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OCTOBER 2018

FUTUREMEDICINEINDIA.COM

COMBO-DRUGS

ON THEIR

WAY OUT?

MICRODELETION:

LOST IN

TRANSLATION

NON-INVASIVE PRENATAL

SCREENING ENTERS

EXCITING FRONTIERS

KNOWING

THE UNBORN

REGULATORY DIAGNOSTICS HEAD & NECK CANCER CASE REPORT

ORAL CANCER

STAGING BY

DEPTH OF INVASION

HOW SHE

REGAINED

HER LOST TASTE


editor’s note

OCTOBER AUGUST 2018 / / Vol: Vol. 5 // Issue: 46

Founder & & Editor Editor

CH Unnikrishnan

Executive Editor Editor

S Harachand

Harachand

Science Editor

Science Editor

Dr Rajanikant Vangala

Dr Rajanikant Vangala

Consulting Editors

Dr Copy Shivanee Editor Shah

Jeetha Sreejiraj D’Silva Eluvangal

Dr Consulting Sumit Ghoshal Editors

Copy Dr Shivanee Editor Shah

Sreejiraj Dr Sumit Ghoshal Eluvangal

Correspondent

Photo Editor

Divya

Umesh

Choyikutty

Goswami

Photo Editor

Illustrator

Umesh Goswami

Mathewkutty J Mattam

Design Editor

Gopakumar Advisory BoardK

Dr Devi Shetty

Illustrator

Mathewkutty

Dr B S Ajaikumar

J Mattam

Dr Shashank Joshi

Advisory

Dr Prof. Arumugam

Board

S

Dr Devi Shetty

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Dr B S Ajaikumar

Dr Dr N Shashank K Warrier Joshi

Dr Sekar Prof. Seshagiri Arumugam S

Dr Knowledge I C Verma Partner

Dr SGRF N K Warrier

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Mr Business Rajesh Head R Nair

Knowledge

Tushar Kanchan

Partner

SGRF Circulation & Subscription Manager

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Tushar Design & Kanchan Graphics

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Dear Doctor,

Dear Doctor

Needless to say, you, and every other honest healthcare provider truly

hold

We know

a respectable

you are busy.

position

It is

in

always

the society.

reassuring

This respect

that the

is

trust

nothing

and

but

faith

the

of

reflection of the trust that men and women in the society have in you as

hundreds of patients in your healing touch keeps you busy in this noble

the custodian of their health. So, naturally, it comes to you with its own

profession. In the hectic practice, it’s quite natural that you might miss

share of responsibilities. In this era of transformative science and research,

out on some of the latest developments in emerging medicine. In this era

the responsibility has a much larger context that goes beyond mere sickcare.

It also includes the care of the health of the society, which will in turn

of innovation, medical science is getting redefined almost by the day. Old

technologies are being replaced by the new in the blink of an eye. Robots

determine the future progress of humanity.

and artificial intelligence are taking over a good part of the procedures,

As Future Medicine always stressed in its mission, we want to seamlessly

while genomics and molecular science unveil the mysteries of life further.

connect the researcher with the doctor, bridging the gap between them. It

We are fortunate to have such breakthroughs as they help specialists like

is the time to translate the benefits of that knowledge to the society at large

in

you

the

rise

form

above

of a

the

real

expectations

transformation.

of today’s

And that

informed

is the real

patient.

responsibility which

you, as a new age clinician, share.

Similarly,

As we all

it is

know,

also a

India’s

time

burden

when India

of non-communicable

is witnessing revolutionary

diseases

growth

is rising

in

rapidly.

healthcare

The

industry,

country’s

especially

peculiar and

in the

complex

private

population

sector, wherein

groups

an

and

increasing

their

genetics number of add doctors the are load taking of inherited up multiple ailments. roles Recent of clinician, advancements researcher in and

human entrepreneur. genomics This have requires proven expansion to be capable of your of focus tracing to a the wider genesis canvas. of many In

of this these context, diseases it becomes accurately, important and to how control a busy them professional to a great extent. like you But can

unfortunately, keep pace with the these awareness latest developments about such advanced in a quick technologies, and easy way. including

parental and prenatal screening and testing that can help take informed

decisions At Future before Medicine, birth, which is still is conceived very poor in and India. crafted by a team of senior

journalists, We, in this scientists issue, are and taking doctors, a closer our look aim is at to the help country’s you do crucial just that. burden We of

genetic are equipped disorders to bring and the you myths the latest and from realities the about science the of latest care technologies

from across

that the world the country in an interesting can take advantage and convenient of in this way, regard, supplemented along with by many the best other

breakthroughs of views and analyses and developments from the masters in the in field each of medicine field. We and present practice. you this

specialised Happy reading, knowledge vehicle that plugs you into the emerging world of

care seamlessly. Come, let’s join hands in this information journey.

CH Unnikrishnan

editor@futuremedicineindia.com

C H Unnikrishnan

editor@futuremedicineindia.com

www.futuremedicineindia.com futuremedicineindia FutureMedIndia

AUGUST 2018/ FUTURE MEDICINE / 3


REGULATORY DIAGNOSTICS HEAD & NECK CANCER CASE REPORT

Vol 5 Issue 6

October 2018

₹ 250.00

VOL 5 | ISSUE 6

PAGES 100

OCTOBER 2018

FUTUREMEDICINEINDIA.COM

COMBO-DRUGS

ON THEIR

WAY OUT?

MICRODELETION:

LOST IN

TRANSLATION

EXCITING FRONTIERS

KNOWING

ORAL CANCER

STAGING BY

DEPTH OF INVASION

NON-INVASIVE PRENATAL

SCREENING ENTERS

THE UNBORN

HOW SHE

REGAINED

HER LOST TASTE

28

DIAGNOSITCS

LOST IN

TRANSLATION

Microdeletion syndrome is one

of a frequently unsuspected

group of disorders in prenatal

evaluation

REGULAR FEATURES

06 Letters

08 News updates

12 Research

32 Drug approvals

48 Education

60 Research snippets

62 Pharma

64 Hospital news

66 Head & neck cancer

68 Insurance

70 Health care

72 Public health

74 Medico legal

80 Devices

86 Products

90 Events

96 Calendar

97 Book review

98 Holy grail

54 14

CASE REPORTS

SLEEP-ONSET

SEIZURE

Here is a case of long QT

syndrome which manifested

as a seizure-like activity while

falling asleep

RESEARCH

PRETERM RISK

HIGHER WITH

ART: STUDY

Lack of surveillance and

the absence of procedural

guidelines are leading

to an alarming rise in ART-linked

preterm births

38

REGULATORY

FDCS ON THEIR

WAY OUT?

India slaps ban on 328 drug

combos finding no therapeutic

justification for the ingredients

contained


76

ETHICS

DOCTORS OWE A

CONSTITUTIONAL DUTY TO

TREAT THE HAVE-NOTS: SC

Test results

must aid clinical

decision-making

and should be

beneficial to

patients.

44

STRAIGHT TALK

“INDIA WILL SOON

MAKE THAT BIG

REVOLUTION OF

CHEAPER

ROBOTIC SURGERY”

Maximilian

Schmid M.D.

Head of Medical

Affairs, Roche

Sequencing Solutions,

California

16

COVER STORY

KNOWING

THE UNBORN

Non-invasive, cfDNA-based

approach opens exciting

frontiers in prenatal genetic probe


CARDIOGENETICS CASE REPORT EDUCATION ONCOLOGY

letters to the editor

CUTTING-EDGE ADVANCES IN

INTERVENTIONAL TECHNOLOGY

ARE TAKING CARDIOVASCULAR

MEDICINE BY STORM

TRANSCATHETER

TRANSFORMATION

INHERITED CVD:

BIGGEST KILLER

GETS OFF SCOT-FREE

HEART RHYTHM

DISORDERS

MIMIC EPILEPSY

Nicely done

DNBs SEEK

EQUIVALENCE

WITH MD

Hi,

Received the September

edition. Useful contents and

nicely done. Congrats.

Dr Hisham Ahmed

Consultant cardiologist

Armrita Institute of Medical

Science, Kochi.

Excellent Concept

₹ 250.00

VOL 5 | ISSUE 5

PAGES 100

SEPTEMBER 2018

FUTUREMEDICINEINDIA.COM

GINGIVO-BUCCAL

CANCERS ARE

DIFFERENT

Hello,

It is a great attempt to create

a fusion of pure science

and clinical practice, which

is also presented in an

interesting way. Doctors will

enjoy reading this. Excellent

concept.

Prof. Bhaskar D Goolab

Dept. of Obstretics

&Gynaecology

University of Witwatersrand,

Johannesburg, SA.

Business insights

Dr Moopen’s views on

hospital entrepreneurship

was really insightful.

Dr Raju Patil

Vasai Polyclinic, Maharshtra

Insightful

Dear Sir,

Read your September

edition. The interview with Dr

Moopen was really insightful

as far as preparation

for healthcare startup is

concerned. His concerns

about unupdated medical

curriculum in India is true

and hope the MCI and other

authorities listens to it.

Dr Jayathilakan

Anna Salai, Chennai-02

Really good

Hello,

I think I must comment

on the cover story of the

September edition of FM.It

is really good. Very topical.

I appreciate the way you

choose the topics. Ovearll,

the layout of the magazine

looks excellent!. Keep it up.

Cheers,

Dr Manish Kakodkar,

Worli Seaface, Mumbai

Serious crisis

Dear Editor,

The September edition was

a good package on the

heart diseases and modern

procedures. As a practicing

cardiologist, enjoyed reading

the same. As reported, the

inherited heart diseases is

still a serious crisis in India,

which is yet to get adequately

addressed.

Dr Vasudev Shirodkar

Shirodkar Clinic, Mumbai

Fresh look

Hi Sir,

Cover story on less-invasive

technologies was interesting.

Looking forward to more such

tech-based articles. Also, the

magazine has got a fresh look

with excellent cover theme

and design.

Dr. Jhanvi Shankar Nagesh

Bangalore

CLARIFICATION

Dr Kirti Chaddha, who shared her

views on TAILORx study findings

in the September issue (Page No.

48) is vice president, Oncomet,

Metropolis Healthcare Ltd.

Please e-mail us your feedback on

editor@futuremedicineindia.com

& GET 30 %

NOW

Please send me my subscription of FUTURE MEDICINE for (Select your plan)

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A medical science and news magazine for every new-age

clinician. It empowers doctors with the most relevant updates,

trends, case studies, expert views, knowledge exchange,

hospital management and latest breakthroughs in medical

science. To be relevant in the future of care, subscribe today.

AUGUST 2018/ FUTURE MEDICINE / 59


news updates

India brings HIV/AIDS Act

into force

India's health ministry has enforced

the Human Immunodeficiency Virus

and Acquired Immune Deficiency

Syndrome (Prevention and

Control) Act, 2017 with effect from

September 10, 2018.

The Act, which aims to

safeguard the rights of people

living with HIV and affected by HIV,

has provisions to address HIVrelated

discrimination, strengthen

the existing anti-discrimination

programme by bringing in legal

accountability and establish

formal mechanisms for inquiring

into complaints and redressing

grievances.

Seeking to prevent and control

the spread of HIV and AIDS, the

Act lists various grounds on which

discrimination against HIV positive

persons and those living with them

is prohibited. These include the

denial, termination, discontinuation

or unfair treatment with regard to:

(i) employment, (ii) educational

establishments, (iii) health care

services, (iv) residing or renting

property, (v) standing for public or

private office, and (vi) provision of

insurance.

The requirement for HIV testing

as a prerequisite for obtaining

employment or accessing health care

or education is also prohibited.

Every HIV infected or affected

person below the age of 18 years

has the right to reside in a shared

household and enjoy the facilities of

the household. The Act also prohibits

any individual from publishing

information or advocating feelings of

hatred against HIV positive persons

and those living with them.

Online pharmacy

Netmeds raises

Rs 247 cr

OOnline pharmacy

Netmeds has raised $35

million (Rs 247 crore) from

Southeast Asian business

group Daun Penh Cambodia

Group based in Singapore, a

company statement said.

Existing investors Sistema

Asia Fund, the venture capital

fund of Russian conglomerate

Sistema JSFC, and Tanncam

Investment, a Cambodian

investment holding company,

also put in money

in

this round, the statement

added.

Netmeds is planning to

use the new funds to increase

awareness through marketing

efforts as well as to enhance

customer experience, reports

said, quoting company

sources.

The company had, in

October last year, raised $14

million from Tanncam and

Sistema Asia Fund.

Promoted by Dadha

& Company, Netmeds

provides a wide range of

medicines listed under

various categories, along

with OTC products including

wellness products, vitamins,

diet/fitness supplements,

herbal products, pain

relievers, diabetic care kits,

baby/mother care products,

beauty care products and

surgical supplies.

Dr Poonam

Khetrapal gets

2nd term at WHO

Dr Poonam Khetrapal Singh

has been nominated as

regional director of WHO

South-East Asia for a second

five-year term.

The 11 member countries

of WHO South-East Asia

Region, which met at the

regional committee session

to elect the next regional

director, selected Dr Khetrapal

Singh unanimously, reports

said.

Dr Khetrapal Singh’s

current term started on 1

February 2014. During the

period, she identified seven

flagship priorities -– achieving

universal health coverage;

strengthening emergency

response capacity; reversing

non-communicable disease

epidemics; finishing off

neglected tropical diseases;

combating antimicrobial

resistance; preventing

maternal, under-five and

neonatal deaths, eliminating

measles and controlling

rubella. She further added

eliminating tuberculosis as her

eighth flagship in 2017.

The region, which was

certified polio-free in 2014,

continues to maintain this

status. It also succeeded

in eliminating maternal

and neonatal tetanus,

8 / FUTURE MEDICINE / OCTOBER 2018


ecoming only the second

WHO region to do so. The

region could also bring down

the maternal mortality rates

by 69 per cent.

Dr Khetrapal's next fiveyear

term will begin on 1

February 2019.

EU partners with

India to develop

flu vaccine

The European Union (EU)

joined hands with India

on research and innovation

to develop a next-generation

influenza vaccine.

EUR 30 million has been

earmarked for the research

and development activity with

the objective of advancing

the efficacy, safety, duration

of immunity and reactivity

against a large number of

influenza strains.

Both the EU and the

Department of Biotechnology

(DBT), Government of India,

have committed EUR 15

million each to fund the

joint project. The EU fund

for this programme comes

from its research and

innovation 'Horizon 2020'

programme.

These joint efforts also aim

to develop cost-effective and

affordable influenza vaccine

rapidly without compromising

quality. Keeping this in mind,

the participating consortia

need to bring together

multidisciplinary stakeholders

who can represent any part of

the chain from the lab to the

market.

Health ministry asks states

to ban e-cigarettes

India's health ministry

has asked states to

ban Electronic Nicotine

Delivery Systems (ENDS),

including e-cigarettes,

vape, e-sheesha,

e-hookah etc..

“As such, the states/

Union Territories are

advised, in larger public

health interest and in

order to prevent the

initiation of ENDS by

non-smokers and youth

with special attention

to vulnerable groups, to

ensure that any Electronic

Nicotine Delivery Systems

(ENDS) including

e-cigarettes, heatnot-burn

devices, vape, e-sheesha,

e-nicotine flavoured

hookah,” according to an

advisory issued by the

ministry.

These devices

enabled nicotine delivery

“In engaging jointly on this

topic, India and the EU are

contributing to an important

global public health challenge.

Improved influenza vaccines

would help the international

and hence should not

be sold either online or

offline. The advisory

also stated that

these should not

be manufactured,

distributed, traded,

imported and advertised

in the state jurisdictions,

except for the purpose

and in the manner and

to the extent as may

be approved under the

Drugs and Cosmetics Act,

1940 and the rules made

thereunder.

The Indian states

of Punjab, Karnataka,

Kerala, Mizoram, Jammu

and Kashmir, Uttar

Pradesh and Bihar have

already prohibited the

use of e-cigarettes and

have prohibited the

manufacture, import, sale

and distribution of ENDS,

reports said.

The Central Drugs Standard

Control Organisation

(CDSCO), India's top drug

regulator, is planning to

change the labelling norms

for fluoroquinolone class of

antibiotics. The intended

change is to bolster the

warnings about the risks of

mental health side-effects

and serious blood sugar

fluctuations.

The proposed regulation

is close in line with a similar

action taken by the US Food

and Drug Administration.The

US drug regulator announced

safety labelling changes

to make warnings more

consistent across the labelling

for all fluoroquinolones

taken by mouth or given by

injection.

India's Minister of State

for Health and Family Welfare,

Anupriya Patel stated in

Parliament that “in view of the

action of US FDA on labelling

changes of fluoroquinolones,

the Drug Controller General of

India is examining the issue

in consultation with subject

expert committee of CDSCO”.

The list of

fluoroquinolones approved by

US FDA include levofloxacin,

ciprofloxacin (Cipro),

ciprofloxacin extendedcommunity

to better prepare

in the event of an influenza

pandemic,” said Tomasz

Kozlowski, Ambassador of the

European Union, launching

the programme.

It is expected that the

outcome of the projects

will also contribute to the

achievement of Sustainable

Development Goal 3 to ensure

health and well-being for all

and boost the Indian National

Health Mission. Addressing

seasonal flu vaccination is

also high on the EU health

agenda with the European

Commission urging EU

member states to commit

to vaccinating 75% of risk

groups against seasonal flu

each year.

Govt may change

labelling for

fluoroquinolones

OCTOBER 2018 / FUTURE MEDICINE / 9


BC Roy awards go to three doctors from Lucknow

Three leading doctors from

Lucknow were conferred

with the country's prestigious

BC Roy awards.

SGPGI director Prof

Rakesh Kapoor and KGMU

Vice-Chancellor Prof MLB

Bhatt have been awarded

as ‘eminent medical

teacher’. Dr Deepak Agarwal,

gastroenterologist, has been

awarded ‘to recognise the

best talents in development of

specialities in different

branches in medicine’

for his contributions to

gastroenterology, stated a

press release from the Medical

Council of India.

Prof Bhatt, who was

part of Operation Meghdoot

launched by the Indian Army

in 1984 to capture the Siachen

Glacier, did his graduation

from KGMU and joined the

Indian Army’s medical corps

under the Short Service

Commission.

He later did his masters

in radiotherapy and started

Prof Rakesh Kapoor Prof MLB Bhatt Dr Deepak Agarwal

teaching. He served as KGMU

medical superintendent in

2006-07. He was appointed

the Vice-Chancellor of KGMU

in 2017. In the area of medical

research, Prof Bhatt has been

instrumental in developing

original biomarkers for testing

oral, breast, and urinary

bladder cancers.

Prof Rakesh Kapoor was

the winner of the prestigious

Hewett Medal in graduation.

Also an alumnus of KGMU,

Prof Kapoor joined SGPGI

Chandigarh for superspeciality

in urology. In 1988, he became

a faculty at SGPGI Lucknow.

A gold medallist in masters

in general surgery, Prof Kapoor

is credited with developing

new vaginoplasty techniques

wherein a vagina is created

from a section of the small

intestine to help women born

without ovaries and vagina.

Dr Deepak Agarwal is

an expert in endoscopic

ultrasound, laparoscopic

surgery and gastric bypass

surgery.

The BC Roy Award,

considered the highest

medical honour in the country,

is given in five categories. The

award to eminent medical

teachers includes Rs 15,000

and a medal for each awardee.

The selections are made

by a managing committee

appointed by the Medical

Council of India.

release tablets, moxifloxacin

ofloxacin, gemifloxacin and

delafloxacin.

The US agency went on

to insist labelling changes

following a recent review

that found instances of

hypoglycemic coma where

users of fluoroquinolones

experienced hypoglycemia.

The US FDA first

added a Boxed Warning

to fluoroquinolones in July

2008 for the increased risk of

tendinitis and tendon rupture.

Dr K K Aggarwal

is pres-elect

of CMAAO

Padma Shri Awardee Dr

K K Aggarwal has been

elected as the president-elect

of Confederation of Medical

Associations of Asia and

Oceania (CMAAO).

CMAAO represents 19

member National Medical

Associations (NMAs).

Dr Aggarwal will take

charge as the president of

CMAAO on September 5, 2019

at Goa.

A leading cardiologist,

Dr Aggarwal was the past

national president of the

Indian Medical Association

(IMA) and the first vice

president of CMAAO and

an advisor to the ethics

committee, World Medical

Association.

Dr Aggarwal, who is

currently the president of

Heart Care Foundation Of

India (HCFI), was elected to

CMAAO at the 2018 General

Assembly held at Penang,

Malaysia.

docprime. com

gets $50m

internal fund

docprime.com, an online

medical services provider

promoted by EtechAces

Marketing and Consulting

Private Limited (Policybazaar

Group), has received initial

internal infusion of US$

50 million from the parent

company.

Presently, docprime.com is

associated with 14,000 doctors

and 5,000 diagnostic labs. The

online medical portal plans to

expand its network to 1,50,000

doctors and 20,000 labs across

over 100 cities, according to

the company.

The online booking of

appointments are currently

restricted to doctors and labs

located in Delhi-NCR, but the

facility will be made available

across all major cities including

Mumbai, Bengaluru, Hyderabad

& Chennai from next month

onwards.

docprime. com, a venture

by the Policybazaar Group,

connects patients with doctors

in real time through stateof-the-art

technology and a

robust offline network.

10 / FUTURE MEDICINE / OCTOBER 2018


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esearch

CANCER VAC TO COMBAT LYNCH

Indian researchers discover that a personalised vaccine could well address a

hereditary form of colorectal cancer

A

recent study by Bengaluru-based

genetics research and diagnostics

player MedGenome has found

that a cancer vaccine would be the

answer for personalized treatment for

Lynch Syndrome (LS), a hereditary nonpolyposis

colorectal cancer (HNPCC).

Lynch Syndrome, one of the

most common hereditary syndromes,

increases the lifetime risk of developing

cancers of other organs, such as colon,

stomach, small intestines, liver, kidney,

uterus, brain, pelvis and prostate.

MedGenome, in collaboration with

Kailash Cancer Hospital and Research

Center (KCHRC), Goraj, examined the

feasibility of treating Lynch Syndrome

using a personalized cancer vaccine

approach by identifying potential

immunogenic tumour specific

alterations.

The company used its proprietary

neoepitope prioritization pipeline

- OncoPeptVAC - to select potential

immunogenic peptides from wholeexome

and RNA-seq data generated

from patient tumour. From a list of

over 50 predicted neoepitopes, three

neoepitopes were tested in an ex vivo

CD8+ T cell activation assay confirming

their immunogenicity.

Explaining the working of this

potential vaccine treatment, Amit

Chaudhuri, Vice-President, R&D

at MedGenome, said since cancer

mutations are recognized by the body’s

immune system as foreign, tumour

cells carrying these mutations are

often eliminated. So, it is often very

challenging to predict which mutations

are potentially immunogenic. The

answer to such challenging conditions

are good cancer vaccines.

MedGenome has built a

bioinformatic pipeline to predict

potential cancer vaccines by analysing a

patient’s tumour using next generation

SCREENING FOR GENETIC

MUTATION IN COLORECTAL

CANCER PATIENTS,

ESPECIALLY THOSE WITH A

FAMILIAL HISTORY, COULD

HELP IN IDENTIFYING THOSE

THAT ARE VULNERABLE TO

THE DISEASE.

sequencing. The process involves

sequencing tumour DNA to identify all

cancer mutations, using RNA sequencing

data to ascertain the mutations that

are expressed by the tumour cells, and

analysing the properties of the mutated

amino acid to predict whether it will be

recognized by the T cell receptor.

In the lynch syndrome study, the

patient’s tumour contained over 900

cancer mutations, of which about 50

were predicted to be immunogenic

- which means that these mutations

or neoepitopes were predicted to be

recognized by the T cells to mount an

immune response. Three predicted

neoepitopes were tested in an assay

and were found to activate T cells,

validating that the prediction was

correct. These three neoepitopes can

be used as vaccines for treating the

patient. It is likely that many of the

50 predicted epitopes will also be

immunogenic, although it was not

tested in the experiment. The assay is

time consuming, laborious and requires

specialized skill-sets to perform.

According to Dr. Rakshit Shah,

surgical oncologist, KCHRC, Vadodara,

the screening for genetic mutation in

colorectal cancer patients, especially

those with a familial history, could help

in identifying those that are vulnerable

to the disease.

“Such genetic-based screening

could be an efficient way of preventing

colorectal cancer. Families with history

of colorectal cancer like Lynch syndrome

should be advised to undergo genetic

screening and if they carry mutations

like MLH1, they are likely to develop the

disease before the age of 50. “Our study

is unique, as genetic screening in familial

colorectal cancer has not been widely

reported in India,” he added.

“Given that Lynch syndrome has

limited treatment options, this study

provides a basis for considering a

cancer vaccine approach that could

be used either as monotherapy or in

combination with established immunooncology

or chemotherapy drugs,” said

Dr. Amit Chaudhuri, who co-authored

the study.

Talking about the potential

development of the vaccine, Dr

Chaudhuri added that the company’s

pipeline is the front-end of a long chain

of processes that will lead to a product

that can be given to the patient. “A

big challenge is GMP manufacturing

of peptides for individual patients,

and formulating the peptides with

appropriate adjuvants so that the

vaccines can evoke a strong immune

response in the patient.,” he added.

12 / FUTURE MEDICINE / OCTOBER 2018


AUGUST 2018/ FUTURE MEDICINE / 85


esearch

PRETERM RISK HIGHER

WITH ART: STUDY

Lack of surveillance and the absence of procedural guidelines are leading

to an alarming rise in ART-linked preterm births

JEETHA D’SILVA

Advances in reproductive

technology have benefited many

women, but it is only recently

that the collateral risks involved in these

procedures have come to light. A recent

study conducted among 113 women

in Mumbai found that the incidence of

preterm births was alarmingly high in

women who have conceived through

Assisted Reproductive Technology (ART).

The study, conducted by the National

Institute for Research in Reproductive

Health (NIRRH) and the Indian Council

of Medical Research (ICMR), found

that 76.23% of such women had

preterm deliveries. Pregnancy related

complications like pre-eclampsia

(15%), gestational diabetes (11%) and

heterotopic pregnancy (3%) were also

found to be significantly high in this

cohort.

Dr Anushree Patil, scientist, NIRRH,

and the lead author of the study said

that the higher incidence of preterm

births was mostly due to the increase

in pregnancies among women over

the age of 35 years and the fact that

most ART procedures have higher order

multiple births.

“The profile of most of the patients

who come in for ART procedures puts

them at high risk. The average age is

above 37 and many of them have been

treated for fibroids and/or diabetes and

other conditions. In addition, some of

them may have undergone previous

surgeries because of which the risk of

preterm deliveries is higher,” says Dr

Ameet Patki, medical director, Fertility

Associates, and the past secretary

general of Indian Society for Assisted

Reproduction (ISAR).

Of the 113 women who were part

of the study, 51 women (45.1%) had

antepartum haemorrhage. Out of

these, 45 women (35.9%) had bleeding

episodes during the 1st trimester,

of which four sustained pregnancy

losses. Ten women had bleeding

episodes during the second trimester,

five of which were terminated. All

the women were given progesterone

supplementation to support the

pregnancy till 12 weeks of pregnancy.

14 / FUTURE MEDICINE / OCTOBER 2018


18 women (15.9%) required the use

of tocolytic agents to arrest or prevent

preterm labor in the late second and

early third trimester.

Multiple gestations were observed

in 51 participants (45.1%) and singleton

pregnancies in 62 participants

(54.9%). The high incidence of multiple

gestations can be correlated with

the high incidence of preterm births

observed in this study.

Higher in India

The World Health Organization reports

that about 15 million babies – or around

10 percent – are born prematurely

around the world every year. In India,

the incidence is higher. According to the

National Health Portal, preterm births

account for about 13% of all births in

India. Preterm births are a significant

health problem. Complications due to

preterm birth is the leading cause of

mortality in neonates, accounting for

almost 1 million deaths worldwide each

year.

