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VOL 5 | ISSUE 10

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FEBRUARY 2019

FUTUREMEDICINEINDIA.COM

STARTING TO

FORGET

THE SPECTRE OF ALZHEIMER’S LOOMS LARGE OVER

INDIA’S FAST-EXPANDING POPULATION OF THE AGED

CASE REPORT EDUCATION RESEARCH ONCO SURGERY

A HARROWING

SWALLOW

INTERNSHIP

FOR FOREIGN

GRADUATES

FLUID DIAGNOSIS

FOR DEMENTIA

NOVEL SURGICAL

OPTIONS FOR

BREAST CANCER


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editor’s note

editor’s note

FEBRUARY 2019 / Vol. 5 / Issue 10

Founder AUGUST & 2018 Editor / Vol: 5 / Issue: 4

CH Unnikrishnan

Executive Editor

S Harachand

Science Editor

Dr Rajanikant Vangala

Consulting Editors

Dr Founder Shivanee & Editor Shah

Jeetha CH Unnikrishnan D’Silva

Dr

Executive

Sumit

Editor

Ghoshal

Copy S Harachand Editor

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Science Editor

Curator-cum-Correspondent

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Dear Doctor,

We are glad you are enjoying the knowledge journey with us, as evidenced by

your encouraging feedback. We are also happy to know that the topics that we

choose to discuss in each of our editions have been helpful in your daily practice.

In

Dear

this

Doctor

edition, we want to touch your mind with the sad story of India’s

growing cases of dementia in the elderly and the greater dilemma of it

remaining We know as you a hidden are busy. problem. It is always The rapid reassuring growth that of the the elderly trust population and faith of will

soon hundreds increase of the patients burden in of your Alzheimer’s healing touch Disease, keeps the most you busy common in this cause noble of

dementia. profession. Unfortunately, In the hectic the practice, issue is yet it’s to quite be addressed natural that adequately you might by miss either

the out community on some or of government the latest developments agencies. in emerging medicine. In this era

To of make innovation, things medical worse, currently science is available getting disease redefined management almost by the options day. are Old

limited technologies and researchers are being are replaced still scrambling by the for new better in the remedies. blink of Thankfully,

eye. Robots

several and artificial drugs are intelligence now clinical are taking trials as over part a of good the search part of for the novel procedures, treatments

for while Alzheimer’s genomics disease and globally molecular and science many of unveil them the are mysteries in advanced of life stages. further.

Prevention We are fortunate studies are to also have looking such breakthroughs to identify the link as they between help lifestyle specialists and like

dementia. you rise Several above the clinical expectations trials are also of today’s underway informed around patient. the world to test

the effect of adopting healthier lifestyle habits to prevent cognitive decline,

Alzheimer’s Similarly, and it is also other a dementias. time when India is witnessing revolutionary growth in

It healthcare is time for industry, the community especially to be in alert the private to this sector, dilemmatic wherein situation an increasing and to

invest number in research of doctors and identify are taking risks up contributing multiple roles to the of clinician, diseases researcher of the ageing and

brain. entrepreneur. We hope our This deeply requires researched expansion cover of your story, focus analysing to a the wider current canvas. situation In

and this emerging context, remedies, it becomes will important help you become how a busy extra professional vigilant about like this you critical can

challenge. keep pace with these latest developments in a quick and easy way.

In this edition, we also touch upon medical education. The State Medical

Councils At Future have Medicine, jointly proposed which is mandatory conceived internship and crafted for by medical a team graduates of senior

who journalists, qualify abroad. scientists If implemented, and doctors, doctors our aim who is to complete help you their do just graduation that. We

from

are

foreign

equipped

countries

to bring

will

you

have

the

to

latest

do a one-year

from the

internship

science of

in

care

India

from

before

across

practicing

the world

here.

in an interesting and convenient way, supplemented by the best

I

of

am

views

sure

and

an insightful

analyses

interview

from the

with

masters

Prof.

in

Rajashekharan

each field. We

Nair,

present

an eminent

you this

neurologist

specialised

and

knowledge

a world renowned

vehicle that

medico-literary

plugs you into

author,

the

touching

emerging

upon

world

the

of

practice of neurology and the changing aspects of medical profession will also

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

add value to your read.

Happy CH Unnikrishnan

reading

editor@futuremedicineindia.com

C H Unnikrishnan

editor@futuremedicineindia.com

www.futuremedicineindia.com futuremedicineindia FutureMedIndia

AUGUST 2018/ FUTURE MEDICINE / 3


CASE REPORT EDUCATION RESEARCH ONCO SURGERY

Vol 5 Issue 10

February 2019

₹ 250.00

VOL 5 | ISSUE 10

PAGES 100

FEBRUARY 2019

FUTUREMEDICINEINDIA.COM

A HARROWING

SWALLOW

INTERNSHIP

FOR FOREIGN

GRADUATES?

STARTING TO

FORGET

THE SPECTRE OF ALZHEIMER’S LOOMS LARGE OVER

INDIA’S FAST-EXPANDING POPULATION OF THE AGED

FLUID DIAGNOSIS

FOR DEMENTIA

NOVEL SURGICAL

OPTIONS FOR

BREAST CANCER

40

CASE REPORT

CYST OR

CYSTICERCUS?

REGULAR FEATURES

06 Letters

08 News updates

28 Research

30 Drug approvals

48 Research snippets

58 Onco surgery

60 Hospital news

62 Policy

68 Devices&gadgets

78 Guidelines

90 Events

96 Calendar

97 Book review

98 Holy grail

Columns

14 THE CATALYST

Muralidharan Nair

52 THE CELLVIEW

Dr Rajani Kanth Vangala

12

EDUCATION

MANDATORY

INTERNSHIP

FOR FOREIGN

GRADUATES?

State medical councils moot

mandatory internship for

medical graduates

who qualify abroad

36

STRAIGHT TALK

“EVERYTHING

CAN BE

MADE A STORY”

Prof K Rajasekharan Nair

Eminent neurologist and

renowned writer


66

EXOTICA

THE MIND-BODY

CONNECTION

IN CANCER

Currently, there is

not enough scientific

evidence to support

the theory that one’s

attitude alone can

directly impact cancer

progression

16

COVER STORY

STARTING TO

FORGET

India faces yet another

healthcare challenge

- Alzheimer’s - as the

country’s elderly

population grows fast

54

DISEASE

INDIA’S

CANCER

BURDEN

Cancers contributed 5% of

the total disabilities and 8.3%

of all deaths in India in 2016,

shows a state-wise study

74

It is currently not

known if the classic

pathologies of

amyloid and tau

represent valid

drug targets and if

these targets alone

are enough to

treat Alzheimer’s

disease.

Dr Howard Fillit

Chief Science Officer

Alzheimer’s Drug

Discovery Foundation

New York

MERIL’S

MYVAL


ORTHOPAEDICS POLICY SPECIALTIES CASE REPORT

letters to the editor

THE BRAVE

NEW WORLD

OF IMAGING

AI, DEEP LEARNING AND BIG DATA USHER IN

A NEW ERA OF MEDICAL IMAGING

ADVANCED

ORTHO IMAGING

CONSUMER BILL:

DOCTORS

DISMAYED

IR: SPEARHEAD

OF LESS-INVASIVE

MEDICINE?

FACTS ON

FANCONI

Great case studies

₹ 250.00

VOL 5 | ISSUE 9

PAGES 100

JANUARY 2019

FUTUREMEDICINEINDIA.COM

Dear Sir,

I found few articles related

to our work by Dr Shivanee

Shah, on Non-functional

platelets, Metabolic Defects,

Dilemma of Diarrhoea & Falling

Neutrophils. These articles

reconfirm the critical nature of

our work and how this is going

to be an important part of

treatment going forward.

All the very best.

Arvind K Agrawal

CFO, Ajanta Pharma Limited

Mumbai

Kudos

Dear Editor,

The magazine (Future

Medicine) has really come

out well. You and your team

deserve congratulations.

Overall presentation and

get up of the magazine is

of high quality.

Kudos once again.

Sreedharan Nair

Director External Relations

Family Planning

Association of India

New Delhi

Fabulous work

Hello,

After returning to Istanbul,

I had the chance to

review your magazine.

I could not drop it from my

hand for an hour and

wanted to read

out all stuff. It is fabulous.

All the article are very

fresh update of the market,

it is a magazine not only

for doctors, It is also for

companies and individuals.

Very good job.

One news attracted my

attention in your January

edition, page 59. It mentions

about number of beds in the

hospital reached 21,551 in

2019. Is that all the beds in all

hospitals in India? It should be

more than that I guess.

Saygilarimla/Best Regards

Mustafa Karamizrak

General Manager

Meril Tibbi Cihazla san. Tic AS.

Atasehir, Istanbul.

Dear Mr Karamizrak,

Thank you for your feedback.

On your query on hospital

beds, would like to inform

you that this number

—21,551 doesn’t include the

government hospital beds,

which is around 14,00,000.

This report in page 58 &

59 are about India’s private

hospital industry. However,

the overall patient: hospital

bed ratio at 0.9 per thousand

patient is still far below in

India as compared to other

developing and developed

countries. —Editor

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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 exempts new drugs

from price control for 5 years

The government of India has decided

to exempt innovative medicines

developed by foreign companies from

price control for five years.

The Centre has brought necessary

amendments to the Drugs (Price

Control) Order (DPCO), which sets

the rules for regulating the prices of

medicines through a National List

of Essential Medicines, known as

Schedule-I.

As per a notification issued by the

Ministry of Chemicals and Fertilisers,

new drugs patented under the Indian

Patent Act of 1970 are exempted

from price regulation for a period of

five years from the date of

commencement of its commercial

marketing by the manufacturer in the

country.

Prior to this amendment, the

exemption for five years was available

only to those new drugs which

were patented in India, but were

not produced elsewhere and were

developed through indigenous research

and development.

The amendment allows any

new drug to get the exemption if

it is patented in India under Indian

Patents Act, 1970 and developed and

manufactured by any patentee across

the globe.

The move is expected to enable

access to novel medicines, especially

orphan drugs for treating rare diseases

in India.

The WHO defines rare disease as

a lifelong disorder with a prevalence

of one or less per 1,000 population.

India, however, is yet to have a

standard definition for rare diseases. It

is estimated that one in 20 Indians is

affected by one of the 7,000 diseases

listed as rare diseases, if we go by

the definition that rare disorders are

those that affect less than one in 2,500

people in India.

docprime.com

expands to more

places

docprime.com, a free online

consultation platform,

will be expanded to 12 major

states of India, the company

announced.

Online services of the

portal will now be available in

Andhra Pradesh, Telangana,

Karnataka, Tamil Nadu,

Gujarat, Maharashtra, Punjab,

Madya Pradesh, West Bengal,

Uttar Pradesh, Rajasthan and

Chhatisgarh.

docprime.com, which

already has a strong presence

new drugs

PRICE

CONTROL

8 / FUTURE MEDICINE / FEBRUARY 2019


in Delhi and NCR, will extend

services to a total of 34

cities of the country with the

expansion.

The platform

allows patients to book

appointments with over

20,000 doctors and 5,000

diagnostic labs at discounted

rates across the country.

The company also plans

to expand to 100 cities with

1,00,000 doctors and 20,000

labs in 2019, reports said,

quoting top company officials.

docprime.com features

cashless transactions that

allow the customers to pay

directly at the time of booking

an appointment and no extra

charge is levied after the

consultation. Customers can

also reschedule bookings and

avail 100% refund in case of

cancellation.

PMC exempts

credit hours

for CME

T

he Punjab Medical

Council (PMC) has given

a one-time exemption of the

mandatory credit hours of the

Continuous Medical Education

(CME) that are necessary for

registration renewal.

The MCI, in February

1997, had recommended 30

credit hours per year, or 150

credit hours per five years, for

renewal of licenses.

PMC guidelines mandate

that all the doctors registered

under the state medical

council have to acquire 50

hours of credit within 5 years

for CME accreditation.

4,677 Jan Aushadhi outlets

functional, says minister

There are 4,677 Pradhan

Mantri Bhartiya Jan

Aushadhi Pariyojana

(PMBJP) currently

functional across the

country, according to the

government.

As on 31.12.2018,

4,677 PMBJP Kendras

are functional in 35 states

and union territories

of the country, stated

Mansukh Mandaviya, Union

Minister for Chemicals and

Fertilizers, in parliament,

recently.

PMBJP was launched

by the Department of

Pharmaceuticals, Ministry

of Chemicals and Fertilizers,

Government of India with

an objective of making

available unbranded

generic medicines at

affordable prices to all.

