 respectively. It’s low PPV implies that when HSG of anovulation. The ovulatory disorders have been reveals obstruction, it can be because of mucus plug or classified by World Health Organization (WHO) into cornual spasm and there is high probability (approx. three groups (Table 1). 60%) that tube is open but when it demonstrates patency, there is only 5% chance that tube is actually Therefore, in women with irregular cycles, basal occluded. (Day 2-4) serum follicle-stimulating hormone (FSH), LH, serum estradiol and prolactin levels should be done to Saline infusion sonography (SIS) involves TVUS find the cause of anovulation and to treat accordingly. after injecting saline into uterine cavity. Apart from Before that, pregnancy must be excluded by a urine delineating intrauterine pathology, it can also be pregnancy test. Serum thyroid-stimulating hormone used to determine tubal patency by appearance of (TSH) levels should be done if signs and symptoms are fluid in cul-de-sac with saline infusion on TVUS. It suggestive of it. does not differentiate between unilateral or bilateral patency. Tubal and Peritoneal Factors Laparoscopy and chromotubation is the definitive test for Tubal pathology is the most common cause (30-35%) of evaluation of tubal factors. It provides both a panoramic infertility among both young as well as older women. view of pelvic reproductive anatomy as well as Tubal damage should be strongly suspected in women magnified view of uterine, ovarian, tubal and peritoneal with history of tuberculosis, pelvic inflammatory disease surfaces. Apart from evaluation of tubal patency, it can (PID), septic abortion, ectopic pregnancy or tubal also identify distal tubal occlusive disease (fimbrial surgery. Other important causes of tubal and peritoneal agglutination, phimosis), pelvic or adnexal adhesions factor infertility include inflammation and adhesions and endometriosis that adversely affect fertility but related to endometriosis, inflammatory bowel disease escape detection by HSG. It also provides advantage of or surgical trauma. treating the pathology at time of diagnosis. Hysterosalpingography (HSG) is the traditional and The detection of antibodies to Chlamydia trachomatis has also been associated with tubal pathology, including standard method for evaluation of tubal patency. It tubal occlusion, hydrosalpinx and pelvic adhesions but is a procedure which directly visualizes uterotubal its clinical utility has not been proved yet. anatomy as well as tubal patency with fluoroscopic screen after injecting radio-opaque dye through cervix. Uterine Factors It is done as an office procedure in the preovulatory phase of menstrual cycle. It is approximately 65% Anatomic and functional abnormalities of uterus are an sensitive, 83% specific with a positive (PPV) and uncommon cause but should always be excluded as a negative predictive value (NPV) of 38% and 94%, part of infertility evaluation. The anatomic abnormalities

Table 1. WHO Classification of Ovulatory Disorders and Serum Concentration of Hormones Hormone Normal Hypogonadotropic Eugonadotropic Hypergonadotropic Hyper- values hypogonadal eu-estrogenic anovulation prolactinemia anovulation anovulation (WHO Class III) (WHO Class I) (WHO Class II) 75-85% 10-20% 5-10% 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 Example Kallmann’s syndrome Polycystic ovary syndrome Premature ovarian Pituitary Excessive exercise failure micro- or macroadenoma Anorexia nervosa

122 IJCP Sutra: "An 1% increase in good HDL cholesterol decreases chances of heart attack by 3%." Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019 Review Article which adversely affect fertility include congenital malformations, leiomyomas, intrauterine adhesions and Ovarian reserve tests 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 Biochemical tests Ultrasonographic measures each having its own advantage and disadvantages. yy Antral follicle count (AFC) yy Ovarian follicle  Ultrasound is a noninvasive method which permits visualization of position and size of Basal (Day 2/3) Provocative test uterus, fallopian tubes and ovaries. Modern 3-D measurements of ultrasonography extends the diagnostic capabilities yy S. FSH yy S. estradiol Clomiphene citrate of ultrasonography and can generate reconstructed challenge (CCC) test yy S. inhibin B images in the coronal plane. It is more useful yy S. antimullerian in diagnosing important uterine pathologies hormone (AMH) particularly congenital anomalies, to measure endometrial volume, locate fibroids and also Figure 2. Ovarian reserve tests. defines their relationship to endometrial canal. It infertility but is best justified for women with any of has diagnostic accuracy comparable to magnetic the following characteristics: resonance imaging.  Age over 35 years  SIS can be used for better identification of intrauterine adhesions and endometrial polyps.  Family history of early menopause  Â HSG accurately defines size and shape of  Previous ovarian surgery (ovarian cystectomy/ uterine cavity. It may help in delineating any drilling, unilateral oophorectomy), chemotherapy, developmental uterine anomaly (unicornuate, radiation bicornuate, septate, didelphys, etc.) and acquired  Unexplained infertility

abnormalities (intrauterine adhesions, endometrial ÂÂ Chronic smoking polyps, submucous myomas). It has relatively low ÂÂ Demonstrated poor response to exogenous sensitivity (50%) and PPV (30%) for diagnosis of gonadotropin stimulation. endometrial polyp and submucous myomas in asymptomatic infertile women. It includes a number of biochemical tests and ultrasonographic measures with each test having its ÂÂ Hysteroscopy is the definitive method for evaluation and treatment of intrauterine pathology. own sensitivity and specificity (Fig. 2 and Table 2). Being more costly and an invasive method, its use Therefore, ovarian reserve tests should always be is reserved for further evaluation and treatment of interpreted with caution as none of the tests available abnormalities detected on TVUS, SIS or HSG. at present can be recommended as a sole criteria of diminished ovarian reserve (DOR). They should only Cervical Factors be used to obtain prognostic information and to choose the best treatment available. It includes abnormalities of cervical mucus production or sperm/mucus interaction which are rarely the sole Key Recommendations: NICE Guidelines cause of infertility. Traditionally, post-coital test (PCT) was considered a basic element of infertility evaluation. ÂÂ A careful history and physical examination can It is inconvenient to patient, does not predict inability identify a specific cause of infertility and help to focus to conceive and rarely changes clinical management. the diagnostic evaluation on the most likely cause. Therefore, PCT is no longer recommended for evaluation ÂÂ A blood test to measure serum progesterone in of infertile female. the mid-luteal phase (Day 21 of a 28-day cycle) is the preferred method to confirm ovulation even if Role of Ovarian Reserve Testing women having regular menstrual cycle.

Ovarian reserve describes the size and quality of the ÂÂ Women with irregular menstrual cycle should remaining ovarian follicular pool. This has become be offered a blood test to measure serum a routine element of the diagnostic evaluation of gonadotropins.

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 Specificity Comment (%) (%) S. FSH (Day2/3) 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 CCC test (Day 10 FSH) 10-22 IU/L 35-98 68-98 Higher sensitivity than basal FSH but needs drug administration AFC (No) 3-10 40-97 78-92 Good reliability; widespread use Ovarian volume >3 mL 11-80 80-90 Limited clinical use

ÂÂ Serum prolactin should only be offered to women 3. Practice Committee of American Society for Reproductive who have an ovulatory disorder, galactorrhea or a Medicine. Diagnostic evaluation of the infertile female: pituitary tumor. a committee opinion. Fertil Steril. 2012;98(2):302-7. 4. National Collaborating Centre for Women’s and ÂÂ Thyroid function test should not be offered Children’s Health. Fertility: assessment and treatment for routinely; rather should be estimated only in people with fertility problems. London, United Kingdom: women with symptoms of thyroid disease. National Institute for Health and Clinical Excellence ÂÂ The routine use of endometrial biopsy and PCT of (NICE); February 2013:1-63. (Clinical Guideline No. 156). cervical mucus is no longer recommended as a part 5. Wathen NC, Perry L, Lilford RJ, Chard T. Interpretation of evaluation of infertile female. of single progesterone measurement in diagnosis of anovulation and defective luteal phase: observations ÂÂ HSG to screen for tubal patency is a reliable test, on analysis of the normal range. Br Med J (Clin Res Ed). less invasive and makes more efficient use of 1984;288(6410):7-9. resources than laparoscopy. 6. Jordan J, Craig K, Clifton DK, Soules MR. Luteal phase ÂÂ Ovarian reserve testing should be best limited to defect: the sensitivity and specificity of diagnostic the women at increased risk of DOR and should be methods in common clinical use. Fertil Steril. 1994;62(1):54-62. interpreted with caution. 7. Soares SR, Barbosa dos Reis MM, Camargos AF. Suggested Reading Diagnostic accuracy of sonohysterography, transvaginal sonography, and hysterosalpingography 1. Practice Committee of American Society for Reproductive in patients with uterine cavity diseases. Fertil Steril. Medicine. Definitions of infertility and recurrent 2000;73(2):406-11. pregnancy loss. Fertil Steril. 2008;90(5 Suppl):S60. 8. Practice Committee of the American Society for 2. Speroff L, Fritz MA. Clinical Gynecologic Endocrinology Reproductive Medicine. Testing and interpreting and Infertility. 8th Edition, Philadelphia, PA, USA: measures of ovarian reserve: a committee opinion. Fertil Lippincott Williams & Wilkins. Steril. 2015;103(3):e9-e17.

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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

iabetes mellitus is a widely spread and one Therefore, in the presence of diabetes, it is important amongst the most common noncommunicable to weigh keratopathy as a potential sight-threatening Ddisease. As of 2017, 72.9 million Indians were condition and appropriate clinical attention and affected by type 2 diabetes. Ocular complications increased research interest should be addressed of diabetes mainly include diabetic retinopathy, towards this condition. In the developed world and glaucoma, cataract and ocular surface disorders. increasingly elsewhere, type 2 diabetes is the major In addition to diabetic retinopathy, diabetes patients cause of nontraumatic blindness and renal failure. can likely develop corneal endothelial damage, Cornea has 6 layers which are epithelium, Bowman’s keratoepitheliopathy as recurrent corneal erosions, layer, stroma, Dua’s layer, Descemet’s membrane and persistent epithelial defects and superficial keratitis. 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 *Professor endothelium include regular fluid and solute transport † Junior Resident and maintenance of corneal optical transparency via Regional Institute of Ophthalmology ‡Professor active Na/K ATPase pump. Thickness of cornea reaches Dept. of Endocrinology adult size by 3 years of age. Pt BD Sharma PGIMS, Rohtak, Haryana Address for correspondence Damage or insult to corneal endothelium leads to increase Dr Rajender Singh Chauhan 15/8FM, Medical Enclave, Rohtak - 124 001, Haryana in central corneal thickness and loss of transparency. E-mail: [email protected] Diabetic keratopathy can cause alterations in all layers

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of cornea especially the endothelium, like decrease in ÂÂ Glaucoma.

endothelial cell density (ED) and hexagonality, as well ÂÂ Previous retinal photocoagulation. as increased polymegathism, pleomorphism and central ÂÂ Contact lens wear. corneal thickness. Reduced corneal ECD and swelling of the cornea are indicators of corneal dysfunction. ÂÂ Corneal disease due to chronic conjunctival or eyelid abnormality. Corneal endothelial morphology can be measured using different instruments, including contact specular ÂÂ Regular use of any eye drops. microscopes, noncontact specular microscopes (NCSM) Patient Evaluation and confocal microscopes while central corneal thickness can be assessed by various techniques such Informed and written consent was taken from all as ultrasound pachymeter (USP), Orbscan, contact patients. Detailed history regarding age, gender, any specular microscopy, NCSM and Pentacam. The previous history of ocular trauma, surgery, usage of eye availability of quick, accurate, noninvasive methods drops if any, was taken. Complete ocular examination of central corneal thickness (CCT) assessment is was performed, including best corrected visual acuity, essential for the effective monitoring of corneal using Snellen acuity chart, anterior and posterior endothelial health. One such technique widely used is segment examination by slit-lamp, intraocular pressure the new automated NCSM Topcon SP-3000P (Topcon measurement, fundus examination and specular Corporation, Tokyo, Japan), which captures an image microscopy. of the corneal endothelium and assesses corneal Methodology thickness simultaneously. Specular microscopy was performed using a noncontact Aims and Objectives TOPCON SP-3000P specular microscope and SP-3000P endothelial cell analysis software (image net) on both To study the corneal thickness and endothelial eyes or one eye, considering the exclusion criteria. This morphology in type 2 diabetes mellitus patients and to instrument takes a picture of the corneal endothelium compare these parameters with nondiabetics. by slit light projected diagonally. Material and Methods Statistical Analysis The present study was conducted at the Regional The data was entered in Microsoft excel spreadsheet Institute of Ophthalmology and Dept. of Endocrinology, and it was analyzed using SPSS version 20.0. Student’s Pt. BD Sharma PGIMS, Rohtak, Haryana. It was a case- t-test was applied for comparison between the study control study in which the study group included 100 group and controls. The comparison among the type 2 diabetes patients and 100 nondiabetic patients diabetes group was made by performing analysis formed the control group. The study was conducted to of variance (ANOVA) test. Pearson correlation test detect the effect of type 2 diabetes mellitus on corneal was also applied. Point of statistical significance was thickness and endothelial morphology. considered if p < 0.05.

Inclusion Criteria Results and Observations ÂÂ Individuals of either gender, age more than 18 years, Fasting mean blood sugar was 143.96 ± 30.83 mg/dL who were diagnosed to have type 2 diabetes mellitus in study group as compared to 77.53 ± 8.44 mg/dL in as per American Diabetes Association (ADA) control group. Similarly, postprandial blood sugar criteria, blood glucose levels ≥126 mg/dL (fasting) level was also very high in study group patients, or blood glucose levels ≥200 mg/dL (postprandial), i.e., 238.48 ± 40.21 mg/dL as compared to 112.38 ± were included as the study population. 8.17 mg/dL in the control group. The difference in blood Control group included age- and gender-matched sugar levels, both fasting and postprandial, between nondiabetic individuals. the two groups was found to be statistically significant (p < 0.001). Mean glycated hemoglobin (HbA1c) in Exclusion Criteria study patients was 8.07 ± 1.24 % (Table 1). ÂÂ Previous history of ocular surgery or trauma. A total of 70% of the patients were taking oral ÂÂ Active or previous eye infection or inflammation. hypoglycemic agents (OHAs). Out of insulin

126 IJCP Sutra: "Cook in cast iron pots as this can add up to 80% more iron to your food." Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019 Clinical Study dependents, 12% were only receiving insulin while the to be slightly lower in the study group (2467.27 ± rest 18% were on both insulin and OHA. 260.37 cells/mm2) as compared to control group (2498.23 ± 235.31 cells/mm2), but the difference in both In our study, 70% patients suffered from microvascular the groups was insignificant. Difference in coefficient complications while both macro- and microvascular of variation (CV) and mean cell area was found to be complications were observed in 35% patients in the insignificant in both the groups. study group. Mean CCT of study group (520.09 ± 25.37 µm) was Discussion higher than mean CCT of control group (514.99 ± 21.80 In our study, mean CCT of 100 diabetes patients of µm). Statistical comparison of both the groups, i.e., study group was 520.09 ± 25.37 µm and that of 100 study versus control group, was found to be significant age- and gender-matched nondiabetics as controls (p < 0.05) (Table 2). was 514.99 ± 21.80 µm. The mean CCT was higher Table 3 and Figures 1-3 show comparison of in diabetes patients when compared with the non- endothelial parameters between both the groups. diabetics. It is well-known that diabetes reduces the We observed a statistically significant lower mean activity of Na+/K+ ATPase of the corneal endothelium hexagonality of endothelial cells, i.e., 56.69 ± 6.86% and thus, causes morphological and functional in the study group as compared to 60.79 ± 5.46% in changes of diabetic cornea. The difference between the the control group (p < 0.001). Mean ECD was found 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) HbA1c (%) 8.07 ± 1.24 - -

SD = Standard deviation; VHS = Very highly significant.

Table 2. Central Corneal Thickness in Study and Control Groups Central corneal thickness Study group (n = 100) Control group (n = 100) Statistical significance Mean ± SD Mean ± SD CCT (µm) 520.09 ± 25.37 514.99 ± 21.80 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) Statistical significance 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 SD 134.29 ± 23.81 139.61 ± 21.83 <0.01 HS

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

accordance with other reports. In our study, percentage

80 of hexagonal cells was observed as 56.69 ± 6.86% in the study group and 60.79 ± 5.46% in the control group. 60.79 60 56.69 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 40 (p < 0.001). Similar decrease in percentage of hexagonal Hexagonality (%) Hexagonality cells was observed in various studies done by Schultz 20 et al and Lee et al. In our study, mean CV in diabetes

0 study group was 0.33 ± 0.04 as compared to 0.32 ± 0.05 Study Group Control Group of the control group. This increase in the cell size variation coefficient in type 2 diabetes patients was Figure 1. Comparison of mean hexagonality in patients of not significant (p > 0.05). Similar nonsignificant CV both groups (200 eyes each). changes were observed between diabetes patients and controls in others studies.

2467.27 2498.23 2500 Conclusion

2000 The study concluded that the corneal health of patients ) 2 with uncontrolled and long-standing diabetes is poor 1500 and can lead to loss of transparency. Hence, it is

1000 recommended to have strict glycemic control of type

ECD (cells/mm ECD 2 diabetes mellitus for better corneal health. 500 Suggested Reading 0 Study Group Control Group 1. International Diabetes Federation. IDF Diabetes Atlas, 8th Edition, Brussels, Belgium: International Diabetes Figure 2. Comparison of mean ECD in patients of both Federation; 2017. groups (200 eyes each). 2. Schultz RO, Matsuda M, Yee RW, Edelhauser HF, Schultz KJ. Corneal endothelial changes in type I and

Study group Control group type II diabetes mellitus. Am J Ophthalmol. 1984; 98(4):401-10. 450 414.03 402.65 3. Schultz RO, Van Horn DL, Peters MA, Klewin KM, 400 Schutten WH. Diabetic keratopathy. Trans Am Ophthalmol 350 Soc. 1981;79:180-99. 300 250 4. Herse PR. A review of manifestations of diabetes mellitus 183.29 200 183.01 in the anterior eye and cornea. Am J Optom Physiol Opt. 1988;65(3):224-30. m sq.) ( µ m Area 150 100 5. Ripsin CM, Kang H, Urban RJ. Management of blood 50 glucose in type 2 diabetes mellitus. Am Fam Physician. 0 2009;79(1):29-36. Minimum cell area Mean cell area 6. Tuft SJ, Coster DJ. The corneal endothelium. Eye (Lond). Figure 3. Comparison of mean of minimum cell area and 1990;4 (Pt 3):389-424. mean cell area of in patients of both groups (200 eyes each). 7. Murphy C, Alvarado J, Juster R, Maglio M. Prenatal and postnatal cellularity of the human corneal endothelium. was in accordance with the results from other studies. A quantitative histologic study. Invest Ophthalmol Vis Sci. In our study, we found out that mean ECD in patients 1984;25(3):312-22. 2 of the study group was 2467.27 ± 260.37 cells/mm and 8. Inoue K, Kato S, Inoue Y, Amano S, Oshika T. The corneal 2 2498.23 ± 235.31 cells/mm in the control group. The endothelium and thickness in type II diabetes mellitus. Jpn ECD was lower in the study group when compared J Ophthalmol. 2002;46(1):65-9. with the age- and gender-matched nondiabetic 9. Siribunkum J, Kosrirukvongs P, Singalavanija A. controls. The difference in cell loss was not statistically Corneal abnormalities in diabetes. J Med Assoc Thai. significant in our study (p > 0.05). This wasin 2001;84(8):1075-83.

128 IJCP Sutra: "It is important to get enough vitamin D as it helps in the absorption of calcium." Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019 Clinical Study

10. Martin R, de Juan V, Rodriguez G, Fonseca S, Martin S. and type II diabetes mellitus. Ophthalmologica. 1999; Contact lens-induced corneal peripheral swelling 213(4):258-61. differences with extended wear. Cornea. 2008;27(9):976-9. 15. Shenoy R, Khandekar R, Bialasiewicz A, Al Muniri A. 11. Martin R, de Juan V, Rodriguez G, Fonseca S, Martin S. Corneal endothelium in patients with diabetes mellitus: a Contact lens-induced corneal peripheral swelling: Orbscan historical cohort study. Eur J Ophthalmol. 2009;19(3):369-75. repeatability. Optom Vis Sci. 2009;86(4):340-9. 16. Matsuda M, Ohguro N, Ishimoto I, Fukuda M. 12. Lee JS, Oum BS, Choi HY, Lee JE, Cho BM. Differences Relationship of corneal endothelial morphology to in corneal thickness and corneal endothelium related to diabetic retinopathy, duration of diabetes and glycemic duration in diabetes. Eye (Lond). 2006;20(3):315-8. control. Jpn J Ophthalmol. 1990;34(1):53-6. 13. Storr-Paulsen A, Singh A, Jeppesen H, Norregaard JC, 17. Sudhir RR, Raman R, Sharma T. Changes in the corneal Thulesen J. Corneal endothelial morphology and central endothelial cell density and morphology in patients thickness in patients with type II diabetes mellitus. Acta with type 2 diabetes mellitus: a population-based Ophthalmol. 2014;92(2):158-60 study, Sankara Nethralaya Diabetic Retinopathy and 14. Roszkowska AM, Tringali CG, Colosi P, Squeri CA, Molecular Genetics Study (SN-DREAMS, Report 23). Ferreri G. Corneal endothelium evaluation in type I Cornea. 2012;31(10):1119-22.

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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 quality- of-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 disease- modifying 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

heumatoid arthritis (RA) is associated to excess cardiovascular disease (CVD) in this with increased cardiovascular mortality population either by potentiating and/or accelerating and morbidity.1 In well-established RA, atherosclerosis or by other mechanisms such as R 5 the median life expectancy is less than in control diffuse subclinical vasculitis. Parallels between populations.2,3 Infection, renal disease and respiratory the inflammatory and immunological mechanisms failure traditionally have been the primary factors operating in atherosclerotic plaque and rheumatoid contributing to excess mortality in RA patients, synovitis have been highlighted and atherosclerosis although it has been belatedly recognized that is widely considered to be an inflammatory disease.6 congestive heart failure, ischemic heart disease and Arterial stiffness is a marker of vascular dysfunction peripheral atherosclerosis deserve the appellation as and an independent risk factor for CVD.7 the prime killers of rheumatoid patients.4 It may be Hydroxymethylglutaryl coenzyme A (HMG-CoA) that chronic systemic inflammation in RA contributes 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 *Dept. of Medicine and Rheumatology property9 and the benefit of statins appears to be even PGIMS, Rohtak, Haryana Address for correspondence greater in the presence of higher C-reactive protein Dr Rekha Mathur (CRP) levels.10 Statins are known to have a number of Dept. of Medicine and Rheumatology PGIMS, Rohtak - 124 001, Haryana immunomodulatory effects, which may affect vascular E-mail: [email protected] function, plaque stability and thrombosis.11 These

130 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." Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019 Clinical Study immunomodulatory effects of statins may be especially atorvastatin group compared to placebo in patients with important in patients with RA who have systemic RA presenting with active disease despite undergoing immune activation. Statins have been demonstrated disease-modifying antirheumatic drug (DMARD) to reduce disease activity and inflammatory responses therapy. in a murine model of inflammatory arthritis and in Although not indicative for first-line use, this effect of patients with RA. atorvastatin could prove beneficial in the context Many data indicate effects for statins in innate immune of DMARD combination design, in which a statin response including effects on endothelial function,12 offers both vascular protective and adjunctive macrophage, natural killer cell and neutrophil effect immunomodulatory potential. Based on the above or functions.13 Similar effects on acquired immune literature, we planned to study the effect of atorvastatin responses via suppression of antigen presentation14 on disease activity of RA as there is scant Indian data and T-cell polarization have been shown in vitro available in this regard. and in vivo. Synovial inflammation in RA is characterized by activated components of both innate Material and Methods and acquired immune responses. Thus, postulated Patients with diseases like (known or detected on effects for statins might reasonably operate within the baseline investigations) hepatic, renal diseases, heart synovial membrane. Findings of an in vitro study15 failure, endocrinological disorders, hematological showed suppression of synovial T-cell and fibroblast- disorders, uncontrolled hypertension, coronary heart like synoviocyte cytokine release, which tends to disease, pregnant or lactating mothers, those belonging support to this notion. to reproductive age group, not willing to practice Data suggest that modulation of inflammation can be contraception and who were taking lipid-lowering achieved by atorvastatin in a proportion of patients therapy (statin or fibrate), had hypersensitivity to with RA, suggesting that some of the above pathways statin, were excluded from the study. The study was may indeed be tractable to HMG-CoA reductase approved by Ethical Committee. After obtaining inhibition.16 Moreover, in vitro cytokine release by RA the informed consent, we recruited 100 patients, synovial mononuclear cells and by synovial fibroblasts meeting the 1987 American College of Rheumatology was also reduced by statins.15 Statins have a satisfactory criteria, with high activity disease (DAS28 >5.5 and safety profile and relatively few adverse effects. In the Clinical Disease Activity Index [CDAI] >22) despite absence of side effects and contraindications, it may ongoing DMARD therapy. All participants were be reasonable to consider statin use in selected cases informed about all possible side effects of drugs. A particularly in patients with a long history of active RA detailed history and clinical examination was done that are at increased cardiovascular risk. in all subjects included in the study. They underwent A previous study “Trial of Atorvastatin in Rheumatoid routine laboratory investigations like serum glutamic Arthritis16 (TARA)” showed significant improvement in oxaloacetic transaminase (SGOT), serum glutamic Disease Activity Score-28 (DAS28) (-0.5, 95% confidence pyruvic transaminase (SGPT), blood urea, ESR and interval [CI] - 0.75 to -0.25) compared with placebo baseline radiograph of hands. (0.03, -0.23 to 0.28; difference between groups -0.52, After baseline evaluation, subjects selected for the 95% CI -0.87 to -0.17, p = 0.004). CRP and erythrocyte study were categorized into two groups of 50 each sedimentation rate (ESR) declined, swollen joint counts by Random No. Table. Subjects in Group I received also fell (-2.69 vs. -0.53; mean difference -2.16, 95% CI tablet atorvastatin (20 mg/day) along with their pre- -3.67 to -0.64, p = 0.0058). Although, authors found existing DMARD therapy. Group II were those subjects only modest change but the significant reduction who continued their pre-existing DMARDs but didn’t in DAS28 provides proof of concept that pathways receive atorvastatin, who were considered as control targeted by atorvastatin offer therapeutic opportunity group. in inflammatory disease. Disease activity using DAS28 and CDAI in each of A double-blind trial studied the effect of either the subjects of either group was evaluated at baseline increased dose of methotrexate (MTX) from 7.5 mg to and every 4 weeks for 3 months by the same observer 15 mg (Group A) or 7.5 mg MTX plus 40 mg atorvastatin at each visit. Patients were also observed for adverse (Group B). This study showed a significant reduction effects in both the groups. All data collected inthe in DAS28, CRP, ESR and swollen joint count in 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 comparable (i.e., statistically insignificant) at baseline, 4, test. Improvement in disease activity was measured by 8 and 12 weeks (Table 5). Both DAS28 and CDAI showed subtraction from baseline value. gradual and significant improvement from high disease activity to moderate disease activity in both groups Results (Figs. 1 and 2). No clinical, hematological adverse events were noted. Atorvastatin when given as adjuvant Baseline variables were comparable in both therapy in active RA patients was well-tolerated. groups (Table 1). There was statistically significant improvement in DAS28 in both groups with DMARD Table 3. Analysis and Comparative Assessment of therapy including adjuvant atorvastatin in Group I DAS28 Between Two Groups at 4, 8 and 12 weeks (Table 2). The DAS28 score was Duration Group I Group II P value comparable (i.e., statistically insignificant) in both Baseline 6.20 ± 1.2 5.50 ± 1.2 0.00 groups at 4, 8 and 12 weeks (Table 3). When both groups 4 weeks 4.74 ± 1.3 4.67 ± 1.1 0.77 were analyzed by CDAI, significant improvement in 8 weeks 4.49 ± 1.2 4.34 ± 1.4 0.59 disease activity was observed at 4, 8 and 12 weeks (Table 4). The comparison of CDAI between groups was 12 weeks 3.68 ± 1.0 3.97 ± 1.3 0.24