Besides, preterm babies that survive

might require prolonged neonatal

intensive care and are at a greater risk

of severe impairment and morbidities

such as cerebral palsy, sensory deficits,

learning disabilities and respiratory

illnesses. The cost associated with

providing medical care and support to

preterm babies could run into several

lakhs, and could hence be well out of

the reach of many people.

“When you talk to couples who

wish to undergo ART, it is important to

counsel them and inform them about

the risks. Providing medical care for

a baby that is born preterm could be

financially draining as the cost could be

between Rs 10,000 to Rs 15,000 a day,”

said Dr Patki.

It is also important that these

pregnancies are closely supervised.

With ART clinics coming up in smaller

cities and towns, more people now have

access to these procedures, but these

mofussil areas often do not have the

infrastructure to care for babies that are

born preterm. “We also need to create

awareness. We now have a test – called

the fibronectin test – which costs

approximately Rs 4,000,

INCIDENCE OF PRETERM BIRTHS

HIGHER IN INDIA

WORLD

15

million

through which we can ascertain the

risk of preterm deliveries. Patients who

show a higher risk can be identified and

managed appropriately,” he added.

In addition, administering

betamethasone as a prophylactic in

the seventh month helps to accelerate

lung maturity in the foetus so this can

greatly reduce complications in babies

that are born preterm. In case of the

early onset of labour in high-risk cases

in remote areas, medicines should be

given as early as possible to slow down

the process, and the patient should be

transferred to a medical centre that is

equipped with NICU facilities to provide

optimum care for the neonate, Dr Patki

added.

Lacking data

10% 13%

ART CLINICS ARE COMING

UP IN SMALLER CITIES AND

TOWNS. BUT MOFUSSIL

AREAS OFTEN DO NOT HAVE

THE INFRASTRUCTURE TO

CARE OF BABIES THAT ARE

BORN PRETERM.

The findings of the Mumbai study, the

first of its kind in India, are similar to

INDIA

babies are born prematurely

around the world in a year -

The WHO reports

those of such studies conducted in

the West. However, as the researchers

point out, there is lack of data in the

Indian context, unlike in the West

where such pregnancies are extensively

documented. “The Centre for Disease

Control in Atlanta has very detailed

records of such pregnancies, which

make it easier for researchers to study

the data,” Dr Patil said, emphasising the

need for setting up a robust surveillance

system in India.

“With the growing use of ART, there

is a strong need to develop a National

ART surveillance system in India like the

one in CDC Atlanta. Mechanisms need to

be built into the reporting systems like

the National ART Registry of India to get

complete data on the pregnancy course

and outcomes of ART conceptions,” the

researchers stated in their study.

The researchers also called for

the formulation of guidelines for

ART procedures. With multi-foetal

pregnancies being very common in

assisted reproductive technologies,

the risk of preterm deliveries is also

subsequently higher. “In most ART

procedures, multiple embryos are

transferred. This often leads to multifoetal

pregnancies which could itself

lead to preterm deliveries. Hence, there

is a need to restrict the number of

embryos that are transferred. This

needs to be done at the policy level,”

Dr Patil said.

OCTOBER 2018 / FUTURE MEDICINE / 15


cover story

KNOWING

THE

UNBORN

Non-invasive, cfDNA-based approach opens exciting

frontiers in prenatal genetic probe

16 / FUTURE MEDICINE / OCTOBER 2018


S HARACHAND

The trajectory to determine the risk of foetal abnormalities

of genetic origin has been made a lot simpler and safer

for clinicians today with the advent of non-invasive

prenatal testing (NIPT).

Till a few years ago, the detection and diagnosis of

autosomal aneuploidies involved a multi-step process. The

combined first-trimester screening (FTS) to assess the risk

comprises the analysis of the pregnancy-associated plasma

protein A and the free beta-human chorionic gonadotropin

in the maternal blood, plus an ultrasound measuring foetal

nuchal translucency (NT) thickness. The detection rate of the

two biochemical marker analysis, in combination with NT

ultrasound, has only been around 75%, with 5% false positives.

A positive finding invariably led to invasive procedures like

amniocentesis or chorionic villus sampling (CVS) to confirm the

diagnosis. Extraction of foetal samples for genetic evaluation

causes considerable distress to both the unborn foetus and

the pregnant woman. Besides, the method itself carries a risk

of miscarriage, especially when carried out in locations where

expertise and facilities are inadequate.

Genomic abnormalities are the leading cause of birth

OCTOBER 2018 / FUTURE MEDICINE / 17


defects, including foetal growth retardation and pregnancy

complications. NIPT, in a technological breakthrough, now

makes it possible to determine the genomic status of the

foetus by analysing the circulating foetal DNA in the maternal

blood.

NIPT has a sensitivity of 99% and a specificity of 99.92%

for trisomy 21, which detects Down’s syndrome and nearly

similar level of accuracy for trisomy 18 and trisomy 13 -- the

common autosomal aneuploidies.

Cell-free foetal DNA, or the DNA of placental origin,

comprises less than 10% of the DNA in the blood of a pregnant

woman. The ’foetal fraction’ analysis can

be done earlier than any other pregnancy

screening or diagnosis. It helps to complete

testing formalities earlier in those receiving a

negative result. As a sufficiently informative

test with better accuracy, it obviates the

need for other investigations.

The increased level of sensitivity and

specificity in detecting aneuploidies makes

NIPT a better option for patients and

clinicians. Even though its use is currently

limited to screening purposes and not for

diagnosing, several countries, including the

Netherlands, have already implemented NIPT as a part of their

national prenatal screening programme.

Evidence from studies conducted in low-risk, general

populations shows that NIPT can be considered an

alternative to the current first-tier testing for first-semester

prenatal screening in many healthcare settings. Also, there

are indications that the number of invasive foetal tests has

decreased considerably since the introduction of NIPT in many

parts of the world, including in the US and Australia. Many

women who previously would have had invasive testing are

choosing NIPT because of the small risk of pregnancy loss.

”NIPT has seen unprecedented, rapid clinical adoption

with studies showing a decrease in both the number of

traditional screening tests and invasive diagnostic procedures,’’

says Maximilian Schmid, MD, Head of Medical Affairs, Roche

Sequencing Solutions, California. Roche’s Harmony prenatal test

to detect trisomy 21, 18 and 13 is currently available in more

than 100 countries, with more than 1.4 million patient samples

tested, he adds.

Expanding potential

THE ’FOETAL FRACTION’

ANALYSIS CAN BE DONE

EARLIER THAN ANY

OTHER PREGNANCY

SCREENING

OR DIAGNOSIS.

Recent advances in genome sequencing have broadened

the scope of NIPT further. Going by the trend, disorders

of monogenic origin are logically the next in line.

Hemoglobinopathies such as thalassaemia and sickle cell

anaemia are already brought under its

purview. Since the principle of cfDNA involves

the analysis of the entire foetal genome

in maternal plasma, NIPT can, technically,

look beyond chromosomal abnormalities

to Mendelian disorders and genetic risk

profiles for multifactorial diseases, studies

say. There is, virtually, no limit to the number

of diseases and conditions that can be

predicted through the technology.

Leading companies have already

expanded their panel portfolio to include

microdeletion syndromes like DiGeorge.

“Deletion of 22q11.2 is the second most common

identifiable genetic cause of developmental delay and major

congenital heart disease after Down syndrome. Occurring

in as many as 1/1,000 pregnancies, it is the most common

microdeletion syndrome,” according to Dr Schmid.

As demonstrated with 22q11.2 deletion, Roche will

continue to focus on adding clinically meaningful content to its

test offerings, he added.

NIPT is the best technology that is available today for

screening chromosomal disorders in pregnancy, and it is being

recommended by obstetric and gynaecological societies the

world over, points out Dr. Priya Kadam, Programme Director

- NIPT, MedGenome Labs, a genomics-based research and

diagnostics company from Bengaluru.

DOWN‘S DETECTION

NIPT has a sensitivity of 99% and a

specificity of 99.92% for trisomy 21,

which detects Down’s syndrome.

FTS/NT scan

DETECTION RATE T21

NIPT

73% 99%

Population risk

set at

1/800

False-positive rate

of FTS

4.8%

False-positive rate

of NIPT:

< 0.1%

Iatrogenic miscarriage:

miscarriage due to

invasive procedures

1%

18 / FUTURE MEDICINE / OCTOBER 2018


According to Dr Kadam, it would be a better idea to have

all pregnant women go through NIPT irrespective of their risk

profile because genomic changes in the foetus can occur due

to many factors. For instance, spontaneous chromosomal

disorders, which is the most common type of chromosomal

disorder, including Down’s syndrome, Edwards syndrome and

22q or DiGeorge syndrome, occurs during the pregnancy sans

any previous family history. “In this case, not even the parents

are carriers. The changes are spontaneous. It is important to

note that in the case of family history or suspected genetic

mutation in parents, one will be careful or cautious about

the pregnancy. But, so far as spontaneous disorders are

concerned, there is no alert factor, so it is recommended that

every pregnancy should be screened for certain chromosomal

disorders,” she explained

At present, India has several tests available for detecting

almost all the disorders.

Of late, companies have even started marketing tests that

track down single point mutation disorders in India.

According to Dr Shailesh Pande, Consultant-HOD, Dept.

of Medical Genetics, Metropolis Healthcare Ltd, a wide range

of maternal serum screening test from dual marker to NIPS

are available. Proper genetic counselling and appropriate test

selection can really help to identify at risk population for foetal

chromosomal abnormalities.

Addressing awareness gap

Even as genomic advances have significantly improved

screening and diagnosis of chromosomal conditions prenatally,

they have also created new challenges for health professionals

and families.

The growing number of available tests are likely to

have positive effects on prenatal care. However, the level

of awareness about them among patients and providers

continues to impede their uptake.

“Obstetricians have poor awareness of foetal therapy

Obstetricians have

poor awareness

of foetal therapy

conditions and

tend not to advise

patients correctly.

Dr Anita Kaul

Clinical Director,

Apollo Centre for Fetal

Medicine, New Delhi

NIPT

AVAILABLE

IN INDIA*

Down’s syndrome

(trisomy 21)

Edward’s syndrome

(trisomy 18)

Patau syndrome

(trisomy 13)

Cri-du-chat syndrome

(5p minus syndrome)

Wolf-Hirschhorn syndrome

(deletion 4p syndrome)

Jacobsen syndrome

(11q deletion disorder)

Klinefelter’s syndrome

(presence of an additional

X chromosome in males)

Turner syndrome

( presence of only a

single X chromosome in

females)

XYY syndrome

XXX syndrome

Certain monogenic disorders

*List incomplete

OCTOBER 2018 / FUTURE MEDICINE / 19


IMPROVING GENETIC QUOTIENT

Genetic screening to enable health assessment today for healthy tomorrow

DR RAJANIKANTH VANGALA

Empowering a mother is enabling

a brighter future for the country.

A major goal of clinicians is to bring

down maternal mortality and premature

births and do prenatal defect detection.

This goal can be achieved by prenatal

screening for birth defects, which, until

recently, required invasive methods like

collecting amniotic fluid, which contains

foetal cells -- mostly of epithelial origin

-- or chorionic villus samples, which

have mesodermal connective tissue

and trophoblastic cells of the placenta.

These invasive techniques do carry a

greater risk, including that of foetal loss.

However, the increasing knowledge about

circulating cell-free fetal DNA (ccffDNA)

and its presence in the mother’s blood

has led to the development of noninvasive

prenatal screening or testing

(NIPS or NIPT). Every human being carries

cell-free DNA. However, pregnant women

carry around 10-15% ccffDNA, depending

on several factors such as the inverse

association with an increase in maternal

weight. These ccffDNA fractions from

each chromosome can help in identifying

specific genetic aspects or defects in the

foetus. For example, statistically significant

higher levels of DNA fragments from

chromosome 21 correlate with trisomy 21

(Down syndrome). The small amounts of

DNA fragments are further analyzed in

bioinformatics by comparing them with

reference human genome to identify

anomalies. Cost-effective, targeted

sequencing has been developed now, for

example, for chromosomes 13, 18, 21, X

and Y.

Adhering to guidelines

NIPS was introduced in India in 2012

and is now spreading quickly in all major

cities. There are approximately 26 million

births every year in India and NIPS

could truly help improve health systems.

WHILE NIPS MAY SOON

BECOME POPULAR IN CITIES

IN INDIA, THE PENETRATION

OF RURAL AREAS WILL BE

A HUGE HURDLE AS EVEN

BASIC MEDICAL SERVICES

ARE YET TO BE MADE

UBIQUITOUS THERE.

However, it is imperative that medical

specialists and obstetricians be aware

of the relevant recommendations and

guidelines so that the test can be used

properly. Based on the guidelines of

American College of Medical Genetics and

Genomics (ACMG), NIPS has been limited

to screening assessments and is not used

for diagnostics. This suggests that there

may be potential residual risk of disease,

albeit very low, even if the test comes

back normal. However, this is true in case

of any other biochemical or ultrasound

study. This aspect must be explained to

the patient clearly. Would-be parents and

family in India may expect these tests

to be 100% accurate, like in the case of

invasive tests such as amniocentesis and

chorionic villi tests. The recommendations

and guidelines must be adhered to in

explaining the scientific rationale of such

tests, and probably, a simplified metaanalysis

of relevant studies could be

presented to the patient.

One of the most important factors

in a healthy pregnancy is the age of

mother at the time of giving birth. In

India, the proportion of women who are

greater than 35 years of age at the time

of delivery is increasing to 2-5%. The

second important factor to be considered

is the high rate of consanguineous

marriages in the country, leading to

increased incidences of birth defects.

Even as chromosomal aneuploidies are

increasing, there are very few centres

that offer quality services for premarital

or prenatal genetic screening / testing

and counselling. While NIPS may soon

become popular in cities in India, the

penetration of rural areas will be a huge

hurdle as even basic medical services

are yet to be made ubiquitous there.

One of the important mechanisms that

can help in reaching out are referrals to

non-governmental clinics and centres.

Furthermore, many rural and peri-urban

patients refuse screenings or procedures

due to socio-cultural and religious reasons

related to the sanctity of pregnancy. There

is an urgent need for bringing awareness

among all sections of the society about

conditions and tend not to advise patients correctly,’’ says Dr

Anita Kaul, Clinical Director, Apollo Centre for Fetal Medicine,

New Delhi. The ever-increasing possibilities of genetic screening

also make doctors a bit uncertain.

“As doctors, we are not reassuring the patients in the way

we used to, because we always keep saying that you haven’t

done all the possible tests that can be run on this foetus, so we

cannot allay your anxiety completely.’’

Earlier, the obstetrician could order for a karyotyping and

inform the patient that “we’ve done the only genetic test

available and as that is fine, the baby should be ok,’’ beams Dr

Kaul. The scenario has changed completely, now.

“There are so many tests available, so naturally there is

confusion in the market,’’says Dr Sheetal Sharda, Consultant

Clinical Geneticist, MedGenome.

The bigger challenge, as far as the genetic tests are

concerned in India, avers Dr Sharda, is the lack of awareness

about which tests are already available in the country.

To address this issue, MedGenome has developed certain

modules to help doctors choose the most appropriate test,

20 / FUTURE MEDICINE / OCTOBER 2018


the value of science when adopted

in correct ways. This also means that

companies and the government must

invest outside sequencing technologies

and personnel training.

Translating scientific knowledge

Improving the molecular or genetic

quotient will determine the future

progress of humanity. Both commercial

and not-for-profit organizations must

come forward with unique models of

translating scientific knowledge to the

layman. We all know that science is the

basis of the modern medical practices

and progress that can truly reduce the

disease burden. The majority of scientists

work in their laboratories and publish

in scientific journals which are not

suitable for general public consumption.

However, scientists always want to

translate their knowledge for public

benefit. Presently there are no platforms

for this purpose, which opens up great

opportunities. It is the right time for

clinicians and scientists to join hands

in grabbing these opportunities and

creating platforms to translate molecular

and clinical knowledge outcomes to

the public. This can truly help devise

an ethical way of bringing change in

the society and in transmitting the true

value of technological development.

The ethical discussion also brings up

the question of pricing and affordability.

Even if prices are reduced, NIPS will

still be a financial burden among lessadvantaged

populations. They may, in

spite of having knowledge of genetics.

give religious or other reasons for not

availing the services. A novel mechanism

of subsidy for economically weaker

sections may see a surge in the usage

of the technology and give better

value addition to scientific discoveries.

Giving birth to a baby with genetic

abnormalities is often seen as a huge

burden by families in the absence of

a support system for the parents

and the children. This can become

a major cause of concern when

there are an increased number of

women seeking abortions, and in places

where such abortions are illegal, they

end up receiving unsafe abortions.

These aspects need to be understood

thoroughly before taking NIPS services

ahead in the future.

The majority of NIPS offered in

low- and middle-income countries,

including India and China, are based

on European or US accreditations. The

genetic screening does not generally

come under local regulatory oversight.

The legal provisions in India, which tend

to focus on abortion and reproductive

technologies, must also consider the

value of giving proper prenatal detection

of foetal aneuploidy. This gives time to

families to be prepared for the birth,

and have all the required resources to

deal with the complications, including

the social, moral and psychological

consequences. The legal provisions

on abortions can vary, including the

regulation on foetal sex determination

imposed in India to prevent sex selection.

As India prohibits sex selection, screening

companies, medical practitioners and

genetic counsellors must be careful to

follow the applicable norms. Ultimately,

the success of any genetic screening will

depend on the inclusiveness of clinicians,

scientists, professionals of other fields,

the public, patients, insurance providers

and local governments.

The author is Full-Time

Director at SciGenome

Research Foundation,

Bengaluru

as they often put forward their queries based on patient

observation and suspected indications.

If there is a differential diagnosis, the scientists in the

company can identify the main etiology or the main genetic

components that cause a particular kind of disorder and

suggest the right kind of tests for the patients instantly.

There could be a number of variations or large chromosomal

abnormalities.

Quite often, Dr Sharda continues, MedGenome gets

requests for spinal muscular atrophy screening after sending

OCTOBER 2018 / FUTURE MEDICINE / 21


the sample for exome sequencing. Since

this disorder is a common case of exome

7 and 8 gene deletions, it can be initially

tested in a PCR based small lab. If found

positive for the said gene deletions, the

samples can be sent to an academic lab

for confirmation. “But, later, if they come to

know that there are other genes such as

SMN2, which is a pseudogene, also involved

and that such information is important for

the prognosis and to know the phenotype,

then the sample needs to be tested with an

MLPA (Multiple Ligation-Dependent Probe

Amplification) test, where we get the ratio

of how many genes are deleted and how

many are duplicated. This is important for

the correct prognosis.” This approach helps

the patient to actually save cost by avoiding

unnecessary tests or methods.

Obviously, a large section of the

obstetricians in India is lacking the

latest advances in the field. This is partly

because genomics is, comparatively, a new

discipline. It is yet to be made part of the

medical curriculum. The super-specialty

DM curriculum has already incorporated

genetic studies and the methods quite

elaborately. But the graduation level courses

are yet to get updated with this emerging,

but crucial area of medicine. Nevertheless,

we are moving fast into the era of

personalised medicine, potentially the most

accurate disease detection and treatment

management approach. Here again,

Obstetrical

healthcare providers

will need to

incorporate more

education into their

care pathways.

Kimberly Martin, M.D.

Senior Global Medical

Director, Women’s Health

Natera Inc

genetic tests play the most critical role, she

comments.

Educating care pathways

In fact, clinicians have a more active role

to play in helping pregnant women with

meaningful options of reproductive choice

in a milieu of overwhelming genomic

information.

“Obstetrical healthcare providers will

need to incorporate more education

into their care pathways,’’says Kimberly

Martin, M.D., Senior Global Medical Director,

Women’s Health at Natera Inc, a leading

global player in cell-free DNA testing based

in San Carlos, California.

Delving into its practicality, Dr Martin

observes that it is unlikely that this can

be achieved using the traditional faceto-face

encounters alone. There are

many opportunities for “tech” based

learning that are currently available and/

or in development, including web-based

videos, apps for phone/computer and even

telemedicine with online genetic counsellors.

Constrained by time, providers are now

receiving assistance from both the industry

and professional societies to meet the

growing educational needs. “This should

translate into them having time to actually

counsel regarding the decision making about

testing, which is consonant with the goals

and values of the family,’’ she recommends.

Counselling is the most important aspect

MARKET SHARE OF

INDICATIONS SCREENED

UNDER NIPT PANELS

2017-2027

Driven by increasing awareness and

adoption, the global NIPT market is

anticipated to grow at an annualized

rate of 15% between 2017 and 2027

44%

56%

24%

28%

22%

14%

2017 2027 2017 2027 2017 2027

SOURCE: www.rootsanalysis.com

CHROMOSOMAL

ABNORMALITIES

Trisomy 21 (Down syndrome)

Trisomy 18 (Edward syndrome)

Trisomy 13 (Patau syndrome)

SEX CHROMOSOMAL

ABNORMALITIES

Turner syndrome

Klinefelter syndrome

Triple X syndrome

Jacob syndrome

MICRODELETION

SYNDROMES

Cri-du-chat syndrome

DiGeorge syndrome

Prader-Willi syndrome

Monosomy 1p36

Wolf-Hirschhorn syndrome

22 / FUTURE MEDICINE / OCTOBER 2018


of NIPT, underscore all the guidelines. The objective of any

prenatal screening activity should be made explicit. In a

country like India, where the awareness level is rather low

and familial, social and ethical considerations galore, this

poses an additional challenge.

“Doctors, of course, are very open, but we have been

confronted by situations where the parents hide the

fact that their daughter is a carrier as it may affect her

likelihood of marriage,’’says Dr Kaul. This sort of issue can

present a significant challenge while implementing routine

prenatal screening to detect hemoglobinopathies as

proposed by India.

All this points to the necessity of social change and the

need to impart the correct knowledge of such conditions

amongst the public, she adds.

The awareness level, however, has gone up

considerably since 2011, when NIPT was introduced,

according to Dr Kadam. A lot of awareness programmes

and direct education workshops among the doctors and

diagnostics players were conducted. Of course, awareness

about technology has been growing all over the world as

well.It supported a positive response in the Indian market

along with exposure to new technologies. The level of

awareness among the parents and pregnant women is

also high nowadays. “In fact, we and our hospital partners

have started getting direct inquiries from pregnant women

asking about the availability of NIPT tests,’’ says Dr Sharda.

“But still, I would emphasise the need for more coordinated

efforts from the industry, the government and the medical

community to maximise the utility of such technology

breakthroughs in India,” she adds.

Some clinicians too seem to corroborate the view

that the awareness among the public is growing pretty

fast. “Many patients now come asking for the test

(NIPT). Sometimes they insist on doing it,’’says Dr Ajay

Kumar, Additional Professor, Department of Obstetrics &

Gyenaecology, Government Medical College, Kottayam.

Most of the time, patients come well-prepared and are

thoroughly informed about genetic tests.

Higher costs: Impeding factor?

Another big barrier that comes in the way is the exorbitant

cost of genetic tests. Advances in NIPT is better, from the

provider standpoint, because they can give answers to

more conditions now. However, for the patient, the costs

are getting enormous. In the earlier days, a karyotyping

was good enough and that did not cost much. But now

a prenatal microarray as the first-line test itself is hugely

expensive compared with earlier tests. And if the test

proves non-informative, then going into the option of

sequencing increases the cost manyfold, says Dr Kaul.

Many clinicians are yet to adopt the screening test as

part of their routine practice, though they are aware of

NIPT.

“We don’t generally ask patients to do NIPT unless

we find a higher risk in an anomaly scan or the patient is

We have started

getting direct

inquiries from

pregnant women

asking about the

availability of

NIPT tests.

Dr Sheetal Sharda

Consultant

Clinical Geneticist,

MedGenome

NIPT TARGETING

SNPS

Single nucleotide polymorphisms

or SNPs are small differences in

the genetic code that do not cause

disease but allow the creation of

a unique DNA fingerprint for every

individual.

These same differences can

now be used to tell if twins are

identical (monozygotic) or fraternal

(dizygotic). Identical twins have essentially

identical DNA fingerprints.

Dizygotic or fraternal twins share

some of the same DNA but also

have differences, just like siblings.

NIPTs use SNPs to evaluate

the 1 percent of DNA that makes

patients genetically different from

one another.

Natera’s Panorama is the only

commercially available NIPT that

specifically analyzes SNPs to determine

chromosome copy number,

according to the US diagnostics

firm. Validated at foetal fraction

as low as 2.8%, this approach

sequences cell-free DNA from

maternal plasma to infer the foetal

genotype.

The ability to differentiate

between maternal and foetal

placental DNA also enables

SNP-based tests to identify the

presence of a vanishing twin and

to minimize false positives due to

maternal abnormalities. It also able

to pinpoint triploidy and complete

molar pregnancies. The company’s

validation data have shown a

combined sensitivity of >99% and

specificity of >99 for its NIPT.

Panorama targets 13,392 SNPs,

covering chromosomes 21, 18, 13,

X, and Y; additional sets of SNPs

are targeted for identification of

microdeletions. A patented algorithm

is then used to determine

the chance for foetal chromosome

abnormalities and foetal sex (when

requested), says Natera.

OCTOBER 2018 / FUTURE MEDICINE / 23


slug

“Many doctors still cling on to

the old concept that genetic

diseases have no treatment”

Dr IC Verma, Professor and Senior

Consultant Adviser, Institute of

Medical Genetics and Genomics, Sir

Ganga Ram Hospital, who is known as

the father of human genetics in India,

talks about the critical nature of the

country’s genetic disease burden in an

interview with C H Unnikrishnan. Edited

excerpts:

How advanced is India, as a country,

as far as genetic screening and testing

technologies and its access are

concerned?

Much effort and expense go into

screening pregnant women for

chromosomal disease, which affects

almost 1 in 200 births. The commonest

of chromosomal disorders is Down

syndrome, in which there is an extra

chromosome 21. Its incidence is about 1

in 800 births, but the incidence is higher

if the mother’s age is more advanced,

especially after 38 years. Some doctors

feel that it is only the older women who

should be screened for Down syndrome

in their baby. However, the majority

of Down syndrome babies are born

to young mothers. So every woman

deserves to be offered screening for

Down syndrome.

Most of the genetic screening and

testing technologies are available in

India. However, some of the tests are

expensive for the general population,

and need to be subsidized by the

government.

How familiar are Indian doctors

with these technologies, as genetic

services are still not fully integrated

into the existing medical education

and services?

Many doctors are ill informed about

genetic screening and testing. They still

harbour the old concept that genetic

diseases have no treatment. Therefore,

they often feel that there is no need to

do genetic testing to make a precise

diagnosis. Most doctors and patients in

rural areas are not aware that many of

the genetic disorders can be treated,.

Do you think there is an urgent

need of establishing medical genetics

as an additional department in

medical education?

Doctors who regularly read medical

journals to update their knowledge

realise the importance of genetics in

everyday practice. Even the standard

medical books are loaded with

information about genetics as applied to

various diseases.

India has already started feeling

the tremendous scarcity of medical

geneticists and genetic counsellors.

Only a handful of institutions are

providing training in medical genetics

(Sanjay Gandhi Postgraduate Institute

afraid of invasive procedures. This is because the cost of the

test is too high. Most of the patients can’t afford it,’’ says an

obstetrician practising in KIMS Hospital, Thiruvananthapuram,

preferring anonymity.

Apprehension about the cost remains the key factor that

makes many refrain from genetic tests. As a matter of fact,

the availability of a large number of tests which help pick up

a variety of genetic disorders has helped costs to come down

drastically in the last few years, bringing the tests within the

affordable range of the majority of patients, notes Dr Kadam.

Yet, many women throughout the world do not have

access to such tests because of a lack of funds, either the

result of restrictive terms and conditions of their health

insurance or due to a total lack of coverage for such

procedures. Often, these women do not have the financial

resources required to pay for these tests out of pocket,

observes Dr Martin of Natera.