Unbranded generic

medicines worth Rs 417

crore of MRP have been

sold through PMBJP

Kendras since the inception

of the scheme till the end

of December 2018. This

sale is roughly equivalent

to the sale of Rs 2,085

“All members unanimously

decided that up to 31.03.2019,

renewal of registration of

all doctors who have not

renewed their registrations

irrespective of time lapse are

being given an exemption

crore of the branded

medicines. Thus, PMBJP

has resulted in the saving

of approximately Rs 1,668

crore to the citizens of

the country, Mandaviya

informed Rajya Sabha, the

upper house of the Indian

parliament.

PMBJP product

basket covers more

than 800 medicines

and 154 surgicals and

consumable across 23

major therapeutic groups

such as anti-infectives,antidiabetics,

cardiovasculars,

anti-cancers, gastrointestinal

medicines, etc.

The minister said the

maximum retail price of

medicine sold through

PMBJP outlets is fixed in

such a way that it is at least

50% below the average

MRP of corresponding

top three brands of

that medicine. In order

to ensure the quality of

medicines sold through

PMBJP Kendras, the

drugs are procured only

from WHO-GMP certified

manufacturers.

of CME credit hours on the

recommendation of Punjab

Medical Council,” says a notice

issued by PMC.

The organization

requested all medical

practitioners who have not

renewed their registration

till date to apply for renewal

even without CME hours up to

31st March.

Th exemption is only up

to the stated period and after

the expiry of the period, the

mandatory clause of CME

hours will be applicable, the

notification says.

PGs in Punjab get

10 credit hours per year,

whereas in other states,

the postgraduate medical

professionals will get only four

credit hours per year.

Reports show that medical

practitioners in Karnataka

need six credit hours per year,

while it is 30 CME credit hours

per year in Gujarat.

HIV undetectable =

untransmittable:

NIH

Clinical evidence has

firmly established

the HIV Undetectable =

Untransmittable (U=U)

concept as scientifically sound,

say officials from the National

Institutes of Health (NIH), US.

U=U means that people

living with HIV who achieve

and maintain an undetectable

viral load by taking and

adhering to antiretroviral

therapy (ART) as prescribed

cannot sexually transmit the

virus to others.

Officials from NIH’s

National Institute of Allergy

and Infectious Diseases

(NIAID) summarise results

from large clinical trials and

cohort studies validating

FEBRUARY 2019 / FUTURE MEDICINE / 9


New autism bill passed

New legislation on autism,

which is scheduled to

be enacted in the country,

is expected to help people

suffering from the condition

live independently.

The Indian parliament

passed the National Trust

for Welfare of Persons with

Autism, Cerebral Palsy, Mental

Retardation and Multiple

Disabilities (Amendment) Bill,

2018. The law amends the

principal Act enacted in 1999.

The new law allows setting

up of a national trust to

enable persons with disability

to live independently by

promoting measures for their

protection in case of death of

their parents.

The bill also includes

procedures for appointment

of guardians and trustees, and

facilitating equal opportunities

in society, agency reports said.

Under the principal Act,

the chairperson and members

of the board of the national

trust could hold office for

three years from the date

of their appointment or

until their successors were

appointed, whichever was

longer. The new bill amends

this provision to fix the tenure

of the chairperson and board

members to three years. Also,

the government will initiate

the process for appointment

of the chairperson or any

member of the board at least

six months prior to the expiry

of their tenure.

U=U. The landmark NIHfunded

HPTN 052 clinical trial

showed that no linked HIV

transmissions occurred among

HIV serodifferent heterosexual

couples when the partner

living with HIV had a durably

suppressed viral load.

Subsequent

studies confirmed these

findings and extended them

to male-male couples, NIH

observed in a commentary in

JAMA.

Validation of the HIV

treatment as a prevention

strategy and acceptance

of the U=U concept as

scientifically sound have

numerous behavioural, social

and legal implications, the

NIAID officials note. U=U

can help control the HIV

pandemic by preventing

HIV transmission, and it can

reduce the stigma that many

people with HIV face.

HIV prevention method

determines the success

of U=U as it depends on

achieving and maintaining

an undetectable viral load by

taking ART daily as prescribed.

Stigma biggest

barrier to ending

leprosy: WHO

Discrimination, stigma and

prejudice are the biggest

barriers to ending leprosy,

says the WHO.

India accounts for

more half of the estimated

2,00,000 cases reported

every year, though the

number of leprosy cases has

steadily declined worldwide.

Leprosy is detected in

significant numbers in the

WHO South-East Asia Region,

Brazil, sub-Saharan Africa and

the Pacific.

WHO’s Global Leprosy

Strategy 2016-2020 outlines

policies that promote inclusion

and keeps the ending of

leprosy-related discrimination,

stigma and prejudice at the

front and centre of all leprosy

programmes.

It is often the disability

and deformity that fuels

leprosy-related discrimination,

stigma, and prejudice, even

though the disease needn’t

cause the disabilities which

are often equated with it. The

percentage of patients that

present with these symptoms

is down to 6%, demonstrating

the disease is being

diagnosed earlier than ever.

Given the fact that the

disease is 100% curable when

detected early, the human

rights of persons affected by

leprosy must be prioritised,

besides empowering people

with leprosy to be agents of

social change, it said. There is

also a need to promote access

to purpose-built social and

financial support for persons

affected by leprosy.

In recent years India,

along with other countries

in the region and beyond,

has repealed legislation that

discriminates against persons

affected by leprosy: In 2016,

for example, it repealed the

draconian colonial-era Lepers

Act, and recently repealed

a law allowing leprosy as

legitimate grounds for divorce.

Both initiatives are to be

commended, WHO notes.

10 / FUTURE MEDICINE / FEBRUARY 2019


education

MANDATORY INTERNSHIP

FOR FOREIGN GRADUATES?

State medical councils moot mandatory internship for

medical graduates who qualify abroad

Doctors who

complete their

graduation from the

foreign countries may have

to do a one-year mandatory

internship in India for practicing

in the country, as state medical

councils are planning to take up the

matter with the union health ministry

and Medical Council of India (MCI). A

decision in this regard was taken in

a meeting of state medical councils

hosted by the Maharashtra Medical

Council.

The meeting held in Mumbai was

attended by representatives of 22

state medical councils. Speaking to

Future Medicine, Dr Shivkumar Utture,

President, Maharashtra Medical Council,

said: “Making internship mandatory for

foreign medical graduates was one of

the topics in the meeting and many of

the state medical councils agreed on

the same. As the decision has to be

taken at the national level now, we are

planning to hold a meeting with MCI

Board of Directors. It may take a long

time to get it done, but the process has

already started.”

Emphasizing on the need to make

internship mandatory for foreign

medical graduates, Dr Utture said the

type of diseases differs from country

to country, as does ethics. “If the

medical professional is not exposed to

diseases, then he

won’t gain practical

knowledge. The

doctor can gain

practical knowledge if

the internship is made

mandatory for foreign

medical graduates before

practising in India. If the doctor

is not exposed to ethics and the

type of patients he is dealing with,

then it will be a loss to the doctor

and for the patient.” He added that

by doing an internship in India, the

medical professional can gain the kind

of practical knowledge required to

practice in this country.

Need for orientation

Agreeing with Dr Utture,

Dr Jayakrishnan AV, Chairman of the

Kerala chapter of IMA Hospital Board

of India, said that though the medicos

learn theory, they get the actual

orientation during house surgency. “The

system existing in India is different from

other countries. Also, the syllabus of

MBBS in India is more comprehensive

than [those in] other countries and

here, the training period is longer.”

Medical professionals who obtain

their degree from countries such

as Mauritius have been doing their

one-year internship in India. But in

case of countries such as China,

they undergo internship in the

respective country. “Everyone

should be made to do

their internship in

India,” said Dr Utture.

Commenting on the development,

Dr A Najeerul Ameen, President, All

India Foreign Medical Graduates

Association, said: “Students who

are pursuing medical graduation in

countries such as Russia and China are

already doing their internship in India.

After doing the internship, foreign

medical graduates should be allowed

12 / FUTURE MEDICINE / FEBRUARY 2019


to directly practice medicine. It will

benefit both society and the graduates.

By allowing foreign medical graduates

to do their internship in India, services

of more doctors can be made available

in hospitals. Also, such candidates need

to wait two to three years to clear the

Foreign Medical Graduate Examination

(FMGE).”

Steep rise in outflow

Due to the shortage of medical seats in

India and the high costs involved, the

number of Indian students pursuing their

medical graduation in countries such as

China, Russia, Bangladesh, Philippines,

Ukraine and other countries has been

witnessing a steady increase over the

years. In the year of 2017–18, the MCI

issued eligibility certificates to more

than 14,000 such candidates compared

to over 8,700 in the previous year. The

National Eligibility cum Entrance Test

(NEET) is not mandatory for those who

wish to do their medical degree in

If the doctor is not

exposed to ethics

and the type of

patients he is dealing

with, then it will be

a loss to the doctor

and for the patient.

Dr Shivkumar Utture

President

Maharashtra

Medical Council

foreign countries. But the government

has decided to make NEET mandatory

from the next academic year.

Presently, in order to practice in the

country, foreign medical graduates have

to pass the Foreign Medical Graduate

Examination (FMGE) conducted by

the National Board of Examination

(NBE). The examination is conducted

twice in a year and medicos have to

score a minimum of 50 percent marks

in the examination. A maximum of

three attempts are allowed. However,

the number of medicos passing the

examination is very low. As per reports,

only 2,411 out of 9,274 medicos cleared

the examination in August 2018. It

was the highest number of candidates

clearing the examination. The pass

percentage was less than 10 in previous

years. Dr Jayakrishnan AV highlighted

the difference between the system

of training in India and those in other

countries as one of the reasons for the

low pass-percentage.

1 year

internship

(compulsory)

FEBRUARY 2019 / FUTURE MEDICINE / 13


column

the catalyst

Smoothen the process

of change

Different stakeholders have definitive roles to play to

in our ambitious healthcare goals

The year 2018 was a momentous year

for the Indian healthcare industry as I

had mentioned in my previous column.

It is in the midst of an unsettling flux, where

the prevailing order finds itself inadequate

to meet the emerging imperatives even as

the new order is struggling to find its form.

In this backdrop, 2019 will again be a very

momentous year, perhaps more so than

2018, and will likely witness the evolution of

a foundation for a future healthcare system,

models and practices. I am very optimistic

that these changes are for the good of

everyone in the long run, even though there

will be unavoidable challenges of transition.

Accordingly, my wishlist for 2019 includes

what I believe should become key imperatives

for different stakeholders to lubricate this

process of change in pursuit of the true north

for the sector.

Wellness Centre) and inpatient care insurance.

Importantly, I look forward

to the passing of the much needed and much

awaited National Medical Commission bill in

2019.

Private Healthcare: Transparency, efficiency

(both capital and operational) and empathy

should be the key elements of private health

care players’ imperatives for 2019 and ahead.

Theirs is the important agenda of building

credibility among stakeholders, both public

and policymakers. It will not help

them to play the victim as much of the

trust deficit emanates from the way the

players have conducted themselves, though

the degree may vary from one to another. This

has resulted in a lack of empathy

even for their legitimate issues. It is imperative

MURALIDHARAN NAIR

Central Government: The most important

expectation from the central government

is to focus on the real implementation of

what has already been conceptualised,

instead of rhetoric and optics for projecting

a transformation. The design of Ayushmann

Bharat (AB) has its heart in the right place,

but the implementation is currently focused

only on cosmetic aspects to derive political

mileage rather than to follow

the spirit of the design: A robust, primary

care-driven, holistic healthcare

management through a strong public

health system ably complemented by private

sector capabilities. Alas, I do not foresee

any change in the current approach till the

elections in May at least. And I sincerely

hope the scheme continues in its essence

— cosmetic changes notwithstanding —

irrespective of who comes to power after the

elections. One of the first things I will look

forward to will be a realistic budget outlay for

the scheme, separately for HWCs (Health and

for them to demonstrate transparency in

their commercial practices, and as a first step,

a robust costing system accompanied by a

true and patient-friendly billing structure is an

urgent need. Equally, given the headwinds on

pricing, the emergence of a value segment

(including extra urban markets) as a key

growth driver and stretched balance sheets,

optimising their infrastructure, the design of

procedures and resource utilisation (man,

material & machine), along with a robust

framework for capital prioritisation and

14 / FUTURE MEDICINE / FEBRUARY 2019


allocation will be a critical need, even while

staying fully committed to the agenda of

quality and patient safety.

Private Equity: I do foresee consolidation

and promoter stake sale in a big way where

PE players are going to play a bigger role in

times to come. While PE players have been

a critical catalyst in driving the efficiency

agenda, they have a time-bound agenda for

value creation and hence have a sharp focus

on short- to medium-term growth. This can,

at times, result in a higher performance in

the short-term but may not be conducive to

the long-term health of the business, or to

building best practices for the industry. This

problem gets compounded if PE bought

into an unrealistic business plan, which is

not uncommon. While PE players have

played and will play a critical role in shaping

the private healthcare industry, it is imperative

that they understand the underlying

nuances of business performance, growth

and sustainability in a dispassionate way

through competent, sincere diligence.

