Ijcp august 2015 by IJCP

Indexed with IndMED

ISSN 0971-0876

www.ijcpgroup.com

August 2015, Pages 01â&#x20AC;&#x201C;40 Peer Reviewed Journal

Cardiology

Community Medicine

Internal Medicine

Practice Guidelines

Photo Quiz

Around The Globe

Lighter Reading

Online Submission

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

August 2015 FROM THE DESK OF THE GROUP EDITOR-IN-CHIEF

All About Depression and Suicide KK Aggarwal

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

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

Anand Gopal Bhatnagar Editorial Anchor

CARDIOLOGY

Ambulatory Blood Pressure Monitoring

Kamal Kumar, Shivanjali Kumar, Ranjana Kumar

COMMUNITY MEDICINE

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

Deepak Arora, MK Mahajan

20 Importance of Pharmacoeconomic Evaluation: Current Scenario in India

Ann Mary Paul, Anil Antony, Sruthi Nu, Hyfa Hameed, Vimal Mathew

INTERNAL MEDICINE

26 Acalculous Cholecystitis in Dengue: Is it Rare?

CR Jothi, R Umarani, K Baburaj

29 Generalized Fatigue, Amenorrhea Due to Snake Bite?

Sreenivasa Rao Sudulagunta, Mahesh Babu Sodalagunta, Hadi Khorram, Mona Sepehrar

Advisory Bodies Heart Care Foundation of India Non-Resident Indians Chamber of Commerce & Industry World Fellowship of Religions

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

PRACTICE GUIDELINES

32 AHA and ASA Release Guideline for Prevention of Future Stroke in Patients with Stroke or TIA

Amber Randel

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

33 Skin Sloughing and Lip Lesions After a Recent Foot Procedure

Printed at Jasmine Art Printers Pvt. Ltd. Navi Mumbai

Stanislav N. Tolkachjov

AROUND THE GLOBE

35 News and Views

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

LIGHTER READING

38 Lighter Side of Medicine

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

IJCPâ&#x20AC;&#x2122;s EDITORIAL & BUSINESS OFFICES Delhi

Mumbai

Kolkata

Bangalore

Chennai

Hyderabad

Dr Veena Aggarwal 9811036687 E - 219, Greater Kailash, Part - I, New Delhi - 110 048 Cont.: 011-40587513 editorial@ijcp.com drveenaijcp@gmail.com Subscription Dinesh: 9891272006 subscribe@ijcp.com Ritu: 09831363901 ritu@ijcp.com

Mr. Nilesh Aggarwal 9818421222 Mr. Pravin Dhakne 8655611025, 24452066

Ritu Saigal Sr. BM 9831363901

H Chandrashekar GM Sales & Marketing 9845232974

Chitra Mohan Sr. BM 9841213823 40A, Ganapathypuram Main Road Radhanagar Chromepet Chennai - 600 044 Cont.: 22650144 chitra@ijcp.com

Venugopal GM Sales & Marketing 9849083558

Unit No: 210, 2nd Floor, Shreepal Complex Suren Road, Near Cine Magic Cinema Andheri (East)

7E, Merlin Jabakusum 28A, SN Roy Road Kolkata - 700 038 Cont.: 24452066 ritu@ijcp.com

Mumbai - 400 093 nilesh.ijcp@gmail.com

Sr.: Senior; BM: Business Manager; GM: General Manager

Arora Business Centre, 111/1 & 111/2, Dickenson Road (Near Manipal Centre) Bangalore - 560 042 Cont.: 25586337 chandra@ijcp.com

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

FROM THE DESK OF THE GROUP EDITOR-IN-CHIEF

Prof. Dr KK Aggarwal

Group Editor-in-Chief IJCP Group and eMedinewS

All About Depression and Suicide ÂÂ Depression, a leading predictor of functional disability and mortality is a major public health problem. ÂÂ Optimal depression treatment improves outcome for most patients. ÂÂ Most adults with clinical significant depression never see a mental health professional but they often see a

primary care physician.

ÂÂ A physician who is not a psychiatrist misses the diagnosis of depression 50% of times. ÂÂ All depressed patients must be specifically enquired about suicidal ideations. ÂÂ Suicidal ideation is a medical emergency. ÂÂ Risk factors for suicide are known psychiatric disorders, medical illnesses, prior history of suicidal attempts or

family history of attempted suicide.

ÂÂ The demographic reasons include older age, male gender, marital status (widowed or separated) and living

alone.

ÂÂ About 1 million people commit suicide every year globally. ÂÂ Around 79% of patients who commit suicide contact their primary care provider in the last 1 year before their

death and only one-third contact a mental health service provider.

ÂÂ Twice as many suicidal victims had contacted their primary care provider as against the mental health provider

in the last month before suicide.

ÂÂ Suicide is the 10th leading cause of death worldwide and accounts for 1.2% of all deaths. ÂÂ The suicide rate in the US is 10.5 per 1,00,000 people. ÂÂ In the US, suicide is increasing in middle-aged adults. ÂÂ There are 10-40 nonfatal suicide attempts for everyone completed suicide. ÂÂ The majority of suicides completed in US are accomplished with fire arm (57%); the second leading method of

suicide in US is hanging for men and poisoning in women.

ÂÂ Patients with prior history of attempted suicide are 5-6 times more likely to make another attempt. ÂÂ Fifty percent of successful victims have made prior attempts. ÂÂ One of every 100 suicidal attempt survivors will die by suicide within 1 year of the first attempt. ÂÂ The risk of suicide increases with increase in age; however, young adults and adolescents attempt suicide more

than the older.

Indian Journal of Clinical Practice, August 2015

FROM THE DESK OF THE GROUP EDITOR-IN-CHIEF ÂÂ Females attempt suicide more frequently than males but males are successful three times more often. ÂÂ The highest suicidal rate is amongst those individuals who are unmarried followed by those who are widowed,

separated, divorced, married without children and married with children in descending order.

ÂÂ Living alone increases the risk of suicide. ÂÂ Unemployed and unskilled patients are at higher risk of suicide than those who are employed. ÂÂ A recent sense of failure may lead to higher risk. ÂÂ Clinicians are at higher risk of suicide. ÂÂ The suicidal rate in male clinicians is 1.41 and in female clinicians it is 2.27. ÂÂ Adverse childhood abuse and adverse childhood experiences increase the risk of suicidal attempts. ÂÂ The first step in evaluating suicidal risk is to determine presence of suicidal thoughts including their concerns

and duration.

ÂÂ Management of suicidal individual includes reducing mortality risk, underlying factors and monitoring and

follow-up.

ÂÂ Major risk for suicidal attempts is in psychiatric disorder, hopelessness and prior suicidal attempts or threats. ÂÂ High impulsivity or alcohol or other substance abuse increase the risk. ■■■■

Indian Journal of Clinical Practice, August 2015

CARDIOLOGY

Ambulatory Blood Pressure Monitoring KAMAL KUMAR*, SHIVANJALI KUMAR†, RANJANA KUMAR*

ABSTRACT Hypertension is a major healthcare concern. With office and home blood pressure monitoring giving insufficient information, ambulatory blood pressure monitoring has emerged as the investigation of choice for hypertension.

Keywords: Ambulatory blood pressure monitoring, white coat hypertension, morning surge, masked hypertension

he specter of hypertension looms large over the world as a leading cause of morbidity and mortality. Almost 1 billion adults representing about a quarter of the world’s population had hypertension in 2000. We are likely to see this number go up to 1.56 billion by the year 2025—an increment of almost 60%. In India, the prevalence of hypertension has increased from 2% to 25% among urban residents and from 2% to 15% among the rural residents in the last 60 years.1 Small reductions in mean systolic blood pressure (SBP) are known to significantly reduce mortality from stroke and ischemic heart disease.2

ÂÂ

Ambulatory blood pressure monitoring (ABPM) using an automatic computer-based programable BP monitoring system.

The superiority of ABPM over HBPM is wellestablished. ABPM provides a good estimate of the ‘true’ or ‘mean BP’ level, a record of the ‘diurnal variation’ of BP and of BP variability.3 INDICATIONS OF ABPM Several recent guidelines now recommend ABPM as the investigation of choice in the following conditions:4-7 ÂÂ

Identification of white coat hypertension

Office blood pressure (BP) recordings are like a single snap-shot in time and give only limited information. They have a low reproducibility as office readings taken by different personnel and/ or on different instruments may differ. With office recordings, we cannot assess variations in BP at different times and in different situations, effect of stress, exercise or sleep. They may, therefore at times, not be truly representative of the BP of the patient. Out-of-office BP measurements, therefore become necessary and these may be obtained by:

ÂÂ

Identification of masked hypertension

ÂÂ

Identification of abnormal 24-hour BP trends:

ÂÂ

Assessment of treatment

Home blood pressure monitoring (HBPM) where the patient or his attendants measure the BP at home at specified intervals.

ÂÂ

Assessment of BP trends in the elderly, in young patients, in high-risk patients and in pregnancy.

ÂÂ

Identification of resistant hypertension, endocrine hypertension and hypertension in Parkinsonism.

ÂÂ

Increased BP variability

Daytime hypertension

Night-time hypertension

Dipping patterns

Morning surges

Obstructive sleep apnea and BP

AMBULATORY BLOOD PRESSURE RECORDING *Senior Consultant †Consultant Heartline Hospital and Cardiac Cath Lab, Allahabad, Uttar Pradesh Address for correspondence Dr Kamal Kumar 29 B/2, Hastings Road, Allahabad - 211 001, Uttar Pradesh E-mail: drkamalkumar@rediffmail.com

ABPM was developed about four decades ago but never gained popularity due to cumbersome equipment and lack of proper standardization. Modern equipment is light-weight and portable. It consists of a cuff, a small monitor typically weighing <1 pound that is attached

Indian Journal of Clinical Practice, August 2015

CARDIOLOGY to a belt, and a tube connecting the cuff and monitor (Fig. 1 a and b). The monitor automatically records BPs every 30 minutes during waking hours and every 60 minutes during rest. These timings are programable. The monitors use the ‘oscillometric technique’, (i.e., they assess oscillations caused by arterial pulse pressure). Data recorded by the monitor is analyzed by devicespecific software. Limits for normal SBP and diastolic blood pressure (DBP) during daytime waking hours and night-time sleeping periods can be programed

separately. Most of the currently available ABPM devices are independently validated according to the European Society of Hypertension International Protocol.8 ABPM TERMINOLOGY

Percentage Successful The machine should record at least 2 readings per hour during waking hours from 6.00 am to 10.00 pm and at least 1 reading per hour from 10.00 pm to 6.00 am. At least 80% of the recordings should be successful for a good record.

Mean Blood Pressure (Mean) Is the average SBP and DBP over a 24-hour period. It includes both the active (awake) and the passive (sleep) periods. Normal value is 130/80 mmHg.

Percent Time Elevation The percent time elevation (PTE) also called ‘pressure load’ is calculated individually for the entire 24-hour period, the active period and the passive period. It is the percentage of time during which the SBP, DBP or both are above limits of normal. A PTE above 25% indicates hypertension.

Hyperbaric Impact/Index The hyperbaric impact/index (HBI) is a quantitative measure of high BP. It indicates the time and magnitude of BP excess above the upper limit of the tolerance level in a given period of time.

Expressed in mmHg × hour, an HBI of >15 mmHg × hour would indicate suspected hypertension and an HBI of >50 mmHg × hour would indicate hypertension. It would also help in evaluating the response to medication.9

Diurnal Index The diurnal index (DI) is the difference in mean BP between awake and sleeping BP calculated as a percentage. ÂÂ

DI = [1 – (night mean SBP/awake mean SBP)] × 100

ÂÂ

Dipping patterns based on the DI are described later.

Morning Surge10 b

Figure 1 a and b. Modern light-weight and portable ABPM device.

Indian Journal of Clinical Practice, August 2015

This is the percentage difference between mean SBP during the first 2 hours of waking-up and the lowest level recorded at night.

CARDIOLOGY Double Product

ILLUSTRATIVE ABPM RECORDINGS

It is also known as rate pressure product (RPP) is a marker of cardiac load. It gives a direct indication of the energy requirements of the heart and is a good measure of energy consumption.

White Coat Hypertension

Normal range is 70-110 mmHg.

White coat hypertension is a condition, where the subject demonstrates raised SBP and DBP in the doctor’s office or in other stressfull situations but has normal BP recordings measured at home or elsewhere. The readings measured by a doctor are usually higher than those measured by a nurse. The patient often has tachycardia and usually does not exhibit evidence of any target organ damage. This condition is more common in women, in the elderly and those with high levels of anxiety. White coat hypertension may be seen in 20-30% of subjects. It is no longer considered to be innocuous. Recent evidence suggests that subjects with white coat hypertension have more than double the risk of developing hypertension, have increased risk of developing diabetes and increased left ventricular mass over time (Fig. 2).5,11,12

Pulse Pressure

Nocturnal Dipping Patterns

Pulse pressure = SBP-DBP

Based on DI nocturnal dipping patterns are described as:5,6

Double product (RPP) = Heart rate (HR) × SBP Based on RPP the hemodynamic response can be classified as: ÂÂ

High: >30,000

ÂÂ

High intermediate: 25,000-29,999

ÂÂ

Intermediate: 20,000-24,999

ÂÂ

Low intermediate: 15,000-19,999

ÂÂ

Low: <14,999.