Tech know-how vis-a-vis clinical ability

NIPT, as mentioned, is recommended only as a screening

test and not as a diagnostic procedure, despite the huge

potential of the technology. The ability of cfDNA analysis to

detect autosomal aneuploidies is far superior to any other

available tests and the results are nearly comparable with

those of invasive analysis such as amniocentesis or CVS.

Nonetheless, the results of NIPT must be confirmed through

an invasive diagnosis before considering medical termination

of pregnancy, mandate the guidelines. This is because NIPT is

less than fully accurate.

The failure, however, to touch 100% mark is purely

technical. Most of the current NIPTs employ whole genome

massive parallel sequencing (MPS) technology and

use counting of cfDNA fragments to detect autosomal

aneuploidies. The DNA sequenced comprise DNA of both

maternal and placental origin. So, factors other than

aneuploid foetal karyotype. including placental mosaicism,

vanishing twin, maternal tumour etc., could inevitably signal

false positives, studies say.

To tide over this problem and minimise false positives,

some commercial companies use another approach based

on single nucleotide polymorphisms.

Targeted sequencing that maps only the chromosome

region of interest is yet another technology approach to NIPT.

Though these tests can give more accurate results, only

diagnostic techniques like amniocentesis or CVS can say

with 100% accuracy whether the DNA has a chromosomal

abnormality. No irreversible decisions should be made based

upon a high-risk NIPT result in isolation.

24 / FUTURE MEDICINE / OCTOBER 2018


in Lucknow, All India Institute of Medical

Sciences in Delhi, Postgraduate Institute

in Chandigarh, Manipal University in

Mangalore). The total medical geneticists

in the country may be about 100, which

is totally inadequate for a country the

size of India.

Similarly, these tests only measure the probability

for a limited number of conditions, while amniocentesis

and CVS can be used to test for a much broader number

of genetic abnormalities, emphasises Nateram, which

makes SNP-based Panorama NIPT.

Clearly, the technical ability to test for a condition

does not necessarily correspond with a clinical benefit.

Hence it is important for the companies to be certain

about the benefit of every new addition.

“Test results must aid clinical decision-making and

should be beneficial to patients. Each condition added to

a screening panel adds to the overall false positive rate

of the test and decreases the positive predictive value,’’

says Dr Schmid of Roche Sequencing Solutions, which

recently included 22q11.2 microdeletion testing as part

of its prenatal test portfolio. Therefore, additional cfDNA

test menu options must focus on clinically relevant

conditions and require comprehensive validation studies

to demonstrate clinical utility in the population to be

tested.

Furthermore, counselling becomes more challenging

with an increase in the complexity of testing options and

the potential of identifying conditions with an uncertain

prognosis, according to Dr Schmid.

Test results

must aid clinical

decision-making

and should be

beneficial to

patients. Each

condition added

to a screening

panel adds to

the overall false

positive rate

of the test and

decreases the

positive predictive

value.

Maximilian

Schmid M.D.

Head of Medical

Affairs, Roche

Sequencing Solutions,

California

HEARING LOSS

MEDGONOME OFFERS

GENETIC TESTING

FOR COUPLES

MedGenome Labs, a genomicsbased

research and diagnostics

company, offers genetic testing

for couples with a family history of

hearing loss.

Awareness and early detection

are the only ways to prevent

genetic hearing loss disorders

from being passed down to next

generations.

Couples should undergo

pre-conception counselling with a

genetic counsellor, especially when

there is positive family history

for a disorder. Such counselling

sessions help the couple better

understand the risk to the child as

well as help recommend a suitable

prenatal genetic test, according

to Dr Sunitha Tella, head, Clinical

Genetics and Fetal Medicine

Department, Institute of Genetics

and Hospital for Genetic Diseases,

Hyderabad.

“In one such case, the

first born child had cognitive

disorders. It was recommended,

to understand if the hearing

impairment was due to genetic

factors basis, which appropriate

screening measures could be

taken when they plan a second

child,” she said. Dr Tella suggested

the family to undergo genetic

testing at MedGenome Labs,

Bengaluru.

The blood samples of the

parents and their first child

revealed their first born had two

mutations or variants in the GJB2

gene, which is associated with

hearing loss, while the parents

were found to be carrying one

mutation each, making them

‘carriers’ of the disease. This meant

that their child may have 25 per

cent chance of being affected with

hearing impairment.

The foetus was tested

for these two variants and

was found that it was only

harbouring one of the two

mutations found in the first

child. In this case the child

would be a carrier of the

disease and wouldn’t suffer

from hearing loss, she added.

2018 / FUTURE MEDICINE / 25


cover story

INDIA’S HIGH GENETIC

DISEASE BURDEN

Thalassaemia screening could open floodgates for similar tests

JEETHA D’SILVA

In August this year, India’s health ministry proposed

mandatory genetic screening of all pregnant women for

thalassemia and sickle cell anaemia. Thalassemia is a

significant health challenge in India with about 10,000 to

15,000 babies with β-thalassemia major born each year. One

of the key points of the draft policy is government’s effort to

reduce the birth of affected children through carrier screening

and prenatal diagnosis.

If implemented, it will be the first instance of genetic

testing becoming widely used in India and could open

the floodgates for similar tests. The potential is immense.

For instance, there are almost 3.6 to 3.9 crore carriers of

β-thalassemia in India, and for sickle cell disease there are

about 25,00,000 carriers of the gene (Hemoglobin AS) and

about 1, 25,000 patients of sickle cell disease.

In addition, India is reported to have one of the highest

incidence of genetic disorders and birth defects. It is

estimated that birth defect pervasiveness is 64.4 over 1,000

live births in the country, with 1 out of every 20 newborns

admitted to the hospital carrying a genetic disease that

eventually accounts for nearly 1 out of 10 infant mortality,

indicating that India has a significant burden of neonates

with genetic disorders. Globally, the prevalence of genetic

conditions varies depending on the use of preventive

strategies, access to prenatal screening, diagnosis and

the option to terminate a

pregnancy in case of severe

birth defects.

Genetic testing is a relatively new

science that involves the analysis of

genes or genetic components, such as

the DNA, RNA, chromosomes, proteins and

certain metabolites, of the human body to

detect variations that could cause disorders or

inheritable disease.

“Genetic testing is used quite extensively

these days. It has applications in every field

of medicine as many diseases have a genetic

component,” said Dr. I. C. Verma, senior

consultant, Institute of Medical Genetics and

Genomics, Sir Ganga Ram Hospital, New

Delhi.

26 / FUTURE MEDICINE / OCTOBER 2018


DISORDERS

&CHALLENGES

About 10,000 to 15,000 babies with

β-thalassemia major born each year.Birth defect

pervasiveness is 64.4 over 1,000 live births

β-THALASSEMIA

CRORE

CARRIERS

SICKLE CELL ANAEMIA

3.6 -3.9 25,00,000

LAKHS

There are different kinds of genetic testing including

newborn screening, in which neonates are tested for treatable

genetic disorders; diagnostic testing, which is used to

identify a specific monogenic genetic disorder, such as, Down

syndrome or Trisomy 18.

Genetic testing is also used for carrier testing, which is

used to identify people who carry one copy of a mutation

that, when present in two copies,

can cause a genetic disorder, such as

thalassemia and sickle cell disease,

and predictive testing that is used to

detect genetic mutations associated with

disorders that appear later in life. These

tests can identify mutations that increase

a person’s risk of developing disorders

with a genetic basis, such as certain

types of cancer.

In the West, genetic testing has

mushroomed into an industry with

centres offering at home diagnostic kits

that can create a risk profile for disease ranging from cancer

to cardiac disease and almost everything in between.

This could potentially help patients pre-empt the disease.

“Once you identify genetic disposition, it is possible to create

tailor made treatments for these diseases,” Dr Verma said.

In India, too, there is a growing awareness about genetic

testing. An internet search leads to numerous outfits within

India that offer to mail kits that one can send saliva samples

to and get a detailed genetic profile.

“More and more people are going in for genetic testing

and facilities are widely available in bigger cities,” said Dr

THERE SHOULD NOT BE

INDISCRIMINATE USE

OF GENETIC TESTING.

INSTEAD, IT IS ADVISABLE

TO GO FOR A TIERED

APPROACH

Jayesh Sheth, chairman of Ahmedabad based Institute of

Human Genetics. “However, there should not be indiscriminate

use of genetic testing. Instead, it is advisable to go for a tiered

approach – the first test should ideally be a karyotype test,

then array complete genetic hybridisation and lastly exom

studies,” Dr Sheth said. This could ensure that the cost burden

to the patient is minimised.

Dr Sheth also recommended the

setting up of regional and nodal centres

for genetic testing. These should ideally

be set up in government hospitals so that

the reach of genetic tests is greater and

that the cost is also reduced. Currently,

though there are many centres for such

tests, their distribution is largely in the

urban setting and the semi-urban and

rural areas have limited or no access.

In the event of the government making

pre-natal testing mandatory, the

implementation of the same could prove

to be a logistical nightmare.

Dr Divya Agarwal, a New Delhi based geneticist, stated that

in a country like ours, it may not be economically possible.

In addition, doctors feel that the government could do

well by recommending simpler screening tests rather than

genetic testing. “Carrier screening for beta thalassemia could

be done by haemoglobin electrophoresis ,” said Dr Sheth. And

they also advocated focusing on other preventive measures

to minimise birth defects, such as encouraging fortification

of food with essential vitamins like folic acid, which has been

found to reduce the incidence of spina bifida.

OCTOBER 2018 / FUTURE MEDICINE / 27


diagnositcs

LOST IN TRANSLATION

Microdeletion syndrome is one of a frequently unsuspected group

of disorders in prenatal evaluation

DR PRIYA KADAM

Thirty nine-year-old Juhi was

cautiously delighted when she

learned she was pregnant again.

She had previously miscarried a foetus

affected with Down Syndrome. During

her current pregnancy, she consulted

a geneticist who suggested a test

for Down Syndrome and a group

of disorders called microdeletion

syndromes. She opted for the test as it

was non-invasive and accurate. Sadly,

this time, the foetus was diagnosed with

another disorder - 22q11.2 microdeletion

syndrome. Though devastated, Juhi

appreciated the information she

received early in pregnancy, and

accordingly made an informed decision.

Such information is vital to expectant

parents for thought-through early

pregnancy decisions and to avoid

the distress caused by the birth of an

abnormal baby unexpectedly.

Down Syndrome, with an incidence

rate of 1 in 800 pregnancies, is the most

common genetic/chromosomal disorder

and is reasonably known to both the

medical fraternity and the general

public. From the 1960s, there have been

continuously improving approaches

to screen for and diagnose this and a

few other significant conditions during

pregnancy, given the seriousness of

these conditions. However, there is

another group of clinically relevant

disorders caused by the deletion (loss)

of a small part of a chromosome,

called microdeletion syndromes. This

chromosomal loss occurs very early

during development and is irreversible.

Microdeletion syndromes are clinically

important as they are associated

with intellectual impairment, learning

difficulties, autism and a host of other

abnormalities, including those related to

the heart and the kidneys. The reported

incidence of microdeletion syndromes is

1 in 1000 pregnancies. These conditions

are not easy to detect during pregnancy.

They were also previously considered

rare and therefore not high-priority

candidates for screening programmes.

Most individuals were/are identified after

birth, during childhood or even during

adulthood.

Unravelling DiGeorge

Initially, microdeletion syndromes

were described when patients

with a cluster of specific features

(phenotype) were observed together.

The genetic basis of these conditions

began to be identified around 30

CAUSED BY A DELETION IN

A SMALL AND VARIABLE

PART OF CHROMOSOME

22, 22Q11.2 DELETION

SYNDROME HAS AN

INCIDENCE OF 1 IN EVERY

2000 BIRTHS.

years ago, with the development of

techniques such as fluorescent in situ

hybridization. With the development

of other advanced techniques such

as chromosomal microarrays, more

and more areas of such repeated and

specific chromosomal losses began to

be identified, which correlated clinically

observed syndromes.

22q11.2 deletion syndrome

is commonly known as DiGeorge

syndrome. Velocardiofacial syndrome

and conotruncal anomaly face

syndrome are the most commonly

used names for the microdeletion

syndrome. It is the second biggest

cause of congenital heart disease and

developmental delays. Caused by a

deletion in a small and variable part of

chromosome 22, it has an incidence of

1 in every 2000 births. The syndrome

is associated with heart defects, cleft

palate, developmental delay, mental

and psychiatric disorders, endocrine

disorders, distinct facial features

and low calcium levels among other

features. The condition is associated

with premature mortality, based on the

severity of individual features. There

is no cure and the best management

strategy is a multidisciplinary approach

aimed at handling individual symptoms.

Early management of symptoms greatly

improves outcome. Most of the cases

occur spontaneously without family

history, while in 5-10% of the cases, it is

inherited with 50% risk of transmitting

the disorder. This risk of carrying an

affected pregnancy with microdeletion

syndrome is not related to maternal

age and the risk remains the same

throughout a women’s reproductive

period.

The syndrome was clinically

described in English language in

1960s in children who presented

with the triad of immunodeficiency,

hypoparathyroidism and congenital

heart disease. However, there is a huge

variability in the presentation and the

age of recognition of symptoms. Though

common, the lack of awareness of the

condition and/or testing methods and

the huge variability in presentation

delay diagnosis. The typical age of

molecular diagnosis is around five

years after numerous visits to different

clinical specialties. Early identification

and management is useful to improve

the quality of life. Though the condition

can be suspected during pregnancy

28 / FUTURE MEDICINE / OCTOBER 2018


y ultrasonography if certain structural

defects and cardiac anomalies are

seen, there is no regular screening

programme. Some cases may not have

signs that can be picked up on an

ultrasound.

Cell-free DNA screening

Over the past two to three decades,

tests for clear molecular diagnosis have

been available. In the past four years,

some of these conditions could be

screened non-invasively by a new test

that examines the cell-free DNA from

maternal blood. Non- Invasive pre-natal

test (NIPT) is a good screening test for

the expectant parents, cost permitting.

NIPT, a simple, non-invasive DNA test,

involves taking a small amount of

blood from the mother’s arm to test

for chromosomal abnormalities in the

developing foetus. Screening during

INVASIVE TESTS,

SUCH AS CHORIONIC

VILLUS SAMPLING AND

AMNIOCENTESIS POSE A

SMALL BUT SIGNIFICANT

RISK OF MISCARRIAGE.

pregnancy can help empower the

expectant parents to be more aware

of the condition and accordingly seek

medical help.

Other diagnostic tests for

microdeletion syndromes include

Fluorescent in situ Hybridisation,

Multiplex Ligation-dependent Probe

Amplification, Quantitative Polymerase

Chain Reaction and Chromosomal

Microarrays. However, these tests are

performed on actual foetal tissue

obtained by invasive tests, such

as chorionic villus sampling and

amniocentesis. They pose a small but

significant risk of miscarriage.

Microdeletion syndromes are a

group of frequently unsuspected and

overlooked disorders at pregnancy

evaluation. Greater awareness among

clinical fraternity as well as general

public and the development of a routine

screening programme would serve the

population well in identifying these

disorders early.

The author is

Programme Director- NIPT,

MedGenome, India

OCTOBER 2018 / FUTURE MEDICINE / 29


column

the catalyst

Revisiting primary care

The success of Ayushman Bharat programme will depend

on the effective transformation of point-of-care capabilities

MURALIDHARAN NAIR

The Alma Ata declaration of 1978, one

of the most significant milestones in

the field of public health, identified

effective primary care as the very bedrock

of a health system that aims for universal

healthcare. The declaration defined primary

health care as follows: “Primary health

care is essential health care based on

practical, scientifically sound and socially

acceptable methods and technology,

made universally accessible to individuals

and families in the community through

their full participation and at a cost that

the community and the country can

afford to maintain at every stage of their

development in the spirit of self-reliance

and self-determination.”

While there cannot be a debate on

the wisdom behind the tenets of the

declaration, it is evident from the state of

healthcare the world over -- developed and

developing included -- that the spirit of

the declaration was not pursued. Instead, a

hospital-centric model gained prominence,

resulting in a universal challenge of a

growing disease burden, a widening gap in

access to care and the unsustainable cost of

healthcare. However, there has been a call

from the WHO in recent times to revisit the

declaration and make it a reference point

while designing the health systems of the

future.

The state of primary health care in India,

particularly in rural areas, where 70 percent

of our population lives, is pathetic, as

evidenced by the statistics below.

In such a scenario, it is very welcome to

see the emphasis placed on primary care

through 1.5 lakhs HWC (health and wellness

centre) as a critical element of Ayushman

Bharat, the incumbent government’s

flagship programme for reforming Indian

healthcare. However, the success of

this endeavour will depend on the

effective transformation of point-of-care

capabilities:

INVESTMENT: While 1.5 lakh HWCs is

an adequate number for the effective

coverage of population, there is no clarity

on the timeline by which these will become

operational, and also on the investment

needed. One estimate available on the

government website puts an amount of Rs

10 lakhs and Rs 7 lakhs as one-time and

recurring expenditure for enhancing an SC

to HWC, which translates to approximately

15,000 cr and 10,000 cr of one time

and recurring expenditure. Where is the

provision for this amount, as the current

provisions being discussed are not enough

even for the hospital care part of NHPS?

TRAINING: The effective manning of this

mega initiative will need innovative thinking

to increase the supply of required human

resource and the government has rightly

planned to upskill nurses and Ayurveda

doctors to man the SCs. With the expansion

of focus to include mental health,

non-communicable diseases and

rehabilitative care and to leverage

30 / FUTURE MEDICINE / OCTOBER 2018


6

5

4

DISORDERS &

CHALLENGES

Mean number of providers with

degree by State

MBBS Degree

Other Degrees

No Degrees

3

2

0

Kerala

West Bengal

Karnataka

Punjab

Andhra Pradesh

Tamil Nadu

Gujarat

technology, even the traditional clinical

staff at the PHC level will need substantial

upgradation of their skills. Hence, it is

imperative that effective resourcing

on such a large scale will necessitate

massive training capability for creating

and sustaining the operations. It will be

necessary to not delegate this critical

function to the states. Instead, it should be

tightly controlled by a central governing

body for training and certification to ensure

consistent quality.

Assam

Uttar Pradesh

Bihar

Rajasthan

Odisha

Chattisgarh

Haryana

Maharashtra

Himachal Pradesh

Madhya Pradesh

USE OF ARTIFICIAL

INTELLIGENCE BASED

APPLICATIONS TO AID THE

PRIMARY CAREGIVER

CAN DEMOCRATISE

CLINICAL KNOWLEDGE.

Jharkand

Uttaranchal

SOURCE: Quality and

Accountability in Health: Audit

Evidence from Primary Care

Providers, J Das, et al

TECHNOLOGY: Effective use of technology

for both enhancing point-of-care

capabilities and bridging access to specialist

advice when needed through telehealth

applications will be critical.

Use of artificial intelligence (AI) based

applications to aid the primary caregiver

can democratise clinical knowledge

(applications for such use are being

tested in the UK and other countries) and

revolutionise the effectiveness of care at the

last mile.

Culture of cost containment: We have a

very large underprivileged population and

the budgets will never be enough. Hence,

being efficient will be a moral need. This

will necessitate laser-like focus on cost

containment, complete with a dedicated

organisation and a holistic approach,

including infrastructure design, process

flow, choice of formulary (e.g.: standardise

centrally, maximise use of quality generics),

choice of technology (e.g.: maximise frugal

technology in diagnostics), contracting

(e.g.: maximise central purchases for

leveraging the economies of scale)

productivity norms, a performance criteria

underpinned by a robust measurement and

a reporting framework to facilitate timely

and effective action

EFFECTIVE SUPPLY CHAIN: Public

health facilities have been notorious for

unavailability of medicines and related

provisions. which can seriously hamper

the outcome expectation from primary

care. Hence it is imperative to have an

agile supply chain management to ensure

near 100 percent availability even while

optimising the burden of inventories..

The author has long-standing association with

EY India but the views are strictly personal.

OCTOBER 2018 / FUTURE MEDICINE / 31


drug approvals

Pembrolizumab

in combo with

pemetrexed

The European Commission

has approved

pembrolizumab (Keytruda),

Merck's anti-PD-1 therapy, in

combination with pemetrexed

(Alimta) and platinum

chemotherapy for the firstline

treatment of metastatic

nonsquamous non-small

cell lung cancer (NSCLC) in

adults whose tumours have

no EGFR or ALK positive

mutations.

This approval, the first

in Europe for an anti-PD-1

therapy in combination with

chemotherapy, is based on

data from the pivotal Phase 3

KEYNOTE-189 trial in patients

with metastatic nonsquamous

NSCLC regardless of PD-L1

tumour expression status.

The data demonstrated a

significant survival benefit

for the combination of

Keytruda with chemotherapy

as compared with standardof-care

chemotherapy alone

– reducing the risk of death

in these patients by half, the

company said.

The approval allows

marketing of the Keytruda

combination in all 28 EU

member states plus Iceland,

Lichtenstein and Norway,

Cassipa sublingual film

for opioid dependence

The US FDA granted

approval to Teva

to market Cassipa

(buprenorphine and

naloxone) sublingual

film for the maintenance

treatment of opioid

dependence.

"We’ve taken a number

of steps to advance the

development of new FDAapproved

treatments for

opioid dependence and

encourage health care

professionals to ensure

patients are offered an

adequate chance to benefit

from these therapies," said

FDA Commissioner Scott

Gottlieb, M.D.

Opioid use disorder

should be viewed similarly

to any other chronic

condition that is treated

with medication, he added.

Medication-assisted

treatment (MAT) is a

comprehensive approach

that combines FDAapproved

medications

(currently methadone,

buprenorphine, or

naltrexone) with counseling

at the approved dose of

200 mg every three weeks

until disease progression or

unacceptable toxicity.

Keytruda is also approved

in Europe as a monotherapy

for the first-line treatment

and other behavioural

therapies to treat patients

with opioid use disorder

(OUD).

Regular adherence to

MAT with buprenorphine

reduces opioid withdrawal

symptoms and the desire

to use opioids, without

causing the cycle of highs

and lows associated

with opioid misuse or

abuse. At proper doses,

buprenorphine also

decreases the pleasurable

effects of other opioids,

making continued opioid

abuse less attractive.

According to the

Substance Abuse and

Mental Health Services

Administration, patients

receiving MAT for treatment

of their OUD cut their risk

of death from all causes in

half, according to an FDA

release.

In June, the FDA also

approved the first generic

versions of Suboxone

(buprenorphine and

naloxone) sublingual film in

multiple strengths.

of metastatic squamous

or nonsquamous NSCLC in

patients whose tumours have

high PD-L1 expression with

no EGFR or ALK positive

tumour mutations and for

previously-treated patients

with locally advanced or

metastatic NSCLC whose

tumours express PD-L1.

Lumoxiti to

treat hairy cell

leukaemia

T

he US Food and Drug

Administration gave its

nod to Lumoxiti

(moxetumomab pasudotoxtdfk)

for the treatment of

adult patients with relapsed

or refractory hairy cell

leukaemia (HCL).

Lumoxiti was approved

under FDA’s Priority Review.

The approval is based on data

from the phase III, singlearm,

open-label ‘1053’ trial of

Lumoxiti monotherapy in 80

patients who have received

at least two prior therapies,

including a purine nucleoside

analog.

The primary endpoint of

the trial was durable complete

response, AstraZeneca and

MedImmune said in joint

press communication.

The median time to

haematologic remission was

1.1 months. At data cut-off, the

median duration of complete

response was not yet reached

after a median 16.7 months of

follow-up.

Capillary leak syndrome

(CLS) and haemolytic uraemic

syndrome (HUS), including

life-threatening cases of each,

have been reported among

patients treated with Lumoxiti.

In the combined safety

database of 129 HCL patients

treated with Lumoxiti, Grade 3

or 4 CLS occurred in 1.6% and

2% of patients, respectively.

Grade 3 or 4 HUS occurred

in 3% and 0.8% of patients,

respectively.

In the ‘1053’ trial of 80

patients, the most common

Grade 3 or 4 adverse

reactions were hypertension,

febrile neutropenia, and HUS.

HUS was the most common

adverse reaction leading to

discontinuation.

Lumoxiti, which targets

CD22 transmembrane protein,

32 / FUTURE MEDICINE / OCTOBER 2018


is AstraZeneca's first antibodydrug

conjugate (ADC).

Merck to launch

two new HIV-1

medicines

Delstrigo and Pifeltro are

cleared for sale in US to

treat HIV-1 infection, Merck

said.

Delstrigo is a once-daily

fixed-dose combination

tablet of doravirine (100

mg), lamivudine (3TC, 300

mg) and tenofovir disoproxil

fumarate (TDF, 300 mg).

Pifeltro (doravirine, 100 mg)

is a new non-nucleoside

reverse transcriptase inhibitor

(NNRTI) to be administered

in combination with other

antiretroviral medicines.

Both Delstrigo and

Pifeltro are indicated for

the treatment of HIV-1

infection in adult patients

with no prior antiretroviral

treatment experience, and

are administered orally once

daily with or without food.

Delstrigo contains a boxed

warning regarding posttreatment

acute exacerbation

of hepatitis B infection.

The approvals are based

on findings from the pivotal,

randomized, multicenter,

double-blind, active controlled

Phase 3 trials, DRIVE-AHEAD

and DRIVE-FORWARD,

evaluating the efficacy and

safety of Delstrigo and

Pifeltro, respectively, in

participants infected with

HIV-1 with no antiretroviral

treatment history.

Jivi cleared for

hemophilia A

treatment

Jivi (BAY94-9027) has

been granted approval

for the routine prophylactic

treatment of hemophilia A in

previously treated adults and

adolescents 12 years of age or

older in the US.

The recommended initial

prophylactic regimen for Jivi is

twice weekly, with the ability

to dose every five days and

further individually adjust to

less or more frequent dosing

based on bleeding episodes,

Bayer said.

The FDA also approved

Jivi for on-demand treatment

and the perioperative

management of bleeding in

the same population.

The US FDA approval is

based on the results of the

pivotal Phase 2/3 PROTECT

VIII trial comprised of

prophylactic dosing, ondemand

treatment, and

perioperative management in

previously treated adults and

adolescents 12 years of age

or older with severe

hemophilia A.

BAY94-9027 was

engineered to have an

Mepolizumab as an add-on therapy for paediatric asthma

Mepolizumab (Nucala)

has been cleared for

marketing by EC as an addon

treatment for severe

refractory eosinophilic asthma

in paediatric patients aged six

up to 17 years.

Mepolizumab is the

first and only approved

biologic therapy that targets

interleukin-5 (IL-5), which

plays an important role in

regulating the function of

eosinophils, GSK said.

Mepolizumab is the firstin-class

monoclonal antibody

that targets IL-5. It is believed

to work by preventing IL-5

from binding to its receptor

on the surface of eosinophils.

Inhibiting IL-5 binding in

this way reduces blood

eosinophils. The drug was first

34 / FUTURE MEDICINE / OCTOBER 2018

approved in 2015 for severe

eosinophilic asthma,

Mepolizumab has been

studied in over 3,000 patients

in 16 clinical trials across

a number of eosinophilic

indications and has been

approved in the US, Europe

and in over 20 other markets,

as an add-on maintenance

treatment for patients with

severe eosinophilic asthma.

In the US, Japan and

Canada, it is approved

as add-on maintenance

treatment for patients with

eosinophilic granulomatosis

with polyangiitis (EGPA).

Mepolizumab is currently

being investigated for severe

hypereosinophilic syndrome,

nasal polyposis and COPD.