Importantly, they should set realistic

expectations for potential exit valuations

before doing a deal.

State Government: The government must

earn the moral right to regulate and dictate

to private players, if there has to be dignity,

balance and synergy in public and private

healthcare partnerships. While public

healthcare has a long way to go in many

states — which also unfortunately tend to

be also the most populous ones — it will be

very welcome to see them target at least a 5

percent increase of public consumption in the

public-private share of hospitalisation in the

states where the public share is less than 50

percent. At the same time, the government

should leverage the Health and Wellness

Centre model of AB to revamp their primary

care set up. Additionally, they should facilitate

greater focus on the quality of care, both by

incentivising quality-conscious players with

superior reimbursement rates and making

quality accreditation mandatory for all

hospitals with more than 30 beds.

People: The patient voice will be the allpowerful

change agent in future and it is

the need of the hour. Exercise your voice

and vote for a better healthcare. Do not

revere or revile the doctor, just respect him/

her like a professional. Trust between the

doctor and patient is crucial for efficient and

effective treatment and let not half baked

information from internet spoil the chemistry

of this relation even as you rightly evolve

from a relation of blind trust in doctors. Solicit

discussion, seek second opinion and be

aware of your treatment but trust him/ her

till there is a reason to doubt rather than the

other way, particularly based on half baked

information from internet. Understand that

knowledge is different from information in

STATES SHOULD FACILITATE

GREATER FOCUS ON THE

QUALITY OF CARE BY

INCENTIVISING QUALITY-

CONSCIOUS PLAYERS WITH

SUPERIOR REIMBURSEMENT

the same way as parenthood is different from

being a parent which even a teenager can

but it takes much experience for an adult

to understand parenthood. Last but not the

least, be accountable for your health.

Clinicians: Frankly, clinicians, as a community,

have to accept that the deepening mistrust

of the public is not without reason and hiding

behind high cost of medical education and

lengthy period of education etc as possible

reasons to explain their susceptibility to

succumb to commercial considerations over

Hippocratic oath, is just hollow and deplorable

I have said this before in a previous column,

repeating it again, know that “morality is

evolved self interest” and with the passing

of Consumer Protection Bill recently, the

element of rhetoric in the statement has been

replaced, substantially, with imminent legality.

In fact it is in their best interest, individually

and collectively, to be pro active and take

the lead in winning back the respect for their

integrity as well.

The author has long-standing association with

EY India but the views are strictly personal.

FEBRUARY 2019 / FUTURE MEDICINE / 15


cover story

STARTING TO

The spectre of the

devastating Alzheimer’s

disease looms large over

India’s fast-expanding

population of the aged

16 / FUTURE MEDICINE / FEBRUARY 2019


S HARACHAND

“Paramjit Rawat, aged 76, wheat complexion, 5’7”, wearing

half-sleeve white kurta and dhoti. Missing since 22/12/2018.

He was without footwear and walks with a stupor. Suffering

from memory disorder but can remember his house name

C4, Mayur Vihar, If found, please contact 991XXXXX76”

These sort of notices alongside the picture of the missing

person are not a rare sighting on the pages of India’s

national and regional newspapers these days.

The number of desolate people who are desperately

groping in the recesses of their memory even to find own

names are going up exponentially by the day as a cloud of

dementia descent upon the elderly in the world’s second

most populous country.

Though the exact figures are not available, an estimated

4.1 million people are suffering from some form of dementia,

according to the ‘Dementia India’ report published by the

Alzheimer’s and Related Disorders Society of India. The

numbers are expected to double in a decade and a half.

The life expectancy of the Indian population is increasing

with improving healthcare. So is the number of aged people.

Today, the majority of Indians live past their 70s. The elderly

population is growing rapidly, by 3 percent annually, according

to the India Ageing Report 2017.

Such long life was a rarity till some decades ago where

not many people lived through their 60s or even their 50s.

FEBRUARY 2019 / FUTURE MEDICINE / 17


A long life comes with its own intrinsic perils,

experts say.

“See, it’s a kind of trade-off. Here you buy

longevity at the expense of [living with] many

a disease,” points out Dr K Rajasekharan Nair,

Emeritus Professor of Neurology at Medical

College Hospital, Thiruvananthapuram, India.

The advances in modern medicine have made

a large number of diseases and conditions —

which could otherwise prove fatal — curable

or manageable. Survival has increased through

effective management of several chronic

conditions.

As the population of the elderly grows, the

number of cases with dementia will also go up,

because Alzheimer’s is, largely, a disease of the

elderly. Most often it begins in people over 65

years of age.

Symptoms subtle; progress slow

A neurodegenerative disease usually

progressing through a span of 8-10 years,

Alzheimer’s often starts with subtle symptoms

which are neglected by most people. Since

memory problems are a part of the ageing

process, most of us won’t pay heed to such

complaints until the disease starts manifesting

in its full and ugly form.

One of the characteristic features of

Alzheimer’s disease (AD) is the loss of

imminent or present memory, explains

Dr Rajasekharan Nair, who is also an expert

in cognitive neurology. “The person will

It’s a kind of tradeoff.

Here you buy

longevity at the

expense of [living

with] many a

disease.

Dr K Rajasekharan

Nair

Emeritus Professor

of Neurology

remember everything that happened 50 or

60 years back. His school days, his childhood

friends, his class teacher... but he would not be

able to recall what he had for lunch an hour

ago or the fact that his wife passed away a

year ago. They would not know the place they

were sitting then… All of a sudden, they begin

to feel that something is amiss.”

Generally, AD courses through different

stages of progression such as anomia (difficulty

in remembering the names of people and

objects); agnosia (inability to recognise things);

apraxia (loss of ability to carry out voluntary

movements) and aphasia (loss of language).

However, these classical symptoms may not

be typical to all patients. Alzheimer’s affects

people in different ways, each person may

experience symptoms — or progress through

the stages — differently. There are cases

where one or the other of these functions

retained. Areas involved with learning and

memory are usually affected first. Later, regions

involved in planning and carrying out tasks

start deteriorating. Ultimately, the areas of the

brain responsible for coordinating basic bodily

activities such as walking, and swallowing are

impaired.

Caring - A formidable challenge

With the progress of the disease, the person

loses interest in everything. Gradually, the

victim starts losing all the inhibitions. Inhibition

is one of the crucial functions of the brain.

WHEN ALZHEIMER’S

STRIKES

Age group of people with

Alzheimer’s dementia in US

44%

16%

4%

37%

85+ years

75-84+ years

65-74+ years


Nearly 100 billion neurons in the

brain exchange trillions of impulses

at a time. Controlling the surge of the

impulses is one of the prominent roles

of the frontal lobe. Inhibition, in a way,

helps us behave as well-mannered

people. It is an essential aspect of

social living. Once inhibition is lost,

we can become unruly. Behaviour

becomes unpredictable. When sitting

at home, they don’t know how to sit or

WHEN THE PATIENT LOSES

SELF-CARE, HE OR SHE

BECOMES A LIABILITY

FOR THE CAREGIVER

if they should be wearing clothes. This

happens due to the degeneration of

neurons. The person becomes unable

to perform everyday activities. When

the patient loses self-care, he or she

becomes a liability for the caregiver.

People in the final stages of the disease

are bed-bound and require aroundthe-clock

care. Naturally, more than the

patient, it is the caregiver who suffers

most in AD.

Estimated Lifetime Risk for

Alzheimer’s Dementia,

by Sex, at Age 45 and Age 65

25

20

15

10

5

0

Men

10.3%

Women

19.5%

11.6%

21.1%

45 Age 65

SOURCE: alz.org

APOE AND RISK OF ALZHEIMER’S

Besides older age and a family

history of Alzheimer’s, carrying

the ApoE-e4 gene is the greatest

risk factor for late-onset Alzheimer’s.

The ApoE gene provides

the blueprint for a protein that

transports cholesterol in the

bloodstream. Everyone inherits

one of the three forms of the ApoE

gene — e2, e3 or e4 — from each

parent. The e3 form is the most

common. The e4 form is the next

most common, and the e2 form is

the least common.

Having the e4 form increases

one’s risk of developing Alzheimer’s

compared with having the e3 form,

while having the e2 form may

decrease one’s risk compared with

having the e3 form. Those who

inherit one copy of the e4 form have

three times the risk of developing

Alzheimer’s compared with those with

two copies of the e3 form, while those

who inherit two copies of the e4 form

have an eight- to 12-fold risk.

Those with the e4 form are more

likely to develop Alzheimer’s at a

younger age than those with the e2

or e3 forms of the ApoE gene.

A meta-analysis including 20

published articles describing the

frequency of the e4 form among

people in the US who had been

diagnosed with Alzheimer’s found

that 56 percent had one copy of the

APOE-e4 gene, and 11 percent had

two copies of the APOE-e4 gene.

Another study conducted among

1,770 diagnosed individuals from 26

Alzheimer’s Disease Centers across

US, 65 percent had at least one copy

of the APOE-e4 gene.

Chromosome 21 and

gene mutations

Certain genetic mutations and the

extra copy of chromosome 21 that

characterises Down syndrome are

uncommon genetic changes that

affect the risk of Alzheimer’s.

An estimated 1 percent or less of

Alzheimer’s cases develop as a result

of mutations involving the gene for

the amyloid precursor protein (APP)

and the genes for the presenilin 1

and presenilin 2 proteins.

Those inheriting an Alzheimer’s

mutation to the APP or presenilin

1 genes are guaranteed to develop

the disease. Those inheriting an

Alzheimer’s mutation to the presenilin

2 gene have a 95 percent chance of

developing the disease. Individuals

with Alzheimer’s mutations in any of

these three genes tend to develop

symptoms before age 65, sometimes

as young as age 30, according to

2018 Alzheimer’s Disease Facts and

Figures by Alzheimer’s Association,

Chicago.

Recently, some more genes have

been identified to affect Alzheimer’s

risk, such as ABCA7, BIN1, CLU,

CR1, CASS4, CD2AP, CELF1, EPHA1,

FERMT2, HLA-DRB5, INPP5D, MEF2C,

MS4A, NME8, PTK2B, PICALM,

SORL1, SlC24A4 and ZCWPW1.

These genes are believed to have

a limited effect on the overall

prevalence of Alzheimer’s because

they are rare or increase risk only

slightly.

FEBRUARY 2019 / FUTURE MEDICINE / 19


Alzheimer’s drug discovery:

Leaving no stone unturned

large number of potential therapeutic

A candidates have been studied for

Alzheimer’s disease for the last two

decades with very few reaching the final

stage of commercialisation.

As per the National Institutes of

Health registry of the US, 244 drugs for

Alzheimer’s were tested in clinical trials

registered in the decade of 2002-2012.

However, only one — memantine — could

win approval from the US FDA.

Traditionally, the drug discovery

for Alzheimer’s has been riddled with

impeding factors like the slow pace of

clinical study recruitment, the inability

of animal models to reliably predict

whether an experimental treatment will

work in humans and the relatively long

time needed to observe whether an

investigational treatment affects disease

progression.

Today, the Alzheimer’s drug

discovery pipeline consists around 120

potential therapies at various stages

of development, according to the data

provided by Alzheimer’s Drug Discovery

Foundation, a non-profit organisation

based in New York, which supports drug

discovery for Alzheimer’s. The studies

explore various targets implicated in the

development and the progression of the

disease as biological processes go awry

with age. They include impaired clearance

of toxic misfolded proteins of amyloid and

tau, chronic systemic inflammation and

neuroinflammation, mitochondrial and

metabolic dysfunctions, vascular problems,

loss of synapses, epigenetic changes, ApoE

gene and neuroprotection mechanisms.

Misfolded protein targets

Nearly two-dozen drugs are in advanced

phase 3 clinical trials. The later-phase trials

are dominated by drugs targeting betaamyloid

and tau, the classic pathological

hallmarks of Alzheimer’s disease. While

52% are targeting amyloid or tau, other

strategies are gaining ground and are in

phase 1 or 2 trials.

One of the most notable candidate

molecules is Eisai’s BAN2401, which has

been found to reduce amyloid in the brain

of 81% of patients and slow cognitive

PICTURE COURTESY: Eisai Co

decline in 30%. BAN2401’s was the first

late-stage study data that successfully

demonstrated potential disease-modifying

effects on both clinical function and

amyloid beta accumulation in the brain,

and provides compelling evidence to

support the amyloid hypothesis as a

therapeutic target for Alzheimer’s disease,

Eisai said.