Mean Arterial Pressure Mean arterial pressure = DBP + [(SBP-DBP)/3]

Normal range is 40-50 mmHg.

x: Time, y: Systole, Diastole mmHg, Pulse 1/min mmHg 300 290 280 270 260 250 240 230 220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0

7/13/2014

7/14/2014

White coat hypertension

14:00

16:00

18:00

20:00

22:00 0 0:00

02:00

04:00

06:00

08:00

10:00

12:00

1/min 300 290 280 270 260 250 240 230 220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 14:00

Figure 2. White coat hypertension.

Indian Journal of Clinical Practice, August 2015

CARDIOLOGY ÂÂ

Normal dipping: The DI is between 10% and 20% (Fig. 3)

ÂÂ

Nondipper: The DI is between 0% and 10% (Fig. 4)

ÂÂ

Extreme dipper: The DI is >20% (Fig. 5)

ÂÂ

Reverse dipper: The DI is <0% (Fig. 6).

Nondipping may be seen in as much as 39% of the population with a much greater prevalence reaching 78% in diabetics. It correlates with cardiovascular (CV) autonomic neuropathy in diabetics. Nondippers, patients with exaggerated nocturnal BP fall (extreme-dippers) and those with increased nocturnal BP (reverse dippers), all have greater hypertensive target organ damage, CV events and stroke. Abnormal dipping patterns are also a risk for left ventricular hypertrophy, silent cerebrovascular disease, microalbuminuria and progression of renal damage.13

mmHg 300 290 280 270 260 250 240 230 220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 14:00

3/13/2014

More than 20% difference between the average SBP of the first 2 hours after awakening and the lowest SBP recorded during the night is taken as an abnormal morning surge (Fig. 7).10 Shearing mechanical stress, inflammatory cascades and endothelial dysfunction associated with morning surge are responsible for the increase in CV and cerebrovascular events caused by it. Morning surge also causes increase in left ventricular mass index, increased carotid intima-media thickness and development of microalbuminuria.11,13

Masked Hypertension Masked hypertension or pseudo-normotension is the reverse of white coat hypertension. The patient has normal BP recordings in the doctor’s office but on ABPM is found to be hypertensive. It has a prevalence of 10-20%. These patients have similar CV risk and complications as hypertensives.8,11

x: Time, y: Systole, Diastole mmHg, Pulse 1/min 3/14/2014

1/min

Normal dipping DI 15% (Range: 10-20%)

16:00

18:00

20:00

22:00

Figure 3. Normal dipping

Morning Surge

Indian Journal of Clinical Practice, August 2015

00:00

02:00

04:00

06:00

08:00

10:00

12:00

14:00

300 290 280 270 260 250 240 230 220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0

CARDIOLOGY

mmHg 300 290 280 270 260 250 240 230 220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0

8/30/2014

x: Time, y: Systole, Diastole mmHg, Pulse 1/min 8/31/2014

Nondipper DI 2% (Range: 0-10%)

16:00

18:00

20:00

22:00

00:00

02:00

04:00

06:00

08:00

10:00

12:00

14:00

1/min 300 290 280 270 260 250 240 230 220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0

Figure 4. Nondipper.

mmHg 300 290 280 270 260 250 240 230 220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0

x: Time, y: Systole, Diastole mmHg, Pulse 1/min 11/7/2014

11/6/2014

1/min

Extreme Dipper DI 21% (Range: >20%)

20:00

22:00

00:00

02:00

04:00

06:00

08:00

10:00

12:00

14:00

16:00

18:00

20:00

300 290 280 270 260 250 240 230 220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0

Figure 5. Extreme dipper.

Indian Journal of Clinical Practice, August 2015

CARDIOLOGY

mmHg 300 290 280 270 260 250 240 230 220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0

x: Time, y: Systole, Diastole mmHg, Pulse 1/min 8/26/2014

8/25/2014

Reverse Dipping DI Minus 13% (Range: <0%)

12:00

14:00

16:00

18:00

20:00

22:00

00:00

02:00

04:00

06:00

08:00

10:00

12:00

1/min 300 290 280 270 260 250 240 230 220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0

Figure 6. Reverse dipper.

mmHg

x: Time, y: Systole, Diastole mmHg, Pulse 1/min 11/5/2014

11/4/2014

300 290 280 270 260 250 240 230 220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0

Morning surge

12:00

14:00

16:00

18:00

20:00

Figure 7. Morning surge.

1/min

Indian Journal of Clinical Practice, August 2015

22:00

00:00

02:00

04:00

06:00

08:00

10:00

12:00

CARDIOLOGY REFERENCES 1. Association of Physicians of India. J Assoc Physicians India. 2013;61(2 Suppl):6-36. 2. Lewington S, Clarke R, Qizilbash N, Peto R, Collins R. Lancet. 2002;360(9349):1903-13. 3. McGrath BP. Med J Aust. 2002;176(12):588-92. 4. NICE-BHS Guidelines on the diagnosis and treatment of high blood pressure (hypertension). (2011). [online] Available from http://guidance.nice.org.uk/CG127 [Accessed on June, 2015]. 5. O’Brien E, Parati G, Stergiou G, Asmar R, Beilin L, Bilo G, et al. J Hypertens. 2013;31(9):1731-68.

7. Flynn JT, Daniels SR, Hayman LL, Maahs DM, McCrindle BW, Mitsnefes M, et al. Hypertension. 2014;63: 1116-35. 8. Stergiou GS, Karpettas N, Atkins N, O’Brien E. Blood Press Monit. 2010;15(1):39-48. 9. Hermida RC, Fernández JR, Mojón A, Ayala DE. Hypertension. 2000;35(1 Pt 1):118-25. 10. Kario K, Shimada K, Pickering TG. J Cardiovasc Pharmacol. 2003;42(Suppl 1):587-91. 11. Leitão CB, Canani LH, Silveiro SP, Gross JL. Arq Bras Cardiol. 2007;89(5):347-54.

12. Mancia G, Sega R, Bombelli M, Quarti-Trevano F, Facchetti R, Grassi G. Pro Diabetes Care. 2009;32 6. 2013 ESH/ESC Guidelines for the management of arterial (Suppl 2):S305-9. hypertension. [online] Available from http://dx.doi. org/10.1093/eurheartj/eht151 [Accessed on June, 2015]. 13. Kario K. Hypertension. 2010;56(5):765-73. ■■■■

ÂÂ

A large proportion of middle-aged men and women who had a similarly aged sibling with recent MI showed no CV symptoms themselves despite significant coronary lesions by coronary CT angiography (CCTA), reported a prospective cohort study presented at the Society of Cardiovascular Computed Tomography (SCCT) 2015 Annual Scientific Meeting.

ÂÂ

Low-dose radiation from cardiovascular computed-tomography (CT) angiography results in DNA and cellular damage, as well as increased expression of cells involved in the regulation of cell repair and apoptosis, suggested a new study published online July 22 in the Journal of the American College of Cardiology: Cardiovascular Interventions. Researchers noted that most of the cells damaged by the CT angiogram were repaired, but a small percentage of cells died.

ÂÂ

The benefits of a healthy diet for the heart may be because of the increase in vitamin C levels that come from a high intake of fruit and vegetables. Evaluation of subjects from the Copenhagen General Population Study (CGPS) and Copenhagen City Heart Study showed that those who ate the most fruit and vegetables had a 13% lower risk of CVD and a 20% lower risk of all-cause mortality compared with those that ate these foods only rarely. The findings are published in the American Journal of Clinical Nutrition.

ÂÂ

The use of a “routine” early invasive strategy for patients with non-ST-segment-elevation ACS (NSTE-ACS) may be no better than a more conservative approach when it comes to improving very long-term clinical outcomes, suggests follow-up from the third Randomized Intervention Trial of Unstable Angina (RITA-3), published in the August 4 issue of the Journal of the American College of Cardiology.

Indian Journal of Clinical Practice, August 2015

COMMUNITY MEDICINE

Evaluation of Hand Hygiene Practice: Role in Prevention of Infection DEEPAK ARORA*, MK MAHAJANâ&#x20AC;

ABSTRACT Nosocomial infections due to poor hand hygiene are a major cause of increasing morbidity, mortality and healthcare costs among hospitalized patients worldwide. Hand hygiene is considered the single most cost-effective public health measure for preventing healthcare-associated infection. Despite evidence and expert opinion that hand hygiene reduces transmission of potential pathogens, adherence to hand hygiene recommendations and proper hand washing technique among section healthcare workers are uncommon, even after educational efforts. The present study was undertaken to assess the level of knowledge and attitude among residents and staff nurses of Advanced Cancer Research Center Bathinda regarding hand hygiene practices and also to identify gaps in knowledge and poor attitudes regarding hand hygiene practices among residents and staff nurses.

Keywords: Nosocomial infections, hand hygiene, healthcare workers

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

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

*Associate Professor Dept. of Microbiology Guru Govind Singh Medical College, Faridkot, Punjab â&#x20AC; Director Advanced Cancer Institute, Bathinda, Punjab Address for correspondence Dr Deepak Arora Associate Professor Dept. of Microbiology Guru Govind Singh Medical College, Faridkot, Punjab E-mail: drdeepakarora78@gmail.com

Indian Journal of Clinical Practice, August 2015

preventing healthcare-associated infection (HCAI).4 The significance of hand washing in patient care was conceptualized in the early 19th century.5-7 Labarraque5 provided the first evidence that hand decontamination can markedly reduce the incidence of puerperal fever and maternal mortality. In 1975 and 1985, the Centers for Disease Control and Prevention (CDC) published guidelines on hand washing practices in hospitals, primarily advocating hand washing with nonantimicrobial soaps; washing with antimicrobial soap was advised before and after performing invasive procedures or during care for high-risk patients. Alcohol-based solutions were recommended only in situations, where sinks were not available.8,9 In 1995, the Hospital Infection Control Practices Advisory Committee (HICPAC) advocated the use of antimicrobial soap or a waterless antiseptic agent for cleaning hands upon leaving the rooms of patients infected with multidrug-resistant pathogens.10 In 2002, the CDC published revised guidelines for hand hygiene.11 The World Health Organization (WHO) has issued guidelines for procedural hand washing in order to reduce the prevalence of hospital-associated infections, but lack of knowledge amongst healthcare workers is associated with poor compliance.12 An alarming revelation was that compliance was found to be worst before high-risk procedures.13,14 Despite evidence and expert opinion that hand hygiene reduces transmission of potential pathogens or antimicrobial-resistant organisms, sustained

COMMUNITY MEDICINE improvements in adherence to hand hygiene recommendations and proper hand washing technique among section healthcare workers are uncommon,15 even after educational efforts. At the same time, in some hospitals, there is not even proper training of the employees regarding hand hygiene practices. This is shown by the lack of even basic awareness about hand washing guidelines among the hospital personnel. With this background, the present study was undertaken to assess the level of knowledge and attitude among residents and staff nurses of Advanced Cancer Research Center, Bathinda regarding hand hygiene practices and also to identify gaps in knowledge and poor attitudes regarding hand hygiene practices among residents and staff nurses to enhance good practices and working ethics in future. INDIAN SCENARIO In India, the quality of healthcare is governed by various factors, the principal amongst these being whether the healthcare organization is government or private-sector run. There is also an economic and regional disparity throughout the country. About 75% of health infrastructure, medical manpower and other health resources are concentrated in urban areas, where 27% of the population lives.16 Like in other developing countries, the priority given to prevention and control of HCAI is minimal. This is primarily due to lack of infrastructure, trained manpower, surveillance systems, poor sanitation, overcrowding and understaffing of hospitals, unfavorable social background of population, lack of legislations mandating accreditation of hospitals and a general attitude of noncompliance amongst healthcare providers towards even basic procedures of infection control. In India, although hand hygiene is imbibed as a custom and promoted at school and community levels to reduce the burden of diarrhea, there is a paucity of information on activities to promote hand hygiene in healthcare facilities (HCFs). Sporadic reports document the role of hands in spreading infection and isolated efforts at improving hand hygiene across the country.17-20 MATERIAL AND METHODS The study was carried out for a period of 6 months from January to June 2015 to assess the knowledge and attitude regarding hand hygiene amongst residents and staff nurses and class 4 employees (including sweepers) of a tertiary care hospital in Bathinda, Punjab, India after obtaining clearance from the Ethical Committee

of the institution. Verbal consent was obtained from those who volunteered to participate. A pre-validated questionnaire was administered to respondents initially and their record and data analysis and management was done using Microsoft Excel software. A total of 50 respondents were included in the study and their level of knowledge was assessed on the basis of questionnaire for healthcare workers. Then a sensitizing program regarding WHO recommendations for the hand washing hygiene and knowledge about most appropriate timing for performing hand hygiene actions that prevent transmission of germs to the patient was given to the healthcare workers. A knowledge questionnaire was again given to them and the record was maintained. It was then compared with the previous questionnaire given before the sensitization. For scoring, 1 point was given for each correct response to good level of knowledge and positive attitude and 0 point was given for poor level of knowledge and negative attitude and they were categorized in category 1, 2 and 3 depending on percentage they scored 75% and above was considered good, a score between 50-74% was moderate/average/fair and below 50% was considered poor. Data analysis and management was done using Microsoft Excel 2010 software. RESULTS No significant difference between response and level of knowledge before and after the sensitization program was observed in first study group (residents). Out of the 10 residents only 4 (40%) could score 75% (good) and 4 (40%) scored between 50-75% (moderate/average) and 2 (20%) scored 50% and less (poor) and after the sensitization program was given 5 (50%) instead of 4 (40%) could score between 50-75%. As such out of 10 residents, 8 (80%) residents had a good knowledge about routes of transmission of infection and attitude regarding correct hand hygiene practices. In second group that included 10 (staff nurses) the attitude regarding correct hand hygiene practices was casual. Before the sensitization program, 1/10 (10%) scored 75% and 1/10 (10%) were in 50-74% category and 8/10 (80%) scored less than 50% and after the sensitization program, 4 instead of 1 entered in 50-74% category. As such out of 10 staff nurses only 2 (20%) had a good knowledge about routes of transmission of infection and attitude regarding correct hand hygiene practices. In third group of 30 class 4 employees, the attitude regarding correct hand hygiene practices was also