This marketing

authorisation is based on a

partial data extrapolation

approach which was agreed

with the paediatrics committee

(PDCO) of the EMA. With this

approach, efficacy and safety

data from the Phase III studies

included in the mepolizumab

severe asthma development

programme for patients 12

and over were extrapolated to

children.


extended half-life by

harnessing proven PEGtechnology

that delivers

higher sustained levels of

FVIII, which extends the

blood’s ability to coagulate

for longer. As a site-specific

PEGylated FVIII, Jivi has a

half-life of 17.9 hours that

delivers sustained levels in the

blood.

The FDA also approved

Jivi for on-demand treatment

and the perioperative

management of bleeding in

the same population.

Eravacycline for

intra-abdominal

infections

The US FDA has granted

marketing authorisation

EU nod for Taf-Mek combo for adjuvant

melanoma therapy

The EC has approved

dabrafenib (Tafinlar)

in combination with

trametinib (Mekinist) for

the adjuvant treatment of

stage III patients with BRAF

V600 mutation-positive

melanoma after complete

surgical resection.

The approval is based

on results from the Phase

III COMBI-AD global study,

which enrolled more than

870 patients with stage

III, BRAF V600E/K-mutant

melanoma without prior

anticancer therapy, and

who were randomized

within 12 weeks of

complete surgical resection.

The BRAF gene

provides instructions for

making a protein that

helps transmit chemical

signals from outside the

cell to the cell's nucleus.

This protein is part of a

signalling pathway known

as the RAS/MAPK pathway,

which controls several

important cell functions.

Specifically, the RAS/

MAPK pathway regulates

the proliferation of cells,

the process by which cells

mature to carry out specific

functions, migrations and

apotheosis.

This approval is

the third for Tafinlar in

combination with Mekinist

in Europe across a variety

of tumour types identified

with a high level of BRAF

mutation, Novartis said.

Combination use

of Tafinlar + Mekinist in

patients with unresectable

or metastatic melanoma

who have a BRAF V600

mutation is approved

in the US, EU, Japan,

Australia, Canada and other

countries.

The combination of

Tafinlar + Mekinist is also

approved for the treatment

of metastatic non-small cell

lung cancer (NSCLC) with

a BRAF V600E mutation

in the US and advanced

NSCLC with a BRAF V600

mutation in the EU.

to eravacycline (Xerava) for

the treatment of complicated

intra-abdominal infections

(cIAI).

In clinical trials,

eravacycline was welltolerated

and achieved

high clinical cure rates

in patients with cIAI,

demonstrating statistical noninferiority

to two widely used

comparators – ertapenem

and meropenem, according

to Tetraphase

Pharmaceuticals, Inc.

Eravacycline is indicated

for the treatment of cIAI in

patients 18 years of age and

older.

The antibiotic drug

was investigated for the

treatment of cIAI as part

of IGNITE (Investigating

Gram-Negative Infections

Treated with Eravacycline)

phase 3 programmes. In the

first pivotal phase 3 trial in

patients with cIAI, twice-daily

intravenous (IV) eravacycline

met the primary endpoint

by demonstrating statistical

non-inferiority of clinical

response compared to

ertapenem and was welltolerated.

In the second phase

3 clinical trial in patients

with cIAI, twice-daily IV

eravacycline met the primary

endpoint by demonstrating

statistical non-inferiority of

clinical response compared

to meropenem and was

well-tolerated. In both trials,

the drug achieved high cure

rates in patients with Gramnegative

pathogens, including

resistant isolates, the drug

maker said.

Lanadelumab

to prevent HAE

attacks

Following priority review,

the US FDA has approved

lanadelumab-flyo (Takhzyro)

injection, for prophylaxis to

prevent attacks of hereditary

angioedema (HAE) in patients

12 years of age and older,

Shire plc said.

Lanadelumab is a

monoclonal antibody that

provides targeted inhibition

of plasma kallikrein, an

enzyme which is chronically

uncontrolled in people with

HAE, to help prevent attacks.

The recommended starting

dose of lanadelumab is 300

mg every two weeks. A dosing

36 / FUTURE MEDICINE / OCTOBER 2018


interval of 300 mg every four

weeks is also effective and

may be considered if the

patient is attack free for more

than six months.

The FDA approval of

lanadelumab was based

on data from four clinical

trials, including the HELP

(Hereditary Angioedema

Long-term Prophylaxis) Study,

the largest prevention study

conducted to date in HAE,

according to Shire.

In the Phase III HELP

study, lanadelumab reduced

the number of monthly HAE

attacks an average of 87%

(n=27) vs. placebo (n=41)

when administered at 300

mg every two weeks and 73%

(n=29) vs placebo (n=41)

when administered at 300 mg

every four weeks.

Lanadelumab has a halflife

of approximately two

weeks and is administered

as one subcutaneous selfinjection

every two weeks at

the recommended starting

dose.

Shire added lanadelumab

to its HAE portfolio with the

acquisition of Dyax Corp.

Oral RTK inhibitor

lenvatinib to

treat HCC

The EC has granted a

marketing authorization

for the oral receptor tyrosine

kinase (RTK) inhibitor

lenvatinib (Lenvima), as a

single agent for the firstline

treatment of adult

patients with advanced or

unresectable hepatocellular

carcinoma (HCC) who have

received no prior systemic

therapy.

Lenvatinib is the first

new, first-line treatment for

advanced or unresectable HCC

in a decade to show an overall

survival treatment effect by

statistical confirmation of noninferiority

against standard of

care, according to a joint press

statement by Eisai and Merck.

Lenvatinib's approval

was based on results from

REFLECT (Study 304), an

open-label, phase 3 trial

where the drug demonstrated

a treatment effect on

overall survival by statistical

confirmation of non-inferiority

when compared with the

standard of care, sorafenib, in

954 patients with previously

untreated unresectable HCC.

Lenvatinib also demonstrated

statistically significant

superiority and clinically

meaningful improvements in

progression-free survival and

objective response rate.

Currently, Lenvima is

marketed in Japan for

the treatment of HCC and

in the United States for

the treatment of first-line

unresectable HCC.

In March 2018, Eisai

and Merck entered into a

strategic collaboration for the

worldwide co-development

and co-commercialization of

Lenvima.

Loteprednol for

pain following

ocular surgery

The US FDA has approved

loteprednol etabonate

ophthalmic suspension 1%

(Inveltys) for the treatment of

post-operative inflammation

and pain following ocular

surgery. Inveltys is the first

twice-daily (BID) ocular

corticosteroid approved for

this indication.

All other ocular steroids

are approved for four-times-aday

dosing. The use of ocular

steroids post-surgery is to

achieve a rapid reduction of

inflammation and to promote

healing of the eye. Therefore,

ensuring close adherence

to the steroid regimen is a

critical factor for physicians in

the post-surgery care of the

patient and eventual overall

success of the procedure, Kala

Pharmaceuticals, Inc said.

Kala has initiated a third

Phase 3 clinical trial, STRIDE

3 (STRIDE - Short Term Relief

In Dry Eye), evaluating KPI-121

0.25% for the temporary relief

of the signs and symptoms of

dry eye disease.The company

expects to report top-line

results for STRIDE 3 in the

fourth quarter of 2019.

Kala also plans to submit

a New Drug Application (NDA)

for KPI-121 0.25% during

the second half of 2018. The

NDA will include data from

three clinical trials studying

approximately 2,000 patients,

including one Phase 2 trial and

two Phase 3 efficacy and safety

trials (STRIDE 1 and STRIDE 2),

the company said.

Oxervate, first rhNGF to treat

neurotrophic keratitis

The US FDA has approved

Oxervate (cenegerminbkbj

ophthalmic solution) to

treat neurotrophic keratitis

(NK), Dompé announced.

Neurotrophic keratitis,

characterised by corneal

scarring and vision loss, is a

rare orphan condition.

Oxervate represents the

first-ever topical biologic

medication approved in

ophthalmology, and is the

first ever application of

a human NGF as drug or

treatment, according to the

company.

Oxervate is based on

cenegermin-bkbj, a novel

recombinant human nerve

growth factor (rhNGF) that

is structurally identical to

the nerve growth factor

(NGF) protein that is made

in the human body, including

in the ocular tissues.

The endogenous protein

supports corneal integrity

though several mechanisms.

NGF acts directly on

corneal epithelial cells to

stimulate their growth and

survival. In addition, NGF

is known to bind receptors

on lacrimal glands to

promote tear production,

which may provide the

eye with lubrication and

natural protection from

pathogens and injury. The

protein also has been shown

experimentally to support

corneal innervation, which is

lost in neurotrophic keratitis.

OCTOBER 2018 / FUTURE MEDICINE / 37


egulatory

FDCs ON THEIR WAY OUT?

India slaps ban on 328 drug combos finding no therapeutic justification

for such concoctions

The recent ban of 328 Fixed Dose

Combinations (FDC) drugs with

immediate effect by the Union

Health Ministry is set to cost roughly

Rs 2500 crore to the pharmaceutical

industry in India. The ban is likely to hit

40-60 pharmaceutical companies and

around 6000 brands, according to the

industry experts.

The health ministry banned

manufacture, sale and distribution of

328 FDC drugs after an expert panel,

which was set up by the Drugs Technical

Advisory Board (DTAB) to study safety,

efficacy and therapeutic justification of

the drugs, recommended that there

is no therapeutic justification for the

ingredients contained in 328 FDCs

and that these FDCs may involve risk

to human beings. The list of banned

FDCs include many popular drugs.

Meanwhile, the ministry has restricted

manufacturing, sale and distribution of

six other FDCs drugs subject to certain

conditions. FDCs are drugs

in combinations of two or more

active ingredients in a fixed ratio in a

single dosage.

“The industry will see an erosion

of about Rs 2500 crores following the

ban of the FDC drugs. There are certain

companies who have majority of these

products and they will be affected

badly,” said Daara B. Patel, Secretary

General, Indian Drug Manufacturers’

Association (IDMA). However, he added

that it won’t have much impact on the

pharmaceutical industry in India, which

has a size of over Rs 1 lakh crore.

FDCs unsafe

Welcoming the ban, All India

Drug Action Network (AIDAN), an

RATIONALITY NEEDS

TO BE DEMONSTRATED

BY SAFETY, EFFICACY

AND THERAPEUTIC

JUSTIFICATION, SAYS AIDAN

independent network of several non

government organizations working to

increase access and improve the rational

use of essential medicine, said in a

statement that none of the FDCs meet

the criteria of a rational and safe FDC.

The people of India have been made

the consumers of unsafe medicines

for too long and this is one step

towards rectifying the grave situation

of a pharma market brimming with

innumerable irrational FDCs.

“It reinforces our constant demand

for approval, and use, of only rational

medicines in India. Rationality needs

to be demonstrated by safety, efficacy

and therapeutic justification. None of

the FDCs meet the criteria of a rational

and safe FDC. The people of India have

been made the consumers of unsafe

medicines for too long and this is

one step towards rectifying the grave

situation of a pharma market brimming

with innumerable irrational FDCs,” said

AIDAN.

Under section 26 A of the Drugs

and Cosmetics Act 1940, the Health

Ministry had banned the manufacture,

sale and distribution of 344 FDCs for

human use in March 2016. Later five

more FDCs were added to the list. The

health ministry banned these FDCs

after an expert committee headed by

Prof CK Kokate declared them unsafe.

However, many affected manufactures

contested the ban in Supreme Court

and various high courts. The ministry

moved the apex court challenging a

Delhi high court order that quashed

the ban. AIDAN had also filed a petition

in the top court against the Delhi high

court order.

In December 2017, the Supreme

Court had asked DTAB, the country’s

top drug advisory body to review

manufacture and sale of FDCs.

38 / FUTURE MEDICINE / OCTOBER 2018


BORON+

SWEPT BY

REGULATORY WAVE

The ban on 328 fixed dose

combinations will lead to a loss of

industry revenue amounting to

₹2500cr

+

CETIRIZINE+

CAFFEINE

+

LEVOFL

DICLO

NIMES

OXACIN+

FENAC+

ULIDE+

CEFURO

LIN

XIME +

EZOLID+

ZINC+

XICAM+

OCTOBER 2018 / FUTURE MEDICINE / 39


slug

HIGH COURT

ALLOWS DRUG

MAKERS TO SELL

EXISTING STOCK

OF FDCS

The Delhi High Court has

allowed the sale and

distribution of already

manufactured stock of the

328 fixed-dose combination

(FDC) drugs banned by the

government on September 7.

Offering an interim

relief to ten pharmaceutical

companies, the Court directed

the firms to file an affidavit

with the court indicating

the ‘batches already

manufactured’ by them as a

measure to ensure the quality

of the drugs.

The Court further ordered

that no coercive action

would be initiated against

the manufactures, stockists

as well as dealers of the

banned FDC drugs, as per

the court directive which

allows the sale of FDC drugs

for the time being. The High

Court, however, directed

the companies to stop all

manufacturing operations

with regard to the banned

FDC drugs.

Subsequent to the apex court direction,

an expert panel was formed under the

chairmanship of Dr. Nilima Kshirsagar,

Professor, Head, Clinical Pharmacology,

G. S. Medical College, KEM Hospital, to

review safety, efficacy and therapeutic

justification of the FDCs. The panel

recommended ban of these drugs citing

safety issues and lack of therapeutic

justification. The board in its report

concluded that there was no therapeutic

justification for the ingredients in 328

FDCs and that these FDCs may involve

risk to human beings. It recommended

banning the manufacture, sale or

distribution of the FDCs in larger public

interest. But 15 out of 344 FDCs in the

original list, which were claimed to be

manufactured prior to September 1988,

were excluded from the current as the

Supreme Court had stated that the

government cannot ban the 15 FDCs on

the basis of DTAB report.

Tip of iceberg?

“When the ban on FDCs was notified,

pharma companies in court cases

questioned the locus standi and powers

of the Central government to ban drugs

in India. That issue has been settled

decisively with the recommendations of

the sub-committee led by Dr. Kshirsagar”

said AIDAN in its statement.

AIDAN has also urged the

government to take swift action on

the 15 FDCs that were excluded from

the notification on the basis of safety

and efficacy considerations. “We note

however, that the FDCs under scrutiny

account for approximately Rs. 2,500

crore in sales and represent only the

tip of the iceberg. In our estimation, the

market of unsafe, problematic FDCs in

India is at least one fourth of the total

pharma market valued at Rs. 1.3 trillion,”

it said.

Meanwhile, another round of legal

tussle is expected to ensue in the

coming days with many companies

approaching courts against the ban.

The Supreme Court allowed sale of

Saridon, Dart, a pain killer and Piriton

Expectorant, which is used for common

cold, cough and other conditions, in

September. The apex court’s interim

order came on petitions filed by

GlaxoSmithKline, Piramal Healthcare

and Juggat Pharma. While Saridon is

manufactured by Piramal Healthcare,

Piriton is owned by GlaxoSmithKline

and Dart by Juggat. The court in its

interim order permitted the companies

to manufacture and sell the drugs until

final judgement is passed. Challenging

the ban, the companies reportedly

claimed that the only reason given

in the notification was that FDCs

had no therapeutic value. In another

development, Indian pharma major

Wockhardt approached Delhi High Court

against the ban as its anti-inflammatory

drug Ace Proxyvon. According to

industry sources, more companies are

expected to approach courts in future

against the ban.

Clinicians say that before banning

the combinations, drug authorities

should ensure that the individual

drugs are available in the market.

Otherwise, it could lead to the shortage

of some crucial medications. “There

were occasions where the ban of

a particular combination drug, for

example, the drugs containing codeine,

was banned leading to severe shortage

of this important medication,’’says Dr

Vinod B Nair, an otolaryngologist from

Kochi, adding that “so long as it is

not going to affect the availability of

the crucial medications the ban

wouldn’t make much impact in day to

day practice.”

40 / FUTURE MEDICINE / OCTOBER 2018


column

trialomics

Harnessing AI

for healthcare

Artificial intelligence is unlikely to replace doctors, but is

expected to optimize and improve their medical skills

DR ARUN BHATT

Writer is a consultant

on clinical research &

development from

Mumbai.

arun_dbhatt@hotmail.com

“I

believe this artificial intelligence is

going to be our partner. If we misuse it,

it will be a risk. If we use it right, it can

be our partner.” - Masayoshi Son, Japanese

business magnate.

Artificial intelligence (AI) is the name

given to techniques that use software to

mimic human cognition in the investigation

of complex health data and information. AI

is revolutionizing healthcare with its access

towards a large amount of health data and

rapid advances in analytical techniques. AI is

considered augmented intelligence as it can

help in reducing diagnostic and therapeutic

errors and provide real-time interpretations

for health risk signals and health outcome

prediction. AI systems analyse a variety

of data – clinical examination, laboratory

data, diagnostic imaging, genetic testing

and electrodiagnosis – to improve medical

decisions.

AI devices consist of 1) machine learning

(ML) techniques and 2) natural language

processing (NLP) methods. ML procedures

analyse structured medical data - e.g.,

imaging, genetic and electrophysiology,

to cluster patients’ characteristics or to

determine the probability of disease

outcomes. NLP methods evaluate information

from unstructured data - e.g., clinical case

notes and medical journals to complement

and enrich structured health data.

AI applications have the potential to be

used in diverse health conditions. However,

most of the AI research focuses on disease

areas with high mortality - e.g., cancer,

nervous system disease or cardiovascular

disease. AI systems have been used for

diagnosis of skin cancer from clinical

images, diagnosis of cardiac disease using

cardiac images, to restore the control of

movements in patients with quadriplegia,

early detection of Alzheimer’s disease, early

stroke prediction by employing a movementdetecting

device and predicting and analysing

the performance of stroke treatment. AI

has also been utilized to detect congenital

cataract disease using ocular image data and

diagnose diabetic retinopathy through retinal

fundus photographs. The accuracy, specificity

and sensitivity of AI diagnostic systems are

high and superior to those of experienced

physicians. However, AI is still in the early

stages of research and adoption in medical

care. Besides, its real-life implementation is

facing regulatory challenges.

AI pose a new challenge for physicians,

some of whom are concerned that this

advanced technology will replace them. But

the fears seem unfounded. AI is unlikely

to replace the doctors but is expected to

optimize and improve their medical skills.

Dr Abraham Verghese, a well-known author

from Stanford University, opined that “the two

cultures – computer and physician – must

work together (JAMA Jan 2, 2018).” AI has

the potential to reduce tedious administrative

tasks, handle large volumes of medical

data and information, and provides an

opportunity to integrate the expertise

of medical practitioners and intelligent

automation.

AI is called the stethoscope of the 21st

century, says Dr Bertalan Meskó. The techsavvy

physician of the 21stcentury should not

fear AI tools, but should be ready to harness

benefits of augmented intelligence in her

practice.

42 / FUTURE MEDICINE / OCTOBER 2018


straight talk

“INDIA WILL SOON MAKE THAT

BIG REVOLUTION OF CHEAPER

ROBOTIC SURGERY”

One of the major breakthroughs

in the area of gynaecological

endoscopy that the world is now

waiting for is cheaper robotic

surgery. And, it is shortly expected

from India, a country that has

already produced many innovative

endoscopic devices and is also

home to many of the the world’s

most skilled endoscopic surgeons,

says PROF. LISELOTTE METTLER,

who is loved and respected as a

great teacher by most of India’s

well-reputed endoscopists.

Prof. Mettler,an Austrian-

German surgeon specialised

in endocrinology, reproductive

medicine, gynaecological

endoscopyand gynaecological

oncology, is a professor emeritus

of the Department of Gynaecology

and Obstetrics at Kiel University,

Germany. Mettler, who conducted

one of India’s first endoscopic

surgeries at Mumbai’s Breach

Candy Hospital in 1973 and has

also authored more than 600

publications and several books

on gynaecological endoscopy,

spoke to C H UNNIKRISHNAN for

Straight Talk on the sidelines of

a three-day International Society

for Gynaecologic Endoscopy

(ISGE) conference held in Pune in

September. Edited excerpts:

You have been very regular to India as many of your

students successfully practice here and you have also

conducted several endoscopic surgeries in Indian hospitals.

What are the key differences that you see in India and the

West as far as the practice of this speciality is concerned?

There is not much of difference in both these markets as far

as the technology and the skill-set of doctors are concerned.

In the field of endoscopy in particular, the technology

and procedures are almost the same that Kiel Hospital --

Gynaecological Endoscopy Department in the University of

Kiel,introduced in the early seventies. But, Indian doctors have

really put more skills into it. I would say Indian doctors are far

more efficient as they manage complex surgeries here despite

limited infrastructure and low affordability of patients. Since

most patients in the West are insured and they don’t have to

pay out of pocket, costly equipment and advanced procedures

are easily affordable there. But, the situation in India is different

and the doctors actually use their capabilities much more

efficiently to overcome the limited resources. Many of the

devices that Indian doctors use in endoscopic surgeries today

are indigenous and very innovative, which have made these

surgeries cheaper here.

But, does it make the surgeries poor in quality as well here

as compared to the West?

Not at all. You have brilliant doctors in India, who are

capable of using the limited resources for optimum utility by

putting their skills in it. The country has technical as well as

manufacturing talent to innovate products that suit this market

in terms of cost. The other important fact that I would like to

add here is that many brilliant doctors in India are also quite

passionate about the work that they do and they put their

hundred percent in such surgical procedures. I have seen

that Indian doctors, who are well-versed with endoscopic

procedures, have really modified the techniques and modalities

to make it much easier for the doctor as well as the patient.

If that is the case, India can very well attract patients from

even Western countries isn’t it?

Of course, there have been patients coming from the West

for such surgeries. I have sent a couple of my own patients

from Germany to India for gynec-oncology surgeries to a

hospital in Pune, where one of my old students, who is a

brilliant endoscopic surgeon, operated on them. I am sure

44 / FUTURE MEDICINE / OCTOBER 2018


OCTOBER 2018 / FUTURE MEDICINE / 45


healthcare set-ups, except a few centres

of excellence, are still poor in terms of

infrastructure and latest technologies, many

in the private sector are comparatively

much better now. Indian hospitals in general

were in a very bad condition as far as

infrastructure and quality standards were

concerned earlier. I myself have witnessed

doctors and other staff eating even in the

operation theatres and throwing the bones

on the floor, which is no more the case

now. Indian hospitals are getting better

and cleaner, though there is still scope for

improvement.

What are the latest breakthroughs in

endoscopic surgery?

Thoughthe basic technologies that are

used in the endoscopic surgery are more or

less the same today as I mentioned earlier,

there have been a lot of improvisations and

modifications that have taken place in the

I myself have witnessed doctors

and other staff eating even in the

operation theatres and throwing

the bones on the floor,

which is no more the case now.

there are all possibilities that patients can come from even

developed countries to India as the procedures and expertise

that is available are not less than any other place and there is

also a significant cost difference as compared to the US and

Europe. I would say that the cost here would be around one

tenth of the cost that prevails in those markets.

How equipped are Indian hospitals as far as quality

standards and the overall healthcare systems are concerned

to cater to patients, who are used to an evolved set-up in the

developed markets?

Indian hospitals are no more the same as they were in

the seventies or eighties. Though the public or government

devices and supportive systems over the

last few years as medical technology is a

fast evolving area. While 3D endoscopy and

robotic surgeries are comparatively later

breakthroughs, it is still very expensive all

over the world. This is the same situation

in India too, though there are only very

few hospitals that have facilities for robotic

surgery and 3D endoscopy here at present.

In this context, one of the most soughtafter

and shortly expected breakthroughs in

endoscopy is a robotic surgery developed

by India using its inherent talent in inventing

cheaper and better variants of expensive

products and systems. As far as I know, the

efforts for developing a cheaper robotic

surgery in India are at a very advanced stage

currently, and once it is out in the market,

it will be a big revolution across the world.

I am eighty now, and I hope I will see this

revolution.

46 / FUTURE MEDICINE / OCTOBER 2018


education

DOCTORS SUE MCI ON NEW TEQ RULES

Petitioners argue that there was no age limit when they joined

A

group of doctors in Tamil Nadu

has filed a petition in Madras

High Court challenging the

maximum age limit of 40 set by the

Medical Council of India (MCI)

for the post of senior resident or

assistant professor in medical

colleges. In their petition, the doctors

have requested the court to

declare the amendment as

unconstitutional, ultra vires,

discriminatory and illegal.

The public interest litigation (PIL),

which came up for hearing before

the bench of Justice S. Manikumar

and Justice Subramaniam Prasad,

was posted for the next hearing on

September 19 as the MCI sought time

for filing counter affidavit.

Last year, MCI had made certain

changes in Teachers Eligibility

Qualifications (TEQ) rules. The changes

include the maximum age limit of

40 for appointment to the post

of senior resident with effect from

June 8, 2017. In their affidavit, the

petitioners stated that they joined

for post graduate courses before the

changes were effected in rules and

there was no age limit when they

joined. In November 2017, the state

government sent a proposal to the

central government asking it to drop

the criteria of age limit as it would

affect medical administration and

career of the doctors who have joined

for PG courses. The government has

also stated that the move will prove

counterproductive.

Subsequent to the notification, MCI

clarified that amendments would be

applicable prospectively from the date

of notification and will not have any

effect on appointments or promotions

made before the date of notification.

Therefore, residents already working

on the post of senior resident after

passing DNB or Diploma Course can

continue to hold the same post. It

has further clarified that those who

are doing post graduation after the

age of 40 years will not be eligible

for the post of Senior Resident and

MCI CLARIFIED THAT

AMENDMENTS WOULD

BE APPLICABLE

PROSPECTIVELY FROM THE

DATE OF NOTIFICATION.

they cannot be appointed as Assistant

Professor directly after PG and

promoted as Associate Professor after

gaining five years of experience as

assistant professor. It further clarified

that if a person has done DNB from

MCI recognised institute, then he or

she will be considered equivalent

to MD/MS to be eligible as Senior

Resident. If the person had done

DNB from institutes not recognised by

MCI, then he or she has to do three

years of Junior Residency in

the concerned subject from MCI

approved institute to be eligible to

become SR.

MCI later clarified that a candidate

having MBBS and DLO (ENT)

qualification has worked as JR for

a period of one year in ENT after

PG would require MD degree in the

subject concerned. Thereafter one-year

senior residency is mandatory for the

post Assistant Professor

in the subject concerned. It has also

clarified that requirement of one

year senior residency for the post of

assistant professor is applicable

only to those disciplines where posts

of senior residents is prescribed

as per the minimum standard

requirement of MCI.

48 / FUTURE MEDICINE / OCTOBER 2018


case reports

HOW SHE REGAINED

HER LOST TASTE

A new lease of life to a 70-year-old lady crippled by multiple progressive

heart disorders —thanks to TAVR

DR ANOOP AGRAWAL

Mrs. Sharma (name changed) couldn’t taste her food

anymore. “Just like my hair, my tastebuds are also

aging,” she thought. Mrs. Sharma, at 70 years of age,

had been a well-kept lady until the previous year. She had

enjoyed a healthy, active lifestyle in her youth and adulthood.

With an academic bend of mind, she used to teach until her

early 60s. At around 61 years of age, she was diagnosed with

a bicuspid aortic valve (BAV) that had led to severe aortic

stenosis (AS), and was advised

to undergo surgical aortic

valve replacement (SAVR).

Overwhelmed by the flow

of information, Mrs. Sharma

ended up refusing surgery

at the time. Over the next

few years, she continued to

function independently and

forgot about the deformed

valve sitting in her heart.

Last year, she started

noticing exertional shortness

of breath upon walking a few

hundred meters. Over the

ON THE TOP OF SEVERE

AS, SHE HAD DEVELOPED

SEVERE AORTIC

REGURGITATION, SEVERE

MITRAL REGURGITATION

AND SEVERE LEFT

VENTRICULAR SYSTOLIC

DYSFUNCTION.

next few months, she slowed down her life to compensate

for her exertional symptoms. Slowly, she started developing

dyspnea on walking within her house. She lost interest in

her food. Her sleep was interrupted with frequent episodes

of breathing difficulty. By the time she touched 70, she had

lost almost 9 kg over a period of six months due to early

satiety and ageusia. She was restricted to her room due to

her inability to walk longer distances. Lately, she also started

fainting at home, only to regain her senses after a minute

or two. It was so frequent that it almost became routine for

her and her family. She did seek medical attention for her

progressive illness and came up with unanimous feedback:

“She needed SAVR, but the risk was too high.” Not ready to

undergo a surgery risking her life, she decided to continue

with medicines alone, which obviously

weren’t working.