However, the additional clinical data

from a sub-trial in prodromal and mild

Alzheimer’s patients presented by the

company in the 11th Clinical Trials on

Alzheimer’s Disease Conference (CTAD)

in Barcelona in October 2018 showed

no significant difference in the rate of

cognitive decline for placebo patients,

based on the presence of ApoE- e4 allele,

a genetic risk factor for Alzheimer’s.

Beside BAN2401, which came out of

a strategic research alliance between Eisai

and BioArctic, the Japanese drugmaker

has three more product candidates for

Alzheimer’s in the clinical stage . These are

β-site amyloid precursor protein cleaving

enzyme (BASE) inhibitor elenbecestat and

anti-Aß antibody aducanumab — both in

Phase 3 — and anti-tau antibody E2814,

which is currently under preparation for

Phase 1, said a spokesperson from Eisai.

”We have three candidates targeting

Aß, as such BAN2401, aducanumab and

elenbecestat. The accumulation of Aß is

considered to accelerate the tau pathology

and might be the cause of neuronal cell

death, resulting from the accumulation of

Caring for a person with Alzheimer’s dementia poses

special challenges as people in the middle-to-later stages of

Alzheimer’s experience losses in judgment, orientation and

the ability to understand and communicate effectively. Family

caregivers must often help people with Alzheimer’s manage

these issues. Changes in the personality and behaviour of a

person with Alzheimer’s are the most challenging for family

caregivers.

Most importantly, individuals with Alzheimer’s require

increasing levels of supervision as the disease progresses.

This is where countries like India fall short due to inadequate

awareness of the disease. The tendency is always to ignore

memory problems in the elderly, simply attributing them as

part of the aging process. So, it is not uncommon that people

like Paramjit Rawat stray from home, often imperiling their

own life.

Imminent threat

Despite the high prevalence, only a small fraction of patients

have been formally diagnosed or treated in India, experts say.

The maximum number of new cases of dementia will

come from India and China, said Vijayalakshmi Ravindranath,

20 / FUTURE MEDICINE / FEBRUARY 2019


tau. The accumulation of aggressive factors

such as Aß and tau is the potential target

of Alzheimer’s disease treatment”, she said.

Two Phase 3 studies for elenbecestat

in patients with early Alzheimer’s disease

are ongoing. According to Eisai, the Phase

2 study conducted in the U.S. was the

first study of a BACE inhibitor to show a

statistically significant difference in amyloid

beta in the brain while also suggesting a

delay in the decline of clinical symptoms in

exploratory endpoints.

Regarding aducanumab, two Phase 3

studies are ongoing, and patient enrolment

was completed in July 2018.

The Swiss drug giant Roche

currently has two phase 3 programmes

for Alzheimer’s - crenezumab and

gantenerumab, both targeting betaamyloid.

They have another monoclonal

antibody in phase 2, targeting tau,

according to World Alzheimer Report 2018

by Alzheimer’s Disease International, UK.

Repurposed candidates

Some of the existing drugs are also being

tested for their potential in Alzheimer’s

treatment through what is called

repurposing. Repurposing involves the

testing of a drug that is effective in one

field to see if it’s effective in another.

The cholesterol-lowering drug

gemfibrozil can be effective in reducing the

levels of amyloid and brain inflammation

in preclinical studies conducted in mice,

showed the result of a study presented

at Alzheimer’s Association International

Conference (AAIC). Gemfibrozil, a micro-

RNA pathways modulator, works as an

agonist of the peroxisome proliferatoractivated

receptor a (PPARa). An early

pre-clinical study of the repurposed

gemfibrozil is underway to understand

its effect on amyloid plaque pathology,

neuroinflammation and memory in

THE DATA SHOWED THAT

NABILONE SIGNIFICANTLY

IMPROVED AGITATION

IN A TRIAL OF 39

MODERATE-TO-SEVERE

ALZHEIMER’S PATIENTS

subjects with intact cognition and mild

cognitive impairment.

The BEACON (Blocking Endothelial

Activation to Curb the Onset of

Neurodegeneration) trial is evaluating

the efficacy of dabigatran, a direct

thrombin inhibitor, to slow down the

harmful cascade in the early stages

of Alzheimer’s disease. Dabigatran is

currently approved to reduce the risk of

stroke and systemic embolism in patients

with non-valvular atrial fibrillation and for

the treatment and to reduce the risk of

reoccurrence of deep venous thrombosis

and pulmonary embolism. Research has

shown that factors such as high blood

pressure, diabetes and stroke can injure

blood vessels in the brain, resulting in

inflammation that could cause damage to

or the death of brain cells that occurs in

Alzheimer’s disease. The Phase I study will

look into the possible role of the brain’s

blood vessels in Alzheimer’s disease and

the effects of the drug dabigatran in a

repurposed use.

Nabilone, a synthetic cannabinoid

antiemetic used in chemotherapy, is

another potential repurposed candidate

being investigated. Researchers from

Sunnybrook Research Institute, University

of Toronto, recently presented the results

of a safety and efficacy study of nabilone

in patients with moderate to severe

AD. The data showed that nabilone

significantly improved agitation in a trial

of 39 moderate-to-severe Alzheimer’s

patients. Improvements were observed

with nabilone as early as two weeks.

Some patients experienced sedation

with nabilone, though 53 percent of

the patients tolerated the highest dose

(2 mg/day). As the pilot study showed

positive results, a larger Phase 3 study

is being planned. Agitation is a common

and persistent symptom in those

with Alzheimer’s disease and current

pharmacotherapies have modest efficacy

and poor safety. This study is funded by

the ADDF and the Alzheimer’s Society of

Canada.

Rotigotine, a dopamine agonist of

the non-ergoline class of medications

indicated for the treatment of Parkinson’s

disease (PD) and restless leg syndrome,

is under investigation as a potential

cognitive enhancer for Alzheimer’s.

Recently, preliminary findings from the

DOPAD trial, which tests the dopaminergic

Ph.D., director, Centre for Brain Research, while addressing

an Alzheimer’s Association symposium held recently in

Bengaluru. The number of the elderly in India would go

up from the current 143 million to 300 million by 2050,

she noted, emphasising the need to invest in research and

identify risk and protective factors that contribute to diseases

of the aging brain.

Globally, as many as 50 million people are afflicted with

dementia, and every three seconds someone in the world

develops dementia. Dementia is the seventh leading cause of

death worldwide, shows the 2018 World Alzheimer Report.

Unlike the western population, India has a high load of

vascular risk factors. That is another reason why the incidence

of dementia is high in the country. “In European countries or

in Japan, people take good control of the vascular risk factors

pretty early in their lives. Dementia numbers there are not

rising for the last couple of years. In India we don’t know how

to age gracefully,” comments Dr Ganesh Chauhan, Assistant

Professor at the Centre for Brain Research, Indian Institute of

Science, Bengaluru.

On the other hand, he adds, Indians do have certain

factors working in their favour, which are supposed to be

protecting them from neurodegenerative diseases, such as

the joint family system, bigger social networks, bilingualism

FEBRUARY 2019 / FUTURE MEDICINE / 21


slug

therapy, were presented. The trial in

94 mild Alzheimer’s patients tested

whether rotigotine improved cognitive

function, including executive function, and

activities of daily living after six months of

treatment.

Focus on synapses

The focus of a few of the clinical studies

are synapses, the junctions between nerve

cells, which are important for memory and

cognition. Current treatments increase

levels of the neurotransmitter acetylcholine

with modest impact on Alzheimer’s

symptoms.

Researchers from Vanderbilt University

Medical Center reported preliminary

results from a Phase 1 study of novel

drug compound VU319 that modulates

muscarinic (M1) synaptic receptors. So far,

a total number of five doses of VU319

have been tested in patients and they

have been well-tolerated. After analysing

the data from a multiple-ascending

dose study to assess the safety and

tolerability of seven consecutive-day

dosing, the researchers are aiming a

Phase 2a VU319 study in people with

mild cognitive impairment in the latter

half of 2019. It will be a proof-of-concept,

double-blind, placebo-controlled study to

assess the ability of VU319 to modulate

brain networks. Previous drugs targeting

M1 produced improvement in cognitive

performance and behavioural disturbances

in Alzheimer’s patients, but failed in Phase

3 trials due to intolerable (cholinergic) side

effects, as per ADDF data.

Other candidates targeting synaptic

activity and neurotransmitters include

Takeda’s TAK-071 (Phase 1) as a

combination treatment with donepezil,

a palliative treatment for Alzheimer’s,

Agenebio Inc’ s AGB101 (Phase2/3),

Heptares’ HTL0009936 (Phase 1),

THE USFDA APPROVED

THE FIRST HUMAN

CLINICAL TRIALS WITH

APOE2 GENE THERAPY

H Lundbeck/Otsuka’s Lu AE58054

(idalopirdine) 5-HT6 receptor antagonist

and Boehringer Ingelheim’s BI 409306

phosphodiesterase 9A inhibitor (Phase 2).

ApoE approach & cell therapy

Several gene therapy and stem cell

approaches for dementia are in the

experimental stage. Among the genes,

ApoE4 is the most targeted genetic risk

factor for Alzheimer’s disease. People

with two copies of the ApoE -e4 variant

of the gene are up to 12 times more

likely to develop Alzheimer’s and to get

it at younger ages. Dr Ronald Crystal of

Weill Cornell Medicine uses ApoE- e2, the

protective variant of the gene delivered

to the brain, to counteract the negative

effects of ApoE -e4. Dr Crystal recently

received FDA approval to proceed to

the first human clinical trials with ApoE2

gene therapy. In a different approach, Dr

Anastasia Khvorova et al. of the University

of Massachusetts Medical School are

developing RNAi constructs, which are

called anti-sense oligonucleotides, to

reduce APOE gene expression, according

to the ADDF, which funds the studies.

Ageless Regenerative Institute is

studying adipose-derived stromal cells as a

cell therapy approach to protect neurons.

The investigations have reached Phase 2

stage.

AstroStem by Nature Cell Co. Ltd is

another stem cell therapy being explored

in Phase 1/2.

Some of the leading pharmaceutical

companies, including Novartis, Eli Lilly,

Janssen, Biogen, AbbVie, AC Immune,

AB Science, AstraZeneca, Genentech,

Sanofi, MSD as well as universities and

Alzheimer’s organisations are also working

on the Alzheimer’s drug pipeline, which is

broadening by the day.

etc. Socialisation is a very protective factor.

The hunt for a cure

Even as Alzheimer’s grows to epidemic proportions,

researchers are scrambling for a remedy for the disease,

which is considered one of the most challenging medical

mysteries of our time.

No pharmacologic treatment is available today to slow or

stop the damage and destruction of neurons. Rivastigmine,

galantamine, donepezil, memantine, memantine combined

with donepezil, and tacrine are the six therapies approved by

the US FDA to temporarily improve symptoms in Alzheimer’s.

Over 120 drugs are now in clinical trials as part of the

search for novel treatments for Alzheimer’s disease. Many of

these trials are in phase 2, with results expected to be out in

the next few years. Presently, a good proportion —about 20%

— of all the clinical studies revolve around beta-amyloid and

tau, the culprit proteins implicated in the development and

progression of the neurodegenerative disease.

It is, however, not clear if amyloid and tau represent valid

drug targets. “We don’t understand the exact mechanism.

But most researchers are not ready to abandon these classic

22 / FUTURE MEDICINE / FEBRUARY 2019


COST OF ALZHEIMER’S

Cost of

Alzheimer’s and

other dementias

in 2018 in US

$277 billion

By 2050, these costs could rise as high as

$1.1 TRILLION

2018 2050

5.7 million

Americans are living

with Alzheimer’s

Between 2000 and 2015, deaths from

Alzheimer’s disease increased

123%

14 million

people will have Alzheimer’s

1 in 3

seniors die

with Alzheimer’s

or another

dementia

GENOME-WIDE STUDY ON

DEMENTIA IN INDIA SOON

A

large, genome-wide study on Alzheimer’s

and other forms of dementia is expected to

start soon in India.

Named the Srinivasapura Aging Neuro

Senescence and Cognition (SANSCOG), the

study will be conducted by the Centre for Brain

Research (CBR), Bengaluru.

“The study aims to look at genetic

susceptibility and also the role of environmental

factors that contribute to complex diseases like

Alzheimer’s,” said Dr Bratati Kahali, Scientist

at the Centre for Brain Research (CBR), Indian

Institute of Science, Bengaluru.

A team of qualified doctors, psychologists

and social workers will examine 10,000 people

above 45 years from Srinivaspura taluk in the

Kolar district of Karnataka annually for a period

of 10 years to comprehend the factors that

cause dementia.