Indian Journal of Clinical Practice, August 2015

COMMUNITY MEDICINE casual. Before the sensitization program, only 2 (6%) scored 75% and 5 (16%) were in 50-74% category and 23 (77%) scored less than 50% but after the sensitization program, the approach was drastically good and their level of education really improved and 4 (6%) scored 75% and 14 (47%) were in 50-74% category and 12 (40%) scored less than 50%. DISCUSSION India is one of the prominent member countries of the World Alliance for Patient Safety. The present study highlights the importance of training sessions regarding hand hygiene practices among the residents and staff nurses to provide the current and updated knowledge in the area of nosocomial infections and prevention of infections. It would also translate in a behavioral change of attitudes and practices that would help in reducing the incidence of nosocomial infections. In our study, residents had good knowledge on hand hygiene. Out of the total 50 participants, 30 (60%) respondents answered correctly when asked about the main route of transmission of potentially harmful germs between patients. Our results are comparable with other studies,9 which reported that 72% of participants knew that unhygienic hands of healthcare workers were the main route of transmission. However, only 45% of residents and 27% of nurses and 14% of the class 4 knew that the most frequent source of germs responsible for HCAIâ&#x20AC;&#x2122;s were the germs already present on or within the patient, with residents having significantly better knowledge in this aspect. About the minimum time needed for effective hand hygiene only residents and nurses (35% and 25%, respectively) were aware about the minimum time needed for effective hand hygiene as mentioned in WHO guidelines. Our findings were similar to a study carried out by Abd Elaziz21 at Ain Shams University, Cairo, wherein 23.2% of observed candidates showed inappropriate hand washing due to both short contact time (less than 30 seconds) and improper drying after hand washing. About the hand hygiene methods, both groups had answered below satisfaction level regarding the hand hygiene method required before palpation of abdomen (33%), before giving an injection (27%) and after making a patients bed (21%). Comparative values reported in study of Ariyaratne in Sri Lanka22 were 31%, 26% and 25%, respectively. However, overall knowledge regarding the hand hygiene method needed in the required clinical situation was unsatisfactory and thus

Indian Journal of Clinical Practice, August 2015

this study identified gaps in their knowledge and areas needed for improvement. The best way to improve hand washing compliance based on the finding of this study was motivation, training and education of healthcare workers. Nurses showed more positive attitudes towards hand hygiene. In a study conducted by Suchitra19 at Dept. of Microbiology, Mysore University, it was revealed that compliance for hand washing was maximum among nurses, intermediate for technicians and the least for doctors. Barriers to practice hand hygiene was attributed to lack of education, high work load, understaffing, working in critical care units, lack of encouragement, lack of role models among senior staff and lack of knowledge of guidelines set by the institution. CONCLUSION The results of this study should be interpreted in light of a limitation that the findings cannot be generalized to other tertiary care hospitals as ACDRC, is an autonomous institute directly funded by the Government of Punjab and similar resources may not be available to other tertiary care hospitals. However, the present study highlights the importance of training sessions regarding hand hygiene practices among the residents and staff nurses to provide the current and updated knowledge in the area of nosocomial infections and prevention of infections. It would also translate in a behavioral change of attitudes and practices that would help in reducing the incidence of nosocomial infections. REFERENCES 1. Trampuz A, Widmer AF. Hand hygiene: a frequently missed life-saving opportunity during patient care. Mayo Clin Proc. 2004;79(1):109-16. 2. WHO. The burden of health care-associated infection worldwide: a Summary. [online] Available from http:// www.who.int/gpsc/country_work/summary_20100430_ en.pdf [Accessed on July, 2015]. 3. Meengs MR, Giles BK, Chisholm CD, Cordell WH, Nelson DR. Hand washing frequency in an emergency department. J Emerg Nurs. 1994;20(3):183-8. 4. Pittet D, Allegranzi B, Sax H, Dharan S, Pessoa-Silva CL, Donaldson L. Evidence-based model for hand transmission during patient care and the role of improved practices. Lancet Infect Dis. 2006;6(10):641-52. 5. Labarraque AG. Instructions and observations regarding the use of the chlorides of soda and lime. In: Porter J (Ed.). New Haven, CT: Baldwin and Treadway; 1829. 6. Semmelweis I. Etiology, concept, and prophylaxis of childbed fever. In: Carter KC (Ed.). 1st Edition. Madison, WI: The University of Wisconsin Press; 1983.

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

contamination and comparison of hand hygiene agents in a hospital. Clin Infect Dis. 2003;36(11):1383-90.

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

16. Mani A, Shubhangi AM, Saini R. Hand hygiene among health care workers. Indian J Dent Res. 2010;21(11):115-8.

9. Garner JS, Favero MS. CDC guideline for handwashing and hospital environmental control, 1985. Infect Control. 1986;7(4):231-43. 10. Hospital Infection Control Practices Advisory Committee (HICPAC). Recommendations for preventing the spread of vancomycin resistance. Infect Control Hosp Epidemiol. 1995;16(2):105-13. 11. Boyce JM, Pittet D. Guideline for Hand Hygiene in HealthCare Settings. Recommendations of the Healthcare Infection Control Practices Advisory Committee and the HICPAC/SHEA/APIC/IDSA Hand Hygiene Task Force. MMWR Recomm Rep. 2002;51(RR-16):1-45. 12. WHO Guidelines on Hand Hygiene in Health Care First Global Patient Safety Challenge Clean Care is Safer Care. (2009). [online] Available from http://whqlibdoc.who.int/ publications/2009/9789241597906_eng.pdf. [Accessed on July, 2015]. 13. Rumbaua R, Yu C, Pena A. A point-in-time observational study of hand washing practices of healthcare workers in the intensive care unit of St. Luke’s Medical Center. Phil J Microbiol Infect Dis. 2001;30:3-7.

17. Mathai E, Allegranzi B, Kipatrick C, Pittet D. Prevention and control of health care associated infections through improved hand hygiene. Indian J Med Microbiol. 2010;28(2):100-6. 18. Chandra P, Millind K. Lapses in measures recommended for preventing hospital acquired infection. J Hosp Infect. 2001;47(3):218-22. 19. Suchitra JB, Lakshmi Devi N. Impact of education on knowledge, attitudes and practices among various categories of healthcare workers on nosocomial infections. Indian J Med Microbiol. 2007;25(3):181-7. 20. Taneja N, Das A, Raman Rao DS, Jain N, Singh M, Sharma M. Nosocomial outbreak of diarrhoea by enterotoxigenic E. coli among preterm neonates in a tertiary care hospital in India: pitfalls in healthcare. J Hosp Infect. 2003;53(3):193-7. 21. Abd Elaziz KM, Bakr IM. Assessment of knowledge, attitude and practice of hand washing among health care workers in Ain Shams University hospitals in Cairo. J Prev Med Hyg. 2009;50(1):19-25.

22. Ariyaratne MHJD, Gunasekara TDCP, Weerasekara MM, Kottahachchi J, Kudavidanage BPJ, Fernando SSN. Knowledge, attitudes and practices of hand hygiene among final year medical and nursing students at the University of Sri Jayewardenepura. Sri Lankan J Infect 15. Trick WE, Vernon MO, Hayes RA, Nathan C, Rice TW, Peterson BJ, et al. Impact of ring wearing on hand Dis. 2013;3(1):15-25. ■■■■ 14. Creedon SA. Hand hygiene compliance: exploring variations in practice between hospitals. Nurs Times. 2008;104(49):32-5.

Indian Journal of Clinical Practice, August 2015

COMMUNITY MEDICINE

Importance of Pharmacoeconomic Evaluation: Current Scenario in India ANN MARY PAUL*, ANIL ANTONY*, SRUTHI NU*, HYFA HAMEED*, VIMAL MATHEW*

ABSTRACT Pharmacoeconomics is the subdivision of health economics, which applies a scientific discipline to compare the value of one pharmaceutical drug or drug therapy to another. In emerging stage, pharmacoeconomics had borrowed principles and practices from basic economics and social sciences for its theoretical models and now it has developed to a self-sustainable stage. In India, pharmacoeconomics evaluations were done in hospital settings, which are engaged in developing hospital formulary, in clinical trials from phase 1 to post-marketing studies, in insurance settings, developing of new health policies, allocation of resources in government services. In the stage of developing pharmacoeconomic evaluation, it is facing many challenges like lack of education programs, sponsorship and current hospital settings.

Keywords: Pharmacoeconomics, health economics, health policies, pharmacoeconomic evaluation

urrent healthcare system in India is an overburden to society mainly due to rapid daily raise in cost of medications and treatment. According to United Nations Development Program in 2010, 300 million people of India lived in extreme poverty and faced deprivation in terms of access to basic services, including education, health, water, sanitation and electricity and this was about one-third of extremely poor people all over world. For people living below poverty line, illnesses not only represent a permanent threat to their income earning capacity; in many cases, they could result in the family falling into a debt trap. In a developing country like India, 85% of total health expenditure is financed by house-hold, out-of-pocket expenditure. India’s total healthcare expenditure increased to 12.4% from 2001 to 2010. And meanwhile, the economic status of India too developed but it was not distributed equally, resulting in an increased economic gap between the poor and the rich and this continuing trend makes the poor and middle class people’s access to good quality healthcare a dream. When comparing with other countries, healthcare financing from insurance sector is

*National College of Pharmacy Address for correspondence Dr Ann Mary Paul E-mail: annmarypaul091@gmail.com

Indian Journal of Clinical Practice, August 2015

below 25% in India which increases the public burden. Now, healthcare sector is most sensitive to cost, which presently is sky rocketing. And to provide quality patient care with minimum cost is a great challenge for healthcare professionals. Economic evaluation, analyzing costs and outcomes of several alternative therapies can also be a useful approach, which can minimize the burden of diseases. The International Society for Pharmacoeconomics and Outcomes Research (ISPOR) defines pharmacoeconomics as “the field of study that evaluates the behavior of individuals, firms and markets relevant to the use of pharmaceutical products, services and programs, and which frequently focuses on the costs (inputs) and consequences (outcomes) of that use”. It adopts and applies the principles and methodology of health economics to the field of pharmaceutical policy. It involves economic evaluation of drug development, drug production and drug marketing, i.e., all the steps that take place from the time the drug is manufactured to when it reaches the patients. Today, health economics has two faces. First relates to macroeconomic issues, which looks at government provision and market structure issues. Practitioners of this area are traditionally trained health economists and are hired by governments, universities and some professional groups, such as medical associations. But, this area is not yet developed to a full grown stage. Larger activities in field of health economic evaluation were done as a part of the second face. Numerous clinicians and

COMMUNITY MEDICINE pharmacists, as well as individuals from other biological disciplines were part of this field. Health economic evaluation on the measurement of quality-of-life, the measurement of outcomes from epidemiology and the measurement of costs from accounting and economics are some of the aspects of this part. GENESIS AND DEVELOPMENT OF PHARMACOECONOMICS Pharmacoeconomics is the subdivision of healtheconomics, which applies a scientific discipline to compare the value of one pharmaceutical drug or drug therapy to another. In emerging stage, pharmacoeconomics had borrowed principles and practices from basic economics and social sciences for its theoretical models. The concept of pharmacoeconomics originated in 1970s, with evolvement of pharmacy as a clinically oriented discipline and the incorporation of clinical pharmacy in the pharmacy curriculum. The first book on health economics was published in 1972 by Cooper. In 1978, McGhan introduced the concept of cost and cost-benefit analysis in pharmaceutical literature. The term pharmacoeconomics was introduced in literature in 1982 by Townsend. In 1983, Pataki offered a graduate level course to provide “an overview of the application of cost-benefit and cost-effective analysis in healthcare with special emphasis on the application of these techniques to the delivery of pharmaceutical care” at the Ohio State University (OSU) College of Pharmacy. In 1992, a journal was started for pharmacoeconomics with the name “Pharmacoeconomics”. Now in pharmacoeconomics, these are mainly four main approaches/techniques for economic evaluation which are as follows: ÂÂ

Cost-minimization analysis

ÂÂ

Cost-effectiveness analysis

ÂÂ

Cost-utility analysis

ÂÂ

Cost-benefit analysis.