Sometime during this hustle, she was

referred to me for further evaluation. What

I saw was a thin, frail lady who had to take

periodic pauses in between her sentences to

catch her breath. Even before taking a look

at her medical records, I knew that patients

with that degree of cardiac cachexia rarely

do well with heart surgery. Her medical

records made me concerned. On the top of

severe AS, she had developed severe aortic

regurgitation, severe mitral regurgitation and

severe left ventricular systolic dysfunction.

Essentially, the blood in her heart was flowing

the wrong way. I voiced my concerns to Mrs.

Sharma and her family regarding the gravity

of the situation and that there wasn’t an

easy way out, with or without surgery. I asked

her about her goals in life. “I want to get

back to shopping,” she replied without any

hesitation. We discussed at length about her

options, what we can do without imposing

a significant procedural risk on her. We

discussed about transcatheter aortic valve

replacement (TAVR).

TAVR is a procedure where a

bioprosthetic valve is crimped and loaded

on to a catheter, inserted through groin in

a minimally invasive fashion, and implanted

in place of the diseased aortic valve. TAVR

is approved for patients with severe AS

who are considered higher risk for SAVR.

We discussed Mrs. Sharma’s case with

cardiothoracic surgeons for her eligibility

for surgery. After the surgeons deemed

her very high risk for surgery, we opted for

TAVR, knowing that TAVR will only address

problems related to the aortic valve. This was

nonetheless her best chance.

50 / FUTURE MEDICINE / OCTOBER 2018


After essential investigations, she underwent successful

TAVR without any complications. The procedure was

performed in the cardiac catheterization laboratory in a

complete sutureless fashion. She was extubated immediately

after the procedure, was able to talk and eat food that

evening. The major hurdle was over and she recovered in

a predictable fashion. She was transferred to the room on

the third day, was discharged home on day 4. Her postprocedural

events were nothing short of magical. She was

able to hold long conversations on the

evening of the procedure itself. The ability

to talk was a luxury to her and she wanted

to talk just about anything. That night she

slept lying flat on the bed without gasping

for breath, something she couldn’t do for

the past one year. Next day, she finished

her entire meal for the first time in months.

On the third day, she reached out for the

television remote and watched a random

show for more than 30 minutes. Her son was

amazed at her behaviour as previously she

would get fatigued at home just by watching

television for less than 10 minutes. She

climbed the stairs up one floor for the first

time in more than three years. On her follow

up in the out-patient clinic after a few weeks,

she reported that she had gained almost 3

kg weight by virtue of being able to eat. Her

taste buds were back, which added pleasure

to what she was eating. And yes, she was

back shopping.

TAVR is the most disruptive medical

innovation that modern medicine has seen

in the past decade. Life-changing outcomes,

as seen in this case, are not exclusive to Mrs.

Sharma. The majority of the patients with

severe AS who have high surgical risk can be

expected to have a similar outcome. TAVR

has evolved into both a bail-out strategy in

otherwise extreme surgical risk patients, as

well as first-line therapy for patients with

intermediate surgical risk profile.

The author is Consultant,

Interventional Cardiology,

CARE Hospitals, Banjara

Hills, Hyderabad

OCTOBER 2018 / FUTURE MEDICINE / 51


case reports

A BOON OR BANE?

Prenatal diagnosis can help parents make a choice about the foetus in a manner

that is more acceptable - emotionally and rationally

Prenatal testing and its perceived benefits have been

in focus for a long time. There has been widespread

debate and passionate arguments on both sides. In

India, where the law allows termination of pregnancy before

20 weeks, there are several prenatal tests that are available

only after 20 weeks. This dichotomy produces considerable

anxiety and stress to would-be parents who may need

such information within the legal timeline for pregnancy

termination.

Here is a success story in which prenatal tests were able

to relieve the parents of their stress and sleepless nights.

Maya (name changed) was extremely excited at being

pregnant and was looking

forward to a healthy baby.

However, the 12-week routine

sonography was about to

WHILE THE AMBIGUITY IN

change her perspective on

the pregnancy. Ultrasound REGULAR SONOGRAPHY

imaging identified a small FINDING WAS THE REASON

dorso-lumbar swelling in the FOR MANY SLEEPLESS

foetus. The doctors treating NIGHTS, AN IN-DEPTH

her, in her rural town of STUDY SUCH AS THE

Maharashtra, were unable to

FOETAL MRI WAS ABLE

provide her further guidance

and decided to follow-up TO ALLEVIATE HER ANXIETY

with a sonogram. The 22- AND CONCERNS.

week sonography confirmed

the presence of the cyst,

while the foetus displayed

normal movement with no other abnormalities detected.

The swelling could be indicative of either a meningocele or

meningomyelocele, which are common congenital defects

caused perhaps due to folic acid deficiency, exposure to

certain drugs such as antiepileptic valproate, or other illnesses

such as diabetes. Genetic and environmental components

may also be involved. In the case of Maya, the cause of the

swelling was not determined.

Meningocele is a cystic swelling formed by the protrusion

of the dura and arachnoid mater without the involvement of

the spinal cord. Treatment is rather straightforward, involving

postnatal surgical repair. By contrast, meningomyelocele is a

far more serious condition where, in addition to meningeal

protrusion, there is the involvement of the spinal cord.

This results in the weakness of both lower

limbs, bowel and bladder incontinence

and ultimately, a wheelchair-bound life.

Hydrocephalus is another associated

condition with meningomyelocele that

involves the enlargement of brain cavities

due to fluid accumulation, resulting in

cognitive dysfunction, papilledema, optic

atrophy and blindness. Though shunt

placement surgery alleviates symptoms of

hydrocephalus, the procedure comes with its

own set of neurosurgical complications. Thus,

the prognosis for a meningomyelocele is far

worse compared to meningocele.

In the case of Maya, since sonography

could not help in differentiating the type of

lesion in the foetus, the patient was referred

to Mumbai to a leading gynecologist and

obstetrician, Dr. Nikhil Dattar, who further

referred Maya to a paediatric neurologist, Dr.

K. N. Shah, to advice on the prognosis of the

foetus. A foetal MRI was done as a further

diagnostic test. The MRI confirmed that there

was no hydrocephalus, and the condition

was diagnosed to be meningocele. Based on

these results, Maya was advised to continue

with the pregnancy and then consult a

neurosurgeon for surgical removal of the cyst

postnatally.

The foetal MRI turned out to be a boon

for the patient. While the ambiguity in

regular sonography finding was the reason

for many sleepless nights for Maya and her

family, a more robust and in-depth study

such as the foetal MRI was able

to alleviate her anxiety and

concerns. “The parents are

extremely relieved and

very happy that

their unborn

foetus

52 / FUTURE MEDICINE / OCTOBER 2018


has a good prognosis and the condition is treatable

by postnatal surgery. They are tremendously

thankful for the advances in prenatal testing and

the closure they have received,” says Dr. Shah.

The outcome for Maya was good. However, had

the foetal MRI indicated a meningomyelocele

as the diagnosis, this narrative would have

been entirely different. The parents would

have had to undergo counselling and

would need to consider aborting the

foetus. Indian laws dictate that

pregnancies beyond 20 weeks

cannot be legally aborted.

Since the pregnancy had already run into the

23rdweek at the time of the foetal MRI, this

case would have needed to be considered

by the Supreme Court. In recent past, the

Supreme Court has been lenient in granting

permission for late abortions for mothers

who request them in the light of poor

prognosis for their foetus. Specially, Dr. Nikhil

Dattar has been instrumental in highlighting

such cases and has been successful in

helping parents in their cause. Prenatal

testing can be a boon not only to alleviate

anxiety, but also in helping parents make a

choice about the foetus in a manner that

would be more mentally, emotionally and

rationally acceptable.

DR SHIVANEE SHAH

OCTOBER 2018 / FUTURE MEDICINE / 53


case reports

SLEEP-ONSET SEIZURE

Here is a case of long QT syndrome which manifested as a seizure-like activity

while falling asleep

Genetic testing can go a long way in determining the

treatment and outcome of a disease in a patient. Here

is a case of a 19-year old girl who presented with a

history of seizures at the neurological department at Amrita

Hospital, Kochi, but turned out to have a heart condition.

Genetic testing helped identify the exact mutations which

dictated her treatment modality.

This patient had a history of seizures, where during

each episode she was reported to become unresponsive

with seizure-like activity while falling asleep. These episodes

were short lived; during her

first attack, she was only

unresponsive for a brief period,

and did not receive any ABOUT 75% OF THE

medical attention. However,

INHERITED LONG QT

during her subsequent

episodes, she had up-rolling SYNDROME IS CAUSED DUE

of eyeballs along with TO MUTATIONS IN 3 ION

unresponsiveness and was CHANNEL PROTEINS THAT

brought to the hospital. CAN RESULT IN ONE OF

Brain CT was normal, and THREE TYPES OF LONG QT

she was diagnosed with

SYNDROME — TYPE 1, 2 OR 3.

epilepsy. She was started

on sodium valproate as the

anti-epileptic drug, but since

she also complained of a vague chest pain, she was referred

to the cardiology department for a consultation. Here she

underwent an ECG, which showed a prolonged QT interval of

506 milliseconds (QTc), which is markedly above-normal. The

working diagnosis was that of ‘long QT syndrome’.

Long QT syndrome may occur in response to certain

medications. However, in the majority of the cases, it is an

inherited autosomal dominant syndrome typically caused

due to a mutation in one of 17 cardiac ion channel proteins.

Symptoms include transient loss of consciousness, seizures

and irregular beating of the heart which prevents circulation

of blood to the brain and can result in loss of consciousness.

About 75% of the inherited long QT syndrome is caused due

to mutations in 3 ion channel proteins that can result in one

of three types of long QT syndrome — type 1, 2 or 3. Type

1 (LQ1) is caused due to a disruption of the potassium ion

channel activity and the consequent disruption of the heart’s

electrical activity. Arrhythmias in such cases are typically

triggered due to physical exertion and such episodes tend to

stop without medical intervention and are

less likely to be fatal. Type 2 (LQ2) is caused

due to insufficient potassium ion activity

in the heart and can be triggered due to

emotional stress and loud noises. While types

1 and 2 are due to mutations in potassium

ion channels, type 3 (LQ3) is due to

mutations in sodium ion channels and occurs

due to low levels of sodium flow in the

heart, leading to arrhythmia. Such episodes

54 / FUTURE MEDICINE / OCTOBER 2018


are typically triggered during sleep or rest and are more

likely to be fatal. Molecular testing is an important aspect of

identifying the type of long QT syndrome and can help in

confirming clinical diagnosis as well as in guiding treatment

strategy. LQT1 and LQT2 are caused due to mutations in the

potassium channel genes, KCNQ1and KCNH2, respectively,

while LQT3 is caused by mutations in a sodium channel gene,

SCN5A.

‘For accurate treatment modality, we recommended

our patient to undergo molecular testing,’ said Dr. Hisham

Ahamed, Associate Professor in Cardiology, Amrita Institute

of Medical Sciences and Research, Kochi. Her family agreed,

and her blood sample was sent to MedGenome Labs,

Bengaluru, for a cardiac channelopathy panel. This panel

can identify mutations in cardiac ion channels that may

result in any abnormal variation in QT interval. The genetic

panel results showed that the patient had a mutation in

KCNH2and was therefore diagnosed as having type 2 long

QT syndrome.

While type 1 patients show good response to using

medications such as beta-blockers, type 2 patients generally

do not respond as well to such treatment and are typically

advised for implantable devices such as

an implantable cardioverter defibrillator

(ICD), if they are considered high-risk. Until

the patient’s family could agree for such a

procedure, the patient was started on betablockers,

since a subset of type 2 patients

can benefit from such medication as well.

The beta-blocker therapy has been effective

thus far for this patient. Two years later, she

has experienced no further episodes and

her heart rhythm has returned to normal

on its own. ‘’Our patient has been fortunate

that the beta-blocker treatment has worked

for her, although we would like to see the

patient follow through on the recommended

ICD implant,” says Dr. Ahamed. ‘’The lesson

learnt from this case is that ECG should be

performed in young individuals with a history

of seizures to rule out cardiac concerns.”

DR SHIVANEE SHAH

OCTOBER 2018 / FUTURE MEDICINE / 55


case reports

A LONG-WINDING PATH TO

SPENCDI

Many a time, a definitive diagnosis is the result of a difficult trajectory

A

one-year-old female child was brought to a tertiary

case hospital in Mumbai with fever, pallor, and

conjunctival and intracranial hemorrhage. Blood

tests revealed low platelet counts and hypothyroidism.

Bone marrow aspirates indicated the presence of platelet

precursors, and suggested that the platelets were being

destroyed. An MRI was also done and showed multifocal

hemorrhagic areas in the cerebral parenchyma and

cerebellum. The patient was thought to have immune

thrombocytopenic purpura (ITP) and was treated with

packed RBCs, platelets, intravenous immunoglobin

(IVIg), methylprednisolone and dapsone for ITP, and for

hypothyroidism with L-thyroxine. Steroids

and dapsone were tapered and stopped

after 6 months along with L-thyroxin. The

patient did well for a few months and then

returned to the hospital at age 2 with fever,

cough, cold, and thrombocytopenia. This

time she was treated with antibiotic therapy,

oral steroids and dapsone. The patient had a

3rd admission to the hospital at age 3 with

purpura and she was started on cyclosporine

syrup and discharged. This treatment regime

was effective for a few years.

56 / FUTURE MEDICINE / OCTOBER 2018


However, at age 4, the

child was brought to Lilawati

Hospital and Research DURING DISCUSSIONS

Center, Mumbai, to consult WITH OTHER DOCTORS, SHE

with Dr. Swati Kanakia, a REALIZED THAT PERHAPS

pediatric hemato-oncologist.

HER CHOICE OF KEYWORDS

The patient presented with

WAS NOT CORRECT.

bleeding in the skin, another

intracranial hemorrhage,

and low platelet count. An

MRI showed calcification in

the basal ganglia and evidence of the previous intracranial

bleeding. Based on the history, the patient was started on

IVIg for treating low platelets. Further, even though normally

platelets are not given as therapy in such cases as they

would be expected to be destroyed in the body, this patient

was again given platelets as well because of the intracranial

hemorrhage, and started with cyclosporine syrup.

In addition, Dr. Kanakia observed certain morphological

abnormalities including short stature, high arched palate,

low set ears, and wider wrists than normal. Wider wrists are

typical signs of rickets and an X-ray of the wrist was done

which indeed showed typical signs of rickets. Blood tests

for vitamin D, calcium, and phosphorous however did not

corroborate with the clinical findings for rickets.

This was indeed an atypical case where the patient

had an early onset of ITP, was not responsive to treatment

over long periods of time, had two intracranial hemorrhages,

calcification of basal ganglia and showed signs of

abnormal facies. In addition to these, she was strongly

positive for alloantibodies against red blood cells as

evidenced in a direct Coomb’s test and thyroid antibodies

causing hypothyroidism. Such autoantibodies are

evidence of autoimmunity. Dr. Kanakia was not satisfied

with the diagnosis and treatment being offered to the

patient, and continued to search for a more accurate

diagnosis and better treatment options. She searched the

OMiM database for other similar cases, but was not able to

come up with anything similar. During discussions with other

doctors, she realized that perhaps her choice of keywords

was not correct. She was including the

keyword ‘rickets’ due to the wider wrists

that are characteristic of rickets. However,

once she replaced ‘rickets’ with ‘metaphyseal

dysplasia’, she was able to find a very similar

condition called spondyloenchondrodysplasia

with immune dysregulation (SPENCDI).

As per the description, ‘SPENCDI is an

immunoosseous dysplasia combining the

typical metaphyseal and vertebral bone

lesions of spondyloenchondrodysplasia

(SPENCD) with immune dysfunction and

neurologic involvement’ The patient’s

condition seemed to fit well with the

description.

SPENCDI is caused by a homozygous

mutation in the APC5gene on chromosome

19p13. Genetic testing was carried out, and

consistent with the clinical symptoms, the

patient was found to carry a homozygous

deletion in the APC gene that results in a

truncated protein. The patient’s parents also

underwent genetic testing, and they were

found to carry the heterozygous mutations.

Based on this genetic identification, the

patient had a confirmed diagnosis of

SPENCDI and was accordingly continued on

cyclosporine. The dosage of cyclosporine

was kept at a minimum dose just to maintain

the platelet levels at a safe count of 30,000-

40,000/uL. The patient is doing well as of

now.

The genetic identification was not only

important for adequate treatment and

management of the patient, but would also

be important in case the parents decided to

have another child. Prenatal testing can be

used to determine whether the child would

be homozygous or heterozygous, allowing

for the option to terminate the pregnancy if

required. Such prenatal testing may therefore

prevent another child with the same genetic

disorder. Genetic testing can also be done for

close family members to assess hereditary

mutations.

“Accurate diagnosis gives the patient/

patient’s family a sense of closure and helps

them prepare for their next child. Even in

this age of technological advances, clinical

judgement is extremely important. To be

able to diagnose accurately, it is important to

understand which tests to run,” Dr. Kanakia

shares her learnings from this case.

DR SHIVANEE SHAH

OCTOBER 2018 / FUTURE MEDICINE / 57


case reports

EXON SKIPPING FOR DMD

Treatment for muscle dystrophy can vary depending on the type.

But it is crucial to carry out a differential diagnosis by genetic testing

Muscular dystrophy is group of muscle disorders

characterized by progressive muscle weakness,

with Duchenne Muscular Dystrophy (DMD) being

the most common. DMD is an X-linked recessive disorder

primarily affecting males, with women being carriers. DMD

is characterized by initial proximal muscle weakness of the

pelvic girdle that eventually progresses to the shoulder

girdle muscles. The onset of symptoms typically occurs

between 3 to 5 years of age and by the age of 13-15 years,

the child is generally wheelchair-bound. DMD is caused due

to mutations in the dystrophingene which lies on the short

arm of the X-chromosome (Xp21.2). The dystrophingene

encodes the protein dystrophin, which plays a key role in

maintaining the integrity of the cell membrane of skeletal

and cardiac muscle cells. In the absence of dystrophin,

muscle fibres disintegrate,

resulting in the muscle

weakness observed in DMD.

One such nine-anda-half-year-old

boy was

brought to consult Dr. K. N.

Shah at Lilawati Hospital

and Research Centre,

Mumbai. His previous history

revealed that he was born

to parents from a nonconsanguineous

marriage

and had one female sibling.

DYSTROPHIN GENE IS

ONE OF THE LARGEST

KNOWN GENES, CONSISTING

OF 79 EXONS, MANY OF

WHICH ARE REPEATING

SEGMENTS.

He was born via a normal, full-term pregnancy, and showed

normal milestones up to 2 years of age. However, after two

years, his parents noticed that his walking was delayed,

though his social and cognitive milestones were normal. It

was also reported that he was unable to climb stairs and

his calf muscles had begun show pseudohypertrophy. As

his condition slowly progressed, he was unable to get up

from a sitting position without additional support to his

knees, an observation that is commonly called the Gower’s

sign and is classically observed in DMD children. Creatinine

phosphokinase (CPK) levels, a marker of muscle injury, are

consistently elevated in patients with Duchenne’s and even

this child had a very high level (20,000 U/L) of CPK, strongly

indicative of muscle dystrophy. However, Dr. Shah also

cautions that elevated CPK levels cannot specifically confirm

a diagnosis of DMD, since it is simply an indicator of muscle

damage, and not indicative of DMD specifically.

While the gold standard of diagnosis

for DMD is muscle biopsy followed by

immunohistochemistry or western blot

for dystrophin protein, new technological

advances involve diagnosis via genetic

testing. To appreciate how genetic testing

can help diagnose DMD, it is first important

to understand the dystrophingene at the

genetic level and the types of mutations

that have been identified in the recent

past. Dystrophin gene is one of the largest

known genes, consisting of 79 exons, many

of which are repeating segments. Typically,

mutations in this gene are either deletions

or duplications of single or multiple exons.

A deletion or duplication of an exon can

result in a change wherein dystrophin

cannot be expressed at all. Such a mutation

is called an ‘out-of-frame’ mutation.

Alternatively, in some instances, even

though some exons maybe deleted

or duplicated, the protein may still be

expressed, albeit one that is not as effective

as the wild-type one. Such mutations are

called ‘in-frame’ deletions. Thus, the type of

mutation can determine quantitative as well

as qualitative changes in the expression of

the dystrophin protein, resulting in different

disorders. For instance, if the mutation

results in the deletion of an exon due to

which dystrophin cannot be expressed at

all, the resulting dystrophy is DMD. However,

if the mutation results in an exon being

deleted, despite which dystrophin can be

formed, then the resulting dystrophy is

a milder version called Becker muscular

dystrophy or BMD.

Since the progression of BMD is much

slower than in DMD, and the treatment

and management can vary depending on

the particular muscle dystrophy, it is often

critical to carry out a differential diagnosis

by genetic testing.

Multiplex Ligation-Dependent Probe

Amplification (MLPA) is a commonly

58 / FUTURE MEDICINE / OCTOBER 2018


employed genetic detection

test, which can detect up to

70% of DMD positive cases. EXON SKIPPING IS A

In the event of a negative MUTATION-SPECIFIC

MLPA result, clinicians THERAPY IN WHICH A

still have the option of

SMALL PIECE OF DNA CAN

confirming the disease using

BE INTRODUCED SUCH

next generation sequencing,

which can pick up about THAT IT WILL BIND TO A

98-99% of the positive PARTICULAR EXON.

cases. However, muscle

biopsy still remains the

final confirmatory test. In

this case, Dr. Shah proposed that MLPA be done, and the

results revealed that exon 43 was deleted, which confirmed

the clinical diagnosis of DMD. Genetic counselling would be

important in case the parents wish to have another child,

since prenatal genetic testing via MLPA at early stages of

pregnancy can help determine whether the male child

would have DMD. The prenatal tests can also help parents

decide whether they should terminate such a pregnancy.

Further, the parents of the boy were advised to get his sister

also genetically tested to determine if she was a carrier for

DMD mutation.

While currently there is no known cure for DMD, there is

hope for the future. Several research studies

have been carried out for different genetic

therapy approaches. Exon skipping is a

mutation-specific therapy in which a small

piece of DNA can be introduced such that it

will bind to a particular exon and encourage

the cell to skip reading that exon, thereby

effectively converting an out-of-frame

mutation to an in-frame mutation. Such

a therapy would allow DMD-type clinical

conditions to mimic BMD-type clinical

conditions, which are far more manageable

and have better prognosis. However, till

date, only a few specific therapies are

approved. For Dr. Shah’s patient, there is no

therapy for a deletion of exon 43. The only

US FDA approved therapy is for deletions

that can be corrected by skipping exon 51,

involved in about 13-20% of DMD cases.

However, research is ongoing, and it is likely

that other, newer exon-skipping targets

become available in the future.

DR SHIVANEE SHAH

OCTOBER 2018 / FUTURE MEDICINE / 59


esearch snippets

Grass pollen exposure in utero shows possible risk

recent study provides new

A insights into the effect of grass

pollen exposure, at birth and shortly

after, being responsible for possible

allergic respiratory diseases. Three

birth cohort studies based in

Australia, Denmark and Germany

conducted by Susanto et al,from

La Trobe University, analyzed the

umbilical cord blood collected from

hundreds of babies born during and

soon after peak grass pollen season.

Immunoglobulin E (IgE), which is

used as a marker to predict the

development of allergic diseases,

were found to be higher in cord

blood of babies born during grass

pollen seasonsin cities from both

hemispheres. But increased pollen

loads in the environment during

the entire pregnancy appeared

protective, which indicates possible

development of a sensitization

barrier. Thus, the study focused

on the effect of pollen exposure

in utero, which was previously a

mere suspected concept relating

to respiratory disorders. The

researchers also stressed the fact

that not all babies born during the

high pollen seasons developed

respiratory diseases or other

allergies. They also emphasized the

need for more research to be done,

though the current study helps

predict and manage diseases like

asthma which are relevant public

health burden.

Source: https://www.sciencedirect.com/

science/article/pii/S0160412017320469

Scientists find more

than 500 new genes

allied to BP

recent study unveils new gene

A areas conferring blood pressure

traits, helping understand the biological

pathway for blood pressure regulation

and thereby controlling the major

risk factors like heart attack or stroke

associated with it. The study was

conducted by a group of researchers

from Queen Mary University of London

(QMUL) and Imperial College London.

The researchers analyzed DNA of more

than 1 million people, which revealed

535 new genetic loci linked with

blood pressure traits. The scientists

found that all of the genetic variants

identified were shown to increase a

person’s risk of high blood pressure

by 3.34 times, and that people in the

higher genetic risk group exhibited a

1.52 times higher possibility to suffer

from consequent cardiac diseases.

60 / FUTURE MEDICINE / OCTOBER 2018

The researchers suggest that knowing

the genes responsible for high blood

pressure may help us to spot the

people who are at risk before the

damage is done, so that they can be

prognosticated earlier and therefore

can be administered for implementing

a healthy lifestyle to prevent the

adverse consequences. The study

also indicates potential new targets

for drug development, suggesting

that some drugs like canagliflozin

prescribed for other diseases like type-

2 diabetes could be repurposed for

treating hypertension due to similar

gene regions targeted by the drug.

The identification of a new biological

pathway for blood pressure regulation

therefore potentiates improved

cardiovascular disease prevention in

future. The study reports to be the

largest genetic association study of

blood pressure traits to date.

Source: https://www.sciencedaily.com/

releases/2018/09/180917111619.htm

“Lab-in-a-drop” tech:

Way to detect deadly

diseases from home

A

new medical breakthrough,

which could diagnose millions

via a completely portable home

kit, has been designed to detect

how likely a person is to suffer from

grave diseases like cancer and other

ailments. Xing Technologies Pty

Ltd developed this nanodiagnostic


technology, claimed to be a game

changer, which would enable rapid,

point-of-care diagnosis, screening and

ongoing monitoring of cancer and

other diseases like tuberculosis, heart

diseases, diabetes and Alzheimer’s,

without requiring access to laboratory

facilities and highly trained personnel.

The technology convenes a whole

laboratory into a single cartridge

which can perform the tests. Each

cartridge has a specific application,

either to diagnose a cancer or an

infectious disease. A sample of the

patient’s urine, sputum or blood

is inserted into the cartridge and

analysed via its portable reader.

Results are transmitted to a cloud

software platform and a report is

then transmitted back to the doctor,

nurse or healthcare worker. The kit is

in insulin resistant adipocyte models

developed from human mesenchymal

stem cells (hMSC). The study found

that overexpression of miR-876-3p

in insulin resistant cells decreased

the adiponectin hormone levels,

which elevated insulin resistance by

altering specific performed adipokine

expression. Lentivirus-mediated

overexpression and suppression

studies were performed in insulinresistant

adipocytes differentiated from

hMSC and high fat-diet fed C57BL/6

obese mice models to validate the

findings in vivo, which were shown

to ameliorate insulin resistance with

inhibition of miR-876-3p. The study

provides a new perspective and the

findings show greater implications

in the development of therapeutic

targets for type-2 diabetes.

Source: Bioscientifica.com

Journal of Endocrinology (2018) 239, 1–17 https://

doi.org/10.1530/JOE-17-0387

currently designed to be sent to

third world countries, and communities

in regional Australia, and promises

to be a revolutionary, life-saving

technology.