The people, belonging to the middle age

group, were chosen to study their susceptibility

to develop or not to develop a neurogenerative

disease later on. How a person leads his life

in his 30s and 40s can determine what he or

she is going to be in his 60s and 70s. Added

to that is one’s genetic susceptibility. These can

be assessed only through population-based

studies, she added.

The study will employ latest tools like next

generation sequencing and high-throughput

screening technologies to cover the entire

genome rather than one gene.

“It is going to be a large study, not only

in terms of numbers, but also in terms of the

technology used,” claimed Dr Ganesh Chauhan,

Assistant Professor at CBR.

Currently, there is no data available from

therapeutic studies in India. Whatever is

available is from certain pockets with a small

sample size. Preliminary work on the study has

started. The project will go full-scale by the end

of March 2019, he added.

Every

65

seconds

someone in the

United States

develops the disease

SOURCE: alz.org

FEBRUARY 2019 / FUTURE MEDICINE / 23


pathologies,” quips Dr Howard Fillit,

MD, Chief Science Officer of Alzheimer’s

Drug Discovery Foundation (ADDF),

New York, a non-profit organisation

which supports scientists around the

globe who are investigating novel drugs

to prevent, treat and cure Alzheimer’s

disease.

Therapeutic attempts to remove

or lower the production of betaamyloid

have been largely unsuccessful

in altering the disease course of

Alzheimer’s disease. Since Alzheimer’s

has a complex and interrelated set of

causes, we will need more than one

drug to treat the disease, like with

cancer.

Probe on lifestyle

As far as late-onset Alzheimer’s is

concerned, the greatest risk factors are

older age, having a family history of

SINCE ALZHEIMER’S HAS A

COMPLEX AND INTERRELATED

SET OF CAUSES, WE WILL

NEED MORE THAN ONE DRUG

TO TREAT THE DISEASE

Alzheimer’s and carrying the ApoE-e4

gene.

Prevention studies are also looking

to identify the link between lifestyle and

dementia. Several major clinical trials

are underway around the world to test

the effect of adopting healthier lifestyle

habits to prevent cognitive decline,

Alzheimer’s and other dementias. In

the U.S., the Alzheimer’s Association is

leading the U.S. Study to Protect Brain

Health Through Lifestyle Intervention

to Reduce Risk (US POINTER). The US

POINTER is a two-year clinical trial to

evaluate whether lifestyle interventions

can protect cognitive function in older

adults at increased risk for cognitive

decline.

Earlier, a landmark study called

the Finnish Geriatric Intervention

“We are at a pivotal

time in Alzheimer’s

research”

Dr Howard Fillit, MD is Founding

Executive Director and Chief

Science Officer of Alzheimer’s

Drug Discovery Foundation (ADDF),

New York. ADDF is a nonprofit

organisation which supports

scientists around the globe who are

investigating novel drugs to prevent,

treat and cure Alzheimer’s disease. A

geriatrician and neuroscientist,

Dr Fillit says he is committed to

conquer Alzheimer’s through drug

discovery. Edited excerpts from an

interview with FM:

A look at the current drug

discovery pipeline shows that most

drugs in late-phase trials target

either beta-amyloid or tau. And

beta amyloid’s exact mechanism in

Alzheimer’s is yet to be conclusively

established. How do you comment

on it?

Historically, drug development

in Alzheimer’s has focused on the

damaged proteins, amyloid and tau,

the hallmarks of Alzheimer’s disease.

Although we don’t understand the

exact mechanism, most researchers

are not ready to abandon beta

amyloid (or tau) as targets. It is

currently not known if these classic

pathologies (amyloid and tau)

represent valid drug targets and if

these targets alone are enough to

treat Alzheimer’s disease. Although

therapeutic attempts to remove

or decrease the production of

beta-amyloid have been largely

unsuccessful in altering the disease

course of Alzheimer’s disease,

researchers learned important

information from those clinical trials

even if they didn’t immediately result

in treatments for Alzheimer’s patients.

And recent clinical trials suggest that

[attempts to overcome] problems with

the clearance of beta-amyloid may yet

prove fruitful.

While many late-stage clinical

trials are targeting amyloid, it’s likely

we’ll need more than one drug to

treat Alzheimer’s, like with cancer,

because it has multiple causes. At the

ADDF, our scientific strategy is based

on the biology of aging - the leading

risk factor for Alzheimer’s disease.

Alzheimer’s has a complex and

interrelated set of causes, so drugs

targeting more than one of those

causes will be needed to effectively

treat it. Targeting the common

biological processes of aging may be

an effective approach to developing

therapies to prevent or delay agerelated

diseases, such as Alzheimer’s.

What are the most promising

candidates for Alzheimer’s that ADDF

is currently supporting?

Since 1998, the ADDF has awarded

over $120 million to fund over 580

drug development programmes in

19 countries. We support a diverse

pipeline of drug targets beyond beta

amyloid. Alzheimer’s drugs aimed

at neuroinflammation, genetics

and epigenetics, neuroprotection

and metabolic and mitochondrial

dysfunction are now in clinical trials

or nearly there. We need to pursue

all these targets and look for new

ones. We need more rigorous trials.

Alzheimer’s is a complex disease; [and

will] likely involve combination therapy

– an approach that’s standard of care

in diseases like diabetes, heart disease,

cancer, HIV/AIDS.

An epigenetic drug being

developed for Alzheimer’s—ORY-2001

by Oryzon Genomics—is preparing for

phase 2 trials. It works by inhibiting

a protein that “turns down” the

expression of several genes that are

beneficial to the brain. By helping

these genes express more, ORY-2001

may slow cognitive impairment and

restore memory deficits in patients

with Alzheimer’s and other disorders.

Another promising candidate is

C-31 (also called LM11A-31), which

was developed by Dr Frank Longo,

a professor at the Stanford School

of Medicine and the founder of the

24 / FUTURE MEDICINE / FEBRUARY 2019


iotechnology firm PharmatrophiX.

Dr Longo is working on a remarkable drug

candidate that could restore lost cognitive

function and lead to the first regenerative

therapy for Alzheimer’s.

A third example is the work of

Dr Michela Gallagher, professor of

Psychology and Neuroscience and the

head of the Neurogenetics and Behavior

Center at Johns Hopkins University. She

is also the founder of AgeneBio, Inc., a

pharmaceutical development company that

has initiated a Phase 3 trial recently to slow

the progression of Alzheimer’s dementia.

The ADDF is a funder of Dr Gallagher’s

therapeutic development of AGB-101,

the first and only treatment to target

hippocampal hyperactivity, a condition

characteristic of the amnestic mild

cognitive impairment stage of Alzheimer’s

disease.

Diagnostic Accelerator, in partnership

with Bill Gates, is reportedly exploring the

possibility of a blood test for Alzheimer’s.

What is the present status of the study?

Critical to our success in finding effective

ways to prevent and treat Alzheimer’s is

the development of reliable, affordable and

accessible biomarkers – just as cholesterol

is an early biomarker for heart disease.

This will allow us to better understand

how the disease progresses, more easily

identify people for clinical trials and more

accurately monitor their response to

treatments. That is why the Alzheimer’s

Drug Discovery Foundation partnered with

Bill Gates, the Dolby family and the Charles

and Helen Schwab Foundation to create

the Diagnostics Accelerator.

This initiative will help to accelerate

the development of novel biomarkers

from blood and other peripheral fluid and

tissue. It is my hope that in the next few

years a blood test will be available for the

diagnosis of Alzheimer’s disease.

Dr Howard Fillit

NEW THERAPEUTICS FOR

AD WILL COME FROM

THE UNDERSTANDING

OF THE EFFECTS OF AGING

ON THE BRAIN

Using the biomarker specific model

of precision medicine, we will be able to

predict more accurately which treatment

and prevention strategies will work in

different at-risk populations of people who

have Alzheimer’s disease or other forms of

dementia.

Despite the increasing burden of

the disease, there are not many real

breakthroughs in Alzheimer’s drug

research. Is it because of the poor

understanding of the disease or due to

other hurdles?

Today we know more about Alzheimer’s

and the human brain than at any other

time in history.

Alzheimer’s research did not result

in real progress until the mid-1980s.

One of the reasons is that Alzheimer’s

disease and related dementias were

thought to be a normal part of aging.

So, until it was realized that Alzheimer’s

disease was not a normal part of

aging, there was little interest in finding

treatments for it.

It typically takes at least 30 years

for drugs to be developed out of basic

scientific research. The first drug to treat

Alzheimer’s was not approved by the U.S.

Food and drug administration until 1993,

decades after drugs for cancer and heart

disease were approved.

Another major challenge has been

the lack of affordable and noninvasive

biomarkers as tools to better diagnose,

monitor disease progression and make

clinical trials more efficient and rigorous.

Where do you see Alzheimer’s drug

discovery in the next five years down the

lane?

Even though we don’t yet have a cure

for Alzheimer’s disease, I’ve never been as

optimistic as I am now about the potential

for new drugs to prevent and treat this

devastating disease. We are at a pivotal

time in Alzheimer’s research with better

diagnostics, a solid scientific understanding

and more than 120 drugs in clinical trials

looking at novel treatments for Alzheimer’s

disease. Many of these trials are in phase 2

and expected to read out within the next

few years.

New therapeutics for Alzheimer’s

disease will come from this understanding

of the effects of aging on the brain. Our

success in fighting Alzheimer’s disease will

likely come from combination therapies -

because Alzheimer’s disease has multiple

underlying causes, it will likely require a

combination of drugs to effectively treat

it. Precision medicine using combination

therapy is likely needed for better

treatment outcomes in Alzheimer’s disease,

just as it is for cancer.

Now more than ever, we need to push

forward the opportunity for new drug

discoveries.

See the detailed version of the interview on

www.futuremedicineindia.com

FEBRUARY 2019 / FUTURE MEDICINE / 25


Study to Prevent Cognitive Impairment

and Disability (FINGER) showed heart

health management, a healthy diet and

increased exercise, plus intellectual and

social stimulation can slow cognitive decline

in at-risk older adults. FINGER studies are

being carried out in China, in Singapore and

in Australia.

Tackling stigma

The costs of long-term care for individuals

with Alzheimer’s are substantial, as

dementia is one of the costliest conditions

to society. The total per-person health

care and long-term care payments from

all sources for Medicare beneficiaries with

Alzheimer’s or other dementias were

over three times as great as payments for

other Medicare beneficiaries in the same

age group in the US, according to 2018

Alzheimer’s Disease Facts and Figures by

Alzheimer’s Association, Chicago.

Such cost estimations are yet to be

carried out through studies in India, where

AD has not become a public health concern

yet like in many other parts of the world.

Stigma is yet another issue. A substantial

amount of stigma is still attached to

dementia in India. “Not only dementia,

almost every disease affecting the brain is

considered ‘paagal’ (lunacy) in many parts

of India. Woh toh paagal hai (the person

is mad) … this is the way people describe

individuals with neurological disorders,”

comments Dr Chauhan.

Chauhan and others in CBR are part

of a soon-to-be-launched large-scale

genome-wide study on Alzheimer’s and

other dementias in the country. Currently,

whatever data on Alzheimer’s is available

is limited to certain pockets, or based on

the information provided by hospitals.

Initial results of the study could be out

within the next couple of years. The data

will put things in perspective. Hopefully, a

clear understanding about the prevalence

and other aspects of the disease could

not only help create appropriate policies,

but also bring down the stigma. As World

Alzheimer’s Report 2018 by Alzheimer’s

Disease International, UK points out: “More

diagnosis means more awareness. More

awareness means less stigma. Less stigma

means more hope.”

Not only dementia,

almost every

disease affecting

the brain is

considered ‘paagal’

(lunacy) in many

parts of India.

Dr Ganesh Chauhan

Assistant Professor

Centre for Brain

Research

Bengaluru

TAU TANGLES AND AMYLOID

Two proteins in the brain are heavily

involved in the development of Alzheimer’s,

agree most scientists. Beta-amyloid (Aβ)

reaches abnormal levels in the brain of

people with Alzheimer’s and forms plaques

that collect between neurons and disrupt cell

function. The amyloid cascade hypothesis

considers that the deposition of the amyloid-β

peptide in the brain parenchyma is a central

event in Alzheimer’s disease pathology.

Tau proteins forms neurofibrillary tangles

inside neurons which block the neuron’s

transport system.

However, it is not clearly known exactly

26 / FUTURE MEDICINE / FEBRUARY 2019


BLOOD TEST FOR

ALZHEIMER’S MARKER?

Washington University scientists, in

collaboration with C2N Diagnostics,

showed that the protein tau increases in

blood after peripheral administration of an

anti-tau antibody.

The study in mice found that the level

of tau increase in blood correlated with the

tau pathology in the brain.