The choice of the evaluation method depends on the nature of outcomes and the context in which the choices need to be made.

Why Pharmacoeconomics in India? With the improvement and sophistication of health technologies, demand and healthcare cost is increasing rapidly. Many poor people frequently face a choice between buying medicines or buying food or other necessities due to limited resources and high pricing of drug. So, medicine prices do matter and the main

challenge for India is to make access of the healthcare affordable. These studies help physicians to measure the cost-effectiveness of interventions and to design programs in managed care. Pharmacoeconomics is an innovative method that aims to decrease health expenditures, whilst optimizing healthcare results. With India playing a prominent role in clinical trials conducted by the pharma industry, the economic analysis flourished along with them. Pharmaceutical expenditure, which constitutes a large part of healthcare expenditure, has been increasing much faster than total healthcare expenditure. Numerous drug alternatives and empowered consumers also fuel the need for economic evaluations of pharmaceutical products. This increasing concern has prompted demand for the use of economic evaluations of alternative healthcare outcomes. This escalation in healthcare spending is due to increased life expectancy, increased technology, increased expectations, increased standards of living and an increased demand in healthcare quality and services. Healthcare resources are not easily accessible and affordable to many patients; therefore, pharmacoeconomic evaluations play an important role in the allocation of these resources.

Formulary Making Decisions Rapid rise in healthcare expenditure has prompted governments, health insurance companies and health providers throughout the world to adopt strategies to manage the high cost of medication, including formulary management and the use of pharmacoeconomics. The formulary is a regularly revised collection of pharmaceuticals based on current clinical judgment and helps the medical staff of a given institution and experts in the diagnosis and treatment of disease. Traditionally, the most formulary decisions were made on the basis of relative clinical efficacy, safety, drug interactions, pharmacokinetics, pharmacology and drug acquisition costs with little consideration for the overall health-systems costs. The medications in formulary have mainly two advantages: (1) availability of cost-contained quality drugs and (2) provision of quality care (healthcare personnel can be better trained to provide cost-effective medications with screening of medications whose drug interactions and adverse reactions they are aware of, which indicates a good health quality). A formulary list is an indicator of good pharmaceutical practice and rational drug usage. Formulary management uses pharmacoeconomics as a

Indian Journal of Clinical Practice, August 2015

COMMUNITY MEDICINE means to reduce these costs by allowing efficient use of the available resources. The American Society of HealthSystem Pharmacists (ASHP) recommends the use of formulary management in hospital setting to manage the quality and costs of pharmaceuticals in order to optimize patient care by ensuring access to clinically appropriate, safe and cost-effective medications. The role of pharmacy and therapeutics (P&T) committees is to make sure deliverance of safe and effective drug therapy. Various strategies can be used to incorporate pharmacoeconomics into formulary decision-making. These include using published pharmacoeconomic studies, economic modeling techniques and conducting local pharmacoeconomic research. Well-controlled formularies lead to decrease in drug expenditures and ultimately the overall cost savings in health economics. Most important challenge in implementing pharmacoecnomic analysis is the lack of knowledge among pharmacists or other healthcare professionals. Implementing awareness programs, workshops for the healthcare professions can decrease the healthcare burden in public by implementing wellcontrolled formularies. Economic evaluations provide healthcare decision makers with valuable information, allowing optimal allocation of limited resources. It will also help for the rationalization of the drug procurement system in the country and for the practical implementation of the standard treatment protocols. ALLOCATION OF RESOURCES Resources such as materials and equipments allocated for healthcare are scarce and their possible usages are infinite. Hence, it is a challenge for healthcare professionals to provide quality patient care with minimum cost. The main application of pharmacoeconomics is to work out the best way to allocate scarce health resource. Expenditure on medicines in Ministry of Health public hospitals and health clinics has escalated sharply in recent years. In 2008, total medical expenditure increased by 397% from 1998, an average increment of 40% per year. This is much higher than the increase in healthcare costs, which is estimated at 10% every year, approximately double the inflation rate. Pharmacoeconomics analyses can assist decision makers and health professionals in allocating resources to achieve maximum benefit for the least cost. Data derived from pharmacoeconomic analyses can be used by different people involved in providing healthcare for taking reimbursement decisions, planning for future healthcare resources and healthcare policy making.

Indian Journal of Clinical Practice, August 2015

HEALTH INSURANCE SECTORS In India, health insurance sector was launched in 1986, but until 2010 only 25% population of India had access to some form of health insurance. Main reason is that most of suppliers often restrict the poor from affordable pre-payment schemes. For the improvement of the healthcare of poor people in India, Ministry of Labor and Employment launched Rashtriya Swasthya Bima Yojana or RSBY from April 2008. This scheme provide the benefactions for the treatment sum assured up to 30,000 per year which is a great relief for people under below poverty line. In the Indian health insurance system, mostly inpatient services are covered, so it is necessary to stay for a day in the hospital to claim the insurance. This, instead of saving costs leads to cost inflation. It is necessary to have some mechanism in place, whereby the insurers can strike a contract with healthcare providers and healthcare systems that can help in cost containment. There is an added need for insurance systems that encourage consumer to contain costs by providing incentives as well as contain their health expenditure. In case of members with multiple coverage, it is necessary that the benefits offered and liability achieved are coordinated and regulated. Increase in the medication costs and treatment costs make the healthcare funders (governments, social security funds, insurance companies) struggle to meet their rising costs. They make many efforts to contain drug costs, by price negotiation, patient co-payments or dedicated drug budgets. Expenditure on drug therapy is a particular target for their attention for several reasons: the size of the drug bill (10-15% of most national healthcare budgets, and usually the second largest item after salaries); the ease of measurement of pharmaceutical costs in isolation, in contrast to most other healthcare costs; evidence of wasteful prescribing; and a perception that many drugs are overpriced and that the profits of the pharmaceutical industries are excessive. Pharmacoeconomics adopts and applies the principles and methodology of health economics to the field of pharmaceutical policy. There is a need for further expansion of insurance services other than inpatient services, and more focus should be placed on preventive care and wellness programs. By implementing the pharmacoeconomic principle in the hospital administration and treatment protocols, both the patients and the insurance industry will benefit. Patients will receive better quality healthcare at reduced costs, and the insurance

COMMUNITY MEDICINE companies will be able to provide enhanced care to their clients at minimum cost.

CLINICAL TRIALS AND PHARMACOECONOMIC STUDIES

PHARMACEUTICAL INDUSTRIES

Pharmaceutical companies spent billions of dollars annually for the development of drugs. There being lower input costs in clinical trials, it is estimated that more than 100-200 million US dollars quoted for the development of New Chemical Entity (NCE) in India. For every 10,000 NCE in discovery, 10 enter preclinical development, five enter human trials and only one might be approved. Accordingly, large amount of money spent on pursuing a useless chemical entity is borne by the consumer. The development of economic studies in clinical trial aims to compare the cost and effects of a new drug with the current standard drug therapy.

Pharmacoeconomics has become an important part of the lexicon of the pharmaceutical industry. It can help design studies to compare the medical costs and health outcomes of a new therapy with the costs and outcomes of existing therapy or medical intervention. Simply put, these studies are designed to assess the value of a medication or treatment. Pharmacoeconomic studies in pharmaceutical industry help support pricing, marketing and reimbursement for drugs with a differential advantage over competitors and meeting pharmaceutical financing committee requirements for reimbursement and formulary listing. The growth in pharmacoeconomics field can be identified by increase in recourses devoted to this field in past decades. And also by significant increase in the availability of pharmacoeconomic and health outcomes information in the medical literature and in the fact that most pharmaceutical manufacturers have created divisions designed to conduct, evaluate and disseminate these data. It is important to emphasize that pharmacoeconomic information was not perceived to be the most important consideration in making drug coverage decisions within healthcare organizations. Efficacy and safety data were the pre-eminent issues for healthcare organizations when making drug coverage decisions. However, drug acquisition cost ranked high along with a drug’s clinical features. In a recent study, information on health-related quality-of-life, nonmedical cost savings and long-term medical savings were rated as the least important factors in drug benefit decisions. The managed care study also found that drug cost, the condition being treated by the drug and contractual issues were rated as the most important factors in drug benefit decisions. This illustrates several important points. First, it reflects the strong pressure in health systems to control short run costs. Also, it illustrates that if information is not closely linked to costs in the short run, it is less useful to managed care decision makers. And finally, the similar results illustrate that pharmaceutical industry representatives are aware of these limitations and perceive them in a similar fashion as the managed care decision makers. Given the limitations on healthcare resources, there is increased interest in assessing the value for money, or economic efficiency of healthcare treatments and programs.

Pharmacoeconomic evaluations can be integrated in clinical trials in three ways. Firstly, a clinical trial can be established with the primary objective of conducting economic evaluation. Secondly, economic studies can be conducted with a secondary objective of efficacy and safety evaluation. Thirdly, pharmacoecnomic studies can retrospectively analyze the data generated by clinical trials and correlate both drugs price and efficacy. Economic analysis should play a vital role in each and every step in drug development and clinical trials including drug developmental phases (phases 1-3) and in post-market surveillance studies. Pharmacoeconomic evaluations conducted alongside clinical trials are often called piggy-back analysis. In these studies, the incremental cost of pharmacoeconomic data collection is less than that if it is done separately in stand-alone health economic trials. Prospective followup of patients in randomized trials reduces diversity of patient groups. Therefore, perceived differences in pharmacoeconomic parameters are not attributable to differences between patient groups, and so the internal validity of costeffectiveness conclusions is strong. Economic analyses are mostly carried out alongside the pivotal clinical trials for registration purposes. Thus, pharmacoeconomic results are available before the submission of full documentation for reimbursement purposes. The reasons for conducting a pharmacoeconomic trial include: ÂÂ

Pricing of a new drug

ÂÂ

Reprising of an old drug

ÂÂ

Convincing a drug formulator

ÂÂ

Generation of data for promotional material

ÂÂ

Mandatory legislative requirement for drug licensing and medical reimbursement (in some countries).

Indian Journal of Clinical Practice, August 2015

COMMUNITY MEDICINE Phase 1 and Phase 2 Clinical Trials In the early, drug development phases, economic analysis promptly aimed to inform the decision makers of sponsors or pharmaceutical companies, to continue or decline the study. Along with the clinical efficiency, the developers look forward for the cost for developing medicine and the benefits that can obtained at a price, which makes further development of the drug worthwhile. During this stage, cost of illness studies should be accomplished, so as to decide whether to further develop the drug and gather background data for future pharmacoeconomic evaluations or not. Cost of illness data may also aid in the development of preliminary models to assess the clinical benefits that must be achieved to have a marketable product. In phase 2 clinical trials, cost of illness is the main pharmacoeconomic tool. It can be initiated or continued from phase 1 studies. During phase 2 clinical trial, drug is administered to large number of people and mainly economic studies are intended to measure quality-oflife and recourse utilization instruments.

Phase 3 Trials In phase 3, larger numbers of patients are given the new drug in the established dosage range and in the final dosage form mainly to identify rare effects of drugs. Pharmacoeconomics in phase 3 trial is mainly incorporated for the final efficacy evaluation. Its planning and implementation are very important. Criticizes in the pharmacoeconomic evaluation in this phase will hinder the new drug application (NDA) process, unless the drug is very innovative and has no other alternatives.

Phase 4 Trials During the post-marketing or phase 4, both the retrospective and prospective pharmacoeconomic analysis can be designed and conducted to gather data to support drug. These are extremely important since they allow evaluation of both cost and consequences of drug therapy without the altered interventions. That means cost and outcomes in real-life setting unlike the clinical trial controlled settings. Pharmacoeconomic evaluations and clinical trials can be conducted in conjunction with each other in several ways: ÂÂ

A clinical trial can be designed to test the safety and efficacy of a drug, followed by a pharmacoeconomic evaluation

ÂÂ

A clinical trial can be designed to conduct a pharmacoeconomic evaluation

Indian Journal of Clinical Practice, August 2015

ÂÂ

Clinical data collected prospectively in a clinical trial can be used to conduct a retrospective or prospective pharmacoeconomic evaluation.