Source: https://xingtech.com.au/xing-media/

media-releases

https://www.9news.com.au/videos/

cjm8y9sg9000j0goyupfjy9xe/medicalbreakthrough-could-change-diagnosis-process

miRNA alteration to

control type-2 diabetes

Regulation of miRNA becomes a

potential target for therapeutic

interventions towards the treatment

of type-2 diabetes and obesityassociated

metabolic syndrome.

miRNA has been increasingly known to

play an important role in the regulation

of various cellular and metabolic

processes. Based on this aspect, a

team of scientists from CSIR-CDRI,

Lucknow, CSIR-IHBT, Palampur and

CSIR-IGIB, New Delhi,investigated the

effect of altered expression of miRNA

Targeting senescent cells may promote

memory restoration

recent research shows causal

A link between senescent cells and

neurodegenerative disease, suggesting

that targeting the former may provide

a therapeutic avenue for the treatment

of these pathologies. Mayo Clinic

researchers, involving J. Bussian et

al, found that senescent cells, on

elimination from naturally aged mice,

were found to extend their healthy

life span. These cells accumulate

with advancing natural age at sites

related to diseases of aging, including

osteoarthritis and atherosclerosis;

and neurodegenerative diseases,

such as Alzheimer’s and Parkinson’s.

The researchers used a mouse

model afflicted with tau-dependent

neurodegenerative disease, which

accumulates p16 positive senescent

cells showing tangles of tau protein

in neurons. Ablation of these cells

using genetically modified, INK-ATTAC

transgenic mice model capable of

eliminating the senescent cells was

shown to prevent the neurofibrillary

tangle deposition and degeneration

of cortical and hippocampal neurons,

thus preserving the cognitive functions,

retaining their memory. Thus the study

puts forward a best case scenario

where prevention of brain damage

was shown to avoid the diseased state.

Since a different approach is required

for clinical establishment, scientists

have started working on models

to examine the specific molecular

attenuation that occur in the affected

cells.

Source:https://www.nature.com/articles/s41586-

018-0543-y

www.sciencedaily.com/

releases/2018/09/180919133024.htm

—Compiled by Divya Choyikutty

OCTOBER 2018 / FUTURE MEDICINE / 61


pharma

UNCERTAIN ABOUT VALSARTAN

India initiates a probe even as recall of valsartan pills, suspected to be tainted

with a potential carcinogenic impurity, continues in leading markets

MANJIT BABU

In July, India’s drug regulator said the

agency was starting an investigation

on all companies importing the active

pharmaceutical ingredient (API) to make

heart drug valsartan from Zhejiang

Huahai Pharmaceuticals of China. This

unprecedented action by the Drug

Controller General of India (DCGI) came

in the wake of a recall of the medicines

containing valsartan by countries

including the US and Germany.

The ongoing probe in the US and

Europe to check for the presence of a

potential carcinogen in valsartan has

put regulators all over the world on high

alert. Valsartan, a commonly prescribed

angiotensin-II-receptor antagonist (ARB)

to manage hypertension, is used for

heart failure indication as well.

The DCGI’s announcement prompted

drug control offices in the country

to be vigilant on the import of the

raw materials for the drug. The drug

regulator said all port offices were asked

to check the consignments imported

into the country and conduct tests on

each batch to address the issue.

Even as Indian manufacturers Torrent

Pharmaceuticals and Hetero Drugs

voluntarily withdrew their valsartan

drugs from the US market, latest reports

indicate that India’s Central Drug

Standard Control Organisation (CDSCO),

the top regulator’s office, has assured

that the ingredient that is suspected to

have the impurity is not present in the

drugs available in India.

NDMA: The suspect

The entire issue came to the fore when

Prinston Pharmaceuticals, Inc. contacted

ZHEJIANG HUAHAI HAD

DETECTED AN IMPURITY

– A CHEMICAL KNOWN AS

N-NITROSODIMETHYLAMINE

(NDMA) — IN THE

VALSARTAN API.

the USFDA’s Center for Drug Evaluation

and Research (CDER) about

some of its products containing

valsartan API manufactured by

Zhejiang Huahai Pharmaceutical

Co. (ZHP), on 19th June, 2018.

Prinston informed CDER that

they had stopped making valsartan

products because ZHP had detected

an impurity – a chemical known as

N-nitrosodimethylamine (NDMA) -- in

the API. NDMA is a probable cancercausing

chemical found in trace

amounts in water and some foods. The

levels of NDMA in ZHP’s valsartan API,

though only in trace amounts, were

unacceptable.

“Although the risk to patients

taking the affected products is

extremely low, we take matters of

pharmaceutical quality very seriously.

We took immediate steps to address

these findings,” said a statement from

FDA Commissioner Scott Gottlieb, M.D.,

and Janet Woodcock, M.D., director

of the Center for Drug Evaluation and

Research, on FDA’s ongoing investigation

into valsartan impurities and recalls.

The US drug regulator is closely

coordinating with the European

62 / FUTURE MEDICINE / OCTOBER 2018


Medicines Agency (EMA), European

Directorate for the Quality of Medicines

(EDQM), Regulatory Operations and

Regions Branch and Therapeutic

Products Directorate of Health Canada,

and the Pharmaceuticals and Medical

Devices Agency (PMDA) in Japan,

sharing the developments on the

investigation.

International regulators have since

identified another API manufacturer,

Zhejiang Tianyu Pharmaceutical Co., with

NDMA in its valsartan API. The USFDA

said that no valsartan products in the US

market use this API.

The FDA estimates that if 8,000

people took the highest valsartan

dose (320 mg) from NDMA-affected

medicines daily for four years (the

amount of time it believes the affected

products have been on the U.S. market),

there may be one additional case of

cancer over the lifetimes of these 8,000

people beyond the average cancer rate

among Americans.

“This estimate represented the

highest possible level of NDMA

exposure. It was a measure of the risk

under the most extreme circumstances.

Most patients who were exposed to the

impurity through the use of valsartan

received less exposure than this worstcase

scenario,” it said.

Difficult to determine

NDMA’s properties make it difficult to

find. To determine if valsartan products

do contain this impurity, CDER’s

scientists have developed the gas

chromatography-mass spectrometry

(GC/MS) headspace testing method.

It has posted this method to the web

to help manufacturers and regulators

detect NDMA in valsartan API and

tablets.

“Specifically, a combination of

conditions, which include certain

chemicals, processing conditions and

production steps, could lead to the

formation of the NDMA impurity. We

believe that these risks are introduced

through a specific sequence of

steps in the manufacturing process,

where certain chemical reactions are

needed to form the active ingredient.

Before we undertook this analysis,

USFDA finds second impurity

The US FDA has found an

additional unexpected impurity

N-Nitrosodiethylamine (NDEA) in the

active pharmaceutical ingredient (API)

valsartan.

NDEA, a known animal and

suspected human carcinogen,

was found in three lots of Torrent

Pharmaceuticals’ recalled valsartan

drug products, the USFDA said while

updating the public on the agency’s

ongoing investigation surrounding the

recent voluntary recall of several drug

products containing valsartan API.

These Torrent products were included

in the company’s recall on August 23,

2018

Like N-Nitrosodimethylamine

(NDMA), which was found in the

recalled valsartan products, NDEA is

also formed from a specific sequence

IF 8,000 PEOPLE TOOK THE

HIGHEST VALSARTAN DOSE

(320 MG) FROM NDMA-

AFFECTED MEDICINES DAILY

FOR FOUR YEARS, THERE

MAY BE ONE ADDITIONAL

CASE OF CANCER OVER

THEIR LIFETIMES,

THE FDA ESTIMATES.

neither regulators nor industry fully

understood how NDMA could form

during this process,” said the FDA

officials.

The US drug watchdog has been

conducting a review of ARBs from

2010, according to the documents. In

light of the valsartan issue, the FDA is

conducting a study on all ARBs to check

for the presence of NDMA.

Low risk potential?

The EMA officials in August said that

the NDMA levels detected in batches of

valsartan from Zhejiang Tianyu are much

lower than the levels seen in the active

substance from Zhejiang Huahai, which

of manufacturing steps and chemical

reactions.

In addition to the FDA’s testing, the

agency will post a preliminary method

for detecting NDEA. Manufacturers and

global regulators can use this method

to screen other products for the

potential presence of this impurity.

triggered a recall of several valsartan

medicines in July 2018.

While the DCGI assures that the

contaminated batches of the ingredient

has not touched Indian shores, experts

say that there are alternatives available

for the drug and that doctors can switch

to other products in order to avoid any

possible risk.

In India, valsartan is available

as a single drug as well as in fixeddose

combinations. Patients taking

this drug should not stop the drug

without consulting their doctors for

two reasons: First, not all valsartan

containing products are recalled and

second, many equally efficacious

alternatives to valsartan are available,

alert experts. "Physicians should take

caution prescribing drugs containing

valsartan unless they can confirm that

the particular API is not sourced from

the companies mentioned above,''

says Dr Anoop Agrawal, Consultant,

Interventional Cardiology, CARE

Hospitals, Hyderabad. FDA has listed the

recalled manufacturers on their website.

He suggests that in India, authorities

should aggressively test the available

drugs for the said impurity and put out

our own list of recalled and not-recalled

brands.

OCTOBER 2018 / FUTURE MEDICINE / 63


hospital news

Aster DM partners with

Nigerian university hospital

CK Birla Hospitals-CMRI

conducts sepsis

programme

CK Birla Hospitals – Calcutta Medical

Research Institute (CMRI) conducted

a comprehensive sepsis management

programme in Eastern India on the

occasion of World Sepsis Day.

Organised in association with the

Indian Sepsis Forum, Hospital Infection

Society of India, SEMI WB chapter and

Indian Society of Critical Care Medicine

(ISCCM), the initiative enlightened the

clinicians about the ways to combat

sepsis in a holistic manner.

The Basic Sepsis Life Support

Programme (BSLS), which included an

in-depth review of sepsis along with its

management and practical application

required for dealing with patients

suffering from sepsis, shared clinical

knowledge, management guidance and

organisation skills with doctors, nurses

and healthcare personnel to improve

clinical outcome.

India currently tackles 7,50,000

cases of sepsis every year, in which the

mortality rate is 12.08 per cent in ICU

patients and 59.26 per cent in those

with critical stage sepsis. More than

90,000 people die every year in India

due to sepsis, making it one of the most

alarming causes of death in the country,

according to Dr Arindam Kar, director &

HOD, critical care unit, CK Birla Hospitals

- CMRI.

Every year, World Sepsis Day

is celebrated internationally on 13

September with awareness campaigns

to facilitate a more comprehensive

outlook into the management of sepsis.

The BSLS programme was one such

national level initiative which promised to

mark the beginning of a more inclusive,

updated and evidence-based approach

to tackle the severity and life-threatening

situations caused by sepsis.

Aster DM Healthcare has entered

into a partnership agreement

with Afe Babalola University Ado Ekiti

(ABUAD), a leading university hospital

in Nigeria.

As part of the deal, Aster would

set up centres of excellence across

specialties in association with ABUAD

to address the need gaps in the

Nigerian healthcare sector.

Aster Centers of Excellence

provide quaternary care across various

specialties such as neuroscience,

cardiac, orthopaedic and oncology.

The agreement also aims to build

a telemedicine unit managed by Aster

DM Healthcare’s certified specialists

chosen from Aster’s network of 11

hospitals in India.

The telemedicine unit in ABUAD

BR Life SSNMC Super Speciality

Hospital, Bengaluru, has joined

hands with Brains Neurosciences to

establish a Centre of Excellence (CoE).

Located at Ideal Homes Layout,

Rajarajeshwari Nagar, Bengaluru, the

centre will provide comprehensive

diagnosis, treatment and rehabilitation

services for brain and spine related

problems.

In addition to this, there will be

specialty clinics for the management of

stroke, headache, dementia, epilepsy,

Parkinson’s and Alzheimer’s. A fully

equipped neurotrauma center for

will provide services such as tele

consulting, tele diagnosis and tele

management, enabling patients to seek

expert advice and virtual treatment

from Aster’s specialists

from across the world, including in

India.

Nigeria spends an average of

US$ 118 per capita on healthcare.

In terms of the doctor-patient ratio,

Nigeria currently has 1:2,500, as

opposed to a minimum ratio of 1:1000

recommended by WHO.

“Our partnership will address

the gaps in the healthcare sector in

Nigeria which is in urgent need of

quality services,'' said Dr Azad Moopen,

founder chairman and managing

director of Aster DM Healthcare, in a

press release.

BR Life SSNMC and Brains Neuro set up CoE

trauma and head injury treatment will be

operational 24x7.

The CoE has set-up the Brain

Wellness Clinic to facilitate early

detection of Alzheimer’s disease.

Early diagnosis, prevention and

identification of treatable dementias as

a therapy goal can help provide effective

treatment and improve the living

conditions of the patient, according to Dr

Venkataramana NK, head, SSNMC-Brains

Neurosicience Center of Excellence.

BR Life SSNMC Super Specialty

Hospital is promoted by Dr BR Shetty, an

Abu Dhabi-based Indian entrepreneur.

64 / FUTURE MEDICINE / OCTOBER 2018


head&neck cancer

REVISED AJCC TNM GUIDELINES

DEPTH OF STAGING

New recommendations bring fresh concepts into head and neck cancer staging.

They, however, face certain definitive hurdles in terms of practicality in India

DR KRISHNAKUMAR THANKAPPAN

The American Joint Committee on

Cancer (AJCC), 8th Edition marks

a major change in the Tumour

Nodal Metastasis (TNM) staging of

head‐and‐neck cancers. It introduces

many new concepts to stage and

prognosticate patients better, with

distinct therapeutic implications.

In oral cancer, it introduces the

depth of invasion as a determinant of

T(tumour)‐stage. This standardises the

staging of oral cancer tumours and

acknowledges the significance of depth

of invasion in nodal spread and overall

survival. It also eliminates “extrinsic

muscle invasion” from stage T4 for oral

tongue cancer; this was a constant

source of confusion since the depth of

invasion required to involve the extrinsic

muscles of the tongue was highly

variable depending on the position of

the tumour in relation

to the tongue. Even very superficial

tumours could invade the extrinsic

muscles of the tongue. The nodal

staging recommendations have also

upstaged extranodal extension, which

has been shown to be a high‐risk

adverse feature associated with worse

survival.

In oropharyngeal cancer, human

papillomavirus (HPV) expression of

tumours has been used to reclassify

tumours into two separate entities

with distinct staging systems. For

HPV‐positive tumours (p16 positive),

the T‐stage no longer has T4b, or

very advanced local disease, which

represents the improved prognosis that

these patients have when compared

to their non‐HPV counterparts. For

66 / FUTURE MEDICINE / OCTOBER 2018

HPV‐positive tumours, nodal staging

has been divided into clinical staging

and pathological staging for better

prognostication of HPV‐positive

diseases treated with surgery.

In carcinoma of unknown primaries

with cervical nodal metastasis,

immunohistochemical staining of

nodal tissue for HPV and Epstein–Barr

virus (EBV) has been recommended

in all cases. This recognizes the high

incidence of metastasis from an

HPV‐positive oropharyngeal or an

EBV‐positive nasopharyngeal primary

tumour, and the need to standardize

the diagnostic evaluation in these

patients to avoid inadequate evaluation

and inappropriate treatment.

These recommendations are

based on high‐quality evidence aimed

at personalizing cancer therapy to

optimize outcomes, while minimizing

morbidity. The practice of oncology in

India, however, is markedly different

from that in the western world.

India spends a small fraction (under

2%) of its gross domestic product

on health‐care services, with an

estimated 65% of all healthcare‐related

expenditure being spent out‐of‐pocket.

This results in a clear majority of

patients with cancer receiving an

insufficient quality and standard of care.

This context of resource constraint has

a significant impact on the practice of

resource‐heavy medical specialties such

as oncology, where newer diagnostic

and therapeutic techniques are often

ORAL CANCER

STAGING BY

DEPTH OF INVASION

New guidelines standardise the staging of

oral cancer tumours and acknowledges the

significance of depth of invasion in nodal

spread and overall survival.

T4b

20 and

more than

20

T1

invasion

5 mm or

less

T3

more than

10 and

less than

20mm

T2

invasion

6-10 mm


out of reach for many patients in

developing countries.

Depth of invasion in oral cancers

Tumours having a depth of invasion of

5 mm or less are classified as T1, those

having a depth of invasion 6–10 mm

are classified as T2, and those with a

depth of invasion higher than 10 mm

and less than 20 mm are classified as

T3. Tumours more than 20 mm depth

or crossing the midline are T4b cancers.

The subjectivity and interobserver

variability in determining the clinical

depth of invasion may be challenging.

For those treated with surgery, the

measurement of the depth of invasion

is pathological, where a plumb line is

dropped from the adjacent mucosa to

the deepest point of tumour invasion.

The issue with this parameter, as seen in

other malignancies, is the interobserver

variability; studies have shown a variable

concordance rate among pathologists

with respect to the depth of invasion.

A significant number of patients

with oral cancer in India are

treated with radiotherapy, either

as brachytherapy or external beam

radiotherapy. The measurement of the

depth of invasion in these patients

poses a bigger challenge, and there

is no consensus on radiological

determination of the depth of invasion

in oral cancer.

Nodal staging in

oropharyngeal cancer

For HPV‐positive oropharyngeal

cancer, clinical nodal staging is

now similar to the nodal staging

for nasopharyngeal cancer: N1 is

one or more ipsilateral nodes with

none >6 cm, N2 is contralateral or

bilateral lymph nodes with none >6

cm, and N3 comprises nodal disease

>6 cm. Pathological staging is N1

when metastasis occurs to ≤4 lymph

nodes. N2 is when metastasis occurs

to >4 lymph nodes. This is meant

to better prognosticate HPV‐related

oropharyngeal cancers at two distinct

points – with a clinical determination

of staging at presentation, and

a definitive pathological staging

following surgery. This is most likely

CATEGORY

a reflection of the increasing use of

transoral robotic surgery (TORS) in the

treatment of oropharyngeal cancer

in the United States. Access to TORS,

however, has been shown to correlate

with socioeconomic status even in a

developed country; and the number of

patients with head‐and‐neck cancer in

India with access to TORS is minuscule.

Unknown primary

CRITERIA

THE TECHNICAL EXPERTISE

AND EQUIPMENT REQUIRED

TO PERFORM ROUTINE

IMMUNOHISTOCHEMISTRY

ARE LACKING IN MANY

CENTRES THAT PROVIDE

CANCER CARE IN INDIA.

For patients with squamous cell

carcinoma demonstrated in cervical

lymph nodes without any demonstrable

primary site of malignancy, strong

recommendations have been

made regarding the addition of

immunohistochemistry to the diagnostic

evaluation. Acknowledging that

around 90% of all unknown primaries

are associated with an HPV‐related

oropharyngeal cancer in the United

States, the AJCC has recommended

that HPV in situ hybridization,

p16 immunohistochemistry, and

OROPHARYNGEAL CANCER

NODAL STAGING

Clinical nodal staging is now recommended

for HPV-positive oropharyngeal cancer

N1 N2 N3

One or more

ipsilateral lymph

nodes, none larger

than 6 cm

Contralateral or

bilateral lymph

nodes, none larger

than 6 cm

EBV‐encoded RNA in situ hybridization

be performed for all unknown primaries

of the cervical lymph nodes. Whether

this recommendation is feasible

in an Indian context is debatable;

the number of unknown primaries

associated with HPV in India is likely

to significantly fewer when compared

to that of the West. The technical

expertise and equipment required to

perform routine immunohistochemistry

and techniques such as in situ

hybridization are also lacking in many

centres that provide cancer care in

India.

In short, the new recommendations

made by the AJCC 8th Edition for the

treatment of head‐and‐neck cancers

address many of the shortcomings of

the previous editions. The majority of

these recommendations are universal.

However, some are likely to face hurdles

in their implementation in India. The

recommendations represent a step

toward standardization in radiological

and pathological reporting. However,

the degree of compliance that can be

attained to these recommendations

remains to be seen.

The author is Professor,

Department of Head

and Neck Surgery and

Oncology Amrita Institute

of Medical Sciences,

Kochi, India

drkrishnakumart@gmail.com

Lymph node(s)

larger than 6 cm

OCTOBER 2018 / FUTURE MEDICINE / 67


insurance

INSURANCE COVER FOR

INFERTILITY TREATMENT

Infertility treatment may soon be made part of standard insurance policies

DR DURU SHAH

Infertility is fast becoming a huge

concern in India. With 30 million

infertile couples currently, it is

estimated that in the year 2020,

2,50,000 IVF cycles will be performed

in the country. Needless to say, the cost

of infertility treatments too continues

to rise, making it unaffordable to a

large number of couples. There is a

huge need for the government to make

necessary budgetary provisions and

insurance companies to cover infertility

procedures as well.

The Indian Society for Assisted

Reproduction (ISAR) had last year

strongly campaigned with insurance

companies and the government to make

necessary provisions to bring infertility

treatment under insurance cover

in India. The change has now been

brought about by the efforts of the Govt

of India, especially the division heading

the Ayushman Bharat programme, and

the Insurance Regulatory Authority of

India.

In August 2018, the Insurance and

Regulatory Authority of India (IRDAI),

asked for the removal of around 10

items, including procedures such

as dental, stem cell, infertility and

psychiatric treatment, from the list of

“optional cover” for health insurance.

This would mean that these procedures

could be made part of standard

insurance policies. Some of them

could even be made mandatory! It is

heartening to note that infertility has

been included in this list—the fact that

the Indian insurance sector will now

provide insurance cover for infertility

treatment will definitely make it more

affordable to the millions of couples

ISAR HAD LAST YEAR

STRONGLY CAMPAIGNED

WITH INSURANCE COMPANIES

AND THE GOVERNMENT

TO MAKE NECESSARY

PROVISIONS TO BRING

INFERTILITY TREATMENT

UNDER INSURANCE COVER.

who need it.

ISAR had proposed to the Ministry

of Health and Family Welfare to make

infertility treatment easier for couples

seeking treatment for infertility by

having it covered under their health

insurance plan. And now, with the

Ministry of Health considering this

proposal, the efforts are bearing fruit.

Research has shown that one

in every six couples has a problem

conceiving on their own, which is a

clear indication of the large number of

people who need assistance to fulfill

their need to have children. Very often,

simple advice or a little help from the

gynecologists can help them in their

pursuit of having their own biological

child. But, occasionally they require

advanced procedures like IVF, ICSI, egg

donation, etc. While simpler treatments

are manageable and affordable

with every gynecologist, advanced

procedures need to be undertaken at

centres that offer assisted reproduction.

However, the fact is that the cost of IVF

ranges upwards of ₹1.5 lakh to ₹2 lakh

per cycle of treatment, mainly because

the cost of the consumables used for

IVF and the expenditure involved in

maintaining a high-quality embryology

lab are high. Hence, a huge number of

couples desist from seeking treatment

or resort to poor-quality care. Infertility

treatment not only involves expenditure,

but it also involves a huge amount of

investment from the couple seeking

treatment. This includes daily injections,

the time spent on treatment, giving up

on their careers due to frequent visits to

the clinic, financial loss, mental agony,

and many a times, disappointment

when the pregnancy test is negative

after such a long ordeal.

Their journey while seeking infertility

treatment will definitely be easier now,

thanks to IRDAI’s change in policy. We

will soon begin to see the effect of

this change in the number of patients

seeking affordable medical treatment

for infertility. In addition, if India can

reduce the dependence on imported

consumables for infertility procedures by

manufacturing them, we will be able to

make IVF much more affordable.

The author is Director,

Gynaecworld Center for

Assisted Reproduction &

Women’s health

Panel Consultant – Breach

Candy Hospital & Jaslok

Hospital, Mumbai.

68 / FUTURE MEDICINE / OCTOBER 2018


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health care

INDIA LAUNCHES WORLD’S LARGEST

PUBLIC FUNDED HEALTHCARE SCHEME

Industry lauds Ayushman Bharat, but says there are areas that need focus

India, a country of 1.3 billion people

with just a fraction of them covered

under medical insurance, has kickstarted

the world’s largest public funded

healthcare programme -- Ayushman

Bharat - Pradhan Mantry Jan Arogya

Yojana. The scheme is expected to

benefit around 10 crore economically

backward families with an annual

healthcare coverage of Rs 5 lakh each

and aims to cover around 550 million

people across the country.

As announced on the country’s

71st Independence Day in August,

Prime Minister Narendra Modi launched

the programme on September 23 in

Jharkhand. Launching the scheme at the

state capital Ranchi, the Prime Minister

said: “It is a big step towards providing

good quality and accessible healthcare

to the poor of India.”

As per the nationwide launch plan,

nearly 31 states and Union Territories

will implement the programme now. As

part of the launch, the Prime Minister

also inaugurated 10 wellness centres in

Jharkhand.

“The government is pursuing

a holistic approach towards the

betterment of the health sector. As

it focuses on affordable healthcare

on one hand, emphasis is also being

laid on preventive healthcare on the

other,” Modi said, while launching the

programme.

“This is the world’s largest such

scheme and the number of Ayushman

THE SCHEME WILL BE

FUNDED WITH 60%

CONTRIBUTION COMING

FROM THE CENTRAL

GOVERNMENT AND THE

REMAINING FROM THE

STATES.

Bharat beneficiaries is almost equal to

the population of Canada, Mexico and

the US put together,” Modi added.

The scheme became operational on

September 25 on the birth anniversary

of Pandit Deendayal Upadhyay and

will be funded with 60% contribution

coming from the central government

and the remaining from the states. Five

states, including Telangana, Odisha,

Delhi, Kerala and Punjab, are yet to sign

the agreement on the scheme with the

centre.

Eligible people can avail the benefits

in government and listed private

hospitals. The beneficiaries are identified

based on mainly four “deprivation”

categories. They need to establish

their identity to avail benefits under

the scheme and it could be through

Aadhaar card or election ID card or

ration card.

In case of hospitalisation, members

of the beneficiary families do not need

to pay anything, provided they go to a

government or an empanelled private

hospital.

Even as the healthcare industry

welcomed the historical launch of the

scheme, it reminded the government

that there are areas that need to

be addressed to ensure that such a

large-scale health-cover programme is

successfully implemented.

“On the historic launch of the

world’s largest health coverage scheme

- Ayushman Bharat, I feel as happy as I

70 / FUTURE MEDICINE / OCTOBER 2018


did when we launched the first universal

insurance scheme in my village in the

year 1999. I am also filled with a sense

of anticipation on the positive effect

this scheme will have on the health of

the 50 crore beneficiaries,”said Pratap

C Reddy, founder and chairman of the

country’s largest corporate hospital

chain, Apollo Hospitals.

“While we all work together to

ensure the success of this scheme,

there are areas that need focus and

fine tuning. These include ensuring the

robustness of the IT backbone, weeding

out potential fraud, ensuring coverage

to only identified beneficiaries and

ensuring more adoption by the private

sector, who are rightly worried about

the pricing and reimbursements. These

issues must remain paramount moving

forward,”he said, adding that he strongly

believes that the scheme is for the

greater public good and everyone must

strive to ensure its success.

Earlier, after the first announcement

of the programme in August, Tedros

Ghebreyesus, Director General of World

Health Organisation, lauded the initiative

by the government of India, calling it a

great commitment.

However, healthcare industry

consultants have expressed concerns

about the lack of clarity in the budgetary

allocation and the availability of funds.

There are also concerns about the

extent of geographical coverage

and the paucity of accredited hospital

capacity.

Mumbai-based healthcare industry

consultant and Future Medicine

columnist Muralidharan Nair had

earlier shared his views saying the

operational success of the programme

will be contingent upon customising

the programme to address the ground

conditions, which vary significantly from

state to state and even within the state.

“This includes the availability of

IT IS IMPERATIVE THAT A

COMPLEX PROGRAMME LIKE

THIS DEPEND HEAVILY ON

TECHNOLOGY SUPPORT FOR

EFFECTIVE EXECUTION, BE IT

FOR PROCESS EFFICIENCY,

PROCESS INTEGRITY, FRAUD

PREVENTION ETC.

relevant human resource, the maturity

of private providers, public health

capability, morbidity profile and the

cost of care. I am certain, the learned

managers of this programme are fully

seized of this matter, but I have a few

other concerns too,” he wrote in a

previous column.