C2N Diagnostics, LLC based St Louis,

Missouri has developed technology

platforms like the Stable Isotope Spike

Absolute Quantitation (SISAQ) and Stable

Isotope Labeling Kinetic (SILK) that

enable the measurement of the absolute

concentration of peptides and specific

proteins in both CSF and plasma.

“We focus on a variety of assays

– using the primary platform of mass

spectrometry – to quantitate proteins

and other biomolecules implicated

in neurodegeneration,” said Joel B.

Braunstein, MD, CEO, C2N Diagnostics.

These assays are currently available

for use in preclinical research and clinical

research drug development settings. Some

of these assays may be used in the future

to serve as a clinical diagnostic aid in the

detection and monitoring of pathways

implicated in Alzheimer’s disease and

other forms of neurodegeneration, he

added.

CASCADE

how these proteins relate to each

other.

Impairments in cholesterol and

glucose metabolism, inflammation,

oxidative stress and dysfunctional

‘garbage collection system of the

brain’ are all supposed to help

push the amyloid accumulation,

which then probably causes

damage to the synapses leading

to tau aggregation.

New findings show both

Aβ and tau oligomers bind to

amyloid-β protein precursor

(AβPP). And the presence of this

protein is required for both Aβ

and tau to enter neurons and

induce abnormal synaptic function

and memory. It is also proposed

that extracellular oligomers of

Aβ and tau act in parallel and

upstream of AβPP in Alzheimer’s

pathogenesis.

However, therapeutic

approaches aimed at decreasing

Aβ levels and tau-based clinical

trials are yet to produce positive

findings.

FEBRUARY 2019 / FUTURE MEDICINE / 27


esearch

FLUID DIAGNOSIS

FOR DEMENTIA

Integration

of molecular

biomarkers could

chart the course of

precision medicine

in Alzheimer’s

disease

DR RAJANI KANTH VANGALA

A

typical diagnosis of dementia

is based on a history of illness,

cognitive deficits and their

patterns. Along with the abovementioned

tests, there is now a shift

towards diagnosing specific forms

of Alzheimer’s disease (AD) using

molecular biomarkers. There has been

enormous progress in identifying fluid

biomarkers for AD in the past 20

years. Pathologically, AD is defined

by 1. a neuronal loss of brain regions,

specifically in medial temporal lobe

structures and temporoparietal cortices,

2. neurofibrillary tangles composed of

truncated and hyperphosphorylated

tau protein, 3. the extracellular neuritic

plaques with deposits of β-amyloid

peptides. There are several subtypes of

dementia

which

are diagnosed using different

biomarkers to evolve better

therapy and precision medicine.

In β-amyloid pathology, the

42-amino-acid isoform of β-amyloid

(Aβ42) forms the major component

of senile plaques leading to cerebral

amyloid angiopathy in AD. Enzymelinked

immunosorbent assay

(ELISA) based Aβ42 concentration

measurement in CSF has been

verified in many studies (Olsson et al.,

2016), where reduced levels reflect

sequestration to senile plaques as

was also shown in positron emission

tomography (PET) imaging. These

reduced levels of Aβ42 can indicate

pre-clinical stages of AD or dementia

with Lewy bodies (DLB), commonly

associated with cerebral Aβ aggregation.

28 / FUTURE MEDICINE / FEBRUARY 2019


In order to make diagnostics more

accessible, blood is preferable, and

plasma Aβ42 measurement using Single

Molecule Array (Simoa) technique could

quantify to sub-picogram per mL levels

(limit of quantification of 0.04pg/mL).

A large-scale Swedish BioFINDER study

found weak, but significant, correlations

between both plasma AB42 and

AB42/40 ratio to corresponding CSF

measurements.

The abnormal phosphorylation

and truncation of tau proteins, which

constitute major neurofibrillary tangles

in AD, are also detectable in blood

samples. It has been shown that

increased levels of plasma tau levels

may correlate with AD. Longitudinal

studies have shown that increased

plasma tau levels have significant

correlation with future cognitive decline

as well as in hypometabolism measured

by FDG PET. However, many clinical

studies reported that there is a large

overlap of tau levels between cases of

tauopathies and controls, suggesting

that more studies may be needed to

take it into clinical practice. Alternatively,

T-tau or P-tau measurement in neuronenriched

exosomes may help as a better

biomarker.

Neurogranin and cognitive decline

One of the key features of AD is

axonal degeneration, which is linked

with the onset of cognitive decline

and Aβ pathology. It has been

demonstrated that higher levels of

CSF T-tau lead to increased intensity

of neurodegeneration. Some more

markers like fatty acid-binding protein

(FABP) family and visinin-like protein

1 (VLP-1; VSNL1) do show a weak but

significant association to AD. T-tau

and neurofilament-light (NF-L) assays

are also being used for performing

ultrasensitive blood tests, but these are

in early stages of development. A recent

study on a cohort of Alzheimer’s Disease

Neuroimaging Initiative (ADNI) study

showed a marked increase in plasma

NF-L levels, with receiver operating

curve (ROC) area under the curve (AUC)

of 0.87, which is comparable to CSF

AD biomarkers.

One of the earliest clinical

characteristic of AD is memory

impairment due to subtle alterations in

synaptic efficiency in the hippocampus

prior to frank neuronal degeneration.

One of the most important proteins,

called neurogranin (Ng; NRGN), is a

dendritic protein highly abundant in

neurons. It is involved in long term

potentiation of synapses, particularly in

hippocampus and basal forebrain. CSF

Ng concentrations were observed to

be increased in AD (Hellwig et al, 2015;

Kvartsberg et al., 2015a,b; Thorsell et

THERE IS A STRONG

CORRELATION BETWEEN

HIGHER LEVELS OF

NEUROGRANIN AND

COGNITIVE DECLINE. SOME

OF THE NOVEL EMERGING

BIOMARKERS INCLUDE

SNAP25 AND RAS-RELATED

PROTEIN RAB3A

al., 2010; Kester et al., 2015), but not in

other neurodegenerative diseases. New

studies have also reported that there

is a strong correlation between higher

levels of Ng and cognitive decline and

brain atrophy (Tarawneh et al., 2016).

Some of the novel emerging biomarkers

include synaptosomal-associated protein

25 (SNAP25) and Ras-related protein

RAB3A.

Emerging biomarkers

Glial cells in the brain are important for

normal nutrient supply and form part

of the blood-brain barrier. These cells

play important roles in repair following

CNS injury and resident macrophages

microglia form the primary active

defense players. Loss of synaptic

plasticity and neuronal function in

AD can be linked to activation of

both cell types, but more so the glial

cells. Interesting findings related to

variants of myeloid cells 2 (TREM2;

TREML2) gene specifically expressed

in microglia cells has raised interest

in the possibility of identifying better

biomarkers for glial activation (Lue

et al., 2015; Guerrerio et al., 2013;

Jonsson et al., 2013). Increased levels

of secreted ectodomain of TREM2 in

CSF were in concordance with that of

T-tau and P-tau levels in AD patients.

Similarly, several other biomarkers of

astrocytes, microglia and macrophagederived

proteins, like CD14, YKL-40

and C-C chemokine receptor 2 with

its ligand C-C chemokine ligand

2 (CCL2) levels were present in

increased levels in AD patients CSF.

The validation of these biomarkers

in blood has not yet resulted in any

conclusive outcomes. Approximately

50% of frontotemporal dementia (FTD)

cases are reported to show increased

levels of hyperphosphorylated TDP-

43 proteinopathy. It has also been

observed to be associated with the

impairment of cognitive capabilities of

aging patients.

Obviously, CSF has proven to be the

best source of biomarkers for detecting

tangle and plaque pathology for

clinical utility, but there are emerging

biomarkers that are reshaping the

diagnosis and therapeutic approaches

in AD. The new discoveries and

findings do suggest that, for now, a

combination of CSF, blood and PET

may be the best option. However,

blood biomarkers are on brink of

being a viable option for the screening

and early clinical management of

patients with AD. The last 20 years

of research on fluid biomarkers has

given extraordinary results and ADCSF

biomarker toolbox looks set to better

define precision medicine.

FEBRUARY 2019 / FUTURE MEDICINE / 29


drug approvals

Chinese nod

for IBS drug

linaclotide

Ironwood Pharmaceuticals,

Inc has received marketing

authorisation from the

National Medical Products

Administration (NMPA) for

linaclotide (Linzess) in China

for the treatment of adult

patients with irritable bowel

syndrome with constipation

(IBS-C).

Linaclotide is a guanylate

cyclase-C (GC-C) receptor

agonist. The drug binds to the

GC-C receptor locally, within

the intestinal epithelium.

Activation of the GC-C results

in increased intestinal fluid

secretion accelerated transit

and a decrease in the activity

of pain-sensing nerves in the

intestine.

The NMPA approval is

based on a phase III global,

multicentre, clinical trial, jointly

conducted by AstraZeneca

China and Ironwood, in five

countries, which evaluated the

efficacy and safety of Linzess

in patients with IBS-C.

Nivolumab plus ipilimumab combo

to treat renal cancer in EU

The European Commission has approved

the combination of nivolumab (Opdivo)

3 mg/kg plus low dose ipilimumab (Yervoy)

1 mg/kg for the first-line treatment of

patients with intermediate- and poor-risk

advanced renal cell carcinoma (RCC).

This decision represents the first

approval of an Immuno-Oncology (I-O)

combination therapy for patients with this

type of cancer in the EU, Bristol-Myers

Squibb Company announced.

The approval is based on results from

the Phase 3 CheckMate -214 clinical trial,

which was stopped early following a

planned interim analysis that showed that

the combination of nivolumab plus lowdose

ipilimumab demonstrated a significant

increase in overall survival, with a 37%

decreased risk of death in intermediateand

poor-risk patients compared to a

current standard of care, sunitinib.

Nivolumab plus low-dose ipilimumab

Launch of linaclotide

in China is expected in the

second half of 2019.

Orphan drug

status for

apraglutide

Therachon AG said the US

FDA granted Orphan Drug

Designation for apraglutide

for the treatment of short

bowel syndrome (SBS).

Apraglutide is a glucagonlike

peptide-2 receptor

agonist.

SBS results from extensive

intestinal resection due to

chronic inflammatory bowel

disease (IBD), acute events

such as mesenteric infarction

or congenital abnormalities.

SBS is a severe, chronic

condition associated with

also demonstrated a higher objective

response rate of 41.6% versus 26.5% for

sunitinib and a complete response rate

of 9.4% for the nivolumab plus low-dose

ipilimumab cohort versus 1.2% for the

sunitinib arm.

CheckMate -214 is a Phase 3,

randomized, open-label study evaluating

the combination of nivolumab 3 mg/kg

plus ipilimumab 1 mg/kg versus sunitinib

in patients with previously untreated

advanced RCC. In the intermediate- and

poor-risk study population, 425 patients

received nivolumab 3 mg/kg plus

ipilimumab 1 mg/kg every three weeks

for four doses, followed by nivolumab

3 mg/kg every two weeks, and 422 patients

received sunitinib 50 mg once daily for four

weeks, followed by two weeks off every

cycle.

Patients were included regardless of

their PD-L1 status.

reduced or complete loss of

intestinal function, known as

‘intestinal failure’. Intestinal

failure caused by SBS can

be life-threatening and is

characterized by malabsorption

and malnutrition. Affected

individuals are dependent

30 / FUTURE MEDICINE / FEBRUARY 2019


on daily parenteral support,

typically requiring between 10 –

15 hours of parenteral feeding

per day. Parenteral support

is associated with infections,

blood clots and poor quality

of life.

In the US, Orphan Drug

Designation provides orphan

status to investigational

therapies aimed to treat

rare diseases and disorders

affecting fewer than 200,000

people.

Therachon is a

clinical-stage global

biotechnology company

pursuing programmes in

rare conditions with wellcharacterized

biological

root causes, including both

short bowel syndrome and

achondroplasia.

Devimistat gets

orphan drug

desig in EU

The European Medicines

Agency (EMA) has granted

orphan drug designation

to devimistat (CPI-613), for

the treatment of metastatic

pancreatic cancer.

Devimistat, developed

on Rafael Pharma’s Altered

Metabolism Directed (AMD)

platform, targets the altered

regulation of metabolic

processes specific to cancer

cells. It is highly specific,

simultaneously attacking

multiple targets, minimally

toxic and has broad spectrum

activity across a wide variety

of cancers, the company said.

Devimistat is currently

being evaluated in 7 trials

as a single agent, as well

as in combination with

standard drug therapies for

hematological malignancies

and solid tumours.

In pancreatic cancer,

devimistat in combination

with modified folfirinox

exhibited an objective

response rate of 61%, median

overall survival of 19.9 months

and median progression-free

survival of 9.9 months.

Devimistat also exhibited

a good safety profile both

as a single agent and in

combination with other

standard-of-care drugs.