PHARMACOECONOMIC STUDIES IN INDIA It is very ironical that the vision laid by Sir Bhor Committee at the dawn of independence is yet to be achieved, even while the problems today are much larger and disease burdens are enormous. The Indian government published their first National Health Policy 35 years post-independence as a consequence of signing of Alma Ata declaration on Primary Health Care. Notably, several governments and 5 years plans later, the goal of health for all still eludes us. Indian expenditure on healthcare still remains at 1.4%. Health Ministry has proposed a new initiative called “Free medicine for all through Public Health Facilities” under the National Rural Health Mission (NRHM). The Cabinet has approved the setting up of a Central Procurement Agency for bulk procurement of drugs and to support in preparing Standard Treatment Protocols. During the implementation, pharmacoeconomics play a great role in rational utilization of funds available. To scale up care, allocation for healthcare must be raised to at least 2.5% of GDP by the end of the 12th plan, and 3% in the subsequent 5 years. This, the expert group estimates, can bring about a dramatic reduction in out-of-pocket spending from 67% of total health expenditures today to 47% by 2017 and 33% by 2020. The ISPOR is one such not-for-profit organization, which has taken the initiative to develop pharmacoeconomic guidelines in India with the help of its regional chapters in the country. Following the 1st International Conference of ISPOR India Chapter on 22-23 October 2012 at New Delhi, it was widely felt that pharmacoeconomics research is helping decision makers globally in taking informed decisions and India should have its own guidelines addressing the needs of the country in many interrelated domains like health policy, pharmaceutical policy, pharma pricing, health insurance and clinical prescription standards. India lacks independent and credible data in terms of health and pharmacoeconomics and the guidelines for conducting pharmacoeconomic studies in India was designed by ISPOR India in the year of 2013. After these guidelines, many of pharmacoeconomic studies were conducted in the clinical trials, pharmaceutical industries and a part of curriculum thesis works. Till date more than 260 articles on pharmacoeconomics have been published in India.

COMMUNITY MEDICINE Challenges for Pharmacoeconomic Analysis ÂÂ In India, prescription of drugs, mainly depend on market pressure and most of the pharmacists give alternate medicines at their own will. ÂÂ For chronic diseases, consideration of bioavailability should have an upper hand over pharmacoeconomics. ÂÂ Lack of professional training. ÂÂ Lack of sponsorship. SUGGESTED READING 1. Townsend RJ. Post marketing drug research and development: an industry clinical pharmacists perspective. Am J Pharm Educ. 1986;50:480-2. 2. American Society of Health-System Pharmacists (ASHP). Statement on the formulary system. In: Hicks WE (Ed.). Practice Standard of ASHP. American Society of HealthSystem Pharmacists; 1995. 3. Tyler LS, Cole SW, May JR, Millares M, Valentino MA, Vermeulen LC Jr, et al. ASHP guidelines on the pharmacy and therapeutics committee and the formulary system. Am J Health Syst Pharm. 2008;65(13):1272-83. 4. McGhan WF, Rowland CR, Bootman JL. Cost-benefit and cost-effectiveness: methodologies for evaluating innovative pharmaceutical services. Am J Hosp Pharm. 1978;35(2):133-40. 5. Cooper MH, Culyer AJ. Health Economics. London: Penguin; 1973. 6. Haycox A, Drummond M, Walley T. Pharmacoeconomics: integrating economic evaluation into clinical trials. Br J Clin Pharmacol. 1997;43(6):559-62. 7. AhmadA, Patel I, Parimilakrishnan S, Mohanta GP, Chung H, Chang J. The role of pharmacoeconomics in current Indian healthcare system. J Res Pharm Pract. 2013;2(1):3-9.

models to managed care organizations. J Manag Care Pharm. 2003;9(2):159-67. 9. Brixner DI. Practitioner update: outcomes research, pharmacoeconomics and the pharmaceutical industry. J Manag Care Pharm. 1996;2(1):48-52. 10. Armstrong EP, Abarca J, Grizzle AJ. The role of pharmacoeconomic information from the pharmaceutical industry perspective. Medscape References, 2001. 11. Gupta SK. Proposed pharmacoeconomics guidelines for India (Peg - I). Second International Conference of Pharmacoeconomics and Outcomes Research. ISPOR India, October 2013. 12. Hinchagri SS, Halakatti P, Devar SB, Biradar BS, Kankanwadi SK, Patil SD. Need of pharmacoeconomics in Indian health care system: a brief review. Pharma Tutor, Pharmacy Infopedia, 2009. 13. Bootman JL, Townsent RJ, Mcghan WF. Introduction to pharmacoeconomics. 1996. 14. Ahuja J, Gupta M, Gupta AK, Kohli K. Pharmacoeconomics. Natl Med J India. 2004;17(2):80-3. 15. Kalra, Aditya. India’s universal healthcare rollout to cost $26 billion. business, Thu Oct 30, 2014. 16. Mauskopf JA. Why study pharmacoeconomics? Expert Rev Pharmacoeconomics Outcomes Res. 2011;1(1):13. 17. Pharmacoeconomics for the pharmaceutical industry in Europe. Intern J Pharm Med. 2003;17(56). 18. Arenas-Guzman R, Tosti A, Hay R, Haneke E; National Institute for Clinical Excellence. Pharmacoeconomics: an aid to better decision-making. J Eur Acad Dermatol Venereol. 2005;19(Suppl 1):34-9. 19. Gattani SG, Patil AB, Kushare SS. Pharmacoeconomics: a review. Asian J Pharm Clin Res. 2009;2(3):15-26. 20. Thwaites R, Townsend RJ. Pharmacoeconomics in the new millennium: a pharmaceutical industry perspective. Pharmacoeconomics. 1998;13(2):175-80.

21. Albert IW. The importance of pharmacoeconomics. 8. Olson BM, Armstrong EP, Grizzle AJ, Nichter MA. J Pharmacovigilance. 2014;2:e115. Industry’s perception of presenting pharmacoeconomic ■■■■

Counseling and Longitudinal Support Recommended for Those at Increased Risk for Type 2 Diabetes The Community Prevention Services Task Force updated recommendations based on a systematic review of 53 studies recommending that healthcare systems and communities provide counseling and longitudinal support to individuals who are at increased risk for type 2 diabetes. The recommendations are published July 13 in the Annals of Internal Medicine.

Indian Journal of Clinical Practice, August 2015

INTERNAL MEDICINE

Acalculous Cholecystitis in Dengue: Is it Rare? CR JOTHI*, R UMARANI†, K BABURAJ‡

ABSTRACT Dengue fever with acute acalculous cholecystitis is rarely reported. The aim is to study the incidence, clinical presentation, laboratory findings and sonographic findings of acute acalculous cholecystitis in patients with dengue fever. We studied 65 patients with dengue fever for a period of 10 months from March 2014 to December 2014. Out of 65 patients, 22 (33.84%) had complication of acalculous cholecystitis in which 14 were males (36.84%) and 8 were females (29.62%). All these 22 patients had severe thrombocytopenia, elevated liver function tests and positive sonographic Murphy’s sign. They improved with hydration and correction of thrombocytopenia.

Keywords: Dengue fever, acalculous cholecystitis, sonographic Murphy’s sign

engue is the most common arboviral disease transmitted globally, caused by four antigenically distinct dengue virus serotypes (DEN-1, DEN-2, DEN-3, DEN-4). Type 2 is apparently more dangerous than other serotypes.1 It is a member of flavivirus group and is transmitted by Aedes mosquitoes. Dengue virus infection manifests with wide range of severity from asymptomatic mild febrile illness to life-threatening disease. After the incubation period of 2-7 days, the typical patient experiences the sudden onset of fever, headache, retroorbital pain and back pain along with severe myalgia that gave rise to the colloquial designation “break-bone fever”. There is often a macular rash on the first day as well as adenopathy, palatal vesicles and scleral injection. The illness may last a week, with additional symptoms usually including anorexia, nausea or vomiting, marked cutaneous hypersensitivity and near the time of defervescence―a maculopapular rash beginning on the trunk and spreading to the extremities and the face, sparing soles and palm. Epistaxis and scattered

*Postgraduate †Professor ‡Associate Professor Division of Medicine Rajah Muthiah Medical College and Hospital Annamalai Nagar, Chidambaram, Tamil Nadu Address for correspondence Dr CR Jothi 32, Chakra Avenue, Phase II, OP Main Road, Annamalai Nagar Chidambaram - 608 002, Tamil Nadu E-mail: drcrjothi@gmail.com

Indian Journal of Clinical Practice, August 2015

petechiae are often noted in uncomplicated dengue and any pre-existing gastrointestinal lesions may bleed during the acute illness.1 Dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) are the life-threatening complications of dengue fever. They are characterized by four manifestations: high-grade fever, hemorrhage, hepatomegaly and circulatory failure.2 Some unusual manifestations include fulminant hepatitis, acalculous cholecystitis, encephalopathy, cardiomyopathy and acute pancreatitis.3 OBJECTIVE To study the incidence, clinical presentation, laboratory findings and sonographic findings of patients with acalculous cholecystitis in dengue fever. METHODS This study was done on patients admitted with dengue fever, as confirmed by immunoglobulin M (IgM) antibody test, over a period of 10 months from March 2014 to December 2014. Patients with gallstone disease, previous history of abdominal surgeries, recent history of burns, trauma or vasculitis and pregnancy were excluded from the study. A detailed clinical examination was done. Hematological profile, liver function tests and renal function tests were done. All the patients were subjected to screening sonography. They were treated with intravenous fluids and other supportive measures. Six patients required platelet transfusion. Duration of hospitalization was 4-7 days. There was no mortality

INTERNAL MEDICINE and all the patients were discharged with stable vital parameters. The results are tabulated as follows. RESULTS

WBC (10³/µL)

Twenty-two out of 65 patients (33.84%) with dengue fever had the complication of acute acalculous cholecystitis. Of these, 14 were males and 8 were females (Fig. 1). The clinical symptoms of the patients are shown in Table 1. All the 22 patients had fever, vomiting and upper abdominal pain. Twelve patients had right hypochondrial tenderness.

Table 3. Laboratory Findings of 22 Dengue Fever Patients with Acalculous Cholecystitis

Dengue without acalculous cholecystitis Dengue with acalculous cholecystitis

Male 14 Female 8

Figure 1. Sex-wise distribution of patient with dengue fever complicated by acalculous cholecystitis.

Table 1. Symptoms and Signs of 22 Dengue Fever Patients with Acalculous Cholecystitis No. of cases

100

Symptoms Fever Vomiting

100

Upper abdominal pain

100

Right hypochondrial tenderness

54.54

Macular rash

63.63

Jaundice

04.54

Signs

Table 2. Sonographic Findings No. of cases

Thickened gallbladder

100

Sonographic Murphy’s sign

100

Splenomegaly

13.63

Pleural effusion

13.63

Ascites

09.09

Hepatomegaly

Pericholecystic collection

(104/µL)

Mean ± SD

Range

Normal range

6.21 ± 2.30

2.6-9.8

3.9-10.6

5.65 ± 2.36

2.8-9.8

15.0-40.0

AST (U/L)

79.59 ± 31.23

42-180

0-37

ALT (U/L)

61.31 ± 18.57

35-96

0-40

ALP (U/L)

185.27 ± 57.29

90-315

28-94

0.81 ± 0.11

0.7-1.1

0-1.2

Platelets

Total bilirubin (mg/dL)

WBC = White blood cell; AST = Aspartate transaminase; ALT = Alanine transaminase; ALP = Alkaline phosphatase.