It is imperative that a complex

programme like this depend heavily

on technology support for effective

execution, be it for process efficiency,

process integrity, fraud prevention,

optimization strategies or customer

feedback. It is unlikely that the

technology capabilities will be

fully deployed before a while, and

importantly, given the rural reach that

is planned. Therefore, it is crucial that

there is a robust plan for the interim and

a sustainable operational ecosystem for

carrying out technology operations in

the future, Nair added.

The critics of the Central

programme say that State cooperation

is important for successfully

implementing a programme of this

scale. Since the many of them are

still not in agreement, it may have a

negative impact on the nation roll out

of the programme.

While Odisha government has

already rejected the programme

saying the existing state government

programme--Biju Swasthya Kalyan

Yojana covers many more people

than Ayushman Bharat and provides

Rs. 7 lakh to women as opposed to

the central programme’s Rs. 5 lakh,

the Southern state Kerala was critical

about the feasibility of the new central

programme. Delhi and Telengana

states were also in disagreement with

Ayushman Bharat. WhileTelangana

rejected the scheme on the grounds

that its Aarogyasri scheme covers 70

per cent of the state’s population while

the Ayushman Bharat will only benefit

80 lakh people, Delhi government said

the central programme’s proposed

target of 6 lakh families covers just

3 per cent of its 2-crore population.

Similarly, the state of Punjab had also

held certain reservations against new

health coverage scheme launched by

the Centre.

OCTOBER 2018 / FUTURE MEDICINE / 71


public health

A QUARTER OF THE WORLD’S

POPULATION HAS TB: WHO

Although global efforts have averted an estimated 54 million TB deaths since

2000, TB remains the world’s deadliest infectious disease

WHO’s 2018 Global TB Report

calls for an unprecedented

mobilization of national and

international commitments. It urges

political leaders gathering for the firstever

United Nations High-level Meeting

on TB to take decisive action, building on

recent moves by the leaders of India, the

Russian Federation, Rwanda, and South

Africa. Nearly 50 Heads of State and

Government are expected to attend the

meeting.

“We have never seen such high-level

political attention and understanding

of what the world needs to do to end

TB and drug-resistant TB, said Dr.Tedros

Adhanom Ghebreyesus, WHO Director-

General. “We must capitalize on this

new momentum and act together to end

this terrible disease,” in an official release

To meet the global target of ending

TB by 2030, countries need to urgently

accelerate their response – including by

GLOBALLY, AN ESTIMATED

10 MILLION PEOPLE

DEVELOPED TB IN 2017. THE

NUMBER OF NEW CASES IS

FALLING BY 2% PER YEAR.

increasing domestic and international

funding to fight the disease. The WHO

report provides an overview of the status

of the epidemic and the challenges

and opportunities countries face in

responding to it.

TB epidemic: Falling numbers

Overall, TB deaths have decreased over

the past year. In 2017, there were 1.6

million deaths (including among 300

000 HIV-positive people). Since 2000,

a 44% reduction in TB deaths occurred

among people with HIV compared with

a 29% decrease among HIV-negative

people;

Globally, an estimated 10 million

people developed TB in 2017. The

number of new cases is falling by 2%

per year, although faster reductions have

occurred in Europe (5% per year) and

Africa (4% per year) between 2013 and

2017.

Some countries are moving faster

than others - as evidenced in Southern

Africa, with annual declines (in new

cases) of 4% to 8% in countries such as

Lesotho, Eswatini, Namibia, South Africa,

Zambia, and Zimbabwe, thanks to

better TB and HIV prevention and care.

In the Russian Federation, high-level

political commitment and intensified TB

efforts have led to more rapid declines

in cases (5% per year) and deaths (13%

per year)

Drug-resistant TB remains a global

public health crisis: In 2017, 558

000 people were estimated to have

developed disease resistant to at least

72 / FUTURE MEDICINE / OCTOBER 2018


ifampicin – the most effective first-line

TB drug. The vast majority of these

people had multidrug-resistant TB

(MDR-TB), that is, combined resistance

to rifampicin and isoniazid (another key

first-line TB medicine).

Under-diagnosis: Big challenge

Underreporting and under-diagnosis of

TB cases remains a major challenge. Of

the 10 million people who fell ill with TB

in 2017, only 6.4 million were officially

recorded by national reporting systems,

leaving 3.6 million people undiagnosed,

or detected but not reported. Ten

countries accounted for 80% of this

gap, with India, Indonesia and Nigeria

MDR-TB were reported to have received

treatment with a second-line regimen.

China and India alone were home to

40% of patients requiring treatment for

MDR-TB, but not reported to be receiving

it. Globally, MDR-TB treatment success

remains low at 55%, often due to drug

toxicity making it impossible for patients

to stay on treatment. A month ago,

WHO issued a Rapid Communication

on key changes to treatment of drugresistant

TB based on the latest scientific

evidence. These changes should result

in better treatment outcomes and more

lives saved. WHO is already working with

countries and partners to roll out these

changes.

to facilitate greater access to preventive

services for those who need it.

Insufficient funds

One of the most urgent challenges is

to scale up funding, the agency said.

In 2018, investments in TB prevention

and care in low- and middle-income

countries fell US$3.5 billion short of

what is needed. The report flags that

without an increase in funding, the

annual gap will widen to US$ 5.4 billion

in 2020 and to at least US$ 6.1 billion in

2022.A further US$ 1.3 billion per year is

required to accelerate the development

of new vaccines, diagnostics and

medicines.

topping the list.

Less than half of the estimated one

million children with TB were reported

in 2017, making it a much higher gap in

detection than that in adults.

Treatment coverage lags behind at

64% and must increase to at least 90%

by 2025 to meet the TB targets.

To urgently improve detection,

diagnosis and treatment rates, WHO,

the Stop TB Partnership and the Global

Fund launched the new initiative in

2018, Find. Treat. All. #EndTB, which set

the target of providing quality care to

40 million people with TB from 2018 to

2022.

Only around half of the estimated

920,000 people with HIV-associated TB

were reported in 2017. Of these, 84%

were on antiretroviral therapy. Most of

the gaps in detection and treatment

were in the WHO African Region, where

the burden of HIV-associated TB is

highest. Only one in four people with

TREATMENT COVERAGE

LAGS BEHIND AT 64% AND

MUST INCREASE TO AT

LEAST 90% BY 2025 TO

MEET THE TB TARGETS.

WHO predicts that at least 30 million

people should be able to access TB

preventive treatment between 2018 and

2022, based on new WHO guidance.

Although preventive treatment for latent

TB infection is expanding, most people

needing it are not yet accessing care.

WHO strongly recommends preventive

treatment for people living with HIV,

and children under 5 years living in

households with TB. Related new

guidance was issued by WHO in 2018,

WHO is guiding national and global

actions to reach everyone with care,

including those with TB, through a

transformative health agenda and push

towards Universal Health Coverage. This

includes proactive engagement with

civil society and other key stakeholders

to jointly help countries get on track to

end TB.

Ending the TB epidemic

requires action beyond the health

sector to address the risk factors

and determinants of the disease.

Commitments at the level of Heads of

State will be essential to galvanize multisectoral

action.

In June this year, an Interactive Civil

Society Hearing was organized by the

Office of the President of the General

Assembly, with the support of WHO, the

Stop TB Partnership, civil society, and

other stakeholders as a key preparatory

step towards high-level meeting, WHO

said.

OCTOBER 2018 / FUTURE MEDICINE / 73


medico legal

INDIA RELEASES CHARTER

OF PATIENT RIGHTS

The draft charter proposes a multi-tier redressal mechanism for patients.

India's health ministry has released the draft

statute of the country’s first ‘charter of patients'

rights’ to address issues in the healthcare sector.

Prepared by the National Human Rights

Commission (NHRC), the draft will act as a guidance

document for the Union government and state

governments to formulate concrete mechanisms so

that patient’s rights are given adequate protection

and operational mechanisms are set up to make

these rights functional and enforceable by law.

RIGHTS OF THE PATIENTS AS PER THE DRAFT PATIENT CHARTER

RIGHT TO FACTUAL

INFORMATION

Every patient has a right

to adequate relevant

information about the nature,

cause of illness, provisional/

confirmed diagnosis,

proposed investigations and

management, and possible

complications To be explained

at their level of understanding

in a language known to

them. The treating physician

has a duty to ensure that

this information is provided

in simple and intelligible

language to the patient to

be communicated either

personally by the physician, or

by means of his / her qualified

assistants.

Every patient and his/her

designated caretaker have the

right to factual information

regarding the expected cost of

treatment based on evidence.

The hospital management

has a duty to communicate

this information in writing

to the patient and his/her

designated caretaker.

RIGHT TO RECORDS

AND REPORT

The relatives/caregivers of

the patient have a right to

get discharge summary or in

case of death, death summary

along with original copies of

investigations.

The hospital management

has a duty to provide these

records and reports and

to instruct the responsible

hospital staff to ensure the

provision of the same are

strictly followed without fail.

RIGHT TO EMERGENCY

MEDICAL CARE

It is the duty of the hospital

management to ensure the

provision of such emergency

care through its doctors and

staff, rendered promptly

without compromising on

the quality and safety of the

patients.

RIGHT TO INFORMED

CONSENT

It is the duty of the hospital

management to ensure that

all concerned doctors are

properly instructed to seek

informed consent, that an

appropriate policy is adopted

and that consent forms with

the protocol for seeking

informed consent are provided

for patients in an obligatory

manner.

It is the duty of the primary

treating doctor administering

the potentially hazardous test/

treatment to explain to the

patient and caregivers the

main risks that are involved in

the procedure, and after giving

this information, the doctor

may proceed only if consent

has been given in writing by

the patient/caregiver or in

the manner explained under

Drugs and Cosmetic Act Rules

2016 on informed consent.

RIGHT TO CONFIDENTIALITY,

HUMAN DIGNITY, AND

PRIVACY

All female patients have

the right to the presence of

another female person during

physical examination by a

male practitioner. It is the duty

of the hospital management

to ensure the presence of

such female in the case of

female patients.

RIGHT TO SECOND OPINION

Every patient has the right to

seek the second opinion from

an appropriate clinician of

patients’ / caregivers’ choice.

The hospital management has

a duty to respect the patient’s

right to second opinion, and

should provide to the patients

caregivers all necessary

records and information

required for seeking such

opinion without any extra cost

or delay.

RIGHT TO TRANSPARENCY

IN RATES

Every patient has a right to

receive health care services

within the range of rates

for procedures and services

prescribed by Central and

State Governments from time

to time, wherever relevant.

However, no patient can

be denied choice in terms

of medicines, devices and

standard treatment guidelines

based on the affordability of

the patients’ right to choice.

RIGHT TO NON-

DISCRIMINATION

The hospital management

must regularly orient and

74 / FUTURE MEDICINE / OCTOBER 2018


instruct all its doctors and staff

regarding the same.

The hospital management has

a duty to ensure that no form

of discriminatory behaviour or

treatment takes place with any

person under the hospital’s

care.

RIGHT TO SAFETY AND

QUALITY CARE ACCORDING

TO STANDARDS

The hospital management has

a duty to ensure the safety

of all patients in its premises

including clean premises

and provision for infection

control guidelines and to

avoid medical negligence or

deficiency in service.

RIGHT TO CHOOSE THE

SOURCE FOR OBTAINING

MEDICINES OR TESTS

When any medicine is

prescribed by a doctor or a

hospital, the patients and

their caregivers have the

right to choose any registered

pharmacy of their choice to

purchase them.

RIGHT TO CONTINUITY

OF CARE

The patient and caregivers

have the right to be informed

by the hospital about any

continuing healthcare

requirements following

discharge from the hospital.

The hospital management

has a duty to ensure proper

referral and transfer of

patients regarding such a shift

in care.

RIGHT TO TAKE DISCHARGE

OF THE PATIENT, OR RECEIVE

THE BODY OF DECEASED

FROM THE HOSPITAL

A patient has the right to

take a discharge and cannot

be detained in a hospital,

on procedural grounds such

as a dispute in payment of

hospital charges. Similarly,

caretakers have the right to

the dead body of a patient

who had been treated in

a hospital and the dead

body cannot be detailed

on procedural grounds,

including nonpayment/dispute

regarding payment of hospital

charges against wishes of the

caretakers.

RIGHT TO CHOOSE

ALTERNATIVE TREATMENT

OPTIONS IF AVAILABLE

In case a patient leaves a

healthcare facility against

medical advice on his / her

own responsibility, then

notwithstanding the impact

that this may have on the

patient’s further treatment

and condition, this decision

itself should not affect the

observance of various rights

mentioned in this charter.

RIGHT TO PATIENT

EDUCATION

The hospital management and

treating physician have a duty

to provide such education

to each patient according

to standard procedure in

the language the patients

understand and communicate

in a simple and easy to

understand manner.

RIGHT TO BE HEARD AND

SEEK REDRESSAL

Patients and caregivers have

the right to seek redressal in

case they are aggrieved, on

account of infringement of

any of the above-mentioned

rights in this charter. This

may be done by lodging a

complaint with an official

designated for this purpose

by the hospital/healthcare

provider and further with an

official mechanism constituted

by the government such as

Patients’rights Tribunal Forum

or Clinical establishments

regulatory authority as the

case may be.

Every hospital and clinical

establishment has the duty

to set up an internal redressal

mechanism as well as to fully

comply and cooperate with

official redressal mechanisms

including making available

all relevant information

and taking action in full

accordance with orders of

the redressal body as per the

Patient’s Right Charter or as

per the applicable existing

laws.

RIGHT TO PROTECTION

FOR PATIENTS INVOLVED IN

CLINICAL TRIALS

RIGHT TO PROTECTION OF

PARTICIPANTS INVOLVED IN

BIOMEDICAL AND HEALTH

RESEARCH

OCTOBER 2018 / FUTURE MEDICINE / 75


ethics

perspectives

DOCTORS OWE A CONSTITUTIONAL

DUTY TO TREAT THE HAVE-NOTS: SC

The Supreme Court of India has observed that a doctor cannot refuse treatment

to a person merely on the ground that he cannot afford it

India’s Supreme Court, while

deliberating on the case pertaining

to the Delhi government’s circular

to hospitals built on subsidised

land, has observed that members

of the medical profession owe a

constitutional duty to treat the

poorer sections of the society.

Doctors cannot refuse to treat

a person who is in dire need of

treatment by a particular medicine or

by a particular expert merely on the

ground that he is not in a position

to afford the fee payable for such an

opinion or treatment, the court ruled.

Setting aside the Delhi High Court

order that had dismissed the circular

issued by the Delhi government, the

SC bench directed all the hospitals in

Delhi to go by the conditions imposed

by the government.

76 / FUTURE MEDICINE / OCTOBER 2018


What the Supreme Court said

THE COURT UPHELD THE

DELHI GOVERNMENT

CIRCULAR SAYING THAT

STIPULATION FOR FREE

TREATMENT DOES NOT

AMOUNT TO RESTRICTION

UNDER ARTICLE 19(6) ON

THE RIGHT ENSHRINED

UNDER ARTICLE 19(1)(G).

The circular issued by the

Government of NCT of Delhi had asked

the hospitals built on subsidized land

to provide free treatment to 10%

indoor patients and 25% outdoor

patients from the economically

backward people.

The court upheld the Delhi

government circular saying that such

stipulation for free treatment does not

amount to restriction under Article

19(6) on the right enshrined under

Article 19(1)(g).

The bench also directed the

government to file periodic reports

for one year on the compliance of the

conditions by hospitals in Delhi.

Describing the denial of proper

treatment to a person belonging to the

lower economic strata of the society as

inhuman, Justice Arun Mishra made some

observations about medical profession and

ethics in his 124-page judgement.

Medical profession deals with the life

of human beings. There has to be a

balancing of human rights with the

commercial gains.

Members of the medical profession

owe a constitutional duty to treat the

have-nots. They cannot refuse to treat a

person who is in dire need of treatment

by a particular medicine or by a particular

expert merely on the ground that he

is not in a position to afford the fee

payable for such an opinion/treatment.

The moment it is permitted, the medical

profession would become purely a

commercial activity. It is not supposed to

be so due to its nobleness.

It would be inhuman to deny a person

who is not having sufficient means, or no

means, to afford life-saving treatment,

simply on the ground that he is not

having enough money. If treatment is

refused due to financial reasons, it would

be against the very basic tenets of the

medical profession and the concept of

charity in whatever form we envisage the

same. Besides being unconstitutional, it

would be violative of basic human rights.

By and large, hospitals have now

become centres of commercial

exploitation and instances have come

to notice when a dead body is kept as

security for clearance of bills, which is

per se illegal and a criminal act. In future,

whenever such an act is reported to the

police, it is supposed to register a case

against the management of the hospital

and all concerned doctors involved in

such an inhumane act which destroys

the basic principles of human dignity and

is tantamount to a criminal breach of the

trust reposed in the medical profession.

The state spends and invests a huge

amount of public money on the making

of a doctor, and it is the corresponding

obligation on the part of the doctor

to serve the needy. Treatment cannot

be refused on the ground of financial

inability of the patient.

Besides wrong reporting, uncalled for

investigation -- inclusive of invasive tests

on the heart and other parts of the body,

which are wholly unnecessary -- are

performed. It is time for soul-searching

for big hospitals in and around Delhi,

Gurgaon and other places. They must

ponder what they are doing. Is it not

a criminal act? The fact that action is

not taken does not absolve them of

the responsibility. Time has come to

fix accountability and to set right the

evils which have rotten the system. The

medical profession had never been

intended to be an exploitative device to

earn money at the cost of the patients

who require a godly approach and

the helping hand of doctors. Every

prescription starts from Rx, not from

the amount of bill. Big commercial

international hospitals, are not above

the ethical standards which they have

to maintain at all costs, including by

extending financial help to the have-nots.

The hospitals nowadays have five-star

facilities. The entire concept has been

changed to make commercial gains. They

are becoming unaffordable. The charges

are phenomenally high, and at times

unrealistic compared with the service

provided. The dark side of such hospitals

can be illuminated only by the sharing

of the obligation towards economically

weaker sections of the society. It would

be almost inhuman to deny proper

treatment to the poor owing to economic

conditions.

78 / FUTURE MEDICINE / OCTOBER 2018


devices&gadgets

MRI-compliant cochlear

implant cleared in US

Once-weekly

exenatide pen

gets EC nod

The European Commission

(EC) has approved

Bydureon BCise (exenatide

2mg prolonged-release

suspension for injection in prefilled

pen) for the treatment of

patients with type-2 diabetes.

The new formulation of

once-weekly Bydureon is an

improved single-dose, pre-filled

pen device that requires no

titration and is approved for

use in combination with other

glucose-lowering medicines,

said AstraZeneca, the maker of

the device.

The EC approval is based

on the data from two clinical

trials, Duration-Neo-1 and

Neo-2. Duration-Neo-1 is a

28-week, randomised, openlabel,

comparator-controlled

trial (n=375), which showed

that once-weekly Bydureon

BCise demonstrated an HbA1c

reduction of 1.4% vs. 1.0% for

twice-daily Byetta (exenatide)

injection at 28 weeks (baseline

HbA1c 8.5% and 8.4%,

respectively). Additionally,

Bydureon BCise demonstrated

a mean weight reduction of

-1.5 Kg as monotherapy vs. -1.9

Kg (baseline was 97 Kg) when

combined with certain oral

antidiabetic medicines.

This new formulation of

once-weekly Bydureon BCise

was approved by the US FDA in

October 2017.

HiRes Ultra 3D cochlear

implant, produced by

Advanced Bionics, has

received clearance from the

USFDA.

The new magnet design

provides alignment with an

external magnetic field in any

direction. This allows cochlear

implant recipients to move

freely around in the strong

magnetic field of an MRI

machine without feeling

pain or discomfort, and

without restrictions

to the orientation of the

head. Even for high resolution

MRI examinations, there is

no need to remove the

magnet and no requirement

for head bandaging,

meaning no hearing

downtime for the patient,

the company said.

Previously, patients and

Philips launches

computational

path software

R

oyal Philips has launched a

new version of TissueMark,

an AI-driven application to

address most critical primary

tumours encountered for

surgeons had to contend with

the strong magnetic field

from MRI machines exerting

force on the magnet, causing

torque and subsequent pain if

the magnet remained in situ,

even with head bandaging.

Therefore, it was common to

remove the magnet for high

resolution MRI examinations,

requiring outpatient surgery

and interrupting the patient’s

molecular research testing. It

now supports region-of-interest

detection for the majority of

molecular testing and helps

research labs improve the

accuracy of tumour estimation.

The new version leverages

deep learning AI to aid in

prostate and ovarian tumour

tissue identification.

The updated TissueMark

hearing during the healing

process.

Advanced Bionics is

developing hearing solutions

for individuals with severe-toprofound

hearing loss who

no longer benefit from

hearing aids.

software now provides tumour

sufficiency guidance for lung

histology, lung cytology, colon

and breast tissue samples in 60

seconds in addition to guidance

to whole slide images (WSI)

of adenocarcinoma prostate

tissue and high-grade serous

carcinoma ovarian tissue.

Using a microscope for

tumour estimation is subjective

and leads to high variability

amongst pathologists,

according to Philips. By

digitizing the tissue slide and

analysing the image with

computational software and

intelligent algorithms, it can

better support pathologists’

workflows and help labs

enhance quality and reliability,

while reducing costs by limiting

the number of molecular tests

performed with insufficient

tumour content.

AI-powered solutions

also have great potential to

make solutions adaptive to

the needs of clinicians to help

80 / FUTURE MEDICINE / OCTOBER 2018


them further improve patient

outcomes.

Baxter's new

bone graft

gets US nod

The US FDA has granted

approval for the Actifuse

Flow Bone Graft Substitute for

use in a variety of orthopaedic

surgical procedures, said Baxter

International Inc.

Actifuse Flow offers

accelerated bone growth in a

new, easy-to-use, prepackaged

delivery syringe for precise

placement into small bony

voids or gaps in the skeletal

system. It comes ready to use

with no mixing or preparation

involved and maintains

its flowable consistency

throughout surgery.

The bone graft substitute

is delivered directly from a

preloaded syringe with the

ability to start and stop delivery,

making it compatible with

open and less invasive surgical

techniques and well-suited for

filling small bone defects and

complex geometries. As the

graft substitute resorbs, it is

replaced by the patient’s own

bone during the body’s healing

process.

Actifuse Flow is a bone

void filler intended only for

orthopaedic applications as a

filler for gaps and voids that

are not intrinsic to the stability

of the bone structure. It is

indicated to be packed gently

into bony voids or gaps of the

skeletal system, i.e., extremities,

pelvis, and spine, including use

in posterolateral spinal fusion

procedures with appropriate

stabilizing hardware. These

defects may be surgically

created osseous defects or

osseous defects created from

traumatic injury to the bone.

Baxter expects it to be

used in a variety of orthopaedic

surgeries in the pelvis,

extremities, and posterolateral

spine.

NephroPlus

launches buttonhole

needles

N

ephroPlus, a network of

dialysis centres in India,

has introduced the buttonhole

needles for painless dialysis.

Buttonhole cannulation is a

technique used often in home

hemodialysis where blunt

needles are used instead of

sharp ones.

Most dialysis patients

report pain during the insertion

of the needles as their biggest

fear in a dialysis treatment. The

Buttonhole needles addresses

this issue by reducing the

amount of pain drastically,

according to a release.

In this technique, first a

tract is formed in the flesh

by pricking a sharp needle

at the same point at the

same angle during five to six

successive dialysis sessions.

Subsequently, a blunt needle

is used for cannulation that

goes through this tract without

Apple Watch Series 4 to

track ECG

The US Food and Drug

Administration has

cleared the Apple Watch

Series 4 to operate as an

OTC device to monitor ECG.

The FDA approval makes

Apple Watch the first device

available to consumers over

the counter to monitor ECG.

The new Apple Watch

Series 4 version has

electrodes placed in the

sapphire crystal and digital

crown that allows users to

take an ECG at any time

using the app provided. The

Apple Watch can show

its first ECG to users

without a doctor

review.

The Health app

allows all ECG

recordings stored

in so that they

can be shared

with healthcare

professionals at a

later time.

Apple plans to add

more capabilities in the

device later this year to

aid detect atrial fibrillation.

Health-care products

on ubiquitous devices, like

smart watches, may help

users seek treatment earlier

and will empower them

with more information

about their health, the FDA

Commissioner Scott Gottlieb

said in a statement. "The

FDA worked closely with the

company as they developed

and tested these software

products, which may help

millions of users identify

health concerns more

quickly," he added.

The Apple Watch Series

4 line starts at $399. It is

$70 more than the starting

price of last year's model.

82 / FUTURE MEDICINE / OCTOBER 2018


much pain. Buttonhole needle

method is not only pain free; it

is safer and easier for dialysis

patients. Patients undergoing

dialysis through this method

have reported reduction of

pain more than 95 per cent

compared with the previous

method.

NephroPlus has 128 centres

currently in 82 cities across 18

states in India.

Novaerus launches

plasma air

purifier in India

Novaerus, an Irish company

specializing in non-chemical

air disinfection, launched the

Defend 1050 in India.

Defend 1050 is a portable,

easy to use device for rapid

disinfection and purification

of the air in large spaces and

high-risk situations such as

operating-theatres, ICUs,

IVF labs, emergency

and waiting rooms, and

construction zones.

Defend 1050 uses patented

dielectric-barrier discharge

(DBD) ultra-low energy plasma

technology. It utilises specifically

designed multi-stage pre-filters,

HEFA filters and carbon filter

systems to reduce infection,

absorb odours, neutralize

volatile organic compounds

(VOCs), and trap particulate as

small as 0.3µm.

“With time, we have seen

a high contamination rate

in the air, which is resulting

toin an alarming increase in

airborne diseases and causing

adverse results to human

health. The plasma technology

Kleresca launches new biophotonic treatment

Kleresca has released a new biophotonic

technology for the treatment of rosacea.

The treatment uses fluorescent light

energy to stimulate the skin’s own repair

mechanisms through photobiomodulation.

The system consists of a patented,

multi-LED Kleresca lamp designed with

specific, pre-programmed wavelength

settings and a specially formulated

photoconverter gel. Chromophores in the

gel convert light waves from the lamp

into dynamic, pulsing fluorescent energy

that stimulates the skin’s own repair

mechanisms. The treatment is non-invasive

and generally perceived as comfortable

even to rosacea patients with enhanced skin

sensitivity.

brought by Novaerus has been

studied by NASA that has

shown how the technology is

an answer to this crisis,” said

Una Ni Raghallaigh, Business

Development Director, EMEAA

region for Novaerus Inc while

launching Defend 1050 at ISAR

(Indian Society for Assisted

Reproduction) conference

organized in Aurangabad,

recently.

Roche's

diagnostic test

for NSCLC

The US FDA has approved

Roche’s cobas EGFR

Mutation Test v2 as a

companion diagnostic test

(CDx) with gefitinib (Iressa).

Gefitinib is a targeted

monotherapy for the treatment

of patients with advanced or

metastatic epidermal growth

factor receptor (EGFR) exon 19

deletions or exon 21 (L858R)

substitution mutation-positive

NSCLC. Iressa acts by inhibiting

the tyrosine kinase enzyme in

the EGFR, thus inhibiting the

transmission of signals involved

in the growth and spread of

tumours.

A CDx test provides

information that is essential for

the safe and effective use of

a corresponding therapeutic

product. Clinical studies have

demonstrated that patients

diagnosed with NSCLC who test

positive for defined mutations

of EGFR gene benefit from

tyrosine kinase inhibitor (TKI)

therapies.

The treatment for rosacea is now available

to patients through aesthetic clinics across 10

markets including Denmark, UK, France, Spain,

Italy, Germany, Belgium, Norway, Australia and

Switzerland.