Devimistat has previously

been granted orphan drug

designation for pancreatic

cancer, AML, MDS, peripheral

T-cell lymphoma and Burkitt

lymphoma by the US FDA.

Tdap vac

for repeat

vaccination

The US FDA has approved

the expanded use of

Tetanus Toxoid, Reduced

Diphtheria Toxoid and

Acellular Pertussis (Tdap)

Vaccine Adsorbed (Adacel) to

include repeat vaccination to

help protect against tetanus,

diphtheria and pertussis. It is

now the first and only Tdap

vaccine in the US approved

for a repeat dose in people

10 through 64 years of age 8

years or more after the first

vaccination, Sanofi Pasteur

said.

The FDA licensure was

based on clinical data from

a study of the safety and

effectiveness of repeat

vaccination in adults. In the

study of more than 1,300

adults (aged 18 through

64 years), participants

received either the vaccine

or a tetanus-diphtheria (Td)

vaccine 8-12 years after a

previous dose of the vaccine.

US FDA panel recommends romosozumab for osteoporosis

The US FDA Bone,

Reproductive and Urologic

Drugs Advisory Committee

(BRUDAC) recommended the

approval of romosozumab

(Evenity) for the treatment of

postmenopausal women with

osteoporosis at high risk for

fracture.

Eighteen of 19 members

voted in favour of the

approval yes for approval,

Amgen and UCB announced.

Romosozumab is an

investigational bone-forming

monoclonal antibody that

inhibits the activity of

sclerostin. This enables

romosozumab to rapidly

increase bone formation

and reduce bone resorption

simultaneously.

The romosozumab

development programme

includes 19 clinical studies

that enrolled approximately

14,000 patients. Notable

phase 3 studies include

FRAME, a placebocontrolled

study with 7,180

postmenopausal women

with osteoporosis at risk for

fracture; ARCH, an active

comparator-controlled study

with 4,093 postmenopausal

women with osteoporosis and

with prior history of fracture;

and STRUCTURE, an active

comparator-controlled study

with 436 postmenopausal

women with osteoporosis.

The BRUDAC evaluated

the FRAME and ARCH studies

in its review of the clinical

benefit and risk profile of

romosozumab.

32 / FUTURE MEDICINE / FEBRUARY 2019


Five new approvals for pembrolizumab in Japan

Pembrolizumab (Keytruda)

has been granted approval

in Japan for the first-line

treatment of advanced nonsmall

lung cancer (NSCLC)

as both monotherapy

and in combination with

chemotherapy.

Pembrolizumab is the first

anti-PD-1 approved in Japan

with new MSI-H indication,

regardless of tumour type,

Merck said.

Pembrolizumab has

simultaneously received

five new approvals from

the Japan Pharmaceuticals

and Medical Devices Agency

(PMDA) for three expanded

uses in advanced NSCLC, one

in melanoma, as well as a

new indication in advanced

microsatellite instability-high

(MSI-H) tumours.

PDMA has granted new

approvals following priority

review for pembrolizumab

in combination with

pemetrexed and platinumbased

chemotherapy

(cisplatin or carboplatin)

for the first-line treatment

of unresectable, advanced/

recurrent nonsquamous

NSCLC regardless of PD-L1

expression; Pembrolizumab in

combination with carboplatin

and paclitaxel or nabpaclitaxel

for the first-line

treatment of unresectable,

advanced/recurrent squamous

NSCLC regardless of PD-L1

expression; Pembrolizumab

monotherapy in the firstline

treatment of PD-L1-

positive unresectable,

advanced/recurrent

NSCLC; Pembrolizumab

monotherapy as adjuvant

therapy for melanoma

and pembrolizumab

monotherapy for the

treatment of advanced/

recurrent MSI-H solid tumours

that have progressed after

chemotherapy.

A companion diagnostic to

detect MSI-H, the MSI test kit

FALCO by FALCO Biosystems

Ltd., has also been approved.

In addition to the adjuvant

therapy approval, dosage and

administration for all patients

with melanoma have been

changed from an intravenous

infusion of 2 mg/kg over

30 minutes at a three-week

interval to intravenous infusion

of the fixed dose of 200 mg

over 30 minutes at a threeweek

interval.

Previously, pembrolizumab

was approved in Japan for

the treatment of curatively

unresectable melanoma;

PD-L1-positive unresectable,

advanced or recurrent

NSCLC; relapsed or refractory

classical Hodgkin lymphoma;

and curatively unresectable

urothelial carcinoma that

progressed after chemotherapy.

Pembrolizumab is

marketed by MSD in Japan

and is co-promoted with Taiho

Pharmaceutical Co., Ltd.

The results of the study

published in the Journal

of the Pediatric Infectious

Diseases Society showed a

second dose of the

Tdap vaccine in adults

administered 8-12 years

after a previous dose found

no significant differences

in adverse events between

vaccine groups.

FDA fast-tracks

stem cell

therapy for SCD

Fast track designation has

been granted for CTX001

for the treatment of sickle cell

disease (SCD) by USFDA.

CTX001 is an

investigational, autologous,

gene-edited hematopoietic

stem cell therapy for patients

suffering from severe

hemoglobinopathies.

HbF is a form of the

oxygen-carrying haemoglobin

that is naturally present at

birth and is then replaced

by the adult form of

haemoglobin. The elevation

of HbF by CTX001 has

the potential to alleviate

transfusion-requirements for

ß-thalassemia patients and

painful and debilitating sickle

crises for sickle cell patients.

In October 2018, CRISPR

and Vertex announced the

FDA acceptance of the

Investigational New Drug

application (IND) for CTX001

for the treatment of SCD, and

enrolment in a phase 1/2 trial

in SCD is currently underway

in the US. The companies are

also evaluating CTX001 for the

treatment of ß-thalassemia,

and enrolment in a Phase

1/2 trial in ß-thalassemia is

currently open at multiple

clinical trial sites in Europe.

Japanese nod to

PNP drug Tarlige

Tarlige tablets has been

granted marketing

34 / FUTURE MEDICINE / FEBRUARY 2019


approval in Japan for the

treatment of peripheral

neuropathic pain (PNP).

This drug, an a2d ligand

created by Daiichi Sankyo,

was submitted for marketing

approval in February 2018

on the basis of the results

of a phase 3 clinical trial

in patients with diabetic

peripheral neuropathic

pain (DPNP) and a phase 3

clinical trial in patients with

postherpetic neuralgia (PHN).

Both trials were conducted in

Asia and including Japan.

a2d (Alpha 2 delta) ligand

binds to the a2d subunits of

voltage-dependent calcium

channels

DPNP leads to numbness

to the extremities and is one

of the most common longterm

3 major complications of

diabetes.

Crizanlizumab

is breakthrough

therapy for VOCs

The US FDA has granted

breakthrough therapy

designation crizanlizumab

(SEG101) for the prevention of

vaso-occlusive crises (VOCs)

in patients of all genotypes

with sickle cell disease (SCD),

Novartis said.

The designation was

granted based on positive

results of phase II SUSTAIN

trial, which compared

the P-selectin inhibitor

crizanlizumab with placebo

in patients with sickle cell

disease.

SUSTAIN showed that

crizanlizumab reduced the

median annual rate of VOCs

leading to health care visits by

45.3% compared to placebo

in patients with or without

hydroxyurea therapy. The

study also demonstrated that

crizanlizumab significantly

increased the percentage

of patients who did not

experience any VOCs vs

placebo during treatment.

Also known as sickle

cell pain crises, VOCs are

unpredictable and extremely

painful events that can lead

to serious acute and chronic

complications.

Tabramycin PARI

for CF in EU

The European Medicines

Agency has approved

tobramycin (Tobramycin

PARI) a new hybrid medicine

for the treatment of chronic

Pseudomonas aeruginosa

infection in cystic fibrosis (CF).

Tobramycin is an

aminoglycoside antibiotic

which primarily affects

bacterial protein synthesis

resulting in rapid

concentration-dependent

bacterial cell death.

Tobramycin PARI is a

hybrid medicine of TOBI

nebuliser solution which

has been authorised in

the EU since 10 December

1999. However, the new

product contains a different

strength of tobramycin and is

administered using a different

nebuliser device, allowing it

to be inhaled over a shorter

period.

According to EMA,

Tobramycin PARI is indicated

for the management of

chronic pulmonary infection

due to Pseudomonas

aeruginosa in patients aged

6 years and older with cystic

fibrosis (CF).

Ibrutinib in

combo with

obinutuzumab

for CLL/SLL

AbbVie announced that

the US FDA approved the

use of ibrutinib (Imbruvica)

in combination with

obinutuzumab (Gazyva) for

adult patients with previously

untreated chronic lymphocytic

leukemia/small lymphocytic

lymphoma (CLL/SLL).

The new approval expands

the use of ibrutinib which can

already be administered as a

single agent or in combination

with bendamustine and

rituximab (BR) for adult CLL/

SLL patients.

Ibrutinib is a once-daily

Bruton’s tyrosine kinase (BTK)

inhibitor that is administered

orally.

The FDA approval is based

on results from the phase

3 iLLUMINATE (PCYC-1130)

study, which showed the

combination of ibrutinib plus

obinutuzumab significantly

improved progression-free

survival (PFS) compared

to chlorambucil plus

obinutuzumab in previously

untreated CLL/SLL patients

who were 65 years or older,

or less than 65 years old with

coexisting conditions.

Patients treated in the

ibrutinib arm experienced

a 77 percent reduction in

risk of progression or death

compared to the chlorambucil

plus obinutuzumab arm.

The chemotherapy-free,

anti-CD20 combination

regimen also showed an

85 percent reduction in risk

of progression or death

compared to chlorambucil

plus obinutuzumab when

evaluating PFS in patients

with high-risk disease (17p

deletion/TP53 mutation, 11q

deletion, or unmutated IGHV).

The FDA also updated

the ibrutinib label to include

additional long-term efficacy

follow-up supporting its use as

a single agent in CLL/SLL from

the Phase 3 RESONATE (PCYC-

1112) and RESONATE-2 (PCYC-

1115, PCYC-1116) international

studies.

The recommended

dose of Imbruvica for CLL/SLL

is 420 mg orally once daily

until disease progression or

unacceptable toxicity as

a single agent or in combination

with obinutuzumab, or BR.

When administering ibrutinib

in combination with rituximab

or obinutuzumab, consider

administering ibrutinib

prior to rituximab or

obinutuzumab when given on

the same day.

FEBRUARY 2019 / FUTURE MEDICINE / 35


straight talk

“EVERYTHING CAN BE

MADE A STORY”

PROF K RAJASEKHARAN NAIR

was the former Director, Professor

& Head, Department of Neurology,

Medical College, Trivandrum. One of the

pioneering leaders in neurosciences

in India, he served as president of

Neurology Society of India (NSI), Indian

Academy of Neurology (IAN) and

Indian Epilepsy Association (IEA). An

eminent neurologist and a well-known

writer, Dr Nair is the recipient of many

awards and honours from different

universities and scientific bodies from

India, UK and USA, including Lifetime

Achievement Award in Neurology by

IAN, Chennai (2017), and Kerala Sahitya

Academy Award for the Best Scholarly/

Scientific Literature (2014). He has

published over 138 papers in different

peer-reviewed neurology and general

medicine journals. He is also the author

of nearly two dozen books, both in

English as well as Malayalam. Currently

Emeritus Professor of Neurology,

Medical College, Trivandrum,

he teaches movement disorders and

cognitive neurology.

Dr Nair discusses the profession,

practice and teaching of neurology and

his pursuits as a writer in

a free-wheeling conversation with

S HARACHAND of Future Medicine.

Excerpts:

You have been practicing as a clinician and a teacher in

neurology for over five decades now. How do you see the

specialty evolved over the years?

When I started the first neurology department at

Medical College, Trivandrum in 1973 soon after completing

my training in Glasgow, I had an extremely tough time

convincing the authorities about the need for such a

specialty. I was the lone neurology teacher in this part

of the world. I used to do everything myself. I needed to

conduct exams. I needed to give training.. all by myself...

In a short time, I formed an association of teachers in

neurology, involving my students, to promote academic

activities. TAN organised around forty CMEs over the years.

As usual, securing funding for the programme was the

biggest challenge at that point of time. We also came out

with ten books for teaching neurology. In these years, I could

also become the president of prestigious organisations

like Neurology Society of India (NSI), Indian Academy of

Neurology (IAN) and Indian Epilepsy Association (IEA). It

was not easy for a southerner like me to get into the top

echelons of these medical bodies.

The practice of neurology has changed dramatically

over the years. I studied neurology in a conventional way.