All patients had thickened gallbladder wall (>3 mm) and a positive sonographic Murphy’s sign. Few patients had pleural effusion, ascites and splenomegaly (Table 2). The mean ± SD (standard deviation) white blood cell count was 6.21 ± 2.30 cells × 10³/µL. The mean ± SD platelet count was 5.65 ± 2.36 cells × 104/µL. All patients had abnormal liver biochemical tests and platelet counts (Table 3). DISCUSSION Reports of dengue fever complicated by acalculous cholecystitis are rare,4-6 but in our study, 33.84% of dengue fever patients had acalculous cholecystitis, which is not an uncommon finding. The etiology of acalculous cholecystitis is well-described in burns, trauma, vasculitis, post-surgical conditions and certain infections like salmonellosis or cytomegalovirus.7 Fever, right hypochondrial pain, abnormality of liver function tests, a thickened gallbladder wall (>3.5 mm)8 without stones and a positive sonographic Murphy’s sign establish the diagnosis of acute acalculous cholecystitis.9 In our study, 22 dengue fever patients were diagnosed with acalculous cholecystitis because of these signs. The pathophysiology behind the development of acalculous cholecystitis in dengue fever is not known. It may be due to viral invasion of gallbladder wall causing edematous change which is due to increased vascular permeability causing plasma leakage and serous effusion with high protein content that induces thickening of the gallbladder wall.10 In dengue fever, there is a significant association between gallbladder wall thickening and severity.11 In severe cases, it may be associated with ascites, peritonitis and pleural effusion. Rapid progression may lead to gangrene and perforation of gallbladder.12 Acalculous cholecystitis in dengue is

Indian Journal of Clinical Practice, August 2015

INTERNAL MEDICINE usually self-limiting and the gallbladder wall thickness will return to normal after several days with good hydration and correction of thrombocytopenia. Even the signs and symptoms also disappear after a week. Hence surgery is not indicated. Surgical intervention is required only when there are complications like gallbladder perforation and peritonitis. The association between dengue fever and acalculous cholecystitis has also been reported in other geographical location in study done by Shaheen Bhatty in Karachi. CONCLUSION Acute acalculous cholecystitis is not as uncommon as reported in the past with dengue viral infection. A high incidence (33.84%) reported in our study highlights the fact that this entity is emerging as a common association in dengue fever and the association may still be higher in patients with shock. The gallbladder involvement in dengue fever defines the usual presentation in obese females with underlying morbid predisposing conditions. Close monitoring of these patients is required as cholecystitis may take an ugly course. REFERENCES 1. Harrison’s Principles of Internal Medicine, 18th Edition, Vol. 1; 2012. pp. 1622-32. 2. Chen TC, Perng DS, Tsai JJ, Lu PL, Chen TP. Dengue hemorrhagic fever complicated with acute pancreatitis and seizure. J Formos Med Assoc. 2004;103(11):865-8.

presenting with signs of acute alithiasic cholecystitis. Med Trop (Mars). 2000;60(3):278-80. 4. Sood A, Midha V, Sood N, Kaushal V. Acalculous cholecystitis as an atypical presentation of dengue fever. Am J Gastroenterol. 2000;95(11):3316-7. 5. Sharma N, Mahi S, Bhalla A, Singh V, Varma S, Ratho RK. Dengue fever related acalculous cholecystitis in a North Indian tertiary care hospital. J Gastroenterol Hepatol. 2006;21(4):664-7. 6. Tan YM, Ong CC, Chung AY. Dengue shock syndrome presenting as acute cholecystitis. Dig Dis Sci. 2005;50(5):874-5. 7. Winkler AP, Gleich S. Acute acalculous cholecystitis caused by Salmonella typhi in an 11-year-old. Pediatr Infect Dis J. 1988;7(2):125-8. 8. Engel JM, Deitch EA, Sikkema W. Gallbladder wall thickness: sonographic accuracy and relation to disease. Am J Roentgenol. 1980;134(5):907-9. 9. Bilhartz LE. Acute acalculous cholecystitis, adenomyomatosis, cholesterolosis and polyps of the gall bladder. In: Feldman M, Sleisenger MH, Scharschmidt BF (Eds.). Gastrointestinal and Liver Disease, 6th Edition. Philadelphia: WB Saunders; 1998. pp. 993-1005. 10. Gubler DJ, Kuno G, Sather GE, Velez M, Oliver A. Mosquito cell cultures and specific monoclonal antibodies in surveillance for dengue virus. Am J Trop Med Hyg. 1984;33(1):158-65. 11. Setiawan MW, Samsi TK, Pool TN, Sugianto D, Wulur H. Gallbladder wall thickening in dengue hemorrhagic fever: an ultrasonographic study. J Clin Ultrasound. 1995;23(6):357-62.

12. Boland GW, Lee MJ, Leung J, Mueller PR. Percutaneous cholecystectomy in critically ill patients: early response 3. Van Troys H, Gras C, Coton T, Deparis X, Tolou H, Durand and final outcome in 82 patients. Am J Roentgenol. 1994;163(2):339-42. JP. Imported dengue hemorrhagic fever: a props of 1 case ■■■■

ÂÂ

New noninvasive treatment, using electrical stimulation therapy and physical rehabilitation exercises, enables men who were completely paralyzed from the waist down to move their legs. The findings were published in the Journal of Neurotrauma.

ÂÂ

For the first time, scientists have discovered that prostate cancer can be categorized into five different types. This finding may prove to be "game-changing," suggested the study published in the Journal EBioMedicine. The finding could open avenues to more tailored cancer treatments.

ÂÂ

New research suggests that the protective effect coffee consumption has on lowering the risk of mild cognitive impairment (MCI) may depend on how coffee consumption habits change over time. The findings were published in the Journal of Alzheimer's Disease. Researchers noted that seniors who increased their coffee consumption to >1 cup daily over a 3.5-year period were found to be at higher MCI risk than those who reduced their coffee consumption to <1 cup daily.

Indian Journal of Clinical Practice, August 2015

INTERNAL MEDICINE

Generalized Fatigue, Amenorrhea Due to Snake Bite? SREENIVASA RAO SUDULAGUNTA*, MAHESH BABU SODALAGUNTA†, HADI KHORRAM‡, MONA SEPEHRAR#

ABSTRACT Envenoming by poisonous animals is an occupational hazard often faced by farmers and farm laborers in tropics. Viperine snake bites cause local cellulitis, tissue necrosis, bleeding manifestations, disseminated intravascular coagulation, acute kidney injury, shock, cardiac arrhythmia, neurotoxicity, coma and death. Worldwide estimates vary from 1.2 to 5.5 million snakebites, 4,21,000 to 2.5 million envenomings, and 20,000 to 1,25,000 deaths. We report a case of a 37-year-old female who was bitten by a saw-scaled viper snake and developed chronic hypopituitarism diagnosed after 6 months. Patient improved with treatment of essential hormones. Hypopituitarism after a snake bite is often insidious in onset and a rare complication. Diagnosis is often delayed due to unawareness causing significant morbidity. Physicians should have a low threshold to suspect hypopituitarism in snake bites.

Keywords: Hypopituitarism, viper bite, procoagulant enzymes, disseminated intravascular coagulation

ndia’s first national survey of the causes of death, the Million Death Study, undertaken in 2001-2003 by the Registrar General of India and the Center for Global Health Research, estimates 46,000 annual deaths by snakebites, whereas the Government of India’s Central Bureau of Health Intelligence reports only 1,350 deaths each year for the period 2004-2009.1 Worldwide estimates vary from 1.2 to 5.5 million snake bites; 4,21,000-2.5 million envenomings and 20,000-1,25,000 deaths.2,3 Each year, approximately 8,000 venomous snake bites occur in the United States. Between 1960 and 1990, no more than 12 fatalities from snake venom poisoning were reported annually. In the 3,000 known species of snakes, about 300 are venomous and India has about 216 species of snakes, of which 52 are known to be poisonous. The major

*Postgraduate (3rd Year) Dept. of General Medicine Dr BR Ambedkar Medical College, Shampura, Karnataka †Postgraduate (3rd Year) Dept. of General Medicine KS Hegde Medical College, Mangalore, Karnataka ‡Dept. of Otolaryngology #Doctor of Pharmacy Dr BR Ambedkar Medical College, Shampura, Karnataka Address for correspondence Dr S Sreenivasa Rao Sudulagunta Postgraduate (3rd Year) Dept. of General Medicine Dr BR Ambedkar Medical College Shampura Main Road - 560 045, Bangalore, Karnataka E-mail: dr.sreenivas@live.in

families of poisonous snakes in India are Elapid which includes common cobra (Naja naja), king cobra and common krait (Bungarus caerulus, banded krait, sind krait), viperidae (Russell’s viper) (Fig. 1), Echis carinatus (saw-scaled or carpet viper) (Fig. 2) and pit viper and hydrophiidae (sea snakes).4 One source of snake in rural areas is Chulha which is a mud made furnace used for cooking. The ash retained is warm in winters and cool in summers and is thus a pleasant environment for krait and cobra to stay during night hours (Fig. 3). Here, we report a case of middle-aged female who was bitten by saw-scaled viper 6 months ago and presented with recurrent hypoglycemia, hypotension and loss of libido as a consequence of snake bite.

Figure 1. Russell’s viper.

Indian Journal of Clinical Practice, August 2015

INTERNAL MEDICINE levothyroxine. Her symptoms persisted, for which levothyroxine dosage was changed many times and multivitamins were prescribed. She had recurrent episodes of hypoglycemia during this period, which responded to dextrose. Her hypoglycemic episodes were associated with anxiety, tremors, mental confusion, sweating, palpitations and loss of consciousness. She also had 4 episodes of generalized tonic-clonic seizures associated with hypoglycemia.

Figure 2. Saw-scaled viper.

Her investigations revealed hemoglobin of 10.6 g/dL, total leukocyte count of 9,100 mm3 (with differential of 70% polymorphonuclear leukocytes, 21% lymphocytes) and platelet count of 2,00,000 mm3. Other laboratory test results were serum creatinine, 1.1 mg/dL; urea, 28 mg/dL; sodium, 141 mEq/L; potassium, 4.1 mEq/L; aspartate aminotransferase, 133 IU/L; alanine aminotransferase, 171 IU/L; total bilirubin, 0.49 mg/dL; albumin, 3.26 g/dL; and total protein, 6.7 g/dL. Abdominal ultrasonography revealed no abnormality. Her other investigations revealed hypopituitarism (Tables 1 and 2). Patient was supplemented thyroxine, estrogen, progesterone and prednisone. Posterior pituitary hormonal tests (vasopressin levels) were normal. Table 1. Thyroid Profile Date

First visit (09/12/14)

Second visit (05/02/15)

TSH

0.04 mIU/mL

0.87 mIU/mL

Reference range Free T3 Reference range Figure 3. Chulha.

0.30-5.5 0.5 pg/mL

2.8 pg/mL

1.7-4.2

Free T4

0.42 ng/dL

Reference range

0.70-1.80

Thyroxine dosage

25 Âľg

1.20 ng/dL 100 Âľg

CASE REPORT A 37-year-old female presented to the Medicine OPD with a 10 months history of generalized fatigue, lethargy, reduced libido, amenorrhea and depression. Patient had history of saw-scaled viper snake bite 11 months ago in her house, while try to cook food in a Chulha. Patient did not consult a doctor and was given local medicine. She had altered sensorium with mucosal bleeding following the snake bite for 20 days. Patient improved over a period of 1 month after which she developed generalized fatigue and amenorrhea. Patient consulted a local hospital after 2 months and was diagnosed with hypothyroidism and started on

Indian Journal of Clinical Practice, August 2015

Table 2. Hormonal Assays Suggestive of Hypopituitarism Hormone profile

Observed value

Normal range

ACTH

4.08

7.3-65 pg/mL

8 am cortisol

0.00

6.1-19.8 mg/dL

0.1

0.3-10.0 mIU/mL

FSH

<0.10

1-18 mIU/dL

Growth hormone

<0.05

0.00-10 ng/mL

IGF-1

<25

101-268 ng/mL

IGF-BP3

0.99

3.30-6.60 ug/mL

Prolactin

1.4

2.0-25.0 ng/mL

INTERNAL MEDICINE DISCUSSION

CONCLUSION

Saw-scaled viper is the smallest member of the big 4 snakes in India and is responsible for causing most of the snake bite cases and deaths, due to frequent occurrence in highly populated regions and inconspicuous nature.4 This species produces on the average of about 18 mg of dry venom by weight, with maximum of 72 mg. It may inject as much as 12 mg, whereas lethal dose for an adult human is only 5 mg.5

Hypopituitarism after snake bite is a rare entity confined to tropics of the world. Diagnosis is often delayed if not suspected. Most cases described are due to Russell’s viper bites and very few reports due to saw scaled viper which is of more common occurrence. Patients presenting with fatigue, hypoglycemia, menstrual disturbances have to be evaluated for hypopituitarism.

Viper venom contains procoagulant enzymes that activate factor V and X and other steps in the blood coagulation cascade leading to defective hemostasis causing cross-linkage fibrin and deposition of microthrombi in the microvasculature.6 The coagulant effect of venom is also due to an enzyme, arginine esterase hydrolase, similar in action to thrombin, which clots fibrinogen and aggregates platelets and aids conversion of prothrombin to thrombin. The hemorrhagic necrosis of the anterior pituitary gland was pathologically demonstrated in patients of viper bites in a study done by Proby et al.7 Than et al and Tun et al, who reported presence of adrenal hemorrhage apart from pituitary hemorrhages in some patients of viper bites. Possible mechanisms described for pituitary damage following snake bite are thrombosis of pituitary vessels as a part of disseminated intravascular coagulation, peripheral vascular collapse followed by spasm of pituitary vessels, thrombosis of local venules causing ischemic pituitary infarction or damaged vascular endothelium, impaired platelet function, depletion of clotting factors and secondary fibrinolysis leading to pituitary hemorrhages.

REFERENCES 1. Global Snakebite Initiative. [online] Available at http:// www.snakebiteinitiative.org/?page_id=454 [Accessed on August, 2015]. 2. Kasturiratne A, Wickremasinghe AR, de Silva N, Gunawardena NK, Pathmeswaran A, Premaratna R, et al. The global burden of snakebite: a literature analysis and modelling based on regional estimates of envenoming and deaths. PLoS Med. 2008;5(11):e218. 3. Animal bites Fact sheet No. 373. World Health Organization. February 2013. Retrieved 5 May 2014. 4. Whitaker Z. Snakeman: The Story of a Naturalist. Penguin Books Ltd.; 1990. p. 192. 5. Daniels JC. The Book of Indian Reptiles and Amphibians. Mumbai: Bombay Natural History Society & Oxford University Press; 2002. p. 252. 6. Cortelazzo A, Guerranti R, Bini L, Hope-Onyekwere N, Muzzi C, Leoncini R, et al. Effects of snake venom proteases on human fibrinogen chains. Blood Transfus. 2010;8(Suppl 3):120-5.