Apart from reducing inflammation, the

in-clinic treatment lowers the presence

of papules and pustules; cuts down

erythema and blushing by improving

microvascularisation; mitigates the overall

stress level of the skin, thereby reducing the

feeling of burning and stinging and induces a

healing response.

The Kleresca biophotonic system has

been available on the market since 2014. The

company recently obtained own CE-mark on

all its products.

The cobas EGFR Mutation

Test v2 is currently the only

FDA-approved diagnostic test

for NSCLC using liquid biopsy.

EGFR testing in plasma offers a

non-invasive option for patients

using a simple blood draw for

those who are not eligible for a

tissue biopsy.

The cobas EGFR Mutation

Test v2 is a real-time

polymerase chain reaction

(PCR) test for the qualitative

detection of 42 defined

mutations of the EGFR gene in

exons 18-21, including L858R,

exon 19 deletions, and T790M

mutations.

Clinical studies such as

AURA, AURA2, FLAURA,

ENSURE, EURTAC, and

FASTACT2, have demonstrated

the reliability of the cobas EGFR

Mutation Test v2, Roche said.

84 / FUTURE MEDICINE / OCTOBER 2018


Non-surgical

option for

hearing loss

Med-El has been granted

marketing approval

for Adhear, a non-surgical

bone conduction hearing

technology.

Adhear offers an option

for people with conductive

hearing loss who are not

candidates for, or who would

not like to undergo, bone

conduction implant surgery.

It is also a treatment option

for candidates with singlesided

deafness and normal

hearing on the contralateral

side.

Adhear is easy to use. An

adhesive adapter is placed

onto the skin behind the

ear and is worn for three to

seven days at a time. The

lightweight audio processor is

simply clicked on and off each

day. The audio processor picks

up sound waves, converts

them into vibrations and

transmits them onto the bone

via the adhesive adaptor.

The bone then transfers the

vibrations through the skull to

the inner ear where they are

processed as normal sound.

Bone conduction uses the

bones of the skull to transmit

sound waves directly to the

inner ear and may be an

appropriate option for people

who have hearing loss due to

problems with the eardrum,

ear canal or middle ear.

Unlike available nonsurgical

bone conduction

devices that cause discomfort

for the user, Adhear

comfortably stays in position

without applying pressure

onto the skin, while its

discreet location behind the

ear makes it cosmetically

appealing.

Med-El acquired the

device’s technology from

Swedish medical device

company Otorix in 2016 and

further developed Adhear

at Med-El’s headquarters in

Innsbruck, Austria.

Conductive hearing loss is

caused by problems with the

ear canal, ear drum, or middle

ear and its tiny bones. Causes

of conductive hearing loss

include congenital absence

of the ear canal or failure of

the ear canal to be open at

birth, and congenital absence,

malformation, or dysfunction

of the middle ear structures.

AI algorithm

to detect wrist

fractures

Imagen’s OsteoDetect, a type

of computer-aided detection

and diagnosis software

designed to detect wrist

fractures in adult patients, will

soon be available in the US

market.

The Osteo Detect software

is a computer-aided detection

and diagnostic software that

uses an artificial intelligence

algorithm to analyse twodimensional

X-ray images for

signs of distal radius fracture,

a common type of wrist

fracture. The software marks

the location of the fracture on

the image to aid the provider

in detection and diagnosis.

Osteo Detect analyses

wrist radiographs using

machine learning techniques

to identify and highlight

regions of distal radius

fracture during the review of

posterior-anterior and mediallateral

X-ray images of adult

wrists.

OsteoDetect can be

used by clinicians in various

settings, including primary

care, emergency medicine,

urgent care and specialty

care, such as orthopedics.

It is an adjunct tool and

is not intended to replace

a clinician’s review of the

radiograph or his or her

clinical judgement.

Imagen submitted a

retrospective study of 1,000

radiograph images that

assessed the independent

performance of the image

analysis algorithm for

detecting wrist fractures and

the accuracy of the fracture

localisation of OsteoDetect

against the performance

of three board-certified

orthopedic hand surgeons.

Imagen also submitted

a retrospective study of 24

providers who reviewed

200 patient cases. Both

studies demonstrated that

the readers’ performance in

detecting wrist fractures was

improved using the software,

including increased sensitivity,

specificity, positive and

negative predictive values,

when aided by OsteoDetect,

as compared with their

unaided performance

according to standard clinical

practice.

Deep TMS system to treat OCD

BrainsWay Ltd has received clearance

from the US FDA for its deep transcranial

magnetic stimulation (Deep TMS) system

for the treatment of obsessive-compulsive

disorder (OCD) in adults.

Deep TMS system is the first non-invasive

medical device for the treatment of OCD.

The system was granted approval in 2013 for

the treatment of treatment-resistant major

depressive disorder (MDD).

BrainsWay’s Deep TMS technology differs

from that of other focal TMS devices as it

can directly stimulate areas of the brain at a

greater depth and breadth. The device can

target previously unreachable areas of the

brain with its H7-coil, allowing it to effectively

treat OCD as well. Clinics that have a Deep

TMS systems can now treat MDD and OCD

patients, the company said.

OCTOBER 2018 / FUTURE MEDICINE / 85


ADVERTORIAL

Cerebrotech Visor

VOLUMETRIC IMPEDANCE PHASE SHIFT SPECTROSCOPY (VIPS)

DETECTS STROKE IN 30 SECONDS

The Cerebrotech Visor, a new

deviceworn like a visor, can detect

emergentlarge-vessel occlusion in

patients withsuspected stroke with

92 percent accuracy,report clinical

investigators at the MedicalUniversity

of South Carolina (MUSC),Mount Sinai,

the University of TennesseeHealth

Sciences Center and elsewherein

an article published in the Journal

ofNeurointerventional Surgery.

The volumetric impedance phase

shiftspectroscopy (VIPS) device works

bysending low-energy radio waves

throughthe brain that change frequency

whenpassing through fluids. Such waves

arereflected back through the brain

and thendetected by the device. When

a patient ishaving a severe stroke, the

brain’s fluidswill change, producing an

asymmetryin the radio waves detected

by the VIPSdevice. The greater the

asymmetry, themore severe the stroke.

The Cerebrotech Visor is a

noninvasivewireless device for assessing

brain fluiddistribution. The Visor

uses low-powerradio waves to detect

bioimpedanceasymmetry, including

asymmetryassociated with large acute

ischemicstroke in patients undergoing

neurologicassessment. In recent clinical

studies,the Visor has been able to

differentiatelarge strokes from small

strokes with anaccuracy over 90%, a

study found.

In the study, the VIPS device

wasdeployed with emergency

medicalpersonnel in regions served

by fiveComprehensive Stroke Centres

equippedwith the endovascular

capabilities totreat large-vessel

occlusions that underliesevere stroke.

Their goal was to use thedevice to

accurately identify severe strokeand

then compare the results to

establishedphysical examination

methods practicedby emergency

personnel such as thePrehospital Acute

Stroke Severity Scale.

Both healthy participants and

patientswith suspected stroke were

evaluatedby emergency personnel using

the VIPSdevice. Three readings were

taken andaveraged—a process that takes

about 30seconds. Patients were also later

evaluatedby neurologists who provided

definitivediagnoses using neuroimaging.

Compared to the neurologists’

diagnoses,the device displayed 92

percentspecificity—the ability to detect

thedifference between patients with

severestroke and those with other

conditionssuch as mild stroke or healthy

participantswith no brain pathology.

This places theVIPS device above

standard physicalexamination tools used

by emergencypersonnel that display

specificity scoresbetween 40 and 89

percent.

This is a sponsored article. FM editorial holds no responsibility for the information therein.

86 / FUTURE MEDICINE / OCTOBER 2018


ADVERTORIAL

WebCardio – Multiday,

Disposable, Wireless Holter

Monitoring Solution for ECG

THE NEXT GENERATION OF AMBULATORY ECG MONITORING

WebCardio is a Wireless, Disposable,

Multiday Holter monitor that can

continuously record ECG up to three

days. It can be used for detection and

quantification of Cardiac Arrhythmias

including Tachycardia, Bradycardia,

Pauses, Conduction delays and blocks,

Ventricular and Supraventricular beats

and runs, and Atrial fibrillation.

The WebCardio solution developed

by GadgEon using LifeSignals’ USFDA

cleared Biosensor Platform, has gone

through clinical validation and

commercially launched in selected cities.

The WebCardio solution consists of

a body worn disposable ECG patch,

a companion mobile App and cloud

based Rhythm interpretation and

report generation service. The nurse or

technician can view the ECG waveform

after affixing the ECG patch on the

patient, by wirelessly pairing it with

a companion mobile App. This helps

technician to ascertain the quality of

ECG before starting the Holter recording

process. Once recording is initiated, the

patient can go home and continue with

their normal activities. The ECG Patch

shall continuously acquire and store the

data in its memory. The stored ECG data

is automatically transferred wirelessly

to the already paired mobile app at a

periodic interval. This data is then pushed

to the cloud server from the Mobile

App, when cellular network is available.

The patch can be worn by the patient

up to 72 hours as prescribed by the

doctor.

Once the complete ECG data is

available in the server, a team of qualified

cardiac technicians analyzes the ECG

and creates the report using USFDA

approved Holter analysis software.

Reports and the full disclosure ECG

are then made available online to the

doctor. The report shall optionally be

emailed to the clinical personnel.

The WebCardio “Pay per Use model”

allows smaller clinics and individual

doctors to add Holter monitoring to their

practice without any capital investment.

For the hospitals, that already has

Holter recorder, WebCardio solution

would help to augment the capacity

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extended Holter monitoring service of up

to 72 hours.

WebCardio solution improves the

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ECG patch can be easily administered on a

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service from WebCardio. The small size

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WebCardio will soon add more features

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WebCardio will deliver advanced

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current mobile revolution, WebCardio

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rural segment.

This is a sponsored article. FM editorial holds no responsibility for the information therein.

88 / FUTURE MEDICINE / OCTOBER 2018


events

debate

ISGE-Pune kicks off debate over

open vs telescopic surgery

Experts debate the shift from vaginal to endoscopic surgeries to find

the optimal approach for patients

The three-day regional meeting

of International Society of

Gynaecology Endoscopy (ISGE)

in Pune shined the spotlight on one

of the most critical discussions in

the field: Should new generation

gynaecology surgeons restrict

themselves to telescopic procedures

or also look at the benefits of a

complementary approach involving

traditional surgeries? The debate came

up in the wake of the increasing trend

of promoting endoscopic surgeries

in India despite the fact that both

procedures have their merits and

demerits as far as patient safety is

concerned.

The conference, which had several

theoretical lectures presented by

renowned speakers in the field of

gynaecological endoscopy, was also

Doctors should not get

carried away by technology

campaigns and blindly say

that they are exclusively

laparoscopic surgeons.

Prof. Bhaskar D Goolab

Department of Obstetrics and

Gynaecology, University of

Witwatersrand, Johannesburg

filled with panel discussions and

practical workshops on different

aspects of endoscopic surgical skills

and the relay of live surgeries from

different parts of the world.

Though the event could

successfully highlight the latest

technical advances and innovations

which are making surgeries safer and

cost effective, a discussion over the

traditional approach versus the new

was an eye-opener, especially to new

age clinicians.

Sharing his decades-long

experience in open as well as

endoscopic gynaecological surgeries

in India and abroad, Prof. Bhaskar

D Goolab, Department of Obstetrics

and Gynaecology, University of

Witwatersrand, Johannesburg, South

Africa, said that there are merits

90 / FUTURE MEDICINE / OCTOBER 2018


Although the cost of

laparoscopic surgeries

are higher compared to

conventional procedures,

these new methods help

reduce the days of hospital

stay.

Dr P G Paul

Chairman of Paul Hospital

in both procedures. But, doctors,

especially new-age gynec-surgeons,

should not get carried away by

technology campaigns and blindly say

that they are exclusively laparoscopic

surgeons. These kind of conferences

are there to put such issues in

perspective, he added..

“There is a debate that has come

up now as to what is the role of

telescopic surgery and what is the

role of the conventional and longtrusted

open surgery. There are merits,

indications and pitfalls on both sides

of the equation, but the key point

of contention here is the paradigm

shift that is predominantly driven by

technology players towards these

expensive surgeries. Gynaecologists

simply follow the trend of telescopic

surgery, unnecessarily turning some

simple traditional procedure into

an expensive technology procedure

instead of weighing the specificity, fit

case, patient choice and safety,” Dr

Goolab said.

“Of course, there is merit in

suitably chosen cases. For example,

diseases like endometriosis or massive

uterine fibroids, which makes the

removal process difficult through

the vaginal route, need to be done

Since the hospital meter

starts running from the

very moment the patient

gets admitted, a reduced

hospital stay is often a big

saving for the patient.

Dr Rishma Dhillion Pai

Senior Gynaecologist &

Endoscopist

through telescopic surgery, depending

on the skill of the doctor. There

are also risk factors like burn and

other complications associated with

endoscopic surgeries as it uses electric

power,” he added.

While others agreed with the view

that the debate remains relevant as far

We wanted to showcase the

Indian skill-set in endoscopy

to the world through this

event and, at the same

time, wanted our young

gynaecologists to learn from

the experienced doctors

from all over the world.

Dr Sunita Tandulwadkar

Organising Chairman, ISGE-Pune

as some specific cases are concerned,

they argued that laparoscopic

technologies have actually made

procedures much easier for the patient

and the surgeon, both technically and

in terms of indirect costs.

According to Dr P G Paul, one

of the most senior gynaecology and

endoscopic surgeons in India and the

chairman of Paul Hospital, it is natural

that technology development drives

the industry to better options, though

doctors always have the opportunity

to choose the best according to

his/her skill-set and the benefit of

the patients.

“It is not only the procedure cost

that matters in the overall treatment.

Although the cost of laparoscopic

surgeries are higher compared to

conventional procedures, these new

methods help reduce the days of

hospital stay and the patients can

resume their routines faster after the

surgery,” Dr Paul said.

“The advanced and innovative

technologies in endoscopy have

effectively helped in saving both

cost and time for patients, though

the cost of the procedure as such

is comparatively higher. Since the

hospital meter starts running from

the very moment the patient gets

admitted, a reduced hospital stay is

often a big saving for the patient,”

said Dr Rishma Dhillion Pai, Senior

Gynaecologist & Endoscopist and

President, Indian Association of

Gynaecological Endoscopists (IAGE).

Dr Sunita Tandulwadkar, the

organising chairman of the 2018

regional conference, said the

conference was unique in several

aspects, including the presence of

live workshops, academic sessions

and a number of senior national and

international speakers.

“Also, we wanted to showcase

the Indian skill-set in endoscopy to

the world through this event and, at

the same time, wanted our young

gynaecologists to learn from the

experienced doctors from all over the

world, who shared their 25-30 years’

experience in handling unique cases,”

she said.

92 / FUTURE MEDICINE / OCTOBER 2018


events

KENTCON-2018 highlights

advancements in otolaryngology

The 3-day event stressed the need for exchanging ideas in multifarious

areas of ENT practice

DIVYA CHOYIKUTTY

The 17thannual conference

of Association of

Otorhinolaryngologists of India

highlighted emerging technology

breakthroughs and surgical techniques,

such as computer assisted navigation,

endoscopic skull base surgery and facial

reanimation.

KENTCON-18, which was held

from 7th to 9th September in

Kochi, was attended by over 500

otorhinolaryngologists from across

the globe. The three-day convention,

organized by the Kerala State Branch

of AOI in association with Cochin

Society of Otorhinolaryngologists for

Medical Society (CSOM), stressed the

need for exchanging ideas and creating

awareness on medical technologies and

advancements in multifarious areas of

ENT.

Dr. Preethy Mary from Medical Trust

Hospital, Cochin said the new concepts

in endoscopic surgery are helping

with the removal of tumours from

inaccessible locations of skull base.

“Some of the tumours located at

extremely inaccessible locations like the

skull base can now be removed through

the nasal route via endoscopy,” she said.

“Earlier, the removal of such tumours of

the pituitary gland was entirely a domain

of neurosurgery. The new techniques in

nasal endoscopy now make it possible

to remove these difficult-to-access

tumours as a combined procedure of

transnasal pituitary surgery,” Dr Mary

added.

The diagnosis of ENT disorders

too have improved with the advent

of technological advancements

involving endoscopy, ultrasonography,

The refinement of ultrasound

technology for noninvasive

localisation of airway

obstruction helps proper

clinical validation and early

diagnosis of OSA.

Dr. Amal Isiah

University of Maryland

implants and surgical navigation, which

has helped in implementing better

treatment and minimizing the number

of complications and hospital stays.

The conference also featured a

live surgical demonstration of facial

reanimation on cadaver, performed

by Dr. Kalpesh Vakharia, to highlight

the management of facial paralysis,

one of the most complex areas of

reconstructive surgery.

Significant advances in the field of

trans-oral robotic surgery (TORS) and

the minimal invasive approach towards

efficient resection of tumours in the

oropharynx area were elucidated by Dr.

Kyle M. Hatten, who also reflected on the

slow, but steady rise in oropharyngeal

cancer seen over the past decades.

He also mentioned the risk of human

papilloma virus, which is expected to be

the major causative organism for head

and neck cancer in the US by 2030.

Stressing the importance of

managing obstructive sleep apnea

(OSA), Dr. Amal Isiah of University of

Maryland, said: ”The refinement of

ultrasound technology for noninvasive

localisation of airway obstruction along

with the conventional technique of

polysomnography, helps proper clinical

validation and early diagnosis of the

disorder.”

The conference also cautioned about

the lack of new research in the field,

and that the country has always been

dependent on technologies invented

and patented elsewhere.

Several experts from across India and

GCC participated in the conference.

94 / FUTURE MEDICINE / OCTOBER 2018


NEXTGEN GENOMICS, BIOLOGY, BIOINFORMATICS

AND TECHNOLOGIES

SEP 30 th - OCT 2 nd , 2018

CONFERENCE

FAIRMONT, JAIPUR, INDIA

The 2018 NextGen Genomics, Biology, Bioinformatics and Technologies (NGBT) Conference

is an international meeting organized by SciGenom Research Foundation (SGRF), a

not-for-profit organization working to promote Science, Research & Education. The

conference will also focus on convergence of clinical and genomic technologies for better

healthcare outcomes.

Key topics include:

Clinical genomics

Cell free DNA

Exome Sequencing

Genome sequencing

Human genomics

Liquid Biopsy

Medical Genomics

Non-Invasive testing

Onco-Genomics

Pharmacogenomics

Protein engineering

Protein structure

RNA-Seq Sequencing

SNP Analysis

Whole Genome Sequencin

Live and Let Live:

Snakebite Cure

Symposia

Oct 1 st 2018, Jaipur, India

Genomics Project Grants

Student Meeting Scholarships

Travel Awards

20 keynote lectures; 50+ talks

1000 delegates; 200+ posters

Vendor Exhibition

Co-hosts

Sponsors Knowledge Partner & Poster prize sponsors Media Partners

Ms. Lakshmi V | M: +91-9591506568 / Mr. Srijith VM | M: +91- 9497118365

ngbt2018@sgrf.org | www.sgrfconferences.org | www.sgrf.org


calendar

Upcoming conferences

OCTOBER

SURGERY

OF THE HAND

5- 7

42nd Annual Conference

of Indian Society for

Surgery of the Hand

(ISSHCON)

Coimbatore, Tamil Nadu

ORTHOPAEDICS

Conference of Indian

Arthroscopy Society

(IASCON)

Kozhikode, Kerala

6-7

SURGERY

Asian Conference of

Tumor Ablation

Chennai, Tamil Nadu

XENOBIOTICS

10-13

Conference of the Indian

Society for the Study of

Xenobiotics

Bangalore, Karnataka

Chennai, Tamil Nadu

PEDIATRIC

DIABETES

11 - 14

44th Annual Conference

of International Society

for Pediatric and

Adolescent Diabetes

(ISPAD)

Hyderabad, Telangana

NANOMEDICINE

12-14

International Conference

on Nanomedicine and

Tissue Engineering (ICNT)

Ettumanoor

ICRAMHS

15-16

Academics World 470th

Intl Conference on Recent

Advances in Medical and

Health Sciences

New Delhi

ANAESTHESIA

19-21

ISACON Gujarat

Surat

DIABETES

25 - 27

International Diabetes

Federation (IDF) Diabetes

Complications Congress

2018

Hyderabad, Telangana

UROLOGY

Zone Conference of

Urological Society of

India-West Zone (ZCUSI)

Raipur

PEDIATRICS

26-28

National Conference

on Pediatric Infectious

Diseases (NCPID)

Ahmedabad

ICMBPS

29-30

IASTEM -485th

International Conference

on Medical, Biological and

Pharmaceutical Sciences

Delhi

NOVEMBER

SKULL BASE SURGERY

1-3

Annual Conference of

Skull Base Surgery Society

of India (SKULLBASECON)

Ludhiana

UROLOGY

Annual Conference of

Urological Society of

India East Zone Chapter

(ACUSIEZC)

Ahmedabadt

TELEMEDICINE

Telemedicon 2018 - 14th

International Conference

of Telemedicine Society

of India

Amravati, Andhra

Pradesh

SLEEP APNEA

10-11

AOCMF Seminar -

Advances in Sleep Apnea

and Orthognathic

Chennai, Tamil Nadu

RESPIRATORY

DRUG DELIVERY

14-16

Respiratory Drug Delivery

(RDD) Asia Conference

2018

Kochi, Kerala

PAEDIATRIC

NEUROLOGY

15-18

15th International Child

Neurology Congress

Mumbai, Maharashtra

IPS

15-18

46th IPS National

Conference Mangalore

2018

Mangalore, Karnataka

NUCLEAR

CARDIOLOGY

22-25

American Society of

Nuclear Cardiology

(ASNC) Society of Nuclear

Medicine

Chandigarh, Chandigarh

NUCLEAR

CARDIOLOGY

Annual Conference of

Cardiological Society of

India

Mumbai

ANAESTHESIOLOGY

25-29

Conference of

Indian Society of

Anaesthesiologists

Agra

INFECTIOUS DISEASES

28-29

World Congress on

Infectious Diseases and

Antibiotics

Bengaluru

GASTROENTEROLOGY

28-Dec 1

Annual Conference

of Indian Society of

Gastroenterology (CISG)

Ernakulam

GENOMICS

29-30

Next Generation

Sequencing in Clinical

Genomics

Bengaluru

OPHTHALMOLOGY

29-Dec 2

Conference of Vitreo

Retinal Society

Jaipur

BURN INJURIES

30-Dec 4

19th Congress of the

International Society for

Burn Injuries (ISBI)

Gurugram, Delhi

The announced dates of the conferences may change

96 / FUTURE MEDICINE / OCTOBER 2018


ook review

FOETUS AS A

PATIENT

PRINCIPLES AND

PRACTICE OF FETAL

MEDICINE

By Raju R Sahetya,

Jaideep Malhotra &

Hema Purandarey

pp381 Jaypee Brothers

The prevalence of genetic diseases

and birth defects in India is far higher

than what is apparent on casual

observation. Advances in genomics and

growing awareness would certainly help

to fathom the situation better. Still, since

genetic disorders are multisystem and

lifelong, genetic services alone won’t entirely

suffice. The efforts should be integrated with

related medical services like prenatal health,

preconception planning, child development

monitoring etc..

This is where the emerging discipline of

Foetal Medicine achieves greater importance.

The scope of prenatal diagnosis, through the

last four decades, has increased from routine

to predictive diagnosis of disorders that are

likely manifest later in life.

Principles and Practice of Fetal Medicine,

authored by Raju R Sahetya, Jaideep

Malhotra and Hema Purandarey, presents an

extensive discussion of the rapidly expanding

field of prenatal and perinatal diagnosis and

treatment.

Spread across forty-three chapters

covering every aspect of foetal medicine, the

book forms a major source of reference and

guidance to a wide range of professionals.

Starting with an overview of prenatal

diagnosis, the ten sections of the book give

in-depth insights into prenatal counselling,

invasive and non-invasive prenatal screening

and diagnostic techniques, lab techniques

on genetic testing and pre-implantation

diagnosis, antenatal use of foetal therapy,

prenatal foetal surgery, ethical and

medicolegal aspects and the future of

prenatal diagnosis.

The concluding section of the book offers

good practice guidelines recommended by

the International Federation of Gynaecology

and Obstetrics (FIGO) and best practice

advice on maternal-foetal medicine.

These sections, coupled with more

than 350 clinical photographs, tables,

illustrations, figures and charts, make

Principles and Practice of Fetal Medicine a

ready-reckoner and a handbook of choice for

obstetricians, geneticists, genetic counsellors,

ultrasonologists, paediatricians and lab

technicians.

The authors, after providing brief

historical and contemporary perspectives,

attempt to trace the influence of genomic

EMPHASISING THE NEED FOR

AN ”ENERGETIC SHIFT” IN THE

RESEARCH FOCUS ON PRENATAL

SCREENING AND DIAGNOSIS,

THEY CALL FOR AN EXPANSION

OF ALL FUTURE STUDIES

TO INCLUDE THERAPEUTIC

STRATEGIES.

medicine in pregnancy management and

pregnancy outcome in coming days.

Emphasising the need for an ”energetic

shift” in the research focus on prenatal

screening and diagnosis, they call for an

expansion of all future studies to include

therapeutic strategies.

Although the ultimate objective of

the book is to promote improved clinical

management of pregnancies affected by

an anomalous foetus, the immediate goals

include better detection, diagnosis and

understanding of ”the Foetal Medicine and

foetus as a patient”, as the authors state in

the preface.

OCTOBER 2018 / FUTURE MEDICINE / 97


FAILURE TO VIEW PATIENT AS A

WHOLE IS A HUGE TRAGEDY

DR M R RAJGOPAL

Founder, Pain and Palliative Care Society, Kozhikode

I

was trained as an anaesthesiologist in the early

part of my career, when the responsibility of

giving relief from pain was gradually coming into

our field. In Calicut (now Kozhikode), where I first

began working at a senior level, I was doing nerve

blocks on various parts of the body.

However, an experience with one patient in the

1980s compelled me to take a fresh look at what I

was doing. This was a 42-year old college professor,

suffering from cancer, and he was referred to me

for pain relief. I did for him what I had done for

numerous others and his pain receded but a day later,

he committed suicide! Everyone in my department

was shocked because here was a case where our

treatment was a success, and yet we lost the patient.

On enquiry, I was told that he had been given the

impression that my treatment was intended to cure

his cancer. Nobody had made it clear that it was for

the limited purpose of relieving the severe pain that

he was suffering from. When he realized that his

cancer was essentially incurable, he gave up all hope

of life itself.

It conveyed to me the invaluable lesson that every

doctor must look at his patient as a whole person, and

not just a collection of organ systems. It is a mistake

that many doctors make even today – they treat the

98 / FUTURE MEDICINE / OCTOBER 2018

disease, and not the person suffering from a disease.

For me as an individual, it brought me face to face

with my calling – to develop the (then) nascent field

of palliative care. My colleagues and I work through an

organization named Pain and Palliative Care Society,

based in Kozhikode. Set up in 1993, it is able to reach

out to patients wherever they are. Thus, we have

managed to cater to over 3 million patients till now.

Our experience has lessons for doctors and

healthcare professionals in other countries as well,

because of which we have worked with the WHO

Collaborating Centre of the Pain and Policy Studies

Group (PPSG) from a very early stage. Here, the

purpose was to bring about changes in the regulatory

policy with regard to opioids and other pain-relief

medicines. In a situation of terminal illness, we can

take the risk of the patient developing an addiction, if

it means improving the quality of life for the patient

in the final stages. In such cases, the priority becomes

different from the usual.

The huge tragedy of healthcare today is that,

because it fails to view the patient as a whole, the

doctors inflict suffering in the process of treating a

disease!

— As told to Dr Sumit Ghoshal


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