Table 1. Baseline Variables in Both Groups Table 4. Analysis and Improvement in CDAI Over 12 Weeks Variables Group I Group II P value Duration Group I Group II Age (years) 42.56 ± 13.3 43.12 ± 9.96 0.237 4 weeks 15.24 7.64 Male 10 10 1.00 8 weeks 17.36 9.68 Female 40 40 1.00 12 weeks 23.32 12.84 Disease (mean) 2.08 years ± 2.00 years ± 0.590 P value <0.001 <0.001 Duration 1.3 1.2

RF 60.45% 61.33% 0.745 Table 5. Analysis and Comparative Assessment of ESR (mm 1st hour) 44.2 ± 19.4 31.92 ± 11.87 0.001 CDAI Between Two Groups Duration Group I Group II P value CDAI 35.48 ± 16.7 27.56 ± 14.4 0.01 Baseline 35.48 ± 16.7 27.56 ± 14.45 0.012 DAS28 6.20 ± 1.2 5.50 ± 1.2 0.06 4 weeks 20.24 ± 12.9 19.92 ± 10.59 0.892 TJC 10.88 ± 8.96 11.48 ± 8.41 0.730 8 weeks 18.12 ± 11.9 17.88 ± 14.30 0.927 SJC 3.2 ± 3.07 2.08 ± 2.13 0.037 12 weeks 12.16 ± 10.3 14.72 ± 10.27 0.217 PGA 3.2 ± 1.51 3.24 ± 1.22 0.884 7 EGA 2.96 ± 1.44 3.12 ± 1.28 0.559 Group I (Atorvastatin) 6.2 Group II (Control) 6 GH 32 ± 15.11 32 ± 12.45 1 5.5

CDAI = Clinical Disease Activity Index; DAS28 = Disease Activity Score-28; ESR = 5 4.74 4.67 4.49 Erythrocyte sedimentation rate; EGA = Evaluator global assessment; PGA = Patient 4.34 3.97 global assessment; RF = Rheumatoid factor; TJC = Tender joint counts; SJC = Swollen 4 3.68 joint counts; GH = Patient’s general health; P = P value (<0.05 = significant). 3 Table 2. Analysis and Improvement in DAS28 Over Mean DAS28 Mean 12 Weeks in Both Groups 2

Duration Group I Group II 1 4 weeks 1.46 0.83 0 8 weeks 1.71 1.16 Baseline 4 weeks 8 weeks 12 weeks Duration 12 weeks 2.52 1.53 Figure 1. Comparative assessment of DAS28 between two P value <0.001 <0.001 groups from baseline to 12 weeks.

132 IJCP Sutra: "If you smoke or drink, it is a good idea to quit both these habits." Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019 Clinical Study

improvement in CDAI score in Group I (15.24) was more 40 Group I (Atorvastatin) than the Group II (7.64) (Table 4). There was significant 35.48 35 Group II (Control) reduction in CDAI by 23.32 and 12.84 from baseline to 12 weeks in the two groups (p < 0.001) (Table 4). 30 27.56 This study showed a significant reduction in various

25 variables of disease activity of RA-like tender joint count (TJC), swollen joint count (SJC), patient global 20.24 20 19.92 assessment (PGA), evaluator global assessment (EGA), 18.12 17.88

Mean CDAI Mean ESR, patient’s general health (GH) over a period of 15 14.72 12 weeks in both groups (atorvastatin and control); 12.16 similar finding was observed for 40 mg atorvastatin in 10 TARA study.16 5 In our study, the results showed that atorvastatin when used as adjuvant therapy with DMARDs had beneficial 0 Baseline 4 weeks 8 weeks 12 weeks effects on parameters of disease activity and also, Duration was well-tolerated when given in combination with DMARDs. Since, the improvement in disease activity Figure 2. Comparative assessment of CDAI between two groups from baseline to 12 weeks. was numerically higher in the atorvastatin adjuvant therapy group when compared with DMARD alone No significant liver function or muscle abnormality group, but this was statistically insignificant; hence, it was detected in those given atorvastatin. is suggested that larger and longer trails are needed so as to evaluate the modest but beneficial effect of well- Discussion tolerated atorvastatin therapy in patients of RA. But thanks to good safety profile, easy administration and RA is a chronic disease with more predispositions to the existence of a broad experience regarding their use atherosclerosis owing to its inflammatory state. This in clinical practice, statins are particularly attractive increased prevalence of atherosclerosis in RA has made therapeutic agents, so even a modest efficacy in the ischemic heart disease, the most common cause of treatment of RA in association with the reduction of death, followed by infection in RA, thus increasing its cardiovascular risk can lead to a beneficial therapeutic mortality two times greater than the general population. ratio. This can make statins particularly useful as Also in RA, the median life expectancy is shortened by adjuvant therapy associated with other conventional an average of 7 years for men and 3 years for women therapeutic methods used in RA, especially in patients compared to control populations. In the studies, with dyslipidemia, where they should be the first DMARDs to some extent reduced the cardiovascular choice of treatment. mortality in RA. Statins have been demonstrated to reduce disease activity and inflammatory responses References in a murine model of inflammatory arthritis and in 1. Van Doornum S, McColl G, Wicks IP. Accelerated patients with RA.15,16 atherosclerosis: an extraarticular feature of rheumatoid arthritis? Arthritis Rheum. 2002;46(4):862-73. In present study, Group I had higher level (6.20 ± 1.2) of DAS28 at baseline than Group II (5.50 ± 1.24), which 2. Pinals RS. Survival in rheumatoid arthritis. Arthritis Rheum. 1987;30(4):473-5. was insignificant (p = 0.06). At 4 weeks, DAS28 was improved significantly from baseline in both groups 3. Vandenbroucke JP, Hazevoet HM, Cats A. Survival and cause of death in rheumatoid arthritis: a 25-year but the improvement in DAS28 score in Group I (1.46) prospective follow-up. J Rheumatol. 1984;11(2):158-61. was more than the Group II (0.83) (Table 2). There was 4. Reilly PA, Cosh JA, Maddison PJ, Rasker JJ, Silman AJ. significant improvement in DAS28 by 2.52 and 1.53 Mortality and survival in rheumatoid arthritis: a 25- from baseline to 12 weeks in Group I and Group II, year prospective study of 100 patients. Ann Rheum Dis. respectively (p < 0.001) (Table 2). Similarly, CDAI was 1990;49(6):363-9. higher in Group I (35.48 ± 16.72) than in Group II 5. Bacon PA, Raza K, Banks MJ, Townend J, Kitas GD. The (27.56 ± 14.45) (Table 5). At 4 weeks, CDAI was improved role of endothelial cell dysfunction in the cardiovascular significantly from baseline in both groups but the 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. 133 Caffeine is a mood-altering drug, and it may worsen symptoms of anxiety disorders." Clinical Study Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

6. Pasceri V, Yeh ET. A tale of two diseases: atherosclerosis Arterioscler Thromb Vasc Biol. 2001;21(11): and rheumatoid arthritis. Circulation. 1999;100(21):2124-6. 1712-9. 7. Arnett DK, Evans GW, Riley WA. Arterial stiffness: 12. Palinski W, Napoli C. Unraveling pleiotropic effects of a new cardiovascular risk factor? Am J Epidemiol. statins on plaque rupture. Arterioscler Thromb Vasc Biol. 1994;140(8):669-82. 2002;22(11):1745-50. 8. Shepherd J, Cobbe SM, Ford I, Isles CG, Lorimer AR, 13. Choi M, Rolle S, Rane M, Haller H, Luft FC, Kettritz R. MacFarlane PW, et al. Prevention of coronary heart disease Extracellular signal-regulated kinase inhibition by statins with pravastatin in men with hypercholesterolemia. West inhibits neutrophil activation by ANCA. Kidney Int. of Scotland Coronary Prevention Study Group. N Engl J 2003;63(1):96-106. Med. 1995;333(20):1301-7. 14. Kwak B, Mulhaupt F, Myit S, Mach F. Statins as a 9. Vaughan CJ, Murphy MB, Buckley BM. Statins do more newly recognized type of immunomodulator. Nat Med. than just lower cholesterol. Lancet. 1996;348(9034):1079-82. 2000;6(12):1399-402. 10. Ridker PM, Rifai N, Clearfield M, Downs JR, Weis SE, 15. Leung BP, Sattar N, Crilly A, Prach M, McCarey DW, Miles JS, et al; Air Force/Texas Coronary Atherosclerosis Payne H, et al. A novel anti-inflammatory role for Prevention Study Investigators. Measurement of simvastatin in inflammatory arthritis. J Immunol. C-reactive protein for the targeting of statin therapy in 2003;170(3):1524-30. the primary prevention of acute coronary events. N Engl J 16. McCarey DW, McInnes IB, Madhok R, Hampson R, Med. 2001;344(26):1959-65. Scherbakov O, Ford I, et al. Trial of Atorvastatin in 11. Takemoto M, Liao JK. Pleiotropic effects of 3-hydroxy- Rheumatoid Arthritis (TARA): double-blind, randomised 3-methylglutaryl coenzyme a reductase inhibitors. placebo-controlled trial. Lancet. 2004;363(9426):2015-21.

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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

ostauricular cutaneous mastoid fistula is a rare Case Report condition, as rare as only about 6 cases were reported in literature.1 Mastoid fistula is a rare A 65-year-old lady presented to us in the ENT OPD P with a complication of chronic suppurative otitis complication of chronic suppurative otitis media. This complication could be secondary to ear surgery, or media in the form of a postauricular mastoid fistula. a complication of congenital cholesteatoma.2 Usual She had uncontrolled diabetes and experienced treatment in all referred literature is surgery using: giddiness while having bath as water was stimulating her labyrinth. Because of her comorbid condition and ÂÂ Temporalis muscle rotational flap for closure of the defect.1 her debilitating giddiness, we tried helping her to buy time till she became fit for her surgery (which ÂÂ Fascio-cutaneo-periosteal advancement flap with is the ideal treatment for a condition like this) by Burow’s triangles.2 making a prosthesis that snugly fits in the fistula However, simple closure is often unsuccessful because area and thus could help her overcome her giddiness, of the necrotic skin edges. while having bath and preventing water entering This article is written as an out of the box thinking in the labyrinth. the treatment of a postauricular mastoid fistula, which The dentists initially approximated the depth of the presented to us a case of complication of chronic sinus by measuring it using a match stick. Semi hot suppurative otitis media. 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 *Dept. of ENT, Pandit General Hospital, Church Road, Sirsi, Uttara Kannada, Karnataka were mixed and poured on a thin plate of acrylic over †Venkatesh Dental Clinic, Near Narashimha Temple, Pramankatta, Keni Road which water was poured and let to set. Mandi Bazar, Ankola, Karwar Dist, Karnataka ‡Dental Care Center, 1st floor, GP Center, Court Road, Sirsi, Karnataka After setting, the acrylic was taken out from the bowl Address for correspondence Dr Subramaniam Vinayak Easweran by splitting of the set dental stone and checked for Dept. of ENT trying on the patient’s sinus cavity. Figure 1 a and Pandit General Hospital Church Road, Sirsi, Uttara Kannada - 581401, Karnataka b show the prosthesis mold and Figure 1c shows the E-mail: [email protected] prosthesis in situ.

136 IJCP Sutra: "Sleep problems and anxiety disorder often go hand in hand. It is important to get adequate rest. Follow a relaxing bedtime routine." Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019 Case Report

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

Discussion could be given a thought for patients who have comorbid conditions making them unfit for surgery We present here an unusual and temporary treatment and have other associated symptoms with regards to of mastoid fistula. What makes this case a special one is that it has never been published in literature, and the disease condition per say, giving a choice to the moreover it could be thought of as an ideal treatment for patient to buy time till the patient could be made fit the patient who wants to buy time for surgery owing to for surgery. the patient’s comorbid conditions. At the same time, it can help the patient get rid of the debilitating giddiness, References which is a consequence of the complication of chronic 1. Choo JC, Shaw CL, Chong Y C S. Postauricular suppurative otitis media. However, surgery to close the cutaneous mastoid fistula. J Laryngol Otol. 2004;118(11): fistula is the mainstay treatment of such a case. 893-4. Conclusion 2. Olusesi AD, Opaluwah E. Postauricular advancement fascio-cutaneo-periosteal flap for closure of mastoid We can keep this as a treatment option, though cutaneous fistula. Otolaryngol Pol. 2014;68(5): surgery is the main treatment. Such a treatment 276-80.

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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

he thalassemic syndromes are inherited disorders Investigations of globin synthesis and present as hemolytic Hemoglobin (Hb) - 10.1 g/dL, mean corpuscular Tanemia. The reduced supply of globin causes volume (MCV) - 69.6 fl, platelet - 2.83 lakhs, erythrocyte hypochromia and microcytosis. In beta-thalassemia, sedimentation rate (ESR) - 40 mm/hr; Mentzer index - there is unbalanced accumulation of alpha-chain and 15.13, reticulocyte count - 0.6%. reduction of beta-chain. This is to some extent corrected by gamma-chain (fetal hemoglobin [HbF]). However, Peripheral smear - microcytic hypochromic picture the clinical severity varies widely even though HbF along with many target cells and few elliptocytes. replaces the hemoglobin A (HbA). Hyperbilirubinemia was mainly indirect (total - 5.2 mg/dL); serum glutamic pyruvic transaminase We are presenting two cases of raised HbF with widely (SGPT) - 133 IU/L. varying clinical picture. USG abdomen - Splenomegaly, minimal ascites, Case Reports distended gallbladder with sludge. Viral markers - negative; Coombs test - negative; Case 1 NESTROFT - positive; Hb electrophoresis - 98.7% HbF, A 13-year-old boy presented with history of fever for 1.3% HbA2. 3-4 days, associated with abdominal pain, along with Past History anorexia, nausea and generalized fatigue since a week. Patient’s parents also noticed icterus and yellowish Patient had blood transfusion three times in the last discoloration of urine since 3-4 days. On examination, 6 years and his lowest Hb was 5 g/dL in 2009 when he patient was anemic, icteric with splenomegaly. 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 *Second Year Resident electrophoresis. Coombs and glucose-6-phosphate †Third Year Resident dehydrogenase (G6PD) was negative. Reticulocyte count ‡Senior Resident #HOD and Professor was 3-6%. On further follow-up, Hb was 8-11 g/dL. ¥Associate Professor Dept. of Medicine On further analysis of patient’s parents: Father was MP Shah Govt. Medical College, Jamnagar, Gujarat diagnosed as thalassemia minor and mother was Address for correspondence diagnosed as hereditary persistence of fetal hemoglobin Dr Jemima Bhaskar 404, Kings Palace, Mehul Nagar (HPFH). Parents never required transfusion and since Opp. BSNL Telephone Exchange, Jamnagar - 361 006, Gujarat last 2 years patient had not required transfusion.

138 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." Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019 Case Report

Case 2 Hb electrophoresis - 100% HbF on HPLC and capillary method. A 33-year-old male patient presented to OPD with chief complaint of abdominal pain in left hypochondrium, Discussion low intensity in nature, nonradiating since 12 days. There was no complaint of nausea or vomiting or any Hemoglobin A is the major normal adult Hb. It consists previous blood transfusion. Patient was conscious, of heme + globin. Globin consists of two alpha chains oriented, hemodynamically stable, nonicteric and and two beta chains. HbF is the major hemoglobin nonanemic. On abdominal examination, mild of the fetus. It consists of two alpha chains and two splenomegaly without tenderness was noted. gamma chains. HbA2 consists of two alpha chains Investigations and two delta chains. It accounts for 1.5-3.5% of normal adult Hb. Thalassemia is an inherited disease White blood cell (WBC) - 9,400 (N ,L ,M ,E ,B ), red 62 30 7 0 0 causing impairment of globin chain production. In blood cell (RBC) - 6.09 lakhs, platelet - 2.88 lakhs, thalassemias, globin chains of normal structure are Hb - 12.4 g/dL, hematocrit - 37.5%, mean corpuscular produced at a decreased rate. The beta-thalassemias hemoglobin (MCH) - 18.7 pg/dL, MCV - 61.6 fl/dL, and their associated biochemical and molecular defects mean corpuscular hemoglobin concentration (MCHC) - are given in Table 1. 30.4%, red blood-cell distribution width (RDW) - 45.7%, ESR - 22/hr, reticulocyte count - 1%, Mentzer index - Beta-thalassemia refers to decreased production of beta 12.3, NESTROFT - positive. Peripheral smear showed chains. This is compensated by increased production microcytic hypochromic anemia. of delta chains. Hence, there is an increase in HbA2. However, it is never more than 12%. The beta- Serum creatinine - 0.5 mg/dL, serum urea - 19 mg/dL, random blood sugar (RBS) - 89 mg/dL, SGPT - 54 mg/dL, thalassemias are clinically classified as beta-thalassemia lactate dehydrogenase - 193.8 mg/dL. major, a severe and transfusion-dependent form; beta- thalassemia intermedia with less severe symptoms; Serum bilirubin (total - 1.2, indirect - 1.0, direct - and beta-thalassemia minor or trait without clinical 0.2 mg/dL), viral markers - negative. symptoms but with hematological abnormalities USG - Hepatosplenomegaly; liver 14.5 cm and spleen (Table 2). With an absence (β0) or marked decrease 15.3 cm. (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 Homozygous states 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 Hb Lepore Lepore/Lepore Thalassemia major 85% HbF, 15% Hb Lepore Heterozygous states 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 Hb Lepore Lepore/β Thalassemia minor HbA, ↑ HbF, ↓ HbA2,10% 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 Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

alpha chains, which precipitate and cause ineffective gamma chains do not compensate for the lack of beta erythropoiesis and form toxic inclusion bodies that kill chains by improving clinical outcome. erythrocytes and cause hemolytic anemia. Thalassemias The other clinical picture is that of delta-beta- are also classified as homozygous and heterozygous thalassemia (homozygous), where HbF is again very states. high (even 100%). HbA is absent and HbA2 may Clinical findings include jaundice, leg ulcers, gall stones, be absent or present in normal range. But unlike high output cardiac failure and splenomegaly evident β0-thalassemia major, it presents clinically as a mild in early childhood. There is a prominence of frontal form of beta-thalassemia intermedia. Patients present bones, cheek bones and jaws due to extreme bone with above 10 g/dL, mild thalassemic indices and marrow hyperplasia, presenting with characteristic minimal hepatosplenomegaly. The raised gamma chipmunk facies. chains compensate to high-degree for the lack of beta X-rays findings of thinned cortex of long and flat bones chains. and thickening of skull with osteoporosis (hair on end At the other end of the spectrum is HPFH, where HbF appearance) are seen. Growth is stunted. Most patients is raised to nearly 100%. Hb levels are normal, red cell require regular transfusions due to profound anemia indices are normal and patients are asymptomatic and and iron over loading occurs. are apparently healthy. They are usually not diagnosed Unlike most hemolytic diseases, the anemia is microcytic as they never need treatment and may not visit a and hypochromic. In b0-thalassemia (homozygous) hospital. HbA is absent, HbF is as high as 98% and HbA2 is 2%. Both our patients had raised HbF to >98%. However, + In β -thalassemia (heterozygous), HbF is 60-95%, HbA 1 patient presented with severe anemia in childhood is present but HbA2 ratio to HbA is always increased. to the extent of requiring 3 blood transfusions with In delta-beta-thalassemia, beta and delta chains are a clinical picture of jaundice, splenomegaly, raised not produced and there is a significant increase in reticulocyte count, Mentzer index of 15.13 and HbF. In the homozygous state, Hb consists only of thalassemic red cell indices, HbF 98.7%, HbA2 1.3%, HbF. The heterozygous state is similar to mild beta- absent HbA and had b0-thalassemia major. thalassemia trait except that HbA2 is not increased The other patient was 33 years old; clinically there or is even reduced and HbF is increased. Clinically, was no anemia, no icterus, mild splenomegaly, with homozygous delta-beta-thalassemia behaves as a mild mild thalassemic red cell indices, reticulocyte count of form of beta-thalassemia intermedia with Hb level of 1%, HbF 100%, absent HbA and HbA2. He had delta- 10-13 g/dL, mildly thalassemic red cell indices and beta-thalassemia, which presented clinically with mild mild hepatosplenomegaly. The mild phenotype is the symptoms of beta-thalassemia intermedia. result of increased production of gamma-chain, which compensate to some degree for lack of beta chains. Conclusion HPFH - In this condition, there is persistence of HbF in adults without significant hematologic abnormalities or The carry home message of this presentation is that clinical illness. although HbF is elevated in the absence of HbA after birth, all is not well. The prognosis depends on the The rise in HbF in adults presents with a wide clinical clinical picture, which can present as 0-thalassemia 0 β spectrum. In one end of the spectrum, in β -thalassemia, in childhood with early death, but it can also present HbF may be raised to even more than 95% with the as delta-beta-thalassemia and HPFH, where they are rest HbA2 and absent HbA. This presents in childhood, asymptomatic and lead normal lives. clinically as homozygous β0-thalassemia major, with profound anemia, microcytic hypochromic picture in Suggested Reading peripheral smear, red cell indices of thalassemia. Target cell, poikilocytosis, Howell-Jolly bodies and anisocytosis 1. Harrison’s Principles of Internal Medicine. 18th Edition, are seen. The reticulocyte count is less elevated than Vol 1. Mc-Grawhill; 2012. expected for degree of anemia because of destruction 2. De Gruchy’s Clinical Haematology. 5th Edition; 2011. of erythroid precursors in the marrow. Intramedullary 3. Henry’s Clinical Diagnosis and Management by destruction of Hb (ineffective erythropoiesis) is Laboratory Methods. 21st Edition; 2007. markedly increased. Extramedullary erythropoiesis 4. Davidson’s Principles and Practice of Medicine. 21th occurs and patients die by the third decade. The raised Edition, Churchill Livingstone; 2010.

140 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

y definition, an ectopic ureter is any ureter, bladder (CT-KUB, Fig. 1) revealed bilateral single or duplex, that does not enter the hydroureteronephrosis with multiple calculi in Btrigonal area of the bladder. It is more common right lower ureter and single calculus in left lower among females and is usually associated with double ureter. Intravenous pyelogram (IVP, Fig. 2) revealed collecting system. About one-fifth of ectopic ureters are bilateral single system gross hydroureteronephrosis 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. 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 Figure 1. Reformatted coronal image of plain CT-KUB scan Dept. of Urology, ESIC SSH, Sanath Nagar, Hyderabad - 500 038, Telangana showing bilateral hydroureteronephrosis with lower ureter E-mail: [email protected] 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 ureteric orifice just distal to bladder neck and left calculus in left ureter. With provisional diagnosis ureteric orifice distal to right ureteric orifice and 1 cm of bilateral megaureters with secondary stones or proximal to the veru with absent trigone and good bilateral lower ureteric calculi with megaureters, capacity bladder. Bilateral retrograde pyelography cystourethroscopy was carried out under spinal showed bilateral single system ectopic megaureters anesthesia. Cystourethroscopy (Fig. 3) showed right 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

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, Figure 2. Post-void IVP film showing bilateral single system the affected renal units do not function appreciably. hydroureteronephrosis with secondary calculi. 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. Right ureteric orifice BSSEUs are even rarer compared to SSEU. It is Left ureteric orifice 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. Veru Overall, female patients are affected twice as commonly Figure 3. The cystourethroscopic picture showing both as males, although SSEU is reported to be more ureteric orifices in prostatic urethra. common in males. Usually, BSSEU presents in infants

142 IJCP Sutra: "Hydrate yourself well by drinking sufficient water throughout the day." Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019 CASE REPORT or children with recurrent UTIs, urinary incontinence presented in late adulthood with only obstructive and a poor capacity of bladder, which requires ureteric symptoms, major reconstructive surgery was avoided reimplantation with or without bladder augmentation. and patient was managed endoscopically. In males, the posterior urethra is the most common site SUGGESTED READING for insertion of the ectopic ureter. Evaluation is usually by ultrasonography, renal nuclear scan, micturating 1. Glassberg KI, Braren V, Duckett JW, Jacobs EC, King LR, cystourethrography and retrograde pyelography. IVP Lebowitz RL, et al. Suggested terminology for duplex and magnetic resonance imaging (MRI) may be used systems, ectopic ureters and ureteroceles. J Urol. occasionally. 1984;132(6):1153-4. 2. Peters CA, Schlussel RN, Mendelsohn C. Ectopic Male patients with BSSEU in posterior urethra proximal ureter, ureterocele, and ureteral anomalies. In: Wein AJ, to external sphincter may be continent with external Kavoussi LR, Novick AC, Partin AW, Peters CA (Eds.). sphincter control and have a good capacity bladder. Campbell-Walsh Urology. 10th Edition, Philadelphia: Patients with good bladder capacity may require Saunders Elsevier; 2011. pp. 3236-66. bilateral ureteric reimplantation alone. 3. Keating MA. Ureteral duplication anomalies: ectopic Our patient presented with obstructive symptoms due ureters and ureteral anomalies. In: Belman BA, King LR, to stone in the right distal ureter obstructing bladder Kramer SA (Eds.). Clinical Pediatric Urology. 4th Edition, London: Martin Dunitz; 2002. pp. 677-733. neck. As the patient presented in late adulthood with secondary stones and a good capacity bladder 4. Redman JF, Lightfoot ML, Reddy PP. Bilateral single ureteral ectopia in a boy. Urology. 2002;60(3):514. with normal continence, endoscopic management alone was done with ureteral meatotomy, lithotripsy 5. Mathews R, Jeffs RD, Maizels M, Palmer LS, Docimo SG. and DJ stenting. Surgical management consisting of Single system ureteral ectopia in boys associated with bladder outlet obstruction. J Urol. 1999;161(4):1297-300. transurethral endoscopic incision of the distal ureter has previously been reported by Mathews et al. Ureteric 6. Dange AS, Sen S, Zachariah N, Chacko J, Mammen KE. reimplantation was not preferred as reflux in late age is Single-system ureteral ectopia - Associated malformations and management in children lacking an orthotopic ureter. not a worrying factor. However, the patient is kept on Pediatr Surg Int. 1994;9:377-80. close follow-up for any late symptoms. 7. Kumar A, Goyal NK, Trivedi S, Dwivedi US, Singh PB. This is one of its kind case of BSSEU with secondary Bilateral single system ectopic ureters: case report with ureteric calculi presenting in adulthood. As patient literature review. Afr J Paediatr Surg. 2008;5(2):99-101.