7. P roby C, Tha-Aung, Thet-Win, Hla-Mon, Burrin JM, Joplin GF. Immediate and long-term effects on hormone levels following bites by the Burmese Russell‘s viper. Q J Med. 1990;75(276):399-411. ■■■■

Long-term Decrease in Cognitive Function Uncommon after Common CV Procedures A long-term decrease in cognitive function is uncommon after undergoing common CV procedures, reported a new meta-analysis of 21 studies, but with a few caveats. No significant differences were noted in cognitivefunction scores between those who underwent surgical carotid revascularization versus carotid stenting or angioplasty, or between those who did or did not undergo CABG at least 3 months prior. The findings were published in the July 21 issue of Annals of Internal Medicine.

Indian Journal of Clinical Practice, August 2015

PRACTICE GUIDELINES

AHA and ASA Release Guideline for Prevention of Future Stroke in Patients with Stroke or TIA AMBER RANDEL

he American Heart Association (AHA) and American Stroke Association (ASA) have updated their guideline on prevention of future stroke in patients with a history of stroke or transient ischemic attack (TIA). Currently, the average annual rate of future stroke in these patients is at a historic low. This is a result of new approaches and improvement of existing approaches to treating these patients. The following recommendations are new or substantially revised from the previous AHA/ASA guideline. RECOMMENDATIONS

Hypertension Blood pressure therapy should be initiated in previously untreated patients with stroke or TIA if, after the first few days, blood pressure is 140 mm Hg systolic or greater, or 90 mm Hg diastolic or greater. Resumption of treatment is recommended for previously treated patients with known hypertension in the first several days after stroke or TIA. The target blood pressure is unclear and should be individualized. However, it is reasonable to keep blood pressure below 140 mm Hg systolic and 90 mm Hg diastolic. In patients with a recent lacunar stroke, a target of less than 130 mm Hg may be reasonable.

Dyslipidemia Statin therapy with intensive lipid-lowering effects is recommended in patients with ischemic stroke or TIA thought to be of atherosclerotic origin who have a lowdensity lipoprotein cholesterol level of 100 mg per dL (2.59 mmol per L) or greater with or without evidence of other arteriosclerotic cardiovascular disease. Statin therapy is also recommended in those who have a low-density lipoprotein cholesterol level of less than 100 mg per dL and no evidence of other arteriosclerotic cardiovascular disease.

Source: Adapted from Am Fam Physician. 2015;91(2):136-137.

Glucose Disorders All patients should probably be screened for diabetes mellitus after stroke or TIA using fasting plasma glucose, A1C, or oral glucose tolerance testing. Decisions about the type and timing of testing should be based on clinical judgment. Acute illness may temporarily affect plasma glucose measurements. In general, an A1C measurement may be more accurate than other screening tests immediately after the event.

Obesity Patients should receive obesity screening and body mass index measurement after a stroke or TIA. Despite the beneficial effects of weight loss on cardiovascular risk factors, the usefulness of weight loss after stroke or TIA in patients who are obese is unclear.

Physical Inactivity Referral to a comprehensive, behavior oriented program to increase physical activity is probably recommended for patients who are willing and able to participate in increased activity.

Nutrition A nutritional assessment for signs of over- or undernutrition is reasonable in patients with a history of stroke or TIA. Those with undernutrition should be referred for individualized nutritional counseling. Routine vitamin supplementation is not recommended. It is reasonable to counsel patients with stroke or TIA to reduce their sodium intake to less than 2.4 g per day (less than 1.5 g per day is even more effective at reducing blood pressure) and to follow a Mediterranean-style diet (emphasizes vegetables, fruits, and whole grains includes low-fat dairy products, poultry, fish, legumes, olive oil, and nuts) as opposed to a low-fat diet.

Sleep Apnea Because the prevalence of sleep apnea is high in patients with ischemic stroke or TIA and treatment of sleep apnea improves outcomes in the general population, a sleep assessment may be considered after stroke or TIA. Cont'd on page 34...

Indian Journal of Clinical Practice, August 2015

PHOTO QUIZ

Skin Sloughing and Lip Lesions After a Recent Foot Procedure STANISLAV N. TOLKACHJOV

n 84-year-old woman presented with a oneweek history of fever, blistering lips, and progressive skin sloughing. She had diffuse muscle aches and increased facial pigmentation and edema without recent sun exposure. Her history was significant for removal of a toenail by a podiatrist three weeks earlier. The podiatrist prescribed an antibiotic.

Physical examination revealed a large area of epidermal skin sloughing on her left upper back and elbows (see accompanying figure). She had hemorrhagic crusting and erosions of the oral mucosa. There were also bullae on her left inner thigh. Nikolsky sign (exfoliation of skin with application of pressure) was present. Initial laboratory tests revealed new acute renal insufficiency with a creatinine level of 3.6 mg per dL (318 μmol per L); it was 0.8 mg per dL (71 μmol per L) at last check one year prior. QUESTION Based on the patient’s history, physical examination, and laboratory findings, which one of the following is the most appropriate next step? A. Intravenous immunoglobulin, 2 to 3 g per kg infused over three to five days. B. Ophthalmology consultation. C. Skin biopsy of the affected area. D. Discontinuation of medications.

DISCUSSION The answer is D: discontinuation of medications. This patient’s physical examination findings and history of recent antibiotic use suggest a diagnosis of druginduced Stevens-Johnson syndrome. The initial step in treatment is stopping all possible causative medications.

Source: Adapted from Am Fam Physician. 2015;91(2):123-124.

Figure.

Subsequently, the patient should be resuscitated with fluids and replacement electrolytes, and possibly transferred to the intensive care or burn unit for support.1 Patients with Stevens-Johnson syndrome present with full-thickness epidermal necrosis over normal underlying dermis. Other symptoms may include confluent edema, facial edema, mucous membrane erosions and hemorrhagic crusting, skin pain and tenderness, bullae, a burning skin sensation, tongue swelling, blistering, and acute renal injury.2 Initial presentation, as shown, was consistent with Stevens-Johnson syndrome because of a smaller body surface area involvement. However, the patient eventually progressed to toxic epidermal necrolysis, which is a mucocutaneous disease usually involving two or more mucous membranes and one-third of the body surface area.2 Patients may recall a prodrome of upper respiratory tract infection, fever, and malaise. The rash typically begins on the face and progresses to

Indian Journal of Clinical Practice, August 2015

PHOTO QUIZ other parts of the body. The rash may begin as painful erythema or target lesions, or as bullae with eventual sloughing. The initial clusters of lesions appear over one to two weeks, and may regress in four weeks in the case of Stevens-Johnson syndrome,3 or progress to full body involvement. Although Stevens-Johnson syndrome involves less than 10% of the body surface area, it has a mortality rate of 1% to 5%.4 Toxic epidermal necrolysis is a more severe reaction that involves greater than 30% of the body surface area, with a mortality rate of 25% to 40%.2 Body surface area involvement usually differentiates the two entities. The estimated incidence of these reactions is one to two cases per 1 million persons annually.2 Medications commonly associated with Stevens-Johnson syndrome and toxic epidermal necrolysis include sulfonamides, allopurinol, antiepileptics, antipsychotics, analgesics, and penicillins.5 Infectious triggers such as herpes viruses and mycoplasma are less likely to lead to severe reactions. Skin biopsy will demonstrate full-thickness epidermal necrosis with normal underlying dermis or a scant lymphocytic infiltrate.3 This histologic finding helps differentiate Stevens-Johnson syndrome or toxic epidermal necrolysis from autoimmune blistering diseases; severe photosensitivity reactions; and infectious causes, such as staphylococcal scalded skin syndrome, that only involve loss of the stratum corneum. Because of the extensive epidermal loss with StevensJohnson syndrome, the same precautions must be made as with severe burns (i.e., isolation, sterile environment, and repeated monitoring for sepsis).6 Supportive treatment includes pain control, fluidized air beds,7 early nasogastric tube feedings, and topical emollients for mucous membranes. Ophthalmology consultation is recommended. A thorough urogenital evaluation should be performed to assess for mucosal

involvement. Intravenous immunoglobulin and systemic corticosteroids are often initiated as treatment; however, the evidence for their use is inconclusive.5,8 Patients should avoid the causative medication and structurally similar drugs. REFERENCES 1. Palmieri TL, Greenhalgh DG, Saffle JR, et al. A multicenter review of toxic epidermal necrolysis treated in U.S. burn centers at the end of the twentieth century. J Burn Care Rehabil. 2002;23(2):87-96. 2. Schwartz RA, McDonough PH, Lee BW. Toxic epidermal necrolysis: Part I. Introduction, history, classification, clinical features, systemic manifestations, etiology, and immunopathogenesis. J Am Acad Dermatol. 2013;69(2):173.e1-13. 3. Schwartz RA, McDonough PH, Lee BW. Toxic epidermal necrolysis: Part II. Prognosis, sequelae, diagnosis, differential diagnosis, prevention, and treatment. J Am Acad Dermatol. 2013;69(2):187.e1-16. 4. Harr T, French LE. Toxic epidermal necrolysis and StevensJohnson syndrome. Orphanet J Rare Dis. 2010;5:39. 5. Schöpf E, Stühmer A, Rzany B, Victor N, Zentgraf R, Kapp JF. Toxic epidermal necrolysis and Stevens-Johnson syndrome. An epidemiologic study from West Germany. Arch Dermatol. 1991;127(6):839-842. 6. Letko E, Papaliodis DN, Papaliodis GN, Daoud YJ, Ahmed AR, Foster CS. Stevens-Johnson syndrome and toxic epidermal necrolysis: a review of the literature. Ann Allergy Asthma Immunol. 2005;94(4):419-436. 7. Heimbach DM, Engrav LH, Marvin JA, Harnar TJ, Grube BJ. Toxic epidermal necrolysis. A step forward in treatment [published correction appears in JAMA. 1987;258(14):1894]. JAMA. 1987;257(16):2171-2175.

8. Barron SJ, Del Vecchio MT, Aronoff SC. Intravenous immunoglobulin in the treatment of Stevens-Johnson syndrome and toxic epidermal necrolysis: a metaanalysis with meta-regression of observational studies [published ahead of print April 2, 2014]. Int J Dermatol. http://onlinelibrary.wiley.com/doi/10.1111/ijd.12423/full (subscription required). Accessed December 8, 2014. ■■■■

...Cont'd from page 32

If sleep apnea is present, treatment with continuous positive airway pressure may be considered.

and cerebrovascular events is unclear; however, it may be warranted in cases of coronary artery stenting.

Antiplatelet Therapy

Other

Aspirin plus clopidogrel may be initiated within 24 hours of a minor stroke or TIA, and continued for 90 days. In patients with stroke or TIA, atrial fibrillation, and coronary artery disease, the benefit of adding antiplatelet therapy to vitamin K antagonist therapy to reduce the risk of ischemic cardiovascular

Other topics that were added or revised include carotid disease, intracranial atherosclerosis, atrial fibrillation, myocardial infarction and thrombus, cardiomyopathy, valvular heart disease, prosthetic heart valves, aortic arch atheroma, patent foramen ovale, homocysteinemia, hypercoagulation, antiphospholipid antibodies, sickle cell disease, pregnancy, and breastfeeding.

Indian Journal of Clinical Practice, August 2015

AROUND THE GLOBE

News and Views ÂÂ

A “urine output-guided diuretic adjustment” protocol may decrease persistent venous congestion in patients with acute decompensated heart failure (ADHF) who have developed cardiorenal syndrome, suggested a new analysis published online in the Journal of Cardiac Failure.

ÂÂ

Hypertensive patients with significant changes in blood-pressure readings over several office visits had an increased risk of stroke, MI, heart failure and death during a 2.8-year follow-up, independent of how well their hypertension was controlled, reported a post-hoc analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), published in the Annals of internal Medicine.

ÂÂ

Transcutaneous posterior tibial nerve stimulation is an effective treatment for non-neurogenic overactive bladder in pediatric patients, suggested an Indian study published online in the Journal of Pediatric Urology.

ÂÂ

The weight loss and diabetes remission achieved with laparoscopic sleeve gastrectomy (LSG) appear to wane by 5 years, suggests a new cohort study published online August 5 in JAMA Surgery.

ÂÂ

Tralokinumab, a human IL-13-neutralizing monoclonal antibody, did not significantly reduce asthma exacerbations in a phase 2b study of patients with severe uncontrolled asthma, but provided signs of benefit in post-hoc subgroup analyses, reported a paper published online in The Lancet Respiratory Medicine.