But I used to teach neurology in a manner which seemed

unconventional at that time. Today, I am studying neurology

as the cutting-edge of medicine. The exponential growth

of the subject is so beautiful, so good. Seeing the way it

has emerged..is absolutely pleasant. The difference is so

remarkably huge that no one can deny it. However, the new

doctors, who go by a technology-oriented methodology,

have a problem. Quite often, they tend to forget the fact

that the person sitting at the other side of the table is a

human being, with his own fear. The man is least interested

in the MRI finding of a tiny growth in the pineal body. He’s

bothered only about his headache. He is worried about what

will happen to his wife and his child if anything goes wrong.

The man sitting at this side of the table does not recognise

the you in you. The you in you or the I in I is different from

what the machine shows. No machine, till date, what should

I say, can truly reflect all emotions of human being or any

living thing...

Medical profession has become much more demanding

and complex in today’s world. What is your view?

I believe that a clinician has a much bigger role in today’s

36 / FUTURE MEDICINE / FEBRUARY 2019


world. He can be instrumental in changing

society. Like treating the sick, the clinician

can treat the society as a whole. But there

are times the medical professionals do not

receive what they legitimately deserve.

Today, we talk a lot about the Kerala

model of health care. It is often touted

as a runaway success story and a great

model which others can look to emulate.

When you look at the success of Kerala’s

well-touted healthcare model, you will

find that it is no one else, but the doctors

who are the real architects and who

made the model a resounding success. It

was the doctors who dared to go to the

Very few people know that it was

Dr Rustom Jal Vakil, a cardiologist

from Mumbai, who pioneered the

use of reserpine for hypertension.

It was the first-ever medicine to be

used against hypertension.

Prof K Rajasekharan Nair

PHOTO: SHIJITH SREEDHAR

far-off hinterlands, the remotest villages;

they were the ones who crossed rivers,

traversed forests and climbed hills to reach

out to communities living in the far-off

locales to make it happen and came back

afflicted with endemic diseases like malaria

and filariasis...

But the credit for the success went to

the so-called planners of the programme.

Again, very few people know that it

was Dr Rustom Jal Vakil, a cardiologist

from Mumbai, who pioneered the use

of reserpine for hypertension. It was the

first-ever medicine to be used against

hypertension. Extracted from the roots of

Rouwolfia serpentina (Sarapagandha),

use of reserpine was popular in India as

a routine anti-hypertensive agent. At that

time, the West did not have any drug

treatment to lower blood pressure. They

regarded the condition as benign.

Vakil, in 1949, published the 1st clinical

report on R. serpentina therapy in the

British Heart Journal. The article really

fired the imagination of the international

FEBRUARY 2019 / FUTURE MEDICINE / 37


esearch community. In his paper, Vakil

summarized 10 years of his experience

with Rauwolfia. After an extensive trial of

various hypotensive remedies in thousands

of cases of hypertension, Vakil found

Rauwolfia to be the most consistently

successful agent. In addition, Vakil sent

a questionnaire to 50 physicians from

all over India, and 46 of those voted for

Rauwolfia as the best hypotensive agent in

their experience.

A well-known neurologist and

academician, you are also renowned for

your writings. Your first published fiction

was a novel. How do you eminently

combine these two diverse streams?

My first published novel ‘Oru Puzhayude

Katha’ (The Story of a River) was not pure

fiction. It is also a scientific novel. The

novel discusses the story of the decay of

a river called Chaliyar river, which was the

bloodstream serving a large number of

villagers in a northern part of Kerala. An

industrial unit in the locale was polluting the river and its

environment with its effluents. It was affecting the lives of

so many poor people living on the banks of the river. For

me, the issue was so compelling. I wanted to write about

it but I was not finding time because of my extremely busy

schedule. In those days, as the head of the department

of neurology at Medical College Hospital, Trivandrum my

routine started in the early morning hours and ended late in

the night.

Fortunately, I chanced to get the time to write the book

while in Libya where I was assigned with the responsibility

of setting up a department of neurology at Garyounis

University, Benghazi... The Libyan authorities took nearly

three weeks to arrange the necessary facilities for me. I

managed to complete the novel within this time gap. Oru

Puzhayude Katha, which was published in 1979, was the first

environmental novel in the Malayalam language. I am not

sure how many people are aware of this fact.

Are you working on any new books presently?

Yes. My latest book is currently in print. It is written in

Malayalam and is expected to be published in the next two

months’ time. The title of the book is ‘Munpe Nadannavar’

(Those Who Walked Ahead). For a change, it is a homage

to my contemporaries, but is also the story of disregard and

neglect. You know, the person who brought neuroscience

to India is a Keralite. His name is Dr Jacob Chandy. He was

living for fifteen years in Kottayam totally unheard of. And

he died there, unknown, forlorn. Nobody, not even anyone

from the medical community, bothered to take care of him,

the great man. The only mistake he did was that he decided

to come back and settle in his homeland. I discussed his

case among our circle. Many of them didn’t even know him.

Since I am the only person who is alive today in the clan and

the only one who can write, I thought it is my duty to pay

homage to that great man.

And the second book that I am working currently on is

about how we understand our perception or experience and

how they can turn, what should I say, faulty? The book has

these ‘faulty’ perceptions and sensations people experience

as its theme. For instance, if you drop a pen before some

of my patients, they will get absolutely frightened. They will

think that it is a snake or something, and will try to wriggle

out of the situation and run away... I thought of the idea of

putting together the cases of these ‘faulty’ sensations. To

achieve this, one needs deep knowledge in the subject. And

secondly, the person should know how to write. Among the

doctors’ fraternity, I don’t see anybody else who can write.

So, again I thought I should do it.

What would you prefer to be known as — a neurologist

or as a writer?

A neurologist. Till the end of my life.

I started teaching neurology even before I joined for

38 / FUTURE MEDICINE / FEBRUARY 2019


PHOTO: SHIJITH SREEDHAR

my DM. In hindsight, when I look back

sometimes, I feel some of my decisions

were not proper. For one, I used to teach

post post-graduate students. A few batches

passed through my hands. In between,

I happened to teach two batches of

undergraduate students. That was purely

out of compulsion by someone whom I

cannot say no to. Then I stopped it as I was

not able to find enough time. But when I

look back at those jam-packed classrooms

which seemed to swell each day, I feel that I

should have done more. I realize there is an

advantage of teaching MBBS students. There

is a large number of students with fresh

minds. They also imbibe and absorb things

much faster...

And the second thing is about not

participating in public functions. As a rule, I

never attended any public meetings. Now, I

see there are so many people around who

would like to listen to speeches. There are

very many who would love to read books.

When I published a book that comes around

1000 pages and cost nearly 900 rupees, it

got sold out like anything in a short time.

I have been

writing since

my childhood.

Everything can

be made a story.

Probably, that is

what a raconteur

does...

Now the second edition is being printed...

But I am exceedingly happy with what I am

doing.

So, your practice, teaching and writing

will all go hand in hand...

I have been writing since my childhood.

Everything can be made a story.

Probably, that is what a raconteur does...

I am teaching my favourite subjects

— movement disorders and cognitive

neurology. And I am practising neurology

even today, even though [it is] for select

patients who come seeking me. Touch

wood, I can say I am very old. It is because

of nothing but God’s grace. A lot many in

my generation have passed away. Many

others are sick. Most of them stopped

working. I have my own problems too, but

still, I keep going. I keep myself awake till

late in the night... studying neurology...

All I wanted to say is that there

exists a power beyond the limits of our

comprehension. To deny it is fashion. Deny

it or not, without the power, we are but a

big zero.

FEBRUARY 2019 / FUTURE MEDICINE / 39


case reports

CYST OR CYSTICERCUS?

Brain infections caused by

tapeworm larvae are

not uncommon in India

Rajesh (name changed), a 10-year-old boy from

Kolhapur, was a studious kid. However, lately, he

had started reading his books while lying down.

His father, who was the principal of a local school, was

unhappy seeing these reading habits and would keep

nagging his son to sit in an appropriate upright position

while reading. Rajesh, however, would get headaches

while reading in a sitting position and for the past

month or two, he was able to read for longer

periods without a headache only if reading while

lying down on his back. The arguments continued

between father and son for several months until

Rajesh’s condition worsened, and his headaches

become more severe and accompanied with vomiting

and visual blurring. Rajesh’s father then realized there

may be more to his reading habits and had to seek

medical advice from a paediatrician. The paediatrician

recommended an ophthalmic checkup and a CT scan of the

brain. Funduscopic examination revealed papilledema and

the CT scan showed a cyst in the third ventricle. Rajesh was

then referred to Dr Uday Andar, a paediatric neurosurgeon at

Bombay Hospital, Mumbai, for further management.

Dr Andar recommended an MRI brain scan which showed a

pedunculated cyst within the third ventricular cavity. Surgery

40 / FUTURE MEDICINE / FEBRUARY 2019


was immediately scheduled, and the cyst was excised micro

endoscopically without any complications.

Interestingly, the cyst turned out to be cysticercus.

Cysticercus is a tapeworm belonging to the genus Taenia.

They look like a small sac-like vesicle similar to a bladder.

These tapeworms commonly reside in the muscles of pigs

and cattle and their eggs are typically ingested with raw or

undercooked contaminated pork or beef or through raw

contaminated vegetables in salads. The eggs hatch inside

the human host and can move anywhere in the body via

the bloodstream, including the brain. Brain infections can be

especially dangerous as they may lead to neurocysticercosis,

which is one of the major causes of acquired epilepsy.

Depending on the location of the cyst in the brain, it

may even result in death in case of high pressure due to

hydrocephalus. Cysticercus is likely to be present at multiple

locations, and upon further investigation, Rajesh was found

to have cysticercus in the leg calf muscles as well. This is

typically visualized as lumps under the skin.

Because of the pedunculated nature of the cyst in the

third ventricle of the brain, whenever Rajesh would sit and

bend forward to read, the foramen of Monro would get

blocked and cerebrospinal fluid would collect

in the ventricles increasing the intracranial

pressure and causing headaches. Whenever

Rajesh was in a supine position, the cyst

would move backwards and the block would

be released, allowing the cerebrospinal fluid

to flow freely and relieve the headache. For

Rajesh, this condition worsened as the cyst

enlarged, and finally, when the cyst was large

enough to block the ventricles, it resulted

in hydrocephalus and consequently visual

blurring. Had it been left untreated much

longer, it could have resulted in death due to

the increase in intracranial pressure.

Cysticercus is not uncommon in India,

especially in a city like Mumbai, where

vegetables are grown along the railway

tracks and exposed to all sorts of human and

animal excreta. Dr Andar advocates that both

vegetables and meats be thoroughly cleaned

and cooked well before being consumed.

WHENEVER THE BOY WOULD

SIT AND BEND FORWARD TO

READ, THE FORAMEN OF MONRO

WOULD GET BLOCKED

Often, early diagnosis is missed in

children, either because the child does

not complain, or the parents ignore minor

complaints until the condition worsens.

Dr Andar advises that ‘children complaining

of headaches for more than 7-10 days be

carefully investigated. Though there is no

literature to support this, clinical experience

teaches one to be more prudent than sorry

and investigate such children early on.’

With the current technological advances

in the field of non-invasive investigations

such as CT scans and MRIs, it is definitely

advisable to investigate early and thereby

prevent catastrophes and the risk of high

morbidity. In Rajesh’s case, it turned out to

be a cysticercus. However, it could have been

a tumour. Early diagnosis and treatment is

essential in such cases.

DR SHIVANEE SHAH

42 / FUTURE MEDICINE / FEBRUARY 2019


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FEBRUARY 2019 / FUTURE MEDICINE / 43


case reports

A HARROWING SWALLOW

Aspirated foreign bodies should be considered as a differential in any

young child with unexplained cough

Small children, especially those younger than 3 years,

are prone to putting small objects in the mouth. With

their limited chewing capabilities and high respiratory

rates, these objects are inadvertently swallowed in. Further

their tendency to laugh and run around while eating also

increases the chances of the object being aspirated into the

trachea. Most often these are food items. However, it is not

uncommon for children to explore non-food items, resulting in

the aspiration of foreign bodies. Some of the most commonly

found non-food items include small toys and jewelry.

Aspirated objects have the propensity to get lodged in the

right bronchus as it is wider and has more direct extensions

from the trachea.

Clinical presentation may be extremely variable depending

on the location of the aspirated object. Most often, the child

experiences sudden coughing bouts or choking. In worst

cases, if the object is large and causes a total or near-total

occlusion of the airway, it can result in death or hypoxic brain

damage. However, the more difficult and tricky cases are the

ones in which the aspiration goes unnoticed and the child

may present with persistent or recurrent coughing bouts,

pneumonia or lung abscess.

Diagnosis can be made through one of several imaging

methods. The first test is typically a chest X-ray, using

anteroposterior and lateral films. Food objects are radiolucent

and may, therefore, be difficult to visualize via radiography.

However, in case of suspicion of