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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 ozone- depleting 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: [email protected] 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 All heart patients who need pacemakers, valve replacement, bypass Heart Care Foundation of India created with an objective to cater to the surgery, surgery for congenital heart diseases, etc. are eligible to apply for assistance from the Fund. The Application form can be downloaded from heart care needs of people. the website of the Fund. http://heartcarefoundationfund.heartcarefoundation. Objectives org and submitted in the HCFI Fund office. Assist heart patients belonging to economically weaker sections of Important Notes the society in getting affordable and quality treatment. The patient must be a citizen of India with valid Voter ID Card/ Aadhaar Card/Driving License. Raise awareness about the fundamental right of individuals to medical treatment irrespective of their religion or economical background. The patient must be needy and underprivileged, to be assessed by Fund Committee. Sensitize the central and state government about the need for a National The HCFI Fund reserves the right to accept/reject any application Cardiovascular Disease Control Program. for financial assistance without assigning any reasons thereof. Encourage and involve key stakeholders such as other NGOs, private The review of applications may take 4-6 weeks. institutions and individual to help reduce the number of deaths due All applications are judged on merit by a Medical Advisory Board to heart disease in the country. who meet every Tuesday and decide on the acceptance/rejection To promote heart care research in India. of applications. The HCFI Fund is not responsible for failure of treatment/death To promote and train hands-only CPR. of patient during or after the treatment has been rendered to the Activities of the Fund patient at designated hospitals. 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. The financial assistance granted will be given directly tothe Apart from its own resources, the fund raises money through donations, treating hospital/medical center. aid from individuals, organizations, professional bodies, associations The HCFI Fund has the right to print/publish/webcast/web post details of the patient including photos, and other details. (Under and other philanthropic organizations, etc. taking needs to be given to the HCFI Fund to publish the medical details so that more people can be benefitted). 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 The HCFI Fund does not provide assistance for any emergent heart interventions. Delhi NCR like Medanta – The Medicity, National Heart Institute, All Check List of Documents to be Submitted with Application Form India Institute of Medical Sciences (AIIMS), RML Hospital, GB Pant

Hospital, Jaipur Golden Hospital, etc. The money is transferred Passport size photo of the patient and the family directly to the concerned hospital where surgery is to be done. A copy of medical records

Drug Subsidy 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 The HCFI Fund has also tied up for providing up to 50% discount Health Govt of India, Rotary Relief Fund, Delhi Arogya Kosh, Delhi on imaging (CT, MR, CT angiography, etc.) Arogya Nidhi), etc., if anyone.

Free Diagnostic Facility Free Education and Employment Facility The Fund has installed the latest State-of-the-Art 3 D Color Doppler EPIQ HCFI has tied up with a leading educational institution and an export house in 7C Philips at E – 219, Greater Kailash, Part 1, New Delhi. Delhi NCR to adopt and to provide free education and employment opportunities This machine is used to screen children and adult patients for any heart disease. to needy heart patients post surgery. Girls and women will be preferred. Laboratory Subsidy HCFI has also tied up with leading laboratories in Delhi to give up to 50% discounts on all pathological lab tests. Help Us to Save Lives About Heart Care Foundation of India Heart Care Foundation of India was founded in 1986 as a National Charitable Trust with the basic objective of creating awareness about The Foundation all aspects of health for people from all walks of life incorporating all seeks support, pathies using low-cost infotainment modules under one roof. donations and HCFI is the only NGO in the country on whose community-based contributions from individuals, organizations health awareness events, the Government of India has released two and establishments both private and governmental commemorative national stamps (Rs 1 in 1991 on Run For The Heart in its endeavor to reduce the number of deaths and Rs 6.50 in 1993 on Heart Care Festival- First Perfect Health due to heart disease in the country. All donations Mela). In February 2012, Government of Rajasthan also released one made towards the Heart Care Foundation Fund are Cancellation stamp for organizing the first mega health camp at Ajmer. exempted from tax under Section 80 G of the IT Act Objectives (1961) within India. The Fund is also eligible for overseas donations under FCRA Registration Preventive Health Care Education (Reg. No 231650979). The objectives and Perfect Health Mela activities of the trust are charitable Providing Financial Support for Heart Care Interventions within the meaning of 2 (15) Reversal of Sudden Cardiac Death Through CPR-10 Training Workshops of the IT Act 1961. 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 Executive Council Members

Sumi Malik Deep Malik Vivek Kumar Geeta Anand Karna Chopra Dr Uday Kakroo Dr Veena Aggarwal Harish Malik Veena Jaju Aarti Upadhyay Naina Aggarwal Nilesh Aggarwal Raj Kumar Daga H M Bangur Shalin Kataria This Fund is dedicated to the memory of Advisors Anisha Kataria Sameer Malik who was an unfortunate victim of sudden cardiac death at a young age. Mukul Rohtagi Vishnu Sureka Ashok Chakradhar 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 – Brief Note

utbreaks of an acute neurologic illness virus, parechovirus, adenovirus, enteroviruses and commonly described as AES (acute parvovirus B19). In previous years, National Institute Oencephalitis syndrome) have been reported in of Virology, ICMR based Nipah testing (PCR) had also Muzaffarpur, Bihar since 1995; there have been several been negative. Further, human biologic specimens sent subsequent outbreaks. In most outbreaks, it was found to the US CDC Pathogen Discovery Laboratory were that the illness primarily affected previously healthy evaluated for any novel bacterial or viral etiologies young children (mostly in age-group 2-5 years), and using 16s ribosomal testing, pan viral PCR, and next was typically characterized by acute onset seizures generation metagenomic sequencing; results indicated and altered mental status in early morning hours, no evidence of an infectious etiology. Additionally, quickly deteriorating to coma and associated with entomology studies by NCDC and previously by the high mortality. Outbreaks have occurred in the dry, Centre for Research in Medical Entomology, ICMR did hot months of May and June, and coincide with not suggest either adequate density of specific vectors Muzaffarpur’s litchi harvesting season. nor presence of antigens in them to suggest any vector- borne infectious etiology. Thus, the illness diagnosis In the years 2013 and 2014, National Centre for Disease was finally concluded to be an acute encephalopathy, Control (NCDC) and partner institutions, US Centers for and not infectious encephalitis. Disease Control and Prevention (CDC), National Vector Borne Disease Control Programme and Indian Council The next steps in the investigation involved evaluating of Medical Research (ICMR), conducted systematic noninfectious etiologies of pesticide toxicity and heavy investigations of this outbreak illness with the use metals. Clinical and epidemiologic parameters were not consistent with pesticide or heavy metal toxicity. of four key methods: examining clinical parameters, The National Institute of Occupational Health (NIOH), conducting descriptive and analytic epidemiologic ICMR analyzed and compared acetylcholinesterase field studies, performing detailed laboratory testing of and butyrylcholinesterase levels between biologic human biologic specimens, as well as collection and specimens of case-patients (affected children) and laboratory analysis of environmental specimens. controls (well children) and found no evidence to Evaluation of Infectious Etiologies suggest organophosphate pesticide toxicity. Specimens submitted to the US CDC National Center for Clinical parameters indicated that the majority of Environmental Health laboratories were additionally patients presented without prodrome or fever on analyzed for the presence of other metabolites admission, that cerebrospinal fluid (CSF) cytology and of herbicides (atrazine) and organophosphates biochemistry were unremarkable, and that the magnetic (dialkylphosphate), which yielded negative results for resonance imaging (MRI) brain showed no evidence of all tests. The NIOH also tested for evidence of pesticide inflammation; together these findings suggested that residues in food grains, water, local vegetation and an infectious etiology was unlikely. Pathogen-based fruits (litchi) specimens taken from case patient homes, testing of human biologic specimens at NCDC using which again tested negative. Additionally, the US enzyme-linked immunosorbent assay for antibodies, CDC laboratories tested for a battery of over 25 heavy polymerase chain reaction (PCR) and virus isolation metals and found no evidence to support heavy metal techniques were negative for Japanese encephalitis toxicity in human specimens. virus, West Nile virus, Chandipura, enteroviruses and The clinical study findings also revealed severe 11 viruses tested with a multiplex PCR platform (Herpes levels of hypoglycemia in the majority of case- simplex viruses 1 and 2, human herpes viruses 6 and 7, patients, suggesting that this was an outbreak of cytomegalovirus, varicella zoster virus, Epstein-Barr acute hypoglycemic encephalopathy, likely due to a

146 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." Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019 Public Health noninfectious agent. Timely glucose assessment and association between consuming litchi in previous correction, which was recommended after the 2013 24 hours and having illness. investigation, demonstrated encouraging response and The US CDC National Center for Environmental Health may have, in part, explained a significant reduction in laboratories evaluated and confirmed the presence mortality observed in 2014 compared to 2013. Further, of both MCPG and hypoglycin metabolites in urine the characteristic finding of an early morning illness specimens of case-patients and also the disruption of onset in a previously healthy child and the seasonal fatty acid metabolic function by identifying biomarkers nature of this outbreak suggested the possibility of a of the same (organic acids, including· dicarboxylic acid, seasonally available exogenous toxin which somehow in urine and medium and long-chain acylcarnitines in acted on the child’s glucose metabolism, and to which blood) in human specimens. These abnormal findings a child might be particularly vulnerable in the early (MCPG, hypoglycin or abnormal elevations in fatty morning fasting hypoglycemia state. Clinical and acids) were not observed on evaluation of any specimens epidemiologic analysis indicated that the case-patients of controls (well children). These laboratories also were found more likely to be malnourished than detected both hypoglycin and MCPG in the aril (fruit) controls (well children in the same area), which again and seeds of litchi fruits collected from Muzaffarpur in suggested that the toxin may have an increased effect on those with depleted glycogen stores. the year 2014. Similar outbreaks of hypoglycemic encephalopathy It is also noted that even in some Asian countries - have been documented in West Africa and West Indies Vietnam and Bangladesh - outbreaks of similar Islands, where the illness was found to be associated unexplained illness in litchi growing regions have been with ackee fruit ingestion, due to the presence in reported and an ecological association of illness and the ackee fruit of a naturally occurring compound litchi plantation surface proportion was established in called hypoglycin, which causes disruptions in Vietnam outbreak investigations. Also, similar outbreaks glucose metabolism which result in abnormal fatty are now reported from Malda district of West Bengal, acid accumulation and severe hypoglycemia. Given another litchi growing region. Characteristically, these that litchi belongs to the same botanical family outbreaks from Vietnam, Bangladesh, Malda and West (Sapindaceae) as the ackee fruit, and also has a natural Africa/West Indies present as similar acute neurological compound called methylenecyclopropylglycine illness in very young age children described as acute (MCPG) that is a homologue of hypoglycin, which is onset seizures and altered mental status, usually in also known to cause a similar disruption of fatty acid/ early morning hours, quickly deteriorating to coma glucose metabolism as the ackee fruit in experimental and with high mortality. These outbreaks have also animal studies, it was decided to proceed with testing similarly been reported to coincide with litchi/ackee for association between the Muzaffarpur outbreak fruits harvesting season. illness and these naturally occurring toxins (MCPG and hypoglycin) along four lines of investigation: 1) NCDC/CDC and PARTNER AGENCIES: COLLABORATIVE Evaluation of an epidemiologic association between INVESTIGATIONS OF MUZAFFARPUR OUTBREAKS, exposure to MCPG/hypoglycin-containing fruits 2013-2014 (litchi) and illness; 2) Assessment for the presence of In 2013 and 2014, NCDC/CDC conducted hospital- hypoglycin or MCPG metabolites (MCPA or MCPF) based surveillance, a field-based epidemiologic study in urine specimens of affected children; 3) Assessment and coordinated laboratory and environmental testing of biomarkers of abnormal accumulation of fatty acids in Muzaffarpur to: (organic urinary acids and acylcarnitines) in biologic specimens of cases and 4) Assessment for the presence ÂÂ Examine clinical features, clinical course, of hypoglycin or MCPG in litchi specimens from the management and outcomes of hospitalized cases in affected areas. the selected hospitals The epidemiologic case-control studies conducted in ÂÂ Determine the etiology of the outbreak illness both years 2013 and 2014 show significant associations ÂÂ Identify risk factors for illness. between visit to fruit orchard in the previous 24 hours The participating tertiary care hospitals in Muzaffarpur and having illness. were Shri Krishna Medical College Hospital (SKMCH) Furthermore, with more detailed questioning, the and Krishnadevi Deviprasad Kejriwal Maternity 2014 case-control study further shows a significant 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. 147 Let it be something that promotes strength, balance and flexibility and most importantly, something that you enjoy." Public Health Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

identify affected/ill children with the suspected outbreak examined, 31 (55%) had normal cytology (white blood illness was: cell [WBC] count ≤5 mm3); 48 of 59 (81%) had normal A child ≤15 years admitted to a participating hospital CSF protein (<45 mg/dL), and 46 of 61 (75%) had normal during surveillance period of late May to mid-July with– CSF glucose (>45 mg/dL) levels. At admission, 20 (21%) of 94 patients had hypoglycemia (blood glucose ÂÂ Altered mental status in the last 7 days 70 mg/dL). ÂÂ New onset seizures in the last 7 days (excluding simple febrile seizures). Laboratory: Infectious Pathogen Testing, 2013 Real time data were collected for all patients admitted CSF samples were tested at NCDC for selected infectious at SKMCH or KDKMH who met the case definition. pathogens known to cause encephalitis in the region. This included clinical history, exam, neurologic Of 60 CSF specimens tested for Japanese encephalitis evaluation, anthropometric measures, outcome, as well virus by immunoglobulin M (lgM) capture enzyme- as routine hospital laboratory tests, and, in a selected linked immunosorbent assay, 33 by PCR, and 33 by number of patients, electroencephalograms (EEGs) and virus isolation, all were negative. Sixteen convalescent MRIs. Specimens were collected from all patients and serum specimens, collected 14 days after illness onset, submitted to specialized referral laboratories, including also were negative for Japanese encephalitis virus by NCDC-based virology laboratory testing, CDC-based lgM assay. Thirty CSF specimens examined by reverse pathogen discovery, NIOH laboratory-based pesticide transcription-PCR for flaviviruses and 13 examined exposure testing and CDC National Center for more specifically for West Nile virus also were negative, Environmental Health-based toxicological testing. as were 23 evaluated for Chandipura virus. Fourteen CSF specimens evaluated by PCR and virus isolation Epidemiologic and environmental investigations for enteroviruses did not demonstrate evidence of included field entomologic survey, as well as an infection. epidemiologic case-control study, which included detailed examination and comparison of exposures to Subsequent infectious disease testing of approximately food, water, insects, animals, agriculture, chemicals 40 patient specimens in the US CDC Pathogen Discovery between ill children (cases) and well children (controls). Laboratory did not reveal any evidence of an infectious etiology on evaluation by 16s ribosomal testing for In the case-control study, for each case enrolled in bacterial pathogens, as well as pan-viral family PCR surveillance, TWO AGE-MATCHED well children and next generation metagenomic sequencing for viral (CONTROLS) were enrolled: one HOSPITAL control, pathogens. who was admitted to a participating hospital without any CNS symptoms, and one COMMUNITY control, Laboratory: Pesticide Testing, 2013 who was residing in same (year 2013) or neighboring Evaluation of case and control blood specimens at NIOH village (year 2014), without any CNS symptoms. for acetylcholinesterase and butyrylcholinesterase Home visits and collection of standardized data on levels to assess for the possibility of organophosphate epidemiologic and environmental exposures (cases and poisoning did not indicate any evidence of poisoning controls) were conducted. by this agent. Additionally, NIOH scientists evaluated 2013 INVESTIGATION food, grains and water specimens collected from the homes of over 10 case patients for pesticide residues of During May 17 to July 22, 2013, a total of 133 children over 29 agents; these test results were also negative. were admitted to the two main referral hospitals in Muzaffarpur with illnesses that met the investigation Epidemiologic Findings, 2013 case definition. Of these, 94 (71%) patients were from Analysis of risk factors for death among 94 affected Muzaffarpur; other patients were from six neighboring children showed that low blood glucose at admission districts. Among the 133 patients, 71% were aged was more common among those who died (odds ratio 1-5 years, 94% had generalized seizures and 93% had [OR] = 2.6; 95% confidence interval [CI] = 1.0-7.2). A case- altered mental status. control study enrolled 101 case-patients and 202 age- matched controls, 101 from the hospital and 101 from Clinical Findings, 2013 the community. Ill children had spent a greater amount Most (61%) patients were afebrile at admission; the of time in agricultural fields or orchards (matched case fatality rate was 44%. Among 56 patients with CSF OR = 2.6; CI = 1.2-5.2) than controls. Anthropometric

148 IJCP Sutra: "Stay updated with immunizations and screenings - Get a preventive screening done before various age-related disease strike." Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019 Public Health data on 24 patients suggested that younger patients team. Among the patients, 213 (55%) were male, the (those aged <5 years) were more likely to have wasting median age was 4 years (range = 6 months-14 years) and (>2 standard deviations below the median weight for 280 (72%) were aged 1-5 years. Most patients were from height of the reference population) than controls in the Muzaffarpur district (70%), although patients also were same age group (p = 0.03). reported from six surrounding districts. As in previous years, clustering of cases was not observed; the illness 2014 INVESTIGATION of each affected child appeared to be an isolated case in various villages (approximate population per village = Building on the 2013 findings, NCDC and CDC again 1,000). The outbreak peaked in mid-June, with 147 cases investigated the outbreak in 2014, using: 1) facility- reported during June 8-14, 2014. The number of cases based clinical surveillance; 2) epidemiologic case-control declined significantly after the onset of monsoon rains and environmental studies to examine risk factors on June 21, 2014 (Fig. 1). for illness, including toxin exposures and nutritional indices and 3) comprehensive laboratory evaluation Caregivers reported that affected children were of patient specimens and environmental samples to previously healthy and experienced an acute search for infectious pathogens as well as selected onset of convulsions, often between 4:00 am and pesticides, heavy metals and naturally occurring plant 8:00 am, frequently followed by a decreased level of or fruit toxins. Suspected patients were promptly tested consciousness. Of 345 patients with recorded data, for hypoglycemia on arrival at the hospital, before 324 (94%) had seizures on admission and 267 (77%) being given any treatment. Patients admitted with had altered mental status. Of 357 patients with body the suspected outbreak illness were recommended to temperature measured on admission, 219 (61%) were receive immediate intravenous dextrose therapy. 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%) During May 26 to July 17, 2014, a total of 390 patients had normal WBC counts, 58 (94%) had normal protein admitted to the two referral hospitals in Muzaffarpur and 49 (79%) had normal glucose levels. Of 327 patients with illnesses that met the same case definition used in with blood glucose measurement on admission, 2013 were evaluated by the NCDC/CDC investigation the median blood glucose level was 48 mg/dL and

30 Case-patients

Died 25

20

15 Number

10

5

0 1-Jul-14 3-Jul-14 5-Jul-14 7-Jul-14 9-Jul-14 1-Jun-14 3-Jun-14 5-Jun-14 7-Jun-14 9-Jun-14 11-Jul-14 13-Jul-14 15-Jul-14 17-Jul-14 11-Jun-14 13-Jun-14 15-Jun-14 17-Jun-14 19-Jun-14 21-Jun-14 23-Jun-14 25-Jun-14 27-Jun-14 29-Jun-14 26-May-14 28-May-14 30-May-14 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

Additionally, case specimens submitted to CDC Epidemiologic Findings, 2014 National Center for Environmental Health for atrazine Key risk factors Cases Controls mOR (herbicide) and dialkylphosphate (organophosphate) (N = 104) (N = 208) (95% Cl) metabolites were also negative. Evaluation for food, Ate litchi* 67/103 98/204 2.1 grains, water, litchi specimens collected from the homes (65%) (48%) (1.2-3.5) of case patients for pesticide residues again tested Ate litchi from 30/90 31/136 1.7 negative. Additionally, specimens of 80 patients tested ground* (33%) (23%) (0.9-3.4) at CDC did not reveal any evidence of elevated levels of >25 metals in blood and urine of 80 cases, including Ate rotten litchi* 23/88 19/130 2.4 (26%) (15%) (1.0-5.5) lead, mercury, arsenic, tin and iodine. Visited fruit 52/100 62/195 2.9 Urinary Organic Acids and Acylcarnitines (to Assess orchard* (52%) (32%) (1.6-5.1) for Abnormal Accumulation of Fatty Acids), 2014 Parent visited fruit 29/95 39/198 1.8 (1.0-3.1) Emory University USA analysis of plasma from 80 orchard* (31%) (20%) cases and urine from 75 cases showed approximately 90% had abnormal profiles of urine organic acids 171 (52%) and 204 (62%) patients had glucose levels and approximately 90% had abnormal profiles of of ≤50 mg/dL and ≤70 mg/dL, respectively. Brain MRI plasma acyl carnitines. These findings indicate of 16 patients selected at random revealed no focal abnormal disruption of metabolic function and fatty abnormalities or changes suggestive of inflammation. acid metabolism that match well with expectations EEG in 30 cases demonstrated findings consistent with from the proposed mechanisms of hypoglycin A and generalized encephalopathy. MCPG. Analysis of 19 of control urine samples (2013) have been analyzed for urine organic acids with 17 Exposures that were examined, but not associated with illness being normal or essentially normal and 2 showing trace amounts of acylglycines - not elevated to the † ÂÂ Peel litchi with mouth, bite litchi seed , eat litchi magnitude found in cases. seed†, chew litchi seed†, eat unripe litchi†, eat litchi peel† Laboratory: CDC Lab Analysis of Urine for Toxins ÂÂ Mother or father work in litchi orchard (Metabolites of Hypoglycin and MCPG), 2014

ÂÂ Other seasonal fruits, vegetables, nuts, herbs The urine metabolites of hypoglycin A and MCPG were measured by isotope-dilution followed by liquid ÂÂ Drinking water source (pump, surface, piped) chromatographic separation and mass spectrometric † † ÂÂ Exposure to insecticides or chemicals sprayed in detection. The assay’s analytical range was linearly and around house or nearby fields/orchards (each proportional (R > 0.99) from the lower limit of detection asked separately) (LOO) of 0.1-20 µg/mL. A set of 96 individual human ÂÂ Exposure to medications†, aspirin†, traditional urine samples were commercially obtained from medicines.† Tennessee Blood Services (Memphis, TN, USA) and †<5% cases or controls reported exposure. found to be below the assay’s LOO when analyzed. Metabolites of both hypoglycin A and MCPG were Laboratory: Infectious Pathogen Testing, 2014 identified in urine samples from cases. Of the 72 case Laboratory diagnostic testing at NCDC of 17 CSF samples from 2014 that had adequate volume for specimens for Japanese encephalitis virus and West Nile analysis, 65% had detectable levels of either metabolite virus by PCR was negative. Additionally, evaluation of of hypoglycin A (MCPA) or metabolite of MCPG 12 CSF specimens with a multiplex PCR platform assay (MCPF). Specifically, 65% had detectable levels of with the capacity to detect 11 viruses* also was negative. the metabolite of hypoglycin A (MCPA) and 46% had detectable levels of the metabolite of MCPG (MCPF). Laboratory: Pesticide, Herbicide, Heavy Metal All but one of the samples with detectable levels of Testing, 2014 the metabolite of MCPG also had detectable levels Specimens submitted to NIOH indicated no significant of the metabolite of hypoglycin A. All 35 control difference detected in RBC acetyl and butyryl urine samples from 2013 had no detectable levels of cholinesterase levels between cases and controls. metabolites of hypoglycin A or MCPG.

150 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." Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019 Public Health

Laboratory Testing: CDC Lab Analysis of Litchi 1 ppm and 10 ppm error, respectively, on a Thermo Fruit QExactive mass spectrometer. Litchi fruits were collected from orchards in four blocks Using high resolution mass spectrometry, the labs of Muzaffarpur, Musahari, Motipur, Bochahan and analyzed unripe and ripe fruit samples from the Minapur. Both Shahi and Chinese variety fruits were following blocks: Bochahan, Musahari and Motipur. collected, and in each fruit variety, samples of unripe, For hypoglycin A, in both ripe and unripe fruit, mass ripe, fallen and rotten fruits were collected. Thus far, spectrometry analysis was consistent with the presence at the CDC National Center for Environmental Health of hypoglycin A in seed and aril portions of fruit from laboratory, unripe litchis and ripe litchis collected from each of the blocks. For MCPG, in both ripe and unripe three blocks of Muzaffarpur district (Musahari, Motipur fruit, the current mass spectrometry analysis (without and Bochahan) have been tested. isotopically labeled standards) was not sufficiently informative to detect or rule out the presence of MCPG In each instance, homogenized extracts of litchi fruits in seed or aril portions of fruit. When isotopically were analyzed by liquid chromatographic separation labeled standards are available, labs will be able to and high-resolution mass spectrometric detection. complete these analyses and quantify the amounts of A readily available hypoglycin A standard was toxin(s) present. Similar qualitative work conducted on provided by colleagues at United States Department these litchis at the USDA laboratory has also identified of Agriculture (USDA) and used to analyze the high- hypoglycin A as well as suspected MCPG in the aril of resolution data obtained from the fruit. Precursor and the litchi fruit (unripe and ripe specimens, of both Shahi product accurate mass spectra were obtained within and Chinese varieties).

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 151 sleepiness in excess are common complaints, talk to your health care provider about such issues." 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.

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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

edicine has undergone tremendous advances, waiting time can be in years, but emergent care must including in India. Nevertheless, there be given without delay. All government hospitals in Mcontinues to be a wide gap in the availability India should provide emergent care to all coming for the of health care service in the country. Medial tourism care and if no bed is available, they should be shifted to is rapidly growing in India, but on the flip side of it, empanelled private sector with billing to the government health care, including essential health care, is still out under the respective Ayushman Bharat scheme. of reach for many in the country. India has a shortage To make emergent health care affordable, government of doctors and nurses; lack of infrastructure coupled should also come out with National lists of essential with quality and affordable health care create further medicines, investigations, devices, reagents, disposables hurdles in universal health care. However, the issue and equipments and they should be price capped. which has recently hit the headlines is the deteriorating doctor-patient relationship. This erosion in trust is One should remember that doctors are service providers disheartening and needs to be urgently restored. and not service generators. They should not be made scapegoats for administrative errors, negligence or A Round Table was organised on the eve of Doctor’s faulty treatment. Day, 30th June, 2019 to discuss the current scenario of health care system in India and give some suggestions No antibiotic should be allowed to be prescribed by and ways to improve it. non-MBBS doctor. There are four types of patients: Ignorant, informed, There should be a transparent redressal mechanism for empowered and enlightened. There has been a rapid patients in every district. shift from ignorance to enlightenment in the society. Public Health Services should be added in the concurrent More and more patients want more time from the list so that there is a proper State-Centre coordination. doctor and want to be a part of shared decision making. Medical Council of India (MCI)-Indian Medical But this is incompatible with the present inadequate Association (IMA) submitted Jacob Mathew guidelines, infrastructure. Parmanand Katara case guidelines and guidelines Today a doctor spends less than 4 minutes per for MCI Ethics Regulation 8.6 should be immediately patient and most of this time is spent on explaining implemented by the Health Ministry. the deficiencies in infrastructure or non-medical The government and/or the police should put up a board counselling. The answer is posting counsellors in the (like the vigilance notice) in every medical establishment establishments apart from improving the infrastructure. informing about the law against medical violence. The Central Government has rightly removed health The time has come to debate to shift from Bolam’s services from Consumer Protection Act, but should consent to informed consent, including the consent for have considered specifically excluding it. unexpected and uninformed complications and chances Once a person has done MBBS, he is a qualified full- of sudden death in every treatment. fledged doctor, then why do we call them junior doctors, One should remember that quality and quantity are trainee doctors or residents? All post-MBBS doctors inversely proportional to each other. More the number up to the age of 40 should be called young doctors and of patients seen in one hour, less will be the quality of not juniors for resident doctors. services. One should differentiate emergent from non-emergent The government policy of refusing to take outside care. delivered newborns; patient on ventilator, BiPAP (bilevel The primary job of a doctor is to alleviate the pain and positive airway pressure) or cPAP (continuous positive sufferings of a person without commercialising it. This airway pressure); patients on dialysis, patients for is also the fundamental duty of the government under chemotherapy or patients needing terminal care should Article 21. Even in the UK, in non-emergent care, the be abolished.

154 IJCP Sutra: "Fill half your plate with fruit and vegetables." Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019 HCFI Consensus Statement

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

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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.

he Drugs and Cosmetics Act & Rules regulate the Drugs and Cosmetics Rules, 1945 as the word used import, manufacture and distribution of the drugs in Clause 23 is ‘Supplied’ as firstly the multipurpose Tin the country. Some drugs have been mentioned workers cannot supply any drugs as they are not in Schedule E1, G, H, H1, X of the Drugs and Cosmetics registered medical practitioner and secondly, if they Rules, 1945, which cannot be sold or purchased without are supplying the drugs, then the patient has to pay proper license; they are commonly known as Scheduled relevant prevailing tax on the price of the drugs. Drugs. All Scheduled Drugs cannot be purchased by So, to understand the interpretation of the word anybody without prescription of the registered medical “Supplied” in Clause 23 of the Schedule K of the Drugs practitioner. The various provisions relating to licence, and Cosmetics Act & Rules, Heart Care Foundation sale, manufacture, etc., of the Scheduled Drugs are of India (HCFI) Round Table on Health and Wellness: enumerated in Chapter IV of the Drugs and Cosmetics Building Consensus discussed this issue in its Round Rules, 1945. Table meeting. After numerous discussions and However, there is an exception to the above i.e., deliberations, HCFI Round Table on Health and Rule 123 of the Drugs and Cosmetics Rules, 1945 which Wellness came out with its consensus statement, which provides that the provisions of Chapter IV of the Drugs is reproduced hereunder: and Cosmetics Rules, 1945 are not applicable to drugs ÂÂ The HCFI Round Table on Health and Wellness: mentioned in Schedule K to the extent specified in Building Consensus was held on 21st June 2019 Schedule K of the Drugs and Cosmetics Rules, 1945. at 4 pm, at the PHD Chambers of Commerce and Industry, PHD House, Siri Fort Institutional Area, In Schedule K of the Drugs and Cosmetics Rules, 1945 August Kranti Marg, New Delhi - 110016 on the there is one Clause 23 as per which Drugs supplied subject “Interpretation of the word ‘supplied by’ by Multipurpose Workers attached to Primary Health in Clause 23 in Schedule K of the Drugs and Centres/Sub-Centres, Community Health Volunteers Cosmetics Act & Rules”. under the Rural Health Scheme, Nurses, Auxiliary Nurse, Midwives and Lady Health Visitors attached to The following consensus was made: Urban Family Welfare Centres/Primary Health Centres/ ÂÂ Under the Clause 23 in Schedule K, of the Drugs Sub-Centres and Anganwadi Workers are exempted and Cosmetics Act, 1940, the health care workers from the provisions of Chapter IV of the Act and the have been empowered to give malaria drugs Rules there under which require them to be covered (by Malaria workers); gentamicin and methergine by a sale licence, provided the drugs are supplied (by Asha workers), etc. under the Health or Family Welfare Programme of the Central or State Government. What is Clause 23? Time and again there has been lot of debate as to “Drugs supplied by Multipurpose Workers attached the interpretation of Clause 23 of Schedule K of the to Primary Health Centres/Sub-Centres: (i) Community

156 IJCP Sutra: "Use the right healthy fats - from roasted nuts and avocados to olive, canola, soybean and other oils." Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019 HCFI Consensus Statement

Health Volunteers under the Rural Health Scheme; A physician should not run an open shop for sale of (ii) Nurses, Auxiliary Nurse, Midwives and Lady medicine or for dispensing prescriptions prescribed Health Visitors attached to Urban Family Welfare by doctors other than himself or for sale of medical Centres/Primary Health Centres/Sub-Centres and (iii) or surgical appliances. (The word dispensing here is Anganwadi Workers. synonymous with prescribing and dispensing).

Exemptions: The provisions of Chapter IV of the Act and ÂÂ Clause 3.7.1 of the Indian Medical Council the Rules there under which require them to be covered (Professional Conduct, Etiquettes and Ethics) by a sale licence, provided the drugs are supplied Regulations, 2002 provides that: 3.7.1 “A physician under the Health or Family Welfare Programme of the shall clearly display his fees and other charges on Central or State Government. the board of his chamber and/or the hospitals he is What was the Consensus? visiting. The prescription should also make clear if the Physician himself dispensed any medicine. “In Clause 23 of Schedule K in the Drugs and Cosmetics (The word dispensed here is synonymous with Act, 1940, (i) the word ‘supplied’ should be read as supplied). synonymous with ‘dispensed’ and/or ‘distributed’.” ÂÂ Non-Schedule Drugs i.e., drugs other than drugs Basis of interpretation mentioned in Schedule H, H1, X (for Modern Systems of Medicine), and Schedule E for (Indian ÂÂ Rule 123 of Drugs and Cosmetics Rules, 1945: “The Systems of Medicine), of the Drugs and Cosmetics drugs specified in Schedule K shall be exempted from the provisions of Chapter IV of the Act and Act & Rules requires no licence to sell or prescribe. the Rules made there under, to the extent and ÂÂ Essential Commodities Act, 1955: Any State subject to the conditions specified in that schedule.” Government has the powers to control production, ÂÂ Under Medical Council of India Code of Ethics supply, distribution of essential commodities Regulations Clause 6.3: “Running an open shop including drugs as specified in Clause (b) of (Dispensing of Drugs and Appliances by Physicians): Section 3 of the Drugs and Cosmetics Act, 1940.

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

ff-label use means that the particular drug is Definition of off-label use of drugs, used for an indication that is not otherwise disposables and devices approved by the regulatory authority, which is O Off-label use of drugs is the use of pharmaceutical the Drug Controller General of India (DCGI) in India, and is not included in the package insert or label carrying drugs (drug, device, disposable) for an unapproved instructions about indications, contraindications and indication or in an unapproved age group, dosage or dosing and other instructions. Off-label use of drugs is route of administration. common in clinical practice all over the world. Marketing of pharmaceuticals for off-label use is The US Food and Drug Administration (FDA) allows usually prohibited. But, both prescription drugs and the promotion of off-label use of drugs when there is over-the-counter (OTC) drugs can be used in off-label strong supporting evidence on the safety and efficacy ways, although most studies of off-label use focus on of such use. But, the benefits and risks of such use prescription drugs. for an individual patient must be balanced before the Off-label use is generally considered legal across the drug is prescribed for an off-label use and the onus of world unless it violates ethical guidelines or safety responsibility lies with the doctor. Despite the widely regulations. prevalent practice, there is no clear guideline on the off- More than 50% of all drugs are prescribed off-label label use of drugs in India. based on available scientific and safety evidence and Hence, there is a need for a policy, which allows the amongst psychiatrists and children, the number is even off-label use of drugs for which there exists high quality higher. scientific evidence. Need for the policy Towards this end, an Expert Round Table on Off-label Use of Drugs, Disposables and Devices was organized In the matter of Balram Prasad vs. Kunal Saha by Heart Care Foundation of India (HCFI) to build a & Ors on 24 October, 2013, the Apex Court said consensus around this issue and send recommendations “73. ……….. In fact punitive damages are routinely awarded to the regulatory authorities to formulate a guideline on in medical negligence cases in western countries for reckless off-label use of drugs in the country. and reprehensible act by the doctors or hospitals in order to send a deterrent message to other members of the medical HCFI Expert Round Table Sutra community. In a similar case, the Court of Appeals in South Carolina in Welch Vs. Epstein [31] held that a neurosurgeon “In absence of any unethical considerations or a safety is guilty for reckless therapy after he used a drug in clear issue AND in presence of strong international or national disregard to the warning given by the drug manufacturer scientific evidence; off-label use in other country; guideline causing the death of a patient. This Court has categorically or consensus statement; prevalent use in the clinical held that the injection Depomedrol used at the rate of 80 mg practice WITH no reported side effects under PvPI and twice daily by Dr Sukumar Mukherjee was in clear violation the drug is not under RISK MAP category, THEN the use of the manufacturer’s warning and recommendation and of the available DCGI approved drug (including medical admittedly, the instruction regarding direction for use of the devices and disposables) is justified for off-label indications medicine had not been followed in the instant case. This Court under implied consent. In all other situations, one has also made it clear that the excessive use of the medicine by needs to take an informed consent.” the doctor was out of sheer ignorance of basic hazards relating

158 IJCP Sutra: "Choose healthy fats. Use fat-free or low-fat milk and/or dairy products." Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019 HCFI Consensus Statement to the use of steroids as also lack of judgment. No doctor Legal implications when there is no policy has the right to use the drug beyond the maximum recommended dose.” In the present scenario, we need to protect ourselves from the legal risks. Even if there is scientific evidence Existent Government Policy showing the beneficial action of the off-label use of a drug, the first step should be to find an answer to As per the reply received by HCFI to a Right to counter the judgment to safeguard ourselves. All Information (RTI) filed HCFI/March/2019/042 dated Supreme Court judgments are guidelines, till they are 18th March 2019, the Central Drugs Standard Control made into law. Once they become a law, they cannot Organization (CDSCO) vide reply Z-28020/233/2019- be challenged. DC dated 3rd May 2019 replied as under “Medical ÂÂ Source of Law: The main sources of law in devices notified under Drugs and Cosmetics Act, 1940 India are the Constitution, statutes (legislation), are regulated as per the provisions of Medical Devices customary law and case law. Statutes are enacted Rules, 2017. As per rule 44 (k) of Medical Devices Rules, by Parliament, State legislatures and Union 2017, if the device is intended for single use, it should Territory legislatures. Besides, there is a vast body be labeled appropriately. Further there is mention in of laws known as subordinate legislation in the Medical Devices Rules to label the device appropriately form of rules, regulations as well as byelaws made if the device is intended for single use. by Central/State governments and local authorities Penalty in case of violation of any provisions of Drugs like municipal corporations, municipalities, gram and Cosmetics Act, 1940 and Medical Devices Rules, panchayats and other local bodies. This subordinate 2017 will be prescribed as per the said Act and Rules. legislation is made under the authority conferred or delegated either by Parliament or State or Union Refurbishing of medical devices and disposables does Territory legislatures concerned. Judicial decisions not come under the purview of CDSCO. However, of superior courts like Supreme Court and High refurbishing of medical equipment comes under the Courts are important sources of law. Decisions of Ministry of Environment, Forest and Climate change. Supreme Court are binding on all courts within the Has DCGI allowed off-label use of drugs? territory of India. Local customs and conventions which are not against statute, morality, etc., are also The government can ban off-label use of any drug as recognized and taken into account by courts while it did in the case of bevacizumab. On January 21, 2016, administering justice in certain spheres (https:// the DCGI took the bold step of prohibiting the use archive.india.gov.in/citizen/lawnorder.php?id=6). of intraocular bevacizumab as off-label treatment for ÂÂ When there is a law, rule or any policy, then any various retinal diseases. Unfortunately, this decision violation of the said law, rule or policy is unethical put a large percentage of the population at risk of and illegal. inaccessibility to treatment for common blinding retinal ÂÂ When there is no government policy, the Court often diseases. But, after 2 months, the DCGI agreed to relies on reliable authentic literature; authentic peer withdraw the alert notice, enabling retinal surgeons to group consensus; published literature, guidelines again use bevacizumab. and consensus statements.

This decision may be a landmark judgment for India ÂÂ The admissibility of evidence in Courts in India is and other countries around the world to look at dependent on its relevancy as per the provisions evidence-based off-label use of drugs. of Indian Evidence Act. Illegality or impropriety Clearly, there is a need for an off-label policy. in obtaining the evidence will not affect its admissibility, if it is otherwise relevant. Test of The pharmaceuticals cannot be promoted or advertised admissibility of evidence lies in its relevancy and legally. The onus therefore falls on the medical not on how it was obtained. In Kuruma v The profession to “certify” the off-label use of drugs. Queen [1955] AC 197, the Privy Council laid down Time has come to formulate guidelines. We need to that if the evidence is admissible, the Court is not build a baseline document and draft suggestions to concerned how it was obtained. The Privy Council be sent to medical specialty societies cum associations observed: “...the test to be applied in considering and/or all medical stakeholders before sending it to the whether evidence is admissible is whether it is relevant regulatory authorities. to the matters in issue. If it is, it is admissible, and

IJCP Sutra: "Drink plenty of water. Avoid sugary drinks." 159 HCFI Consensus Statement Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

the Court is not concerned with how the evidence was patient still does not survive or suffers a permanent obtained.” These observations of the Privy Council ailment, it would be difficult to hold the doctor to be were quoted with approval by the Supreme Court guilty of negligence.” in P ooran Mal v Director of Inspection AIR 1974 ÂÂ The opinion has to be by an authentic body. In the SC 348. After quoting the above observations of matter titled as “Vinitha Ashok versus Lakshmi the Privy Council, the Supreme Court observed Hospital, AIR 2001 SC 3914”, the Hon’ble Supreme as follows: “It would be thus seen that in India, as in Court has held that: English, where the test of admissibility of evidence lies in its relevancy, unless there is an express or necessarily “[28] Thus in large majority of cases, it has been implied prohibition in the Constitution or other law, demonstrated that a doctor will be liable for negligence evidence obtained as a result of illegal search or seizure in respect of diagnosis and treatment in spite of a body of is not liable to be shut out.” professional opinion approving his conduct where it has not been established to the court's satisfaction that such Can a doctor be held liable for mere opinion relied on is reasonable or responsible. If it can be deviation from normal practice? demonstrated that the professional opinion is not capable of withstanding the logical analysis, the court would be ÂÂ The Hon’ble Supreme Court of India in the matter entitled to hold that the body of opinion is not reasonable titled as “Jacob Mathew versus State of Punjab & or responsible.” Anr on 5 August, 2005” has held that: ÂÂ In the matter titled asKusum “ Sharma & Others “A mere deviation from normal professional practice is versus Batra Hospital & Medical Research Centre, not necessary evidence of negligence. Let it also be noted 2010 (3) SCC 480”, the Hon’ble Supreme Court of that a mere accident is not evidence of negligence. So India has held that: also, an error of judgment on the part of a professional is not negligence per se. Higher the acuteness in emergency “In the realm of diagnosis and treatment there is scope for and higher the complication, more are the chances of genuine difference of opinion and one professional doctor error of judgment.” is clearly not negligent merely because his conclusion differs from that of other professional doctor.” …..The degree of skill and care required by a medical practitioner is so stated in Halsbury’s Laws of England “The medical professionals are entitled to get protection (Fourth Edition, Vol 30 Para 35): “…… and a person is so long as they perform their duties with reasonable skill not liable in negligence because someone else of greater and competence and in the interest of the patients. The skill and knowledge would have prescribed different interest and welfare of the patients have to be paramount treatment or operated in a different way; nor is he guilty for the medical professionals.” of negligence if he has acted in accordance with a practice ÂÂ Indian Penal Code Section 92 - Act done in good accepted as proper by a responsible body of medical men faith for benefit of a person without consent: skilled in that particular art, even though a body of “Nothing is an offence by reason of any harm which it adverse opinion also existed among medical men.” may causes to a person for whose benefit it is done in ÂÂ In the matter titled as Achutrao“ Haribhau Khodwa good faith, even without that person’s consent, if the vs. State of Maharashtra, 1996 SCC (2) 634”, the circumstances are such that it is impossible for that Hon’ble Supreme Court has held that: person to signify consent, or if that person is incapable of giving consent, and has no guardian or other person in “The skill of medical practitioners differs from doctor to doctor. The very nature of the profession is such that lawful charge of him from whom it is possible to obtain there may be more than one course of treatment which consent in time for the thing to be done with benefit.” may be advisable for treating a patient. Courts would ÂÂ IPC Section 88 - Act not intended to cause death, indeed be slow in attributing negligence on the part of done by consent in good faith for person’s benefit: a doctor if he has performed his duties to the best of his “Nothing, which is not intended to cause death, is an ability and with due care and caution. Medical opinion offence by reason of any harm which it may cause, or be may differ with regard to the course of action to be taken intended by the doer to cause, or be known by the doer by a doctor treating a patient, but as long as a doctor to be likely to cause, to any person for whose benefit it is acts in a manner which is acceptable to the medical done in good faith, and who has given a consent, whether profession, and the Court finds that he has attended on express or implied to suffer that harm, or to take the risk the patient with due care, skill and diligence and if the of that harm.”

160 IJCP Sutra: "Avoid foods that have high sodium levels such as snacks, processed foods." Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019 HCFI Consensus Statement

Law on off-label use of drugs in the US ÂÂ Using injection methotrexate for sarcoidosis, one and UK may need to take an informed consent.

ÂÂ In the United States, the law permits a physician HCFI Expert Round Table Sutra or other health care practitioner to prescribe an approved medication for indications other than their “In absence of any unethical considerations or a safety specific FDA-approved indications. Pharmaceutical issue AND in presence of strong international or national companies are not allowed to promote a drug for scientific evidence; off-label use in other country; guideline any other purpose without formal FDA approval. or consensus statement; prevalent use in the clinical However, once a drug has been approved for sale practice WITH no reported side effects under PvPI and for one purpose, physicians are free to prescribe the drug is not under RISK MAP category THEN the use it for any other purpose that in their professional of the available DCGI approved drug (including medical judgment is both safe and effective, and are not devices and disposables) is justified for off-label indications limited to official, FDA-approved indications. under implied consent. In all other situations, one This off-label prescribing is most commonly done needs to take an informed consent.” with older, generic medications that have found new uses but have not had the formal (and often “Anticipate and prepare ourselves”

costly) applications and studies required by the ÂÂ To begin with, sensitize the medical profession on FDA to formally approve the drug for these new this issue. Most doctors are unaware of off-label use. indications. However, there is often extensive medical literature to support the off-label use. ÂÂ Identify situations in which drug/s can be used off- label; supported by strong scientific evidence; being ÂÂ Regulation in the United Kingdom: Physicians in used for the said indication for years and PvPI has the United Kingdom (UK) can prescribe medications not recorded any adverse effect with the drug. off-label. According to General Medical Council guidance, the physician must be satisfied that ÂÂ Seek recommendations from professional there is sufficient evidence or experience of using associations and societies as they understand safety the medicine to demonstrate safety and efficacy. issues and scientific evidences. Prescribing may be necessary when no suitably ÂÂ Sensitize the ethics committees of institutions licensed medicine is available to meet the patient’s regarding this issue.

need (or when the prescribing is part of approved ÂÂ National workshops: Invite specialists with scientific research). 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 Few Examples of Off-label Use in India for the off-label indication?

ÂÂ Metformin in India is used off-label for polycystic zz Is the drug approved for off-label indication/s ovarian disease (PCOD), which is used by in other countries? gynecologists across the country; Federation of zz Are there enough international/national studies Obstetrics & Gynaecological Societies of India on the off-label use? (FOGSI), Indian Menopausal Society, Endocrine Society of India recommend this use in their ÂÂ Invite government participation guidelines. No consent needs to be taken if used ÂÂ Include off-label use as part of informed consent; for this indication; but, it is not DCGI-approved hospitals must have their individual “Ethics for this indication. Use of metformin-myoinositol Committee guidelines” on this till a national policy combination in PCOD is also an off-label use. is available.

ÂÂ Amlodipine is approved for use only for mild and ÂÂ Phase 4 post-marketing trials should be regulated. moderate hypertension, but it is also being used for Adverse events should be reported. This will severe hypertension, which is an off-label use. strengthen PvPI.

ÂÂ Use of aspirin in acute myocardial infarction is not ÂÂ Robust data including level of evidence is needed a DCGI-approved indication. along with risk-benefit analysis.

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ÂÂ Commercial bias and conflict of interest needs to be reused, the number of recommended reuses, the taken care of. procedure for reuse and validating effectiveness of reprocessing procedures, to ensure sterility and ÂÂ Expert evidence by peer group is accepted by the Courts as “prevalent practice”, “peer group intact functionality of these devices and ensure recommendations” or “society recommendations” quality control. unless there is a national existing policy. Till a law ÂÂ An adverse event record should be maintained for is formulated, this can be followed. all reused devices and there should be a periodic review and audit. ÂÂ Submit the draft to DCGI with copy to Health Ministry and other regulatory bodies; follow-up ÂÂ Third party reprocessing units should be with RTIs; file PIL if no satisfactory reply. encouraged and need to be stringently regulated and accountable for quality control. Guidance on Reuse of Cardiovascular Catheters ÂÂ The reused catheters/devices should not be billed and Devices in India on the new item rate to the patient as the reuse ÂÂ Each medical establishment should have its own policy is primarily done to reduce the cost.

off-label, list of devices which can be reprocessed; ÂÂ The cost of sterilization process should be accounted number of times a device can be reused; Reprocess, for in the catheterization laboratory charges and/or Reuse, Re-Sterilize Committee consisting of doctors, should not exceed 10% of the original cost of the infection control officers, microbiologists, nurses, catheters. and administrators to oversee central sterilization, ÂÂ Reused cardiac implantable electronic devices re-processing, infection control, biomedical (CIEDs) should not be charged. engineering and cost accounting. ÂÂ Made or make in India concept for these single ÂÂ The above committee should have approval of the use devices (SUDs) should be encouraged and Institutional Ethics Committee. facilitated to offset the cost, issues related to reuse ÂÂ The in-house committee should take responsibility and improve penetration of therapy. for the protocol linked to safety issues. ÂÂ Engagement with the health regulatory authorities ÂÂ The medical establishment should provide adequate and price control for all imported medical devices space for reprocessing, trained personnel and other should be addressed. Sealing the maximum retail consumables that are required. price (MRP) based on the landing price with a

ÂÂ Standard and validated written protocols should well-defined formula for different SUDs should be be followed for reprocessing for each type of single established. use device. ÂÂ ICMED: There is a basic policy on reprocessing of single use devices; it needs to be expanded. This ÂÂ Establishment should ensure a mechanism for tracking of such devices. assumes significance given the waste generated causing environmental hazard, an important public ÂÂ There should be a periodic review and audit. health problem today. Three important issues to ÂÂ Cardiology and other specialties reusing catheters be taken care of with regard to SUDs: Identify should formulate common guidelines and standard which SUDs can be reused safely, consent and operating procedures for reuse. These guidelines that the benefit of cost has been passed over to the should include the list of items that can be 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 Chairman, Vision Eye Centre, Siri Fort Road and West Patel Nagar, New Delhi

162 IJCP Sutra: "Refrain from going outdoors at dusk or dawn when the mosquitoes are highly active." Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019 HCFI Consensus Statement

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†

n India, the Cabinet Secretariat functions directly question. Also, the answer given by the Directorate under the Hon’ble Prime Minister. The Cabinet General of Health Services (DGHS) is different. Secretariat is responsible for the administration I The answers given by three departments and DGHS are: of the Government of India (Transaction of Business) Rules, 1961 and Government of India (Allocation of National Centre for Disease Control, Integrated Business) Rules, 1961 facilitating smooth transaction Disease Surveillance Programme (IDSP) of Ministry of business in Ministries/Departments. The Secretariat of Health and Family Welfare vide reply stated that: assists in decision-making in Government by ensuring “IDSP is a disease surveillance programme which is routinely Inter-Ministerial coordination, ironing out differences collecting data of 22 communicable diseases. Health is a state amongst Ministries/Departments and evolving subject and each State has its own list of notifiable diseases.” consensus through the instrumentality of the standing/ The PH (IH) Division of Ministry of Health and Ad-HoC Committees of Secretaries. Family Welfare vide reply dated 23.10.2018 stated that: However, is there really coordination at the Inter- “This division deals with implementation of International Ministerial level and even among various Departments Health Regulations (IHR) at Points of Entry and Public of the same Ministry? Health Emergencies of International Concern (PHEIC). This division does not have any information pertaining to notified The answer is NO. The main problem in India is lack diseases and their vaccinations in India.” of coordination among various departments within the same ministry. Forget about Inter-Ministerial Immunisation Division of Ministry of Health and coordination. Family Welfare vide reply dated 15.10.2018 has stated that: “in this regard, the matter regarding list of notifiable Heart Care Foundation of India (HCFI), a national communicable diseases doesn’t pertain to Immunisation level Public Charitable Trust vide Right to Information section hence your RTI application is being transferred (RTI) Application dated 27.08.2018 had asked a simple under Section 6(3) of RTI Act, 2005 to DGHS for providing question from Ministry of Health and Family Welfare. information directly to you. However, the list of diseases The question was: “Is there any notified list of communicable against which vaccination provided under Universal diseases in India?” Immunisation Programme (UIP) is enclosed herewith.” The Public Information Officer of Ministry of Health DGHS vide reply dated 17.10.2018 has stated: “in this and Family Welfare forwarded the said RTI to its three regard, the matter regarding list of notifiable communicable departments and asked all the three departments to diseases doesn’t pertain to Immunisation Section hence your give relevant information. It is quite astonishing that all RTI application is being transferred under Section 6(3) of the three departments of the same Ministry of Health RTI Act, 2005 to DGHS for providing information directly to and Family Welfare gave different answers for same you. However, the list of diseases against which vaccination provided under UIP is enclosed herewith.” Vide RTI application, HCFI has also asked “Is there *Group Editor-in-Chief, IJCP Group any policy or law or scheme under which a person can get †Advocate and Legal Advisor, HCFI vaccination for all notified communicable diseases?”

164 IJCP Sutra: "Cover yourself with long-sleeved shirts and trousers." Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019 RTI Analysis

All the different departments of Ministry of Health and such information is required to be given which already exists Family Welfare stated that there is no law, policy or and, it is not required to create information or to interpret data available and it is quite astonishing that there is information or to solve the problems raised by the applicant/ no law/policy/scheme under which a person can get appellant of to furnish replies to hypothetical question.” vaccination for all notified communicable diseases. Instead of just giving reply in Yes or No to the query Further, it is surprising that none of the departments of raised by HCFI, the Immunisation Division stated Ministry of Health and Family Welfare have data of any that it is required to give only such information which vaccination notified for such communicable diseases already exists. in India. We are talking about ONE INDIA. But from the reply Also, vide RTI application dated 27.11.2018, HCFI given by different departments, the dream of achieving had asked “Is this UIP operating in all private as well as ONE INDIA is quite impossible. The Cabinet Secretariat government hospitals?” The Immunisation Division of needs to work out some stringent and effective measures Ministry of Health and Family Welfare does not have for ensuring better Inter-Ministerial coordination and any information relating to the same. also among various departments of same Ministry. Till Vide reply dated 28.12.2018, the Immunisation Division the time, the different departments of single ministries of Ministry of Health and Family Welfare gave following have coordination and better data availability, the answer to the question “Does government apply these Ministry as a whole will not be able to work effectively. vaccines to the people living on street and beggars The new Cabinet is requested to ensure better under this UIP?”: “It is to state that, the RTI Act, 2005 coordination not just at the Inter-Ministerial level but and guidelines issued there under make it clear that, only also among various departments of the same ministry.

Analysis of Communicable Diseases RTI

Sr. RTI application dated Reply by Ministry of Health and Family Reply by PH (IH) Reply by National No. 27.08.2018 Welfare, Immunisation Division dated Section of Ministry Centre for Disease 15.10.2018 & reply By DGHS dated of Health and Family Control, Integrated 17.10.2018 Welfare, dated Disease Surveillance 23.10.2018 Programme (IDSP) 1. Is there any notified list of Vide reply dated 15.10.2018, the The PH (IH) IDSP is a disease communicable diseases Immunisation Division of Ministry of Health Division deals with surveillance in India? and Family Welfare, Government of India implementation of programme has stated: International Health which is routinely “in this regard, the matter regarding list of Regulations (IHR) collecting data of notifiable communicable diseases doesn’t at Points of Entry 22 communicable pertain to Immunisation section hence your and Public Health diseases. Health is RTI application is being transferred under Emergencies of a state subject and Section 6(3) of RTI Act, 2005 to DGHS International Concern each State has its for providing information directly to you. (PHEIC). This division own list of notifiable However, the list of diseases against which does not have any diseases. vaccination provided under UIP is enclosed information pertaining herewith.” to notified diseases and their vaccinations List of vaccines under Universal in India. Immunisation Programme and Diseases prevented: Vaccine Disease prevented Bacillus Calmette- Severe form Guerin (BCG) of childhood tuberculosis Oral Polio vaccine Poliomyelitis (OPV) 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 Pentavalent Vaccine Diphtheria, pertussis, ‘Nil’ keeping in view of List of notifiable “Yes”, then please provide tetanus, hepatitis B, information on point diseases for each the said notified list of pneumonia and one above. State may be communicable diseases meningitis caused by obtained from in India? H. influenzae type b respective State Rotavirus vaccine Rotavirus diarrhea 3. Is there any vaccination Information not notified for such Inactivated Polio Poliomyelitis available with IDSP communicable diseases vaccine in India? Pneumococcal Pneumococcal conjugate vaccine pneumonia 4. If answer to query no. 3 is Yes, then please Measles vaccine Measles provide the details of all Measles & Rubella Measles and Rubella vaccinations notified for (MR) vaccine all notified communicable diseases in India? Japanese Japanese encephalitis (JE) encephalitis 5. Is there any policy or vaccine law or scheme under DPT vaccine Diphtheria, pertussis which a person can get and tetanus vaccination for all notified communicable diseases? Tetanus toxoid Tetanus 6. 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. RTI application dated 27.08.2018 Reply by Immunisation Division of Ministry of Health and No. 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 Yes poor patients?

3. If answer to query no. 2 is “No”, then provide the details Question does not arise. of the vaccines which are available free of cost for the poor patients?

4. Is this UIP operating in all private as well as government No such information available. hospitals?

5. Does government apply these vaccines to the people It is to state that, the RTI Act, 2005 and guidelines issued there living on street and beggars under this UIP? 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 As per the reply given on point no. 5 question does not arise. or policy or law, the government provides immunisation vaccine to the people living on street and beggars?

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

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).

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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 breast- cancer 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

ardiovascular disease (CVD) including coronary notably women, may have high levels of BP or heart disease (CHD) is the commonest cause cholesterol which, when projected through their Cof death in hypertensive patients. In elderly life time, would reduce life expectancy, but under hypertensives, notably the diuretic-treated group in current guidelines, would not warrant therapeutic the Medical Research Council (MRC) elderly trial and intervention. in two trials of isolated systolic hypertension (SHEP ÂÂ An estimated 10-year coronary risk of 15% and SYST-EUR), there was significant reduction (30%) (equivalent to a CVD risk of 20%). in coronary disease events with reduction of blood pressure (BP). There is no doubt that it is essential to Pharmacological Agents Used Vary in their reduce the level of systolic and diastolic BP to prevent Ability to Prevent CV Mortality cardiovascular (CV) mortality, but there are many pros and cons. These are: when to intervene- at any Antihypertensive agents, which achieve similar particular level of BP or in presence of any particular reduction of level of BP, differ in their ability to clinical feature? prevent CV mortality, due to the differences of their mechanism of action or their effect on central or What Associated Risk Factors Need Special peripheral pulse pressure. It is found that central pulse Attention? pressure i.e., mean aortic pressure, which is the chief determinant of arterial wall stiffness, is the predictor How to intervene, when first detected? By of all-cause mortality including CV mortality. Very stiff pharmacological agents or by nonpharmacological arteries cause increase in circumferential arterial wall means? Which agents are most helpful? Attempts stress, and this is likely to cause breakdown of medial have been made to find out the most effective drug elastic tissue and it increases possibility of endothelial treatment strategies. Systolic and diastolic thresholds damage and development of atherosclerosis. So, of 160 and 100 mmHg, respectively are clear indicators antihypertensive drugs need to be effective not only in of drug treatment. Systolic pressure in the range of 140- reducing brachial artery BP but also in reducing central 159 mmHg and diastolic pressure in the range of 90- arterial wall stiffness. 99 mmHg indicate treatment under certain situations. It is remarkable from different observational studies Calcium channel blockers, though may have very little that international guidelines are inconsistent in their effect on large central elastic arteries, through their recommendations on thresholds for intervention to effect on peripheral muscular arteries, they reduce prevent CHD and CVD. In recent years; however, the wave reflection amplitude and markedly lower systolic following recommendations have been made: and pulse pressure, hence ventricular afterload. The Antihypertensive and Lipid-Lowering Treatment to ÂÂ When there is evidence of end-organ damage, like Prevent Heart Attack Trial (ALLHAT) study failed left ventricular hypertrophy (LVH). to identify any treatment benefit attributable to a ÂÂ When coexistent clinical situation, like diabetes, particular class of agent, but the Anglo-Scandinavian may increase the risk of CV mortality. Cardiac Outcomes Trial (ASCOT) study shows ÂÂ When dyslipidemia adds to the risk factor; BP reduction with b-blockers and diuretics as premature mortality from hypertension among the best recorded intervention for prevention of first-degree relatives. CV mortality.

ÂÂ In elderly hypertensives: Most elderly people The Losartan Intervention For Endpoint reduction (LIFE) exceed the threshold for intervention both on BP in Hypertension study and Perindopril pROtection and lipid-lowering. In contrast, younger people, aGainst REcurrent Stroke Study (PROGRESS) clearly

168 IJCP Sutra: "There should be a provision of a clean place for birth." Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019 EXPERT’s VIEW showed that angiotensin-converting enzyme (ACE) Hypertension (DASH) done to investigate the effects of inhibitors prevent CV mortality more than b-blockers diet on hypertension has recommended: for a similar reduction of BP. ÂÂ A diet with decreased content of dairy produce ‘Pressure-independent’ effect of ACE inhibitors and ÂÂ A diet with increased fruit and vegetable content receptor blockers may be explained by their optimal effects on arterial stiffness, augmentation of aortic ÂÂ A diet avoiding salty and processed food pressure, left ventricular wasted energy, all of which ÂÂ A diet rich in starchy food (which promotes should be reduced to lowest possible level to prevent weight loss by flat glycemic response, reduces BP CV mortality. and protects against atherosclerosis by providing phytoestrogens, helpful for raising high-density Lipid-Lowering Drugs lipoprotein [HDL]: total cholesterol ratio). These drugs, formerly set at a higher threshold for Salt Restriction global risk of intervention, are brought down by the joint British guidelines. With introduction of statin, Studies on salt restriction show that a reduction in the West of Scotland Coronary Prevention Study salt intake by 76 mmol/day (4.6 g/day) results in (WOSCOPS) and ASCOT-Lipid-Lowering Arm 5.0 mmHg and 2.7 mmHg falls in systolic and diastolic (ASCOT-LLA) studies showed that a 20% reduction in BP, respectively. There is evidence of additive effect cholesterol was associated with a 30-40% reduction of of salt restriction in hypertensive patients when used the incidence of CHD. The issue relating to treatment in conjunction with drugs which block the renin- of patients with lower levels of cholesterol becomes angiotensin-aldosterone system (RAAS). an economic argument rather than one demanding an evidence base. Smoking Cessation Smoking cessation may reduce CHD by about 25%. Antioxidants In hypertensives, endothelial dependent dilatation is Moderation of Alcohol Intake impaired. This dilatation is mediated largely by release Moderation in alcohol intake shows a significant fall of nitric oxide (NO), which plays an important role in in both systolic and diastolic BP, though relationship maintaining vascular integrity by modulating vascular of alcohol intake and CHD is more complex due tone, inhibiting thrombosis and leukocyte adhesion and to beneficial effect of alcohol on HDL cholesterol. influencing smooth muscle proliferation. So, reduced Therefore, preventive strategies for CV mortality in endothelial NO may contribute to vascular injury and essential hypertension include: hence increase CV mortality. Despite the plausibility ÂÂ Early detection for antioxidant therapy in CVD risk reduction, there ÂÂ Lifestyle modification is lack of evidence of benefit in prospective placebo- controlled trials. ÂÂ Timely therapeutic intervention ÂÂ Appropriate choice of therapeutic agents

Lifestyle Modifications ÂÂ Adoption of preventive program not only at Lifestyle modifications produce important effect in personal and clinical level, but also at national level. lowering BP and prevention of CV mortality. In obese Suggested Reading patients, a 10 kg loss of weight might well normalize the BP. Short-term studies of physical exercise program 1. Hanson L, Hedner T, Lund-Johnasen P, Kjeld SE, Lindholm demonstrated a 10% fall in mean arterial pressure, a LH, Syvertsen Jo, et al. Lancet. 2000;356(9227):359-65. 25% fall in total peripheral resistance and a 20% rise in 2. Yusuf S, Sleight P, Pogue J, Bosch J, Davies K, Dagenais G. cardiac index. Epidemiological studies demonstrated N Engl J Med. 2000;342(3):145-53. that potassium intake, given as potassium chloride 3. du Cailar G, Ribstein J, Mimran A. Am J Hypertens. tablets, brings about a significant fall in BP. Potassium 2002;15(3):222-9. intake, as potassium chloride tablet, is not recommended 4. Frolich ED, Varagic J. Nat Clin Pract Cardiovasc Med. but intake may be increased as fruits and vegetables. 2004;1:24-30. A major American study, Dietary Approaches to Stop 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. 169 In case of complications, a cesarean delivery should be done in women within 4-6 hours or sooner of membranes breaking." MediFinance Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019 Budget 2019-20 Highlights

Arun Kishore, CA

Income-tax any account maintained with a banking company or cooperative bank or post office exceeds Rs. 1 crore. The threshold limit for reduced tax rate of 25% in case of domestic companies has been increased from The sunset date for transfer of residential house Rs. 250 crores to Rs. 400 crores. Thus, a domestic property, for claiming exemption under Section 54GB company whose total turnover or the gross receipt in the in respect of investment made in eligible start-ups, has been extended from 31st March, 2019 to 31st March, previous year 2017-2018 does not exceed Rs. 400 crore 2021. Further, the conditions of minimum shareholding shall be taxable at the rate of 25%. or voting rights has been relaxed from 50% to 25%. A new Section 80EEA has been inserted to provide for Application under Section 195(2) and 195(7) for lower deduction of up to Rs. 1.50 lakhs for interest on loan or nil deduction of tax from sum paid or payable to taken from any financial institution for acquisition of non-resident person can be filed electronically. a residential house property whose stamp duty value does not exceed Rs. 45 lakhs. A new Section 194M has been inserted to require any individual or HUF (who is not required to deduct tax A new Section 80EEB has been inserted to provide for under Section 194C or 194J) to deduct tax at source from a deduction of Rs. 1.5 lakhs in respect of interest on sum paid to a contractor or professional if aggregate loan taken for purchase of an electric vehicle from any payment during the year exceeds Rs. 50 lakh. The tax financial institution. can be deposited under this provision without any The new rate of surcharge for Individual, HUF, AOP, requirement to obtain TAN. BOI and AJP shall be - 10% (for income of Rs. 50 lakhs As per Section 194-IA, a buyer is required to deduct to Rs. 1 crore), 15% (for income of Rs. 1 crore to tax at source from the consideration paid to buy an Rs. 2 crores), 25% (for income of Rs. 2 crores to immovable property. An explanation has been inserted Rs. 5 crores) and 37% (for income exceeding 5 crores). that “consideration for immovable property” shall Any sum of money paid, or any property situated in include all charges paid towards club membership India transferred, on or after July 5, 2019 by a person fee, car parking fee, electricity and water facility fees, resident in India to a person outside India shall be maintenance fee or any other charges of similar nature, deemed to accrue or arise in India under Section 9. which are incidental to transfer of the immovable property. Furnishing of return of income shall be mandatory under Section 139, if an individual has deposited In case of failure to file an Income-tax return, Rs. 1 crore or more in current account or he has the prosecution proceedings are initiated under incurred expenditure of Rs. 2 lakhs or more on foreign Section 276CC if the tax payable by the assessee travel or he has incurred expenditure of Rs. 1 lakh or is Rs. 3,000 or more. This threshold limit has been more on electricity consumption. increased to Rs. 10,000. Income-tax return can be filed using Aadhaar Number, Constituent entity of an International group shall if a person hasn't been allotted PAN. If a person has now be required to keep and maintain information linked his Aadhaar number with PAN, he may also and document under Section 92D and file required furnish his Aadhaar number in place of PAN in the form even when there is no international transaction Income-tax return. undertaken by such constituent entity. There are various provisions in the Act which requires PAN allotted to a person shall be deemed to be invalid, a person to make payment by account payee cheque/ if he failed to intimate the Aadhaar to the Dept. draft or ECS. In order to encourage other electronic A new Section 194N has been inserted to require modes of payment, the Government has proposed to deduction of tax at source at the rate of 2% if aggregate amend relevant provisions to include other electronic of cash withdrawn during the financial year from modes of payment.

170 IJCP Sutra: "Eat a balanced diet that is high in fiber and low in fat. Drink plenty of water." Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019 MediFinance

Tax shall be deductible under Section 194DA at the rate ITR filing is mandatory, if total income of assessee of 5% only on the income component of life insurance before claiming the benefit of capital gain exemption pay-out. The existing rate of TDS was 1% on the gross under sections 54, 54B, 54EC, 54F, 54G, 54GA and 54GB, amount. doesn't exceed the maximum amount not chargeable Relief under Section 89 shall be considered while to tax. computing the tax liability under Section 140A, Goods and Services Tax Section 143, Section 234A, Section 234B and Section 234C to avoid genuine hardships to the taxpayers who are A Proviso has been inserted to clarify that interest for claiming such relief. late payment of tax shall be levied only on that portion of Every person, carrying on business, shall provide tax which has been paid by debiting the electronic cash facility for accepting payment through electronic ledger. Earlier there was a confusion among taxpayers modes if his turnover or gross receipts exceeds Rs. 50 on this issue whether such interest would be charged on crores. The Payment and Settlement Systems Act, 2007 gross tax liability or only on net tax liability. However, is proposed to be amended to provide that no bank or there is one exception to this rule wherein interest shall system provider shall impose any charge upon anyone, be levied on gross tax liability. Where returns are filed either directly or indirectly, for using the electronic subsequent to initiation of any proceedings under GST modes of payment. Act, the interest shall be levied on the gross tax liability. A taxpayer has been allowed to withdraw 60% of total Every registered person shall authenticate, or furnish amount from NPS as tax free. Currently, the exemption proof of possession of Aadhaar number. If an Aadhaar is allowed only up to 40% of the total corpus amount. number is not assigned to the registered person, such person shall be offered an alternate and viable means of Benefit of first proviso of Section 201(1) has been identification. In case of failure to undergo authentication extended in case of failure to deduct tax at source from or furnish proof of possession of Aadhaar number or sum paid to non-residents. Thus, a deductor shall not furnish alternate and viable means of identification, be deemed to be an assessee in default even if he fails to registration allotted to such person shall be deemed to deduct tax from sum paid to a non-resident, if such non- be invalid. resident discloses such income in his return of income and pays tax due on such income and a certificate from Now a registered person can transfer any amount of a Chartered Accountant is furnished to this effect. tax, interest, penalty, fee or any other amount available in the electronic cash ledger to the electronic cash Deduction of up to 10% of salary is allowed under ledger for Integrated Tax, Central Tax, State Tax, Union Section 80CCD in respect of contribution made by Territory Tax or Cess through a new form PMT-09 an employer to NPS. The limit has been proposed subject to the conditions and restrictions prescribed to be increased to 14% of salary in case of Central under GST Act. Such transfer shall be deemed to be a Government's employees. refund from the electronic cash ledger. Section 12AA has been amended to provide that The Central Government has been authorized to pay the at the time of granting of registration to a trust or amount of refund towards State taxes to the taxpayers. institution, the Pr. CIT or CIT shall also satisfy himself that the applicant trust or institution also satisfy the The Government shall constitute an Authority “National requirements of any other law which is material for the Appellate Authority for Advance Ruling (NAAAR)” for purpose of achieving its objects. hearing appeals. It shall pass an order within 90 days from the date of filing of appeal. The Pr. CIT or CIT has been empowered to cancel the registration under Section 12AA, if after granting The value of exempt supply of services provided by registration it has been noticed that the trust or way of extending deposits, loans or advances (where institution has violated requirements of any other law consideration is received in form of interest or discount) which was material for the purpose of achieving its shall not be considered for determining turnover under objects. Composition Scheme. Section 115QA which requires payment tax on Simplified return forms will be implemented soon. distributed income in case of buy-back of shares has Composition registered dealers are required to pay tax proposed to be extended to listed companies as well. 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 Haryana, Punjab and Chandigarh (Ghosh D, et al. Indian Muzaffarpur Pediatr. 1999), etc., they were all pointing toward HME syndrome secondary to Cassia consumption. (Inputs from Dr Vipin M. Vashishtha) Recurrent, seasonal outbreaks of acute brain disease in children All these illnesses were confused with encephalitis with high case-fatality rates have been occurring almost or with Reye-syndrome. In fact, now we can claim every year in some regions of the country. All outbreaks that any Reye-like illness presenting in epidemic need not have been due to one specific disease/ form must be investigated for the possibility of some syndrome. Cases may be occurring sporadically also, environmental toxin as a putative etiologic agent. but whether sporadic and epidemic cases represent one A precise case definition is necessary for any outbreak syndrome needs clarification. investigation. Strict case definitions were applied in only a few investigations and in all of them the disease Currently, there seems to be two sets of these outbreaks was clinically not encephalitis. dominating the entire scenario; first caused by viruses like Japanese encephalitis, Chandipura, influenza, Outbreak investigations in India are lacking on this enteroviruses, etc., or bacteria such as Orientia front right from the days of ‘Jamshedpur fever’ tsutsugamushi (e.g., Scrub typhus in Gorakhpur). described by late Dr Najeeb Khan in 1954 (Indian J Med Sci. 1954;8:597-9). Another group of these outbreaks is caused by environmental toxins like Cassia occidentalis, toxins in Similarly, the enigma of so called ‘Nagpur encephalitis’, litchi fruits like MCPG and MCPA (hypoglycins), etc. which was earlier attributed to JE virus and later to heat hyperpyrexia (Sriramachari S, et al. Indian J Med Res. While former group is constituted by a true encephalitic 1976), still persists. illness, the latter is not true encephalitis but a multisystem disease in which brain is involved secondarily, i.e., Coming to the Muzaffarpur illness, these recurrent the encephalopathy illness. However, often this key outbreaks are caused by some toxins involved in either difference is not appreciated owing to faulty case the litchi fruit itself like MCPG or MCPA or some hitherto definition that leads to unnecessary investigations. undiagnosed compound used in the litchi cultivation. The disease is not a true encephalitis but an encephalopathy We, a group of four health professionals, investigated fatal, that needs further elucidation. Rapid correction of recurring outbreaks of acute brain illness in many district hypoglycemia may prevent death in few cases. of Western UP, Uttarakhand and Haryana during late 90s’ and early 2000, and found it was not an encephalitis but Heart Failure Registry Underway to Create a a Reye-like encephalopathy that presented in outbreak Data Bank form every year during winter months. Later, we found Thiruvananthapuram: A National Heart Failure Registry it was caused by consumption of beans of a ubiquitous is being prepared to create a data bank on heart diseases weed, C. occidentalis that lead to the genesis of acute across the country. Funded by Indian Council of Medical hepatomyoencephalopathy (HME) syndrome. Research, the idea is to collate data on 10,000 patients The anthroquinones present in the beans were responsible in 1 year. Already 5,000 patients have been listed in the for this syndrome. This was a landmark study that registry. The Sree Chitra Tirunal Institute for Medical presented a new paradigm in outbreak investigations in Sciences and Technology here is among the nodal agencies India and some neighboring countries. It also brought that is preparing the registry. “The registry work began the role of environmental toxins to the forefront. Later, in January and we intend to study the impact of the a mysterious outbreak in Bangladesh was found due heart diseases with this registry. In the first 1,000 cases to consumption of ‘Ghaghra Shak’ by the natives, litchi ‘enrolled’ in the registry, it has been found that ischemic consumption behind Muzaffarpur outbreaks, Cassia heart disease is the highest among various forms of poisoning in Malkangiri, Odisha outbreaks, etc. When heart diseases in the country. Its mortality rate is higher we retrospectively analyzed some of the unexplained compared to that of cancer,’’ said Dr S Harikrishnan, outbreaks in the past like the one in Bengaluru National Principal Investigator and Coordinator of (Benakappa DG, et al. Indian Pediatr. 1991), another near National Heart Failure Registry... (ET Healthworld)

172 IJCP Sutra: "Get enough sleep and avoid stress." Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019 Medical Voice for Policy change

Can One Use Expired Injections? person in lawful charge of him from whom it is possible to obtain consent in time for the thing to EpiPens and other autoinjectors filled with epinephrine be done with benefit. to treat severe allergic reactions may still be potent enough to work many months past their labeled ÂÂ IPC 88: Act not intended to cause death, done by expiration date, according to a new study online in the consent in good faith for person’s benefit —Nothing Journal of Allergy and Clinical Immunology. which is not intended to cause death, is an offence by reason of any harm which it may cause, or be The US Food and Drug Administration (FDA) requires intended by the doer to cause, or be known by the autoinjector expiration dates to ensure that the devices doer to be likely to cause, to any person for whose never contain less than 90% of the original dose of benefit it is done in good faith, and who has given epinephrine. For the study, researchers tested the a consent, whether express or implied, to suffer that contents of 46 different autoinjectors to see how much harm, or to take the risk of that harm. epinephrine remained after the expiration dates on the labels. Half of the devices were tested at least 2 years Illustration A, a surgeon, knowing that a particular after their labeled expiration date. At this point, 80% operation is likely to cause the death of Z, who of the devices still retained 90% or more epinephrine, suffers under a painful complaint, but not intending indicating they were still effective under the FDA rules. to cause Z’s death and intending in good faith, Z’s benefit performs that operation on Z, with Z’s Devices 6 months past their labeled expiration date in consent. A has committed no offence. the study still had 100% of the original epinephrine dose. One year after the labeled expiration date, Fecal Transplant Linked to Death, the FDA Warns devices still had 95% of the original epinephrine dose. As per FDA, two patients received donated stool that And all of the autoinjectors tested that were up to had not been screened for drug-resistant germs, leading 30 months beyond their labeled expiration date still had it to halt clinical trials until researchers prove proper 90% of the dose remaining. testing procedures are in place. The authors also note that they did not test the expired Fecal transplants have come into increasing use to treat injectors’ effectiveness in stopping an anaphylaxis severe intestinal disorders, particularly an infection episode. caused by a bacterium called Clostridium difficile, which Right now, the expiration date is 18 months from the can be deadly and tends to occur in hospitalized time the product is manufactured, a duration that patients who have been heavily treated with antibiotics. is shorter than the expiration date for most other The idea behind the transplants is to use stool from a medications. healthy donor to restore the normal balance of bacteria and other organisms in the intestine, the microbiome. Legal implications Both transplants came from the same donor’s fecal As per the Supreme Court of India, any violation of matter. The report does not state whether the fecal the manufacturer’s warning and recommendation is material was given in liquid form as an infusion into the not to be done (Balram Prasad vs. Kunal Saha & Ors digestive tract or swallowed as pills. Other samples from on 24 October 2013). But in life-threatening situations the same donor were tested after the patients got sick. in absence of any other available alternative there are The samples were found to harbor the same dangerous exceptions: germs found in the patients, known as multidrug- ÂÂ Section 52 in The Indian Penal Code: Good faith— resistant organisms. They were Escherichia coli bacteria Nothing is said to be done or believed in “good that produced an enzyme called extended-spectrum faith”, which is done or believed without due care b-lactamase, which makes them resistant to multiple and attention. antibiotics. The stool had not been tested for the germs before being given to the patients. ÂÂ Section 92: Act done in good faith for benefit of a person without consent - Nothing is an offence by The FDA issued a warning to researchers that stool reason of any harm which it may cause to a person from donors in studies of fecal transplantation should for whose benefit it is done in good faith, even be screened for drug-resistant microbes, and not used if without that person’s consent, if the circumstances those were present. It is also warning patients that the are such that it is impossible for that person to procedure can be risky, is not approved by the agency signify consent, or if that person is incapable of and should be used only as a last resort when C. difficile giving consent, and has no guardian or other does not respond to standard treatments.

IJCP Sutra: "Avoid using tobacco, alcohol or other drugs." 173 Medical Voice for Policy change Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

Muzaffarpur Encephalopathy: A Multi-ministry Clinical Case Coordination and Comprehensive Action Plan is Does a very low coronary artery calcium (CAC) the Answer score signify very low risk? The outbreak of acute encephalitis syndrome (AES) in A 46-year-old female came with atypical chest pain Muzaffarpur has claimed more than a hundred lives. with reported wall motions on echo and questionable AES has been occurring every year for the past so coronary artery disease (CAD) on CT angiography. many years with no solution in sight. A visit by the She was put on treatment for the last 6 months Chief Minister of the state, or the state or central health and was now advised enhanced external counter minister is alone not the answer. pulsation (EECP) and chelation therapy. The patient Since this is a local outbreak in Muzaffarpur and came for a third opinion. adjoining districts, the state should declare a A: On reviewing the CT report it was found she public health emergency and invoke the Essential had a coronary calcium score of zero. She was put Commodities Act. This would bring the entire state of lifestyle advise. health services, both government and private sectors, Discussion under the gambit of the Essential Commodities Act and Essential Services Maintenance Act as ‘essential American Heart Association: CAC score of zero medical services’. (CAC = 0; i.e., no calcified plaque detected) indicates that: A multi-ministry coordination and comprehensive action plan should be drawn up and acted upon. ÂÂ The presence of atherosclerotic plaque, including unstable or vulnerable plaque is highly unlikely. ÂÂ Health Ministry: Should arrange for 24x7 ICU, ventilators, ambulances; Asha workers should be ÂÂ The presence of significant luminal obstructive provided with glucometers and thermometers so disease is highly unlikely (negative predictive that they can monitor the temperature and blood value on the order of 95-99%). sugar levels. They should be taught how to prevent ÂÂ The risk of a cardiovascular event in the next deaths due to hypoglycemia in children. They 2-5 years is quite low (0.1 per 100 person-years). should be advised to give 1 teaspoon of sugar ÂÂ CAC = 0 is useful in the emergency room setting sublingually (not as a drink) every 20 minutes as a tool to rule out myocardial ischemia in in children <15 years of age. Make sure that the symptomatic patients. child does not clinch teeth or swallow the sugar. All health care providers should do home-to-home The presence of CAC is highly sensitive for the survey. presence of ≥50% angiographic stenosis in moderately specific, especially in older patients. The absence ÂÂ ICMR/DST/ all medical colleges: Should spearhead of CAC, particularly in an asymptomatic patient, is research in the illness to understand its cause, to highly predictive of the absence of significant coronary prevent future such outbreaks. artery stenosis and implies a favorable prognosis. ÂÂ Agriculture Ministry: To act on rotten litchis; CAC screening, especially for borderline and advise farmers to destroy the rotten fruits; create intermediate risk patients, can enhance the awareness on harms of eating only litchis by prediction of risk in asymptomatic individuals and malnourished children. increase the predictive value of the Framingham risk ÂÂ Ayush Ministry: Should deliberate if their pathy score. Among asymptomatic patients with a low has some alternative treatment to offer. Framingham risk score (<10% 10-year risk), only a ÂÂ Women & Child Development Ministry: Should small number (<15%) of those with CAC will have a look after the nutrition of the children in the area; cardiac event over the ensuing 5 years. an Evening Day Meal Scheme for the children can CAC screening is unlikely to benefit low- or be started in addition to the Mid-day Meal Scheme high-risk (>20% 10-year risk) patients, and is not already in place. recommended. It has not been established that ÂÂ Transport Ministry and Civil Aviation Ministry: instituting or intensifying pharmacologic risk factor To arrange for airlifting patients and shift them modification in asymptomatic patients with CAC to other states for management, as and when improves outcomes. required.

174 IJCP Sutra: "To keep the reproductive system healthy, keep the genitals clean and avoid coming into contact with body fluids, like blood or semen." Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019 Medical Voice for Policy change

ÂÂ Law Ministry: Should ensure that no law and order Pediatricians should Screen their Patients for problems arise in such situations and the action Alcohol Use, Recommends American Academy of plan is implemented smoothly. Pediatrics

ÂÂ Environment Ministry: Should take all measures In an updated policy statement “Alcohol Use by Youth”, to prevent heat stroke in the area by providing the American Academy of Pediatrics (AAP) has urged makeshift shelter homes. parents to talk with their teens about the risks of alcohol and set firm rules against its use. ÂÂ Military: Can be called in for house-to-house visits to identify probable cases; when Zika threatened The statement is published in the July issue of Pediatrics Brazil in 2015-16, when it was preparing to (published online June 24). An accompanying technical host the 2016 Olympic Games, the army was report outlines the evidence for AAP recommendations called into action and asked to join the efforts to and states that alcohol remains the most common control the virus, which was made into a public substance used by teens. movement. “The teen years are a critical time for brain growth, Its time some concrete steps are taken to prevent when connections responsible for emotional regulation, recurrence of this illness. planning and organization are being formed and fine- tuned,” said Joanna Quigley, MD, FAAP, lead author Health Care Workers Often Work While Sick of the policy statement. “Alcohol paves a pathway for addiction when the brain is still maturing, affecting Most health care workers (HCWs) with an acute the area that governs decision-making. As parents, respiratory illness (ARI) have worked during most we don’t want to downplay those risks, but keep the episodes of ARI, putting their patients and coworkers at conversations open and model healthy habits.” risk for infection, finds a recent study published online “Binge drinking is especially dangerous and is known in Infection Control & Hospital Epidemiology. to lead to other risky behaviors, such as drinking and HCWs from 9 Canadian hospitals were prospectively driving,” said Sheryl Ryan, MD, FAAP, who chairs the enrolled in active surveillance for ARI during the AAP Committee on Substance Use and Prevention and is 2010-2011 to 2013-2014 influenza seasons. Daily illness lead author of the technical report. “Pediatricians should diaries during ARI episodes collected information on screen their patients for alcohol use and help them symptoms and work attendance. understand the impact on the brain and behaviors.” ÂÂ At least 1 ARI episode was reported by 50.4% of The AAP recommends that pediatricians screen for participants each study season. alcohol use and provide education to teens and their

ÂÂ Overall, 94.6% of ill individuals reported working families about hazards, consequences and potential at least 1 day while symptomatic, resulting in an interventions. estimated 1.9 days of working while symptomatic Other recommendations include:

and 0.5 days of absence during an ARI per ÂÂ Send a clear message against the use of alcohol participant season. under age 21.

ÂÂ In multivariable analysis, the adjusted relative ÂÂ Support existing state laws for a minimum purchase risk of working while symptomatic was higher age of 21 for alcohol and advocate for taxes on for physicians and lower for nurses relative to alcohol products. other HCWs. ÂÂ Support strengthening graduated driver licensing ÂÂ Participants were more likely to work if symptoms programs... The laws indirectly affect drinking and were less severe and on the illness onset date driving by restricting night-time driving and the compared to subsequent days. transportation of younger passengers.

ÂÂ The most cited reason for working while ÂÂ Advocate for more research on the impact of alcohol symptomatic was that symptoms were mild and use on the developing brain. the HCW felt well enough to work (67%). ÂÂ Support the role of schools in screening for ÂÂ Participants were more likely to state that they underage alcohol use and providing general health could not afford to stay home if they did not have education and community programs. paid sick leave and were younger. ÂÂ Ban the sale and distribution of powdered alcohol.

IJCP Sutra: "To check for cancer, women should perform monthly self-exams of their breasts, 175 and men should perform monthly self-exams of their testes." Medical Voice for Policy change Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

Do These 7 Things Today, to Save Your Sight Addiction Terms Tomorrow, Says AAO to Young Adults Harvard: People sometimes confuse the words tolerance, The American Academy of Ophthalmology (AAO) urges physical dependence and withdrawal. These terms are young adults to protect their eyes to prevent vision loss not interchangeable, though they are related: in the future. It recommends adults under age 40 have a ÂÂ Tolerance means that, over time, a person will need comprehensive medical eye exam every 5-10 years. larger doses to get the same effect first experienced 1. Wear sunglasses (even when it’s cloudy). Long- with smaller doses. Because tolerance to some side term exposure to the sun without proper protection effects does not occur, people with tolerance often can increase the risk of eye disease, including face worsening side effects as they take larger and cataract, macular degeneration, growths on the eye larger doses. and a rare form of eye cancer. Wear sunglasses that ÂÂ Physical dependence means that the body gets used block 99-100% of both ultraviolet A and B radiation. to having the substance or activity and “misses it” 2. Exercise. Regular physical activity can protect if it’s taken away. People with physical dependence you from serious eye diseases, such as age-related who stop using their object of dependence or who macular degeneration (ARMD) and glaucoma. decrease their dose might develop uncomfortable withdrawal symptoms. 3. Stop smoking. Smoking increases the risk for eye diseases such as cataract and ARMD. Smoking also ÂÂ Withdrawal refers to a range of typical symptoms raises the risk for cardiovascular diseases, which can that vary depending on the substance or activity indirectly influence your eye health. Tobacco smoke, in question, but they often reflect the opposite of including second-hand smoke, also worsens dry eye. the high. How long withdrawal symptoms last and how severe they are depends on which substance 4. Protect your eyes at work and at play. Every year, (or activity) a person uses, at what dose and for how thousands of people in the United States get a long. The fear of withdrawal symptoms sometimes serious work-related eye injury or sports-related makes people nervous about stopping or lowering eye injury. Wearing protective eyewear can prevent their dose. That’s sometimes true even for people most of these injuries. To make sure you have the who no longer derive pleasure from their object of right kind of protective eyewear and you’re using it addiction. correctly, talk with your eyecare professional. 5. Be aware of eye fatigue. If you spend a lot of time NIH Launches Large TB Prevention Trial for People at the computer or staring at your phone, you may Exposed to Multidrug-resistant TB forget to blink and that can tire out your eyes. Try National Institute of Health (NIH): A large phase 3 clinical using the 20-20-20 rule throughout the day: Every trial called PHOENIx MDR-TB (Protecting Households 20 minutes, look away from the screens and focus on Exposure to Newly Diagnosed Index Multidrug- about 20 feet in front of you for 20 seconds. Eye Resistant Tuberculosis Patients) to assess treatments fatigue won’t damage your vision, but if it persists, for preventing people at high risk from developing it can be a sign something else is wrong. You may multidrug-resistant tuberculosis (MDR-TB) has begun. have dry eye, presbyopia or spectacles with lenses that are not properly centered. The study is comparing the safety and efficacy of a new MDR-TB drug, delamanid, with isoniazid, the standard 6. Take proper care of contact lenses. Sleeping, anti-TB drug for preventing active MDR-TB disease in showering and swimming in contact lenses increases children, adolescents and adults at high risk who are your risk for a potentially blinding eye infection. exposed to adult household members with MDR-TB. Learn how to properly care for contact lenses. Study participants are at high risk for MDR-TB because 7. Know your family history. Certain eye diseases they either have latent TB infection, immune systems can be inherited. If you have a close relative with suppressed by HIV or other factors, or are younger macular degeneration, you have a 50% chance of than age 5 years and therefore have a weak immune developing this condition. A family history of system. The study investigators hypothesize that glaucoma increases your glaucoma risk by 4-9 times. prophylactic treatment with delamanid will prove Talk to family members about their eye conditions. better than isoniazid at reducing the likelihood that at- It can help you and your ophthalmologist evaluate risk household members of individuals with MDR-TB your risk. will develop active TB disease.

176 IJCP Sutra: "Be aware of the products you use in your home and on your skin. For example, cleaning products with harsh chemicals." Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019 Medical Voice for Policy change

“It is important to perform randomized, controlled ÂÂ Only foods that contain 20 mg gluten/kg or less can clinical trials on how best to provide preventive care be labeled as ‘gluten-free’. for people who come in close contact with individuals ÂÂ The patients with celiac disease should: with MDR-TB, since this is a major gap in global public health policy,” said Anthony S Fauci, MD Director of zz Buy foods that are labelled ‘gluten- free’. the National Institute of Allergy and Infectious Diseases zz Check the ingredient list and confirm that there (NIAID), which is co-funding the study and is part of is no gluten in the food. the NIH. zz Check the food package for ‘gluten free’ label Study Identifies Early Warning Signs of Eating in the immediate proximity of the name of the Disorders product. zz Should not buy flour from local mills where New research from the Swansea University Medical wheat may also be grounded for other School has identified early warning signs that someone customers and there are high chances of cross may have an eating disorder such as anorexia nervosa, bulimia nervosa and binge eating disorder, which may contamination. 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 zz Always read the manufacturing/packaging by the Royal College of Psychiatrists, showed that date and best before date before buying food. people diagnosed with a disorder had higher rates of zz Check the labels, even on foods one buys other conditions and of prescriptions in the years before regularly, as there may be some changes in their diagnosis. The researchers examined anonymized ingredients used and that may contain gluten. electronic health records from general practitioners (GPs) and hospital admissions in Wales. Overall, 15,558 people (Source: FSSAI) in Wales were diagnosed as having eating disorders Long-term Increased Risk of Cancer Death Following between 1990 and 2017. In the 2 years before their Radioactive Iodine Treatment for Hyperthyroidism diagnosis, data shows that these 15,558 people had:

ÂÂ Higher levels of other mental disorders such as (NIH): Findings from a study of nearly 19,000 patients personality or alcohol disorders and depression. who received radioactive iodine (RAI) treatment for hyperthyroidism and none of whom had had cancer ÂÂ Higher levels of accidents, injuries and self-harm. at study entry show an association between the dose ÂÂ Higher rate of prescription for central nervous system of treatment and long-term risk of death from solid drugs such as antipsychotics and antidepressants. cancers, including breast cancer. The study, led by ÂÂ Higher rate of prescriptions for gastrointestinal researchers at the National Cancer Institute (NCI), part drugs (e.g. for constipation and upset stomach) and of the National Institutes of Health, was published for dietetic supplements (e.g. multivitamins, iron). July 1, 2019 in JAMA Internal Medicine. Most of the Therefore, looking out for one or a combination of these radiation is absorbed by the thyroid gland, but other factors can help GPs identify eating disorders early. organs like the breast and stomach are also exposed during treatment. FSSAI Guidance Note on Gluten-free Foods The relationship was statistically significant for female Recognizing the challenges faced by celiac patients, breast cancer, for which every 100 mGy of dose led to Food Safety and Standards Authority of India (FSSAI) a 12% increased relative risk of breast cancer mortality, has established the standard for ‘gluten free foods’ and and for all other solid tumors considered together, for their labeling requirements under the Food Safety and which relative risk of mortality was increased by 5% per Standards Regulations, 2011. It has released a guidance every 100 mGy. Based on these findings, the researchers note, set up standards and made easy to perform rapid estimated that for every 1,000 patients aged 40 years tests available for the common consumer. The key with hyperthyroidism who were treated with the takeaways from the guidance note: radiation doses typical of current treatment, a lifetime ÂÂ People with celiac disease should not consume food excess of 19 to 32 radiation-attributable solid cancer product containing gluten (wheat, barley, etc.) deaths would be expected.

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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 ÂÂ In LM with LAD disease to decide which lesion is Intervention significant, place the pressure wire distal to LAD lesion; achieve adenosine hyperemia and record Dr Renu Virmani, USA FFR: Mitral valve is a complex structure. The entire structure zz FFR >0.80: Both lesions insignificant, no stenting of mitral valve consists of anterior and posterior leaflets, zz ≤0.80 and ≤0.60: Treat LAD and repeat FFR to chordae tendineae, papillary muscles, left atrium and a assess LM stenosis partial annulus which is D-shaped. The pathophysiology of mitral regurgitation is also complex, involving defect zz ≤0.80 and >0.60: Place pressure wire in LCx to in leaflets, chordae, annulus and papillary muscle and assess LM FFR LV wall. Surgical repair has worked but not surgical zz FFR apparent: >0.80 - Stent LAD lesion; ≤0.80 - valve replacement. Therefore, repair is more likely to Consider treating both LM and LAD lesions. be a better treatment. In patients with high operative surgical risk, transcatheter valve repair is more What is the Role of OCT Guidance in Calcified reasonable than surgical replacement. Lesions?

Aortic Dissection During Coronary Dr Balbir Singh, Gurugram Intervention The presence of calcified and rigid lesions makes PCI challenging. Adjuvant techniques are often required Dr Ruchit Shah, Mumbai to achieve satisfactory stent results. Angiography has Aortic dissection is a rare complication (0.005%). low sensitivity (48%) for calcium detection, except for Most of the dissections occur during guide catheter severe calcification. Optical coherence tomography manipulation. Right coronary artery is more frequently (OCT) is a tool that precisely detects calcium as a involved. JR and AL are responsible for most of the signal poor heterogeneous region with sharply defined aortic dissections. It is best to prevent this complication borders. OCT estimates the area of calcification more by ensuring the correct guide size, curvature and accurately than intravascular ultrasound (IVUS) as the coaxial alignment. Always look for pressure, damping light penetrates calcium without shadowing. OCT also or ventricularization and give gentle contrast helps the operator to distinguish between superficial injections. Aortic dissection during PCI is detected by and deep calcium with accurate measurement of the aortogram, bedside echocardiography, transesophageal minimum distance from the lumen, the thickness of echocardiography and CT scan. Dissection of aorta the calcium, and arc of calcium. OCT could thus be limited to the ipsilateral cusp or <4 mm from cusp can be a more useful clinical tool for quantifying calcified treated by stenting and has good prognosis. Dissections lesions. Total calcium arc >180° and increased calcium which extend >4 mm from the cusp may require thickness of >0.5 mm are associated with greater risk surgery and have a guarded prognosis. Management of of stent underexpansion. OCT is the ideal method to hemodynamics and life-threatening arrhythmias is of capture these parameters and indicate or defer the use prime importance. of atherectomy before stent implantation and guide optimization of PCI. FFR in Special Subsets How can we Benefit the Patients by Incor­ Dr CG Bahuleyan, Thiruvananthapuram porating Newer Technologies into Practice? ÂÂ In serial lesions, the FFR of individual lesions should not be used. Measure the pressure gradients Dr Rajesh Dave, USA across lesions during pull back with hyperemia to Interventional technologies in the field of Cardiology decide which lesion is to be stented. have changed the way diseases are diagnosed and

178 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 Conference Proceedings treated. Interventional Cardiologists are faced with Durable Polymer DES vs. Biodegradable challenging situations every day with decision- Polymer DES making in terms of whether to proceed with stenting Dr Keyur Parikh, Ahmedabad or surgery, ascertaining the correct stent placement, especially in case of multivessel disease, calcified Durable polymer DES (DP-DES) have been studied lesions, long blockages, edge dissection as well as need in a large number of patients and also in those with for revascularization in intermediate lesion. comorbidities like diabetes, high bleeding risk, etc., along with complex lesions like chronic total occlusion Newer technologies, like OCT, are a great help in (CTO), left main, etc. Biodegradable polymer DES (BP- planning of interventional strategies and optimization DES) have not demonstrated superiority to DP-DES. before and after the stent deployment, particularly with BP-DES still have to prove superiority in terms of safety complex diseases. New age imaging tools help improve and efficacy in complex lesions. BP-DES change to BMS patient outcomes by limiting geographic misses, stent following drug-elution, and in clinical and pre-clinical malapposition, under-expansion, etc., thus translating trials, DP-DES have proven to be superior to BMS. into better long-term clinical results. BP-DES have still not shown superiority of safety and efficacy vs. current generation DP-DES in randomized FFR to Guide Precision PCI of CAD clinical trials. Dr Ajit Mullasari, Chennai Researchers showed in ISAR-TEST (Intracoronary Unlike coronary angiography alone, fractional flow Stenting and Angiographic Results: Test Efficacy reserve (FFR) assists interventional cardiologists in of 3 Limus-Eluting Stents) 4 that in head-to-head accurately determining whether coronary atherosclerotic comparisons between three DES, biodegradable plaques are responsible for myocardial ischemia, and polymers did not make for better long-term outcomes. need to be revascularized. BP-DES have, at best, been shown to be noninferior to the durable-polymer standard. There seems to be no FFR is unparalleled in diagnostic accuracy when real late advantage to BP-DES. compared to nonhyperemic indices and noninvasive techniques. It continues to be the gold standard for DAPT Duration and Regimen detection of ischemia-inducing coronary stenoses. FFR-guided PCI has been found to be superior to Prof (Dr) Ashok Seth, New Delhi angiography-guided PCI and over medical therapy Dual antiplatelet therapy (DAPT) is the cornerstone alone. of pharmacological treatment­ aimed at preventing the atherothrombotic complications in patients with FAME 2 trial investigators clearly demonstrated that in several coronary artery disease (CAD) manifestations. patients with stable CAD, FFR-guided PCI, as compared Physicians face several challenges while prescribing with medical therapy alone, improved the outcome. A DAPT that include selecting the appropriate P2Y12 meta-analysis supported current guidelines advising inhibitor and determining the optimal duration of FFR-guided PCI strategy for CAD. DAPT while minimizing the risk of ischemic and FFR-guided PCI was found to be associated with lower bleeding complications in light of each patient’s clinical MACE/MACCE, death, MI, repeat revascularization, characteristic and circumstance. and death or MI than angiography-guided PCI strategy. The ACC/AHA guidelines recommend that for patients Revascularization guided by FFR in patients with with ACS treated with DAPT following BMS or DES CAD and stenoses >50% yields better outcomes implantation, P2Y12 inhibitor therapy (clopidogrel, than revascularization based on a visual analysis of prasugrel, or ticagrelor) should be given for at least angiographic stenosis severity alone. 12 months. In patients treated with DAPT, a daily aspirin dose of 81 mg (range, 75 mg to 150 mg) is DEFER and FAME trials have shown that in patients recommended. The guideline further recommends with stable CAD, conservative management of stenoses that in patients treated with DAPT after coronary stent that could be angiographically severe, but are not implantation who subsequently undergo CABG, P2Y12 hemodynamically relevant, is safe. inhibitor therapy should be resumed postoperatively FFR is, therefore, an ideal tool to guide treatment in so that DAPT continues until the recommended CAD. 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 Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

(NSTE-ACS or STEMI) being treated with DAPT who (0%) versus 5 patients (0.3%)]. The study concluded undergo CABG, P2Y12 inhibitor therapy should be that stopping DAPT at 3 months in selected patients resumed after CABG to complete 12 months of DAPT after CoCr-EES implantation was at least as safe as the therapy after ACS. Additionally, in patients with prolonged DAPT regimen adopted in the historical ACS managed with medical therapy alone (without control group. revascularization or fibrinolytic therapy) and treated Decisions about the timing of surgery and whether to with DAPT, P2Y12 inhibitor therapy (clopidogrel discontinue DAPT after coronary stent implantation or ticagrelor) should be continued for at least must be individualized. Such decisions involve 12 months. weighing the particular surgical procedure and the According to the ESC guidelines, for stable CAD risks of delaying the procedure, the risks of ischemia patients treated with PCI, the duration of DAPT and stent thrombosis, and the risk and consequences of is 1-6 months depending on the bleeding risk. For bleeding. patients in whom the ischemic risk prevails over the risk of bleeding, a longer DAPT duration may be Why is Stent Quality Important? considered. For ACS patients irrespective of the final Dr MS Hiremath, Pune revascularization strategy (medical therapy, PCI, or CABG), the default DAPT duration is 12 months. Six- A stent, once implanted, stays in the patient’s body month therapy duration should be considered in high forever. Stent technologies are complex and all stents bleeding risk patients, while >12-month therapy may are not same. Each brand undergoes varied innovation be considered in ACS patients who have tolerated and testing procedures. DAPT with a low bleeding risk. Clopidogrel is Therefore, it is important that a good quality stent, with considered the default P2Y12 inhibitor in patients with a proven safety and efficacy profile from long-term stable CAD treated with PCI, those with an indication clinical data from various clinical trials is selected for for concomitant oral anticoagulation, as well as the patients. DES brands approved by US FDA offer the in ACS patients in whom ticagrelor or prasugrel most robust technology, stringent approval process and are contraindicated. Some studies have found no best clinical evidence. increased risk of stent thrombosis with shorter- The key expectations from a stent include - Good duration DAPT (3-6 months). A shorter duration of deliverability and flexibility; good scaffolding; high DAPT results in fewer bleeding complications. Shorter- radial strength with minimum recoil; good visibility; duration DAPT may be most reasonable in patients minimal foreshortening; side branch accessibility; currently being treated with “newer-generation” (eg, appropriate metal to artery ratio; biocompatibility; everolimus-eluting) DES, which are associated with optimal stent delivery system; variety of size and lower stent thrombosis and MI rates than those of lengths; drug and polymer. “first-generation” DES. Along with all of these factors the comorbidity of the In line with this, the STOPDAPT trial assessed the patient and lesion should be taken into account, so it is outcome with 3-month DAPT duration after CoCr-EES very important to select a stent which has an indication implantation. The event rates beyond 3 months were approval such as diabetes mellitus, CTO, ACS, etc., very low (cardiovascular death: 0.5%, MI: 0.1%, ST: 0%, which is suitable for the lesion and the patient. stroke: 0.7%, and TIMI major/minor bleeding: 0.8%). Cumulative 1-year incidence of the primary endpoint How can OCT Help in Improving Outcomes in (composite of cardiovascular death, MI, stroke, definite Bifurcations Lesions? stent thrombosis (ST) and TIMI major/minor bleeding) was 2.8%, which was lower than the pre-defined Dr Rajneesh Kapoor, Gurugram performance goal of 6.6%. Using the CoCr-EES group Optical coherence tomography (OCT) has in the RESET trial as a historical comparison group, approximately 10 times higher resolution than IVUS. where about 90% of patients had continued DAPT at It can precisely measure lumen diameters in the 1 year, cumulative incidence of the primary endpoint variable geometry of a bifurcation lesion and identify tended to be lower in the STOPDAPT than in the RESET superficial lipid laden plaques and calcium, relevant (2.8% versus 4.0%) and adjusted hazard ratio was 0.64. to confirm the severity of the lumen obstruction prior The cumulative incidence of definite/probable ST was to treatment and guide location and diameter of the lower in the STOPDAPT than in the RESET [0 patient stent. OCT produces fewer strut-induced artifacts and

180 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." Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019 Conference Proceedings offers precise evaluation of strut apposition in a real- OCT in CTO: Strong Clinical Evidence life clinical setting. The increase in the speed of image acquisition with the introduction of frequency domain Dr Girish Navasundi, Bengaluru OCT allows rapid pull-back at a speed of 36 mm/sec, PCI of CTOs is challenging. It is associated with low minimizing the amount of contrast required to clear success rates, increased restenosis and reocclusion. blood during image acquisition. This enables serial CTOs of arteries are more challenging lesions to treat OCT acquisitions, particularly before treatment if the with angioplasty and stenting as compared to stenotic lesion is not very severe and flow is expected to be vessels primarily on account of the difficulty in guiding present around the OCT catheter, after predilatation the wire across the lesion. Angiography alone cannot and to assess and guide stent expansion. differentiate between the occluded lumen and the vessel wall and to characterize the content of the occlusion. Repeated OCT examinations at follow-up can help in Angiography provides a two-dimensional image of the detection of presence and characteristics of strut contrast-filled lumen, and does not allow an accurate coverage, which can predict late stent thrombosis. assessment of the plaque. These applications are of particular interest in the context of bifurcation lesion treatment as this condition OCT is a high resolution imaging technique that can is still associated with a higher number of malapposed improve the understanding of the vascular response stent struts and frequent impairment of stent after stenting of chronically occluded vessels. OCT expansion. correctly identifies tissue composition within the CTO, such as the presence of collagen and calcium and can OCT can provide unique insights in the setting of identify intraluminal microchannels. OCT imaging of bifurcation lesions by enabling detailed evaluation CTO anatomy and tissue characteristics can possibly of coronary bifurcation pathology and facilitating result in significant improvements in PCI interventions procedural planning. OCT imaging has contributed by providing novel guiding capabilities. enormously to the optimization of bifurcation stenting techniques. With its high resolution, OCT enables In the ACE-CTO study, OCT was performed 8-months interventionalists to re-cross proper stent cell, which post stenting. High rates of stent strut malapposition is the key procedure in both provisional stenting and and incomplete stent strut coverage were observed 2-stent techniques. Poststenting OCT imaging provides after CTO PCI using EES. The study highlighted unique information for further optimal treatment unique challenges associated with stent implantation strategy. in CTOs. OCT is a better tool as compared to angiography as The PRISON-IV trial showed inferior outcome in it depicts ostial lesions in bifurcation without the patients with CTOs treated with the ultrathin-struts (60 μm for stent diameter ≤ 3 mm, 81 μm >3 mm) misleading two-dimensional appearance of angiography hybrid-sirolimus eluting stents (SES) compared with such as overlap and foreshortening. OCT can help everolimus eluting stents (EES, 81 μm). A recent reconstruct a bifurcation in three dimensions and can study evaluated if the use of smaller stents (≤3 mm) assess the side branch ostium from 3D reconstruction was responsible for the inferior outcome reported in of the main vessel pull-back, which can be applied to the trial. The study population was divided according ensure optimal re-crossing position of the wire after to the different size of stents implanted in those main vessel stenting. receiving only stents with diameter ≤3 mm (Group-A, Its ability to provide unique information on the plaque 178 patients), only stents >3 mm (Group-B, 59 patients), at high risk for rupture, plaque composition, thickness and those receiving stents of both sizes (Group-C, of fibrous cap, the presence of macrophage and thrombi 93 patients). OCT was performed in 60 patients at has assisted in simple PCI as well as in complex follow-up, and documented a mild trend toward bifurcation lesions PCI. lower values of minimum in stent area in Hybrid-SES 2 2 OCT helps provide valuable anatomic information to arm of Group A (4.4 ± 1.02 mm vs 5.0 ± 1.28 mm , optimize stent implantation and adapt PCI strategy in respectively, P = 0.16). individual patients. OCT can thus provide significant information in CTOs.

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IJCP Sutra: "Exercises and stretches can help maintain strength and stop joints becoming stiff in children with spinal muscular atrophy. 181 Although the amount of exercise will depend on the condition, it's best to try and stay as active as possible." Around the Globe Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019 News and Views

Clinical Practice Guidelines 2019 should be used in clinically stable patients who need RBC transfusion. The trigger and target should be Acute lower gastrointestinal bleeding: 10 Key 80 g/L and 100 g/L, respectively in patients with a Takeaways history of cardiovascular disease. This year, the British Society of Gastroenterology 7. Interrupting warfarin therapy at presentation is released clinical practice guidelines on the diagnosis recommended. In patients with low thrombotic and management of acute lower gastrointestinal (GI) risk, warfarin should be restarted at 7 days after bleeding published online April 8, 2019 in the BMJ. hemorrhage. In patients with high thrombotic Here are 10 key takeaways from the guidelines. risk (i.e., prosthetic metal heart valve in mitral 1. Patients who present with low GI bleeding should position, atrial fibrillation with prosthetic heart be first categorized as unstable (shock index >1) or valve or mitral stenosis, <3 months after venous thromboembolism), low molecular weight heparin stable. The Oakland score can be used to categorize (LMWH) should be considered at 48 hours after the stable bleeds as minor or major. Patients with minor bleeding. self-terminating bleed (Oakland score ≤8) can be discharged for urgent outpatient investigation, if 8. Permanently discontinue aspirin for primary there are no indications for hospitalization. But prophylaxis of cardiovascular events. But, restart patients with major bleed should be hospitalized aspirin for secondary prevention, if stopped, as for colonoscopy on the next available list. soon as hemostasis is achieved. 2. Before planning endoscopic or radiological therapy, 9. Routine stopping of dual antiplatelet therapy with localize the site of bleeding quickly and least a P2Y12 receptor antagonist and aspirin is not invasively via CT angiography in hemodynamically recommended in patients with coronary stents in situ; unstable patients or those who have shock index a cardiologist should be part of the management >1 after initial resuscitation and/or in whom active team. Continue aspirin if P2Y12 receptor antagonist bleeding is suspected. is interrupted in unstable hemorrhage; restart P2Y12 receptor antagonist within 5 days. 3. If no source of bleeding can be identified on initial CT angiography in hemodynamically 10. Direct oral anticoagulant therapy should be unstable patients, an upper GI endoscopy should interrupted at presentation. Treatment with be performed immediately. Gastroscopy may be inhibitors such as idarucizumab or andexanet the first investigation when patient stabilizes after should be considered for life-threatening initial resuscitation. hemorrhage in patients on direct oral anticoagulants. Restart direct oral anticoagulant drug treatment at 4. If a source of bleeding is found on CT angiography, a maximum of 7 days after the bleeding. a catheter angiography with a view to embolization should be done at the earliest. Centers with a (Source: Oakland K, Chadwick G, East JE, et al. Diagnosis 24/7 interventional radiology service should be and management of acute lower gastrointestinal bleeding: capable of performing catheter angiography guidelines from the British Society of Gastroenterology. for hemodynamically unstable patients within Gut. 2019;68(5):776-89). 60 minutes of admission. Evaluate Gait Speed as a ‘Vital Sign’ to Predict 5. Patients should not proceed to emergency Prognosis in Older Adults with Blood Cancers laparotomy unless an exhaustive effort has been Gait speed is an easily obtained ‘vital sign’ that made to localize the source of bleeding using accurately identifies frailty and predicts survival and radiologic and/or endoscopic modalities. unplanned hospital visits regardless of age, cancer or 6. Restrictive red blood cell (RBC) thresholds treatment type, or other factors among older patients (Hemoglobin [Hb] trigger 70 g/L and Hb with hematologic cancers, according to a new study concentration target of 70-90 g/L post transfusion) published June 5, 2019 in the journal Blood. This

182 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 non- New Guidelines Issued on Sexually Transmitted Hodgkin lymphoma. Infections For every 0.1 meter per second decrease in gait speed, Updated guidelines on sexually transmitted infections the risk of dying, unexpectedly going to the hospital, (STIs) address a number of dermatologic manifestations or ending up in the emergency room increased by 22%, that are not always included in recommendations from 33% and 34%, respectively. other specialty groups, delegates heard at the World Every 5 kg decrease in grip strength was associated Congress of Dermatology 2019. with worse survival, but not hospital or ED use. Diagnosing and treating genital lumps and lacerations Monitoring gait speed not only helps to recognize are necessary, said Marco Cusini, MD, from the individuals who are frail and may fare worse, it also Fondazione IRCCS Ca’ Granda Ospedale Maggiore identifies people who are in much better shape than Policlinico in Milan, who was onsite representing the expected based on age alone. International Union Against Sexually Transmitted Diseases (IUSTI), which recently issued the guidance Researchers suggest that gait speed should be used (J Eur Acad Dermatol Venereol). as a routine part of medical assessments along with other vital signs to improve patient assessment, An important aspect of the updated IUSTI guidelines prognostication and individualization of care. is that they urge doctors to be mindful of several high-risk populations. Sex workers, gay men and Collaboration Between France and WHO to Realize transgender people are all at risk for STIs. The update the Vision of the WHO Academy expands information on how to treat transgender Emmanuel Macron, President of the French Republic patients. and Dr Tedros Adhanom Ghebreyesus, WHO Director- TAVR on Bicuspid Valves may Carry Early Risks General met at WHO Headquarters in Geneva and signed a Declaration of Intent to establish the WHO People with bicuspid aortic stenosis had an early Academy that will revolutionize lifelong learning disadvantage for stroke after getting transcatheter aortic in health. valve replacement (TAVR) with a balloon-expandable The Academy aims to reach millions of people with valve, researchers found from the TVT Registry. innovative learning via a state-of-the-art digital learning While post-TAVR mortality rates were similar between experience platform at a campus in Lyon and embedded Sapien 3 recipients with two- and three-leaflet anatomy, in the six WHO regions. The WHO Academy Lyon early stroke was more common with bicuspid valves hub will feature high-tech learning environments, a before reaching statistical equivalency at 1 year. world-class health emergencies simulation center and The bicuspid group also experienced significantly more collaboration spaces for learning co-design, research procedural complications requiring open heart surgery and innovation...(WHO) (0.9% vs. 0.4%), according to a group led by Raj Makkar, One-in-Five Suffers Mental Health Condition in MD, of Cedars-Sinai Medical Center in Los Angeles, in Conflict Zones: UN Figures a preliminary report in JAMA. More than one-in-five people living in conflict-affected No Link Between HIV Infection and Contraceptive areas suffers from a mental illness, according to a new Methods, Says Study report based on UN figures, prompting the WHO to A large clinical research study conducted in four African call for increased, sustained investment in mental health services in those zones. countries found no significant difference in risk of human immunodeficiency virus (HIV) infection among Around 22% of those affected, suffer depression, women using one of three highly effective, reversible anxiety or post-traumatic stress disorder, according to contraceptive methods - depot medroxyprogesterone an analysis of 129 studies published in The Lancet. acetate (DMPA) intramuscular, levonorgestrel implant The study also shows that about 9% of conflict-affected and a copper-bearing intrauterine device (IUD). populations have a moderate to severe mental health Published in the Lancet, the study showed that each condition; substantially higher than the global estimate method had high levels of safety and effectiveness in for these mental health conditions in the general preventing pregnancy, with all methods well-accepted population...(UN) 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. 183 A dietitian can offer advice about feeding and diet." Around the Globe Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

“These results support making available to women and Levels of normal hemoglobin levels rose >1.0 g/dL girls a broad choice of effective contraceptive methods from baseline at week 24 - a degree associated with that empower them to make informed decisions about significantly decreased rates of multiorgan failure their own bodies - including if and when to have and death in natural history studies, and considered children,” said Dr James Kiarie, from the Dept. of a “response” - for 51% of patients randomized to the Reproductive Health and Research at the WHO…(WHO) 1,500 mg of voxelotor group compared with 7% of those on placebo (p < 0.001) in the intention-to-treat analysis Yemen: Maternal and Newborn Health “on the Brink for the primary endpoint. The findings were published of Total Collapse”, UNICEF Alerts online in the New England Journal of Medicine. After more than 4 years of grinding conflict in Yemen, health care for mothers and their babies is “on the brink Meeting of the International Health Regulations of collapse”, the UN Children’s Fund (UNICEF) warned (2005) Emergency Committee for Ebola Virus in a report that highlights the difficulties of childbirth Disease in DRC and parenting in a war zone. The meeting of the Emergency Committee convened According to UNICEF, 1 woman and 6 newborns die by the WHO Director-General under the International every 2 hours from complications during pregnancy or Health Regulations (IHR) (2005) regarding Ebola virus childbirth. The years of intense fighting in the country disease in the Democratic Republic of the Congo (DRC) have contributed to limited access to crucial health took place on June 14, 2019. care, with only 3 out of 10 births taking place in regular The Committee expressed its deep concern about health facilities. the ongoing outbreak, which, despite some positive The results are part of a series compiled by the agency, epidemiological trends, especially in the epicentres Childbirth and parenting in a war zone…(UN) of Butembo and Katwa, shows that the extension and/or reinfection of disease in other areas like Fecal Transplants may Transmit Deadly Drug- Mabalako, presents, once again, challenges around resistant Infections, FDA Warns community acceptance and security. The US Food and Drug Administration (FDA) alerted It was the view of the Committee that the outbreak is a health care providers and patients that fecal microbiota health emergency in DRC and the region but does not for transplant (FMT) may transmit multidrug-resistant meet all the three criteria for a PHEIC under the IHR. organisms, leading to serious or life-threatening While the outbreak is an extraordinary event, with risk infections. In a safety communication, the FDA said of international spread, the ongoing response would not two immunocompromised adults who received FMT be enhanced by formal Temporary Recommendations developed invasive bacterial infections caused by under the IHR (2005)…(WHO) extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli. One of the patients died…(Medscape) Federal Officials Seized Adulterated Dietary Supplements from Life Rising Corporation due to Restless Legs Syndrome Tied to Gut Health Poor Manufacturing Practices Preliminary research suggests an association between At the request of the US FDA, US Marshals seized small intestine bacterial overgrowth (SIBO) and restless more than 3,00,000 containers of dietary supplements, legs syndrome (RLS), supporting emerging research including tablets, capsules and teas from Life Rising linking gut microbial health to sleep health. Corporation. The seized goods consisted of more than While the study is ongoing and recruitment just 500 products bearing brand names Life Rising, Holicare beginning, the researchers found SIBO in all 7 RLS or HopeStream, and are valued at approximately patients studied to date. The study was presented at $3.5 million. SLEEP 2019: 33rd Annual Meeting of the Associated The FDA inspection at Life Rising found that its dietary Professional Sleep Societies. supplements were prepared, packed and/or held under conditions that violated Current Good Manufacturing Novel Sickle Cell Drug Improves Hemoglobin Practice (CGMP) regulations. Among other observed Characteristics deficiencies, the company failed to establish product For sickle cell disease, novel oral agent voxelotor improved specifications for the identity, purity, strength and hemoglobin characteristics in the phase III HOPE trial. composition of each finished batch of dietary supplement,

184 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." Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019 Around the Globe and for limits on certain types of contamination, to to receive insufficient amounts of their medicine, thus ensure the quality of the supplement... (FDA) reducing the benefits of treatment,” the EMA said in a news release. Gabapentinoids Tied to Suicidal Behavior and Unintentional Overdose The review only covered depot formulations that are given by injection under the skin or into a muscle and that Gabapentinoid prescriptions were associated with an release the active substance slowly over 1 to 6 months. increased risk of suicidal behavior and unintentional These products include implants as well as powders and overdose, a population cohort study in Sweden showed. solvents for the preparation of injections…(Medscape) The risks were strongest for people who were prescribed pregabalin over gabapentin, especially among young Incivility in ORs Linked to Diminished Clinical Performance people, reported Seena Fazel, MD, of the University of Oxford in England, and colleagues in The BMJ. Research on anesthesiology residents exposed to incivility in a simulated operating room (OR) IL-17a Drug Rescues Many Refractory Psoriatic environment indicates that rudeness in the OR has a Arthritis Cases negative impact on clinician performance. Despite having been treated with numerous regimens, The recent research published in BMJ Quality & Safety including multiple attempts with biologic agents, many exposed anesthesiology residents to an impatient patients with psoriatic arthritis benefited from a 6-month surgeon-actor in a simulated OR hemorrhage scenario. course of secukinumab in a “real-world” analysis Compared to a control group of residents who were not reported at the European Congress on Rheumatology. exposed to an impatient surgeon-actor, the experimental Among 177 heavily pretreated patients, 47% achieved residents scored lower on all four performance metrics remission or low disease activity as measured by in the study: vigilance, diagnosis, communication and the DAPSA (Disease Activity in Psoriatic Arthritis) patient management. score, reported Maria Martin-Lopez, MD, of Hospital Father’s Smoking During Pregnancy Tied to Asthma Universitario 12 de Octubre in Madrid. in Kids Amid Measles Outbreak, New York Ended Religious Children who are exposed to tobacco smoke from their Exemptions for Vaccines fathers while they are in the womb may be more likely Amid a measles outbreak, New York required than those who are not to develop asthma by age 6, schoolchildren to be vaccinated, even if parents have according to a study of chemical changes to DNA. religious objections. While prenatal smoke exposure has long been linked Gov. Andrew Cuomo signed a legislation that removes to an increased risk of childhood asthma, the current nonmedical exemptions from school vaccination study offers fresh evidence that it’s not just a pregnant requirements. mother’s smoking that can cause harm. The findings are published in Frontiers in Genetics. The move, which came despite opposition from anti- vaccination activists and religious freedom advocates, FDA Approves New Treatment for Pediatric Patients put New York alongside other states that do not allow with Type 2 Diabetes nonmedical exemptions: California, Mississippi, West The US FDA approved liraglutide injection for Virginia and Maine…(CNN) treatment of pediatric patients 10 years or older with Leuprorelin Depot Handling Errors Prompt EMA type 2 diabetes. Liraglutide is the first non-insulin drug Review approved to treat type 2 diabetes in pediatric patients since metformin was approved for pediatric use in 2000. Reports of handling errors with depot formulations The drug has been approved to treat adult patients with of leuprorelin (leuprolide acetate) prompted the type 2 diabetes since 2010... (FDA.) Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) to launch a Researchers Find Way to Convert Type A Blood review. to Type O The reports indicate that “handling errors during Researchers have found a way to use a pair of enzymes preparation and administration can cause some patients 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 Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

universal donor type O blood, according to a report aspiring chefs were challenged to share dishes that were published in Nature Microbiology. not only delicious, but good for people and the planet, The researchers say the high activity and specificity of with an emphasis on reducing meat and promoting these enzymes “make these very promising candidates plant-based diets...(UN) for cost-efficient implementation into the already Convicted Physicians Received Message of Support existing automated routines of blood collection, from World’s Doctors processing and storage, with major implications for the flexibility of our blood supply and possible applications On behalf of millions of physicians globally, the World in organ transplantation.” Medical Association (WMA) delivered an open message of support to all Turkish doctors, and in particular to Necrotizing Infections Rise with Warming Oceans, those sentenced to prison, for declaring in a press release Study Shows that “war is a public health problem’. In an open letter, WMA leaders denounced ‘the pervasive obstruction As ocean temperatures increase, serious Vibrio vulnificus campaign” by the Turkish state against doctors and infections are on the rise in previously nonendemic declared: “We are shocked and deeply disturbed by the areas, according to a case series published online in recent decision of the Criminal Court of Ankara which Annals of Internal Medicine. This emerging Vibrio risk condemned TMA’s Central Council members to prison in nonendemic areas means clinicians need to be sentences for their call for peace. This is pure aberration”. aware of the infection, especially if they have never seen a case in their practice. The bacterium typically The public statement “War is a Public Health Problem” lives in warm seawater. was issued as a press release on January 24, 2018 by 11 doctors as members of the Central Council of Turkish WHO Offers a New Tool and Sets a Target to Medical Association...(WMA) Accelerate Action Against Antimicrobial Resistance Osteoporosis Drugs may Help Oldest, Sickest WHO has launched a global campaign urging Women Most governments to adopt a tool to reduce the spread of antimicrobial resistance, adverse events and costs. Frail, very elderly women with osteoporosis may benefit the most from osteoporosis drugs, according to a study The AWaRe tool was developed by the WHO Essential published online in JAMA Internal Medicine. Medicines List to contain rising resistance and make antibiotic use safer and more effective. It classifies Women older than 80 years with osteoporosis and antibiotics into three groups – Access, Watch and multiple medical problems or poor prognosis had more Reserve – and specifies which antibiotics to use for than triple the risk for hip fracture in the next 5 years, the most common and serious infections, which ones compared with women in the same age group who had should be available at all times in the healthcare system, increased fracture risk but no osteoporosis. and those that must be used sparingly or preserved “Clinicians should consider the initiation of drug and used only as a last resort. The new campaign aims treatment to prevent fracture in late-life women with to increase the proportion of global consumption of osteoporosis (bone mineral density [BMD] T-score -2.5 antibiotics in the Access group to at least 60%, and to or below) and multiple comorbidities, as this group reduce use of the antibiotics most at risk of resistance of women may derive the greatest absolute benefit of from the Watch and Reserve groups...(WHO) treatment in preventing future hip fractures,” author Kristine Ensrud, MD, MPH, University of Minnesota, UN Environment Agency Tackles Climate Change Minneapolis, said. One Bite at a Time If we all change the way we eat, we can make significant Novel Agent Shows Promise as First Possible progress in the fight against climate change. This was Therapy for Achondroplasia the message from the` UN environment agency (UNEP) The results are preliminary, but a novel investigative on Sustainable Gastronomy Day - June 18, as it launched agent has shown promise in a small trial in children a new campaign to encourage healthy and sustainable for the treatment of achondroplasia, the most common food choices. form of human dwarfism. As part of its #ActNow initiative, a global call to A phase 2, proof of concept study found that treatment individual action on climate change, professional and with vosoritide, a recombinant C-type natriuretic peptide

186 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 Around the Globe analogue, demonstrated a favorable safety profile agent can be extended to older patients and those with and efficacy at a dose of 15 μg/kg. The findings were worse kidney function, researchers report. published online in the New England Journal of Medicine. The findings were presented at the American Diabetes WHO Flags Critical Funding Gap, Calls for Political Association (ADA) 2019 Scientific Sessions. Parties to Join Fight Against Ebola New Multi-Partner Trust Fund Launched to Combat The Ebola outbreak in the DRC will only end with Antimicrobial Resistance Globally bipartisan political cooperation and community Noordwijk, the Netherlands: In a major boost to combat ownership, according to the WHO’s Director-General, one of the gravest risks to global health, a dedicated Dr Tedros Adhanom Ghebreyesus. He was speaking to funding vehicle allowing partners to devote resources to Member States in Geneva after returning from a visit to accelerate global action against Antimicrobial Resistance DRC, where he reviewed the health response and met (AMR) was unveiled at a Ministerial Conference. with leaders from multiple sectors to galvanize their commitment. The Tripartite - a joint effort by the Food and Agriculture Organization (FAO), the World Organization for WHO’s funding needs for the response are US$98 Animal Health (OIE) and the WHO, launched the AMR million, of which US$44 million have been received, Multi-Partner Trust Fund, which is being supported leaving a gap of US$54 million. The funding shortfall by an initial contribution of US$5 million from the is immediate and critical: if the funds are not received, Government of the Netherlands. The AMR Trust Fund WHO will be unable to sustain the response at the has a 5-year scope, through 2024, and aims to scale up current scale…(WHO) efforts to support countries to counter the immediate threat of AMR…(WHO) Cardiac MRI Safely Reduces Invasive Tx for Stable Angina FDA Expands Approval of Treatment for Cystic A noninvasive approach to imaging for stable angina Fibrosis to Include Patients Ages 6 and Older in patients with risk factors for coronary artery disease The US FDA has expanded the indication for a (CAD) reduces invasive treatment without greater risk combination of tezacaftor/ivacaftor tablets for treatment of a major cardiac event, the MR-INFORM trial showed. of pediatric patients ages 6 years and older with cystic A strategy of myocardial-perfusion cardiovascular MRI fibrosis who have certain genetic mutations. Last year, led to revascularization for 35.7% of patients, whereas the the FDA approved the combination to treat patients rate was 45.0% for those who had invasive angiography ages 12 and older who had the same specific genetic and measurement of fractional flow reserve (FFR). mutations. The approval for children as young as 6 years old provides an important treatment option for younger Only 48.2% of the MRI group ended up with invasive patients, and also provides more context on the safety angiography (compared with nearly the entire FFR and dosing specific to this population…(FDA) group), despite a pretest likelihood for CAD of 75%, Eike Nagel, MD, of Goethe University Frankfurt, Expected Shortage of TB Tests Prompts New CDC Germany, and colleagues reported online in the New Recommendations England Journal of Medicine. The CDC issued new recommendations for tuberculosis CARMELINA: Linagliptin Safe in Diabetes Across (TB) skin testing in response to the anticipated 3- to Age, Renal Groups 10-month nationwide shortage of a purified-protein derivative (PPD) tuberculin antigen approved by the In patients with type 2 diabetes and either US FDA for tuberculin skin tests (TSTs). cardiovascular disease or impaired kidney function, the dipeptidyl peptidase 4 (DPP-4) inhibitor linagliptin The report was published in MMWR. The CDC’s demonstrated cardiovascular safety, no increased risk recommendations were intended to address the of hospitalization for heart failure and “reassuring” potential decrease in TB testing because of the shortage. kidney safety including a reduction in albuminuria - across renal function and age groups - over 2.2 years. CDSCO Issues Alert for Security Risk to Certain Medtronic Insulin Pumps These findings, from the Cardiovascular and Renal Microvascular Outcome Study With Linagliptin Vide a notice File No: 29/Misc/03/2019-DC (100) dated (CARMELINA) outcome trial, showed that safety of the 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 Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019

Organization (CDSCO) has issued a medical device alert In a meeting held to review the preparedness for for some insulin pumps manufactured by Medtronic. prevention and control of vector-borne diseases (malaria, dengue and chikungunya) in the national The MiniMed™ Paradigm™ series insulin pumps (MMT- capital, the Union Health Minister, Dr Harsh Vardhan 715, MMT-712, MMT-722, MMT-754) are designed to urged the state government and the Mayors to work communicate using a wireless radio frequency (RF) towards making hospitals, schools and government with other devices such as a blood glucose meter, buildings 'Vector-Free'. glucose sensor transmitters and CareLink™ USB devices. Security researchers have identified potential He also suggested that Malaria should be made a cybersecurity vulnerabilities related to these insulin notifiable disease, which was assured by the Delhi pumps. Health Minister. An unauthorized person with special technical skills In the meeting, it was also suggested that all hospitals, and equipment could potentially connect wirelessly to including the private ones, should appoint a nodal person a nearby insulin pump to change settings and control for vector-borne diseases to ensure that the Government and private interventions and efforts to prevent/cure insulin delivery. vector-borne diseases are in tandem. The focus should be The CDSCO has advised the following actions on active case finding of cases and reduction of vectors. for Medical Directors/Health care professionals, Distributors and the Users and Staff involved in the What each doctor can do management of patients. ÂÂ Ask every suspected case of dengue, chikungunya or malaria to trace the mosquito breeding site in the ÂÂ Check to see if the model and software version of vicinity of 50 houses. your insulin pump is affected. ÂÂ Surgical strikes on all the mosquitoes in the vicinity ÂÂ Talk to your health care provider about a of identified cases can make the difference. prescription to switch to a model with more cybersecurity protection. Low Vitamin D in Early Childhood Predicts High ÂÂ Keep your insulin pump and the devices that are BP in Adolescence connected to your pump within your control at all Deficiency or insufficient levels of vitamin D in early times whenever possible. childhood predisposes children to greater risk of ÂÂ Do not share your pump serial number. high blood pressure (BP) during later childhood and

ÂÂ Be attentive to pump notifications, alarms and adolescence. alerts. ÂÂ Compared to children born with adequate vitamin D levels, low vitamin D status at birth was ÂÂ Monitor your blood glucose levels closely and act associated with higher risk of elevated systolic BP appropriately. at ages 3-18 years: OR 1.38 (95% CI, 1.01-1.87). ÂÂ Immediately cancel any unintended boluses. ÂÂ Low vitamin D status in early childhood was ÂÂ Connect your Medtronic insulin pump to other associated with a 1.59-fold (95% CI, 1.02-2.46) Medtronic devices and software only. higher risk of elevated systolic BP at age 6-18 years.

ÂÂ Disconnect the USB device from your computer ÂÂ Children with persistently low levels of vitamin D when you are not using it to download data from through early childhood was associated with higher your pump. risk of elevated systolic BP (OR, 2.04 [95% CI, The alert comes a week after the US FDA issued 1.13-3.67]) at ages 3-18 years. a warning to patients and health care providers The prospective birth cohort study published in the that certain Medtronic MiniMed insulin pumps are journal Hypertension followed 775 children from birth being recalled due to potential cybersecurity risks… to age 18 at the Boston Medical Center. Most lived in (Source: CDSCO) a low-income urban area, and about two-thirds were African American. Malaria to be Made Notifiable Disease Based on their findings, the researchers suggest that Monsoons bring welcome relief from the scorching screening and treatment of vitamin D deficiency with heat, but they also bring with them a host of illnesses, supplementation during pregnancy and early childhood notably dengue, Chikungunya. may prevent or reduce high BP later in life.

188 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." Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019 Around the Globe

Venezuela: More Than 2.8 Million People to Gain for 14 days or more, which exceeds gout attack’s normal Access to Safe Drinking Water with UNICEF Support expected length, the researchers reported in Arthritis More than 2.8 million people, including Venezuelan Care & Research. children, adolescents and families, will gain improved New Guideline for Trigeminal Neuralgia Released access to safe drinking water after a collaboration agreement signed between UNICEF and the Government All patients with trigeminal neuralgia (TN) should of Venezuela. undergo MRI, a new guideline for diagnosing and treating this condition recommends. As part of the agreement with the Ministry of Water, UNICEF will work on expanding the supply of The guideline, developed by a task force of the European safe drinking water through systems repair and Academy of Neurology (EAN), also recommends that extension, water-trucking and other alternative sources, neurovascular contact (NVC) should not be used to strengthening of priority sanitation systems, and confirm a diagnosis of primary TN but to determine providing technical assistance and cooperation in water whether surgery is warranted. In addition, the guideline quality monitoring. recommends carbamazepine and oxcarbazepine as first-line prophylactic treatments of TN. Highlights of “Water is fundamental to families’ life and dignity. the guideline were presented at the Congress of the This agreement will help children and adolescents European Academy of Neurology (EAN) 2019. access safe water, which is critical to their survival and healthy development,” said María Cristina Perceval, A Few Pathogens Account for Most Severe UNICEF Regional Director for Latin America and the Pneumonias in African, Asian Kids Caribbean… (UNICEF) A short list of pathogens accounts for most cases of Most Older Adults with “Prediabetes” don't Develop pneumonia requiring hospital admission in children Diabetes without HIV infection from Africa and Asia, according to results from the PERCH study. Older adults with slightly elevated blood sugar, sometimes called “prediabetes”, usually don’t develop Researchers noted that pneumonia was most commonly full-blown diabetes, a Swedish study suggests. due to viral pathogens (61.4%), with respiratory syncytial virus (RSV) causing the greatest number of cases (31.3%). Researchers followed 2,575 men and women aged 60 Bacterial pathogens other than Mycobacterium tuberculosis and older without diabetes for up to 12 years. At the accounted for 27.3% of cases. Other pathogens accounting start of the study, 36% of the group did have higher- for 5% or more of the etiological distribution included than-normal blood sugar levels that were still below the human rhinovirus, human metapneumovirus (HMPV) A threshold for diabetes. Only 119 people, 13% of those or B, human parainfluenza virus (types 1-4 combined), who started out with elevated blood sugar, went on Streptococcus pneumoniae, M. tuberculosis and Haemophilus to develop diabetes. Another 204, or 22%, had blood influenzae, the team reports in The Lancet. sugar levels drop enough to no longer be considered prediabetic… (Reuters) Assam Doctors' Leaves Canceled as Japanese Encephalitis Claims 49 Lives Across State Opioids Overused in Acute Gout Assam government has canceled all leaves of doctors, Opioids were commonly given to patients as a treatment paramedical staff and surveillance workers in order to for acute gout attacks, despite the availability of other deal with the outbreak of encephalitis that has claimed effective and appropriate therapies, a retrospective 49 lives across the state from January till July 5. study found. In an order issued by the Health and Family Welfare Among 456 patients who were discharged from the Department, all leaves of the government medical staff hospital or emergency department (ED) with a primary in the state were canceled in order to effectively deal diagnosis of gout, 28.3% received an opioid prescription, with the present situation of rising acute encephalitis according to Deepan S. Dalal, MD, of Brown University syndrome (AES)/Japanese encephalitis (JE) cases. Warren Alpert School of Medicine in East Providence, To deal with rising number of cases of AES and JE, Rhode Island, and colleagues. the government has decided to involve the private While the median duration of the prescription was hospitals. "Critical AES/JE patients, who are admitted 8 days, one-quarter of these patients had prescriptions in the ICUs of private hospitals/nursing homes... will

IJCP Sutra: "Trust your own comfort level rather than a shoe’s size or description. 189 Sizes vary from one manufacturer to another. You’re the real judge." 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 Highlighting that the world’s poorest countries will be order stated... (News 18 – PTI) worst affected, particularly in West Africa and South- East Asia, the International Labour Organization (ILO) Screen All Pregnant Women for GBS Colonization warned that the lost output will be equivalent to to Prevent Newborn Infections 80 million full-time jobs - or 2.2% of total working hours The updated recommendations from the American worldwide - during 2030. Academy of Pediatrics (AAP) on management of The total cost of these losses will be $2.4 trillion every infants at risk for group B streptococcal (GBS) disease year, ILO’s Working On A Warmer Planet report support universal antenatal microbiologic-testing maintains, based on a global temperature rise of only of pregnant women for the detection of maternal 1.5°C by the end of this century. GBS colonization so that appropriate intrapartum antibiotic prophylaxis may be administered to prevent “The impact of heat stress on labor productivity is a transmission of the bacteria from mother to the newborn serious consequence of climate change”, said Catherine before or during delivery as also recommended Saget, Chief of Unit in the ILO’s Research Department by the American College of Obstetricians and and one of the main authors of the report. “We can Gynecologists (ACOG). expect to see more inequality between low and high- Published online July 8, 2019 in the journal Pediatrics, income countries and worsening working conditions the AAP recommendations for infant care include: for the most vulnerable.”

ÂÂ Administering antibiotic during childbirth, when In the ILO report, heat stress is defined as generally indicated and as recommended by the ACOG to occurring at above 35°C, in places where there is high protect the newborn from transmission of GBS. humidity. Excess heat at work is an occupational health

ÂÂ In evaluating the risk of GBS infection in the risk and in extreme cases can lead to heatstroke, which newborn, infants born at ≥35 0/7 weeks gestation can be fatal. and those born at ≤34 6/7 weeks gestation should be Besides agriculture and construction, other at-risk considered separately. Infants born at 34 6/7 weeks sectors include refuse collection, emergency services, gestation are preterm and are at highest risk for transport, tourism and sports, with southern Asian and early-onset sepsis, including GBS disease. western African States suffering the biggest productivity ÂÂ Early-onset GBS infection should be diagnosed by losses, equivalent to approximately 5% of working blood or cerebrospinal fluid culture. hours by 2030… (UN) ÂÂ Evaluation for late-onset GBS disease, which is After Bihar, Assam on Alert for Japanese Encephalitis associated with preterm birth, should be based on Outbreak clinical signs of illness.

ÂÂ The preferred antibiotic for confirmed GBS disease Following nearly 170 deaths from acute encephalitis in infants is penicillin G, followed by ampicillin. syndrome (AES) in just 2 months in Bihar, Assam is now on alert for a Japanese encephalitis outbreak. A healthy pregnant woman might be colonized with no At least 57 people have died in the last 3 months from evident signs and symptoms of the illness. GBS infection Japanese encephalitis and 234 positive cases have been in infants can be potentially fatal due to complications reported in the state in this fresh outbreak. like sepsis, meningitis or pneumonia. Over the past 3 months, Assam has also seen over Heat Stress Spike Predicted to Cost Global 50 deaths due to AES. While the state's health Economy $2.4 Trillion a Year establishment is on the highest alert, the biggest worry An increase in heat stress at work linked to climate is that this time, cases have been reported from 26 out change is set to have a massive impact on global of Assam's 27 districts, and many new areas have productivity and economic losses, notably in agriculture become vulnerable to the killer disease, officials said... and construction, UN labor experts said. (NDTV.)

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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

fter returning from a free health check-up camp in promoting number two by superseding another sometime back, I met a Professor of Cardiology senior deserving person, it is not regarded as a help Afrom Lucknow and began to boast that I had because the person you have helped will give you seen 100 patients today free of charge. He said do not only one blessing but the person whom you have get excited. Charity is positive, but still not the absolute harmed may curse you 10 times. So, ultimately you positive, unless it is done without any motive or done end up with minus 9 points. Helping other means secretly. He said that you were honored on the stage, you that it should give happiness to you, to the persons received blessings from the patients and people talked you have helped and also to others to whom you have about you in positive sense. It was an investment in the not helped. long run and not an absolute charity. When you never get honored on the stage by the people you are serving Helping always pays or have served, then it is like give and take. The purpose of life should be to help others without any expectations. The difference between American and Indian models is that Indians always think of now and do not invest Understanding helping others in future. Americans always plan for the future. When you help somebody, you want that the same person Helping others should not harm somebody else. should help you when you are in need in a shorter Even with your unconditional help, if you end up 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. Group Editor-in-Chief, IJCP Group Help should never be linked to returns.

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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

nce upon a time, there lived a big mango tree. One hot summer day, the man returned and the tree A little boy loved to come and play around it was delighted. “Come and play with me!” The tree Oevery day. He climbed to the tree top, ate the said. “I am sad and getting old. I want to go sailing mangoes and took a nap under the shadow… He loved to relax myself. Can you give me a boat?” “Use my the tree and the tree loved to play with him. trunk to build your boat. You can sail far away and be Time went by… The little boy grew, and he no longer happy.” played around the tree. One day, the boy came back to So, the man cut the tree trunk to make a boat. He went the tree with a sad look on his face. “Come and play sailing and didn’t come back for a long time. Finally, with me,” the tree asked the boy. the man returned after he had been gone for so many “I am no longer a kid, I don’t play around trees years. “Sorry, my boy, but I don’t have anything for anymore.” The boy replied, “I want toys. I need money you anymore. No more mangoes to give you.” The tree to buy them.” “Sorry, I don’t have money… but you said. can pick all my mangoes and sell them so you will have “I don’t have teeth to bite,” the man replied. “No more money.” trunk for you to climb on.” “I am too old for that now,” The boy was so excited. He picked all the mangoes on the man said. “I really can’t give you anything… the the tree and left happily. The boy didn’t come back. only thing left is my dying roots,” the tree said with The tree was sad. One day, the boy, grown into a man, sadness. “I don’t need much now, just a place to rest. returned. The tree was so excited. “Come and play with I am tired after all these years,” the man replied. “Good! me,” the tree said. Old tree roots are the best place to lean on and rest. “I don’t have time to play. I have to work for my family. Come sit down with me and rest.” We need a house for shelter. Can you help me?” “Sorry, The man sat down and the tree was glad and smiled. I don’t have a house, but you can chop off my branches to build your house.” So, the man cut all the branches Moral: The tree in the story represents our parents. off the tree and left happily. The tree was glad tosee When we are young, we love to play with them. When him happy but the boy didn’t come back afterward. we grow up, we leave them and only come back when The tree was again lonely and sad. we need help. Parents sacrifice their lives for us.

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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] 0.07- 0.15) 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.“ In dex e ISS d N wit 0971-08h In Volume 1, Number 1 dM 76 ED

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Online subscription: http://subscription.ijcpgroup.com/Default.aspx lighter reading Indian Journal of Clinical Practice, Vol. 30, No. 2, July 2019 Lighter Side of Medicine

Communication technician Get yourself a train!

A communication technician drafted by the army Dear Dad HUMOR was at a firing range. At the range, he was given Berlin is wonderful, people are nice and I really like it some instructions, a rifle and 50 rounds. He fired here, but Dad, I am bit ashamed to arrive to my college several shots at the target. The report came from with my Gold Mercedes, when all my Teachers travel the target area that all attempts had completely by train. missed the target. The technician looked at his weapon, and then at the target. He looked at the Your Son weapon again, and then at the target again. He Nasser then put his finger over the end of the rifle barrel Sometime later Nasser gets reply to his e-mail from and squeezed the trigger with his other hand. his Dad: The end of his finger was blown off, whereupon he yelled toward the target area: “It’s leaving Loving son here just fine, the trouble must be at your end!” Twenty Million Dollars transferred to your account, please stop embarrassing us, go and get yourself a New hearing aid train too. Seems an elderly gentleman had serious hearing Dad problems for a number of years. Don’t thank me He went to the doctor and the doctor was able to have him fitted for a set of hearing aids that Looking down at the defendant, the judge said, “Mr allowed the gentleman to hear 100%. Riley, I’ve decided to give you a suspended sentence.” The elderly gentleman went back in a month to Tears pouring from his eyes, Riley cried, “Oh, thank the doctor and the doctor said, “Your hearing is you, Your Honor!” perfect. Your family must be really pleased that “Don’t thank me,” the judge replied. “I’m sentencing you can hear again.” you to be hanged.” To which the gentleman said, “Oh, I haven’t told my family yet. I just sit around and listen to the Dr. Good and Dr. Bad conversations. I’ve changed my will three times!” Situation: A 45-year-old male with NAFLD was warned about the development of type 2 diabetes in Weight loss the future. A blonde woman is terribly overweight, so her doctor puts her on a diet. “I want you to eat NAFLD does not increase the The risk of developing risk for type 2 diabetes type 2 diabetes is high 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.” 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?” © IJCP GROUP © IJCP The blonde nodded. “I’ll tell you though, I thought Lesson: Several studies display a link between the presence I was going to drop dead that third day.” and severity of NAFLD and increased risk of incident type 2 diabetes and hypertension. In addition, it has been reported that “From hunger, you mean?” asked the doctor. the presence and severity of NAFLD also act as independent predictors of fatal and nonfatal cardiovascular events. “No, from skipping.” J Hepatol. 2017;68(2):335-52.

194 IJCP Sutra: “To make your overall diet healthier, eat more plant-based foods, such as fruits, vegetables and whole-grain carbohydrates.“ Indexed with IndMED ISSN 0971-0876 Indexed with MedIND RNI 50798/1990 Indian Citation Index (ICI) University Grants Commission 20737/15554

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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.

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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 [email protected].

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 name of the corresponding authors, acknowledgment of the ‘Uniform requirements for manuscripts submitted to financial support and abbreviations used. biomedical journals’ compiled by the International Committee – The title should be of no more than 80 characters and of Medical Journal Editors (Ann. Intern. Med. 1992;96: should represent the major theme of the manuscript. 766-767). A subtitle can be added if necessary. Indian Journal of Clinical Practice strongly disapproves of – A short title of not more than 50 characters (including the submission of the same articles simultaneously to inter-word spaces) for use as a running head should different journals for consideration as well as duplicate publication and will decline to accept fresh manuscripts be included. submitted by authors who have done so. – The name, telephone and fax numbers, e-mail and postal The boxed checklist will help authors in preparing their addresses of the author to whom communications are manuscript according to our requirements. Improperly to be sent should be typed in the lower right corner of prepared manuscripts may be returned to the author without the title page. review. The checklist should accompany each manuscript. – A list of abbreviations used in the paper should be Authors may provide on the checklist, the names and included. In general, the use of abbreviations is addresses of experts from Asia and from other parts of the discouraged unless they are essential for improving World who, in the authors’ opinion, are best qualified to the readability of the text. review the paper. Summary Covering letter – The summary of not more than 200 words. It must – The covering letter should explain if there is convey the essential features of the paper. any deviation from the standard IMRAD format – It should not contain abbreviations, footnotes or (Introduction, Methods, Results and Discussion) and references. should outline the importance of the paper. Introduction – Principal/Senior author must sign the covering letter – The introduction should state why the study was carried indicating full responsibility for the paper submitted, out and what were its specific aims/objectives. preferably with signatures of all the authors. – Articles must be accompanied by a declaration by all Methods authors stating that the article has not been published – These should be described in sufficient detail to permit in any other Journal/Book. Authors should mentioned evaluation and duplication of the work by others. complete designation and departments, etc. on the – Ethical guidelines followed by the investigations should manuscript. be described. Manuscript Statistics – Three complete sets of the manuscript should be The following information should be given: submitted and preferably with a CD; typed double – The statistical universe i.e., the population from which spaced throughout (including references, tables and the sample for the study is selected. legends to figures). – Method of selecting the sample (cases, subjects, etc. – The manuscript should be arranged as follow: Covering from the statistical universe). letter, Checklist, Title page, Abstract, Keywords (for indexing, if required), Introduction, Methods, – Method of allocating the subjects into different groups. Results, Discussion, References, Tables, Legends – Statistical methods used for presentation and analysis of to Figures and Figures. data i.e., in terms of mean and standard deviation values – All pages should be numbered consecutively or percentages and statistical tests such as Student’s beginning with the title page. ‘t’ test, Chi-square test and analysis of variance or non-parametric tests and multivariate techniques. Note: Please keep a copy of your manuscript as we are not responsible for its loss in the mail. Manuscripts will not be – Confidence intervals for the measurements should be returned to authors. provided wherever appropriate.

Title page Results Should contain the title, short title, names of all the authors – These should be concise and include only the tables (without degrees or diplomas), names and full location of the and figures necessary to enhance the understanding departments and institutions where the work was performed, of the text.

196 IJCP Sutra: “Prevent exposure to dust mites. These are tiny insects and one of the most common asthma triggers.“ Discussion Figures – Two complete sets of glossy prints of high quality – This should consist of a review of the literature and relate the major findings of the article to other should be submitted. The labelling must be clear and publications on the subject. The particular relevance of neat. the results to healthcare in India should be stressed, – All photomicrographs should indicate the magnification e.g., practicality and cost. of the print. – Special features should be indicated by arrows or References letters which contrast with the background. These should conform to the Vancouver style. References – The back of each illustration should bear the first should be numbered in the order in which they appear in the texts and these numbers should be inserted above the lines author’s last name, figure number and an arrow on each occasion the author is cited (Sinha12 confirmed indicating the top. This should be written lightly in other reports13,14...). References cited only in tables or in pencil only. Please do not use a hard pencil, ball point legends to figures should be numbered in the text ofthe or felt pen. particular table or illustration. Include among the references – Color illustrations will be accepted if they make a papers accepted but not yet published; designate the journal and add ‘in press’ (in parentheses). Information from contribution to the understanding of the article. manuscripts submitted but not yet accepted should be cited – Do not use clips/staples on photographs and artwork. in the text as ‘unpublished observations’ (in parentheses). – Illustrations must be drawn neatly by an artist and At the end of the article the full list of references should include the names of all authors if there are fewer than photographs must be sent on glossy paper. No seven or if there are more, the first six followed by et al., captions should be written directly on the photographs the full title of the journal article or book chapters; the title or illustration. Legends to all photographs and of journals abbreviated according to the style of the Index illustrations should be typed on a separate sheet of Medicus and the first and final page numbers of the article paper. All illustrations and figures must be referred or chapter. The authors should check that the references to in the text and abbreviated as “Fig.”. are accurate. If they are not this may result in the rejection of an otherwise adequate contribution. Examples of common forms of references are: Please complete the following checklist and attach to the manuscript: Articles 1. Classification (e.g. original article, review, selected Paintal AS. Impulses in vagal afferent fibres from specific summary, etc.)______pulmonary deflation receptors. The response of those receptors to phenylguanide, potato S-hydroxytryptamine 2. Total number of pages ______and their role in respiratory and cardiovascular reflexes. 3. Number of tables ______Q. J. Expt. Physiol. 1955;40:89-111. 4. Number of figures ______Books 5. Special requests ______Stansfield AG. Lymph Node Biopsy Interpretation Churchill 6. Suggestions for reviewers (name and postal address) Livingstone, New York 1985. Indian 1.______Foreign 1.______Articles in Books 2.______2.______Strong MS. Recurrent respiratory papillomatosis. In: 3.______3.______Scott Brown’s Otolaryngology. Paediatric Otolaryngology 4.______4.______Evans JNG (Ed.), Butterworths, London 1987;6:466-470. 7. All authors’ signatures______Tables 8. Corresponding author’s name, current postal and – These should be typed double spaced on separate e-mail address and telephone and fax numbers sheets with the table number (in Roman Arabic ______numerals) and title above the table and explanatory notes below the table. Online Submission Legends Also e-Issue @ www.ijcpgroup.com – These should be typed double spaces on a separate sheet and figure numbers (in Arabic numerals) For Editorial Correspondence corresponding with the order in which the figures are Dr KK Aggarwal presented in the text. Group Editor-in-Chief Indian Journal of Clinical Practice – The legend must include enough information to E-219, Greater Kailash Part-1 permit interpretation of the figure without reference New Delhi - 110 048. Tel: 40587513 to the text. E-mail: [email protected] 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

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For More Information call: 9582363695, E-mail [email protected] Website: http://talkingpointcommunications.com R.N.I. No. 50798/1990 POSTAL REGISTRATION NO. DL (S)-01/3200/2018-2020 Date of Publication 13th of Same Month Posted in N.D. PSO New Delhi Date of Posting 13-14 Same Month