ÂÂ

Coffee drinkers were about half as likely to develop type 2 diabetes as those who did not drink coffee, and researchers speculated an inflammationlowering effect to be the key, reported a long-term study published online in the European Journal of Clinical Nutrition.

ÂÂ

Serum biomarker assays measuring neo-epitopes can discriminate between Crohn’s disease (CD) and ulcerative colitis (UC), suggests new research published in the Journal of Crohn’s and Colitis. Researchers said that these neo-epitopes are increasingly released into the circulation as part of the inflammatory condition. Men with newly diagnosed prostate cancer are initially treated with hormonal therapy, and chemotherapy is used only when the disease is

no longer responsive. However, it has now been shown that using chemotherapy early on in the treatment of prostate cancer can improve survival. The results are published online August 5 in the New England Journal of Medicine. ÂÂ

Insulin resistance is associated with lower brain glucose metabolism and poorer memory in latemiddle-aged adults at risk for Alzheimer’s disease, suggests a new study published online July 27 in JAMA Neurology.

ÂÂ

Researchers looking into the health of women aged 40-70 have suggested that the amount of exercise they participate in during their teenage years appears to have an impact on their risk of dying from cancer or other causes as adults. The findings are published in Cancer Epidemiology, Biomarkers & Prevention.

ÂÂ

Persistent severe back pain may indicate vertebral osteomyelitis, a rare spine infection that must be diagnosed and treated correctly to prevent serious complications, suggests a new Infectious Diseases Society of America (IDSA) guideline. The guideline was published online July 30 in Clinical Infectious Diseases.

ÂÂ

Novel “antisense” drugs may be effective in targeting different apolipoproteins in patients with dyslipidemia, suggest the results from two early studies. Both the studies revealed that the apolipoprotein C-III (apoC-III) inhibitor known as ISIS 304801 reduced plasma apoC-III and triglyceride levels. The first study was published in the July 30 issue of the New England Journal of Medicine, while the second one appeared in The Lancet.

ÂÂ

Among heart-failure patients with low left ventricular ejection fraction (LVEF) who received an implantable cardioverter defibrillator (ICD), the EF improved in 40% of patients during follow-up, and was associated with lower all-cause mortality and fewer appropriate shocks, reported a new study published in the August 4.

ÂÂ

According to a meta-analysis of 11 studies in the August 2015 issue of Clinical Gastroenterology and Hepatology published online, neither childhood immunizations nor H1N1 influenza vaccination increased the risk of inflammatory bowel disease. issue of the Journal of the American College of

Indian Journal of Clinical Practice, August 2015

AROUND THE GLOBE Cardiology. However, even among patients whose LVEF improved to >35% during follow-up, a few patients still had appropriate shocks in this cohort. ÂÂ

Babies conceived by women who drink alcohol around the time of conception face dramatically increased risks of type 2 diabetes and obesity in early middle age, suggested a University of Queensland study.

ÂÂ

New research suggests that being physically active not only reduces cognitive decline and improves neuropsychiatric symptoms in patients with dementia but may actually reduce biomarkers of Alzheimer’s disease (AD), including amyloid and tau protein in the brain. The findings were presented at the Alzheimer’s Association International Conference (AAIC) 2015.

ÂÂ

Eliminating the bacterium Helicobacter pylori can reduce the risk for gastric cancer in healthy individuals, reported a systematic review of six trials published online July 22 in the Cochrane Database of Systematic Reviews.

ÂÂ

Patients with bilateral adrenal incidentalomas appear more likely to have subclinical Cushing syndrome, as compared to those with unilateral incidentalomas, but surgery may not be the best approach to management, reported a study published online July 22 in JAMA Surgery.

ÂÂ

Treatment with an immunosuppressant drug, alefacept,previously used for psoriasis, may have led to preservation of insulin-producing betacell function at 1 year after treatment cessation in patients with newly diagnosed type 1 diabetes, suggested a follow-up analysis from the Inducing Remission in New-Onset Type 1 Diabetes With Alefacept (T1DAL) study published July 21 in the Journal of Clinical Investigation.

ÂÂ

Two types of drugs that are now available as inexpensive generic products, aromatase inhibitors and bisphosphonates, can reduce breast cancer mortality in postmenopausal women and could be used together to further improve outcomes, reported two meta-analyses published online July 24 in The Lancet.

ÂÂ

Inhaled corticosteroids cannot adequately protect children with asthma from high levels of air pollution and may actually exacerbate the effects of pollutants, reported a clinical study published online in the Journal of Clinical Allergy and Immunology. European Union (EU) regulators have approved the world’s first malaria vaccine for use outside the EU among children aged 6 weeks to 17 months.

Indian Journal of Clinical Practice, August 2015

The new vaccine, which includes a vaccine for hepatitis B, now awaits a review by the World Health Organization (WHO). ÂÂ

The FDA granted approval to alirocumab (Praluent) for heterozygous familial hypercholesterolemia (FH) and for patients with clinical atherosclerotic cardiovascular disease, making it the first in the new class of lipid-lowering PCSK9 inhibitors. The FDA approval for alirocumab is widely expected to be followed closely by approval of evolocumab (Repatha) by Aug. 27.

ÂÂ

In HIV patients coinfected with hepatitis C virus genotype 1 or 4, rates of sustained virologic response — defined as the absence of hepatitis C RNA — at 12 weeks reached 96% with a fixeddose combination of ledipasvir and sofosbuvir (Harvoni, Gilead Sciences), results from the ION-4 study show. (Medscape)

ÂÂ

Inhaled cannabis can blunt the pain of diabetic neuropathy without seriously impairing cognitive function (July issue of the Journal of Pain).

ÂÂ

By targeting inflammation, adult allogeneic bonemarrow-derived mesenchymal precursor cells may represent a novel treatment for type 2 diabetes (July 7 in Diabetes Care).

ÂÂ

Proprotein convertase subtilisin kexin 9 (PCSK9) is a serine protease produced predominantly in the liver that leads to the degradation of hepatocyte LDL receptors and increased LDL-C levels. Therapies that lower circulating PCSK9 levels significantly lower LDL-C levels. Monoclonal antibodies that inhibit PCSK9 (anti-PCSK9 abs) reduce LDL-C in a dose-dependent manner, by as much as 70% and by as much as 60% in patients on statin therapy. Anti-PCSK9 abs reduced allcause mortality, cardiovascular mortality and MI. In particular, anti-PCSK9 abs appear to result in additional reductions in risk even in patients already on intensive or maximal statin therapy.

ÂÂ

Regional nodal irradiation can reduce breast cancer recurrence in patients with node-positive or highrisk node-negative disease, but offers no survival benefit, reported two large clinical trials published in the July 23 issue of the New England Journal of Medicine.

ÂÂ

Knowing the amyloid status of patients could help direct anti-Alzheimer’s disease drugs to those most likely to benefit from them and prevent prescribing these agents unnecessarily, suggests new research presented at the Alzheimer’s Association International Conference (AAIC) 2015.

AROUND THE GLOBE ÂÂ

Final 10-year results from the HIV Prevention Trials Network (HPTN) 052 study — in which the HIV-positive partner in a serodiscordant couple received antiretroviral therapy to protect the negative partner from HIV transmission — revealed that antiretroviral therapy, when taken until viral suppression is achieved and sustained, is a highly effective, durable intervention for HIV prevention. The findings were presented at the 8th International AIDS Society Conference.

ÂÂ

A behavioral intervention that combines diet and exercise did not prevent gestational diabetes (GDM) or large-for-gestational age (LGA) babies in obese pregnant women, according to results from one of the largest randomized controlled trials to look at this issue. Results from the UK Pregnancies Better Eating and Activity Trial (UPBEAT) were published online in the Lancet Diabetes and Endocrinology on July 10, 2015.

ÂÂ

Eye surgeons in developing countries can use fibrin glue on the scleral rim to increase the number of donor corneas they can use for transplant, suggests new research published online in the British Journal of Ophthalmology.

ÂÂ

The US Food and Drug Administration (FDA) approved a topical gel combination of adapalene 0.3% and benzoyl peroxide 2.5% for the treatment of moderate to severe acne vulgaris in patients aged 9 years and older.

ÂÂ

Two new studies published in the BMJ suggest that regular sugary drink consumption and a combination of low birth weight and an unhealthy lifestyle in adulthood are associated with increased risk of type 2 diabetes.

ÂÂ

Blood levels of arginine vasopressin (AVP) were significantly and positively correlated with scores on the Developmental Neuropsychological Assessment (NEPSY)–II Theory of Mind subscale among children with autism spectrum disorder (ASD) but not in neurotypical children, reported a study published online July 22 in PLos One.

The American Thoracic Society (ATS), the European Respiratory Society, the Japanese Respiratory Society, and the Latin American Thoracic Association have together updated the 2011 guidelines for the treatment of idiopathic pulmonary fibrosis (IPF) that summarize the significant advances that have been achieved in the clinical management of IPF. The guidelines are published in the July 15 issue of the American Journal of Respiratory and Critical Care Medicine.

ÂÂ

Ferric pyrophosphate citrate administered via dialysate, reduces erythropoiesis-stimulating agent use in dialysis patients, while maintaining hemoglobin levels, suggested the PRIME study published online in Kidney International.

ÂÂ

New diagnostic criteria have been introduced for neuromyelitis optica (NMO), which is now to be known as neuromyelitis optica spectrum disorder (NMOSD). The new criteria were developed by an international consensus panel and were published in the July 14 issue of Neurology.

ÂÂ

The Mediterranean diet may help preserve structural connectivity in the brain in older adults, suggests a French study published online in Alzheimer’s & Dementia.

ÂÂ

The US Food and Drug Administration has approved the Orbera Intragastric Balloon System as a weight-loss device that deposits a balloon in the stomach, through the mouth, via a minimally invasive endoscopic procedure with the patient under mild sedation.

ÂÂ

In children, vitamin D levels, as measured by serum 25-hydroxyvitamin D (25[OH]D) concentrations, are inversely associated with non-HDL cholesterol levels, fasting triglycerides, and total cholesterol levels, suggests a new study published in PLos One. Physicians and medical groups such as the American College of Surgeons and the American Academy of Orthopaedic Surgeons have spoken out about restricting nonmedical cell phone use in healthcare settings and in the operating room. They say that checking smart phones for anything other than vital health data can be a distraction and lead to medical errors. No federal regulations have been put in place to prohibit physicians or other healthcare professionals from using their phones while in surgery or anywhere else. And no group tracks whether hospitals have adopted rules for cellphone use. A new oral recombinant vaccine protects children against infection with Helicobacter pylori, researchers from China report.

■■■■

Indian Journal of Clinical Practice, August 2015

LIGHTER READING

A woman customer called the Canon help desk with a problem with her printer. Tech support: Are you running it under windows?

HUMOR

Lighter Side of Medicine

Customer: “No, my desk is next to the door, but that is a good point.

During their silver anniversary, a wife reminded her husband: Do you remember when you proposed to me, I was so overwhelmed that I didn’t talk for an hour?”

--A guy is walking up to a doctor’s office when a nun comes running out screaming and crying.

The hubby replied: “Yes, honey, that was the happiest hour of my life.”

The doctor says, “No. But it certainly cured her hiccups!” --A friend and I stayed at a Chicago hotel while attending a convention. Since we weren’t used to the big city, we were overly concerned about security. The first night we placed a chair against the door and stacked our luggage on it. To complete the barricade, we put the trash can on top. If an intruder tried to break in, we’d be sure to hear him. Around 1 a.m. there was a knock on the door. “Who is it?” my friend asked nervously.

QUOTE

The guy walks in and says, “Doc, what’s with the nun?”

The guy says, “The nun’s pregnant?”

“Well, I knew sooner or later some idiot would ask me. So I measured it!” replied the carpenter. ---

The man sitting in the cubicle next to me is under a window, and his printer is working fine.

The doctor says, “Oh, I just told her she’s pregnant.”

“What? How come you are so sure of that distance?” asked the lawyer.

“Any change, any loss, does not make us victims. Others can shake you, surprise you, disappoint you, but they can’t prevent you from acting, from taking the situation you’re presented with and moving on. No matter where you are in life, no matter what your situation, you can always do something. You always have a choice and the choice can be power.” — Blaine Lee

Dr. Good and Dr. Bad SITUATION: A diabetic with A1c 6% had a BP of 130/88 mmHg.

This is very good control of diabetes

This is very good control but we also need to control BP

©IJCP Academy

“Honey,” a woman on the other side yelled, “you left your key in the door.” --A carpenter was giving evidence about an accident he had witnessed. The lawyer for the defendant was trying to discredit him and asked him how far away he was from the accident. The carpenter replied, “Twenty-seven feet, six and one-half inches.”

Indian Journal of Clinical Practice, August 2015

LESSON: Cardiovascular morbidity can only be reduced with aggressive management of hypertension, cholesterol (LDL <100 mg/dL) and aspirin (75-150 mg/day) in patients with or at high risk for cardiovascular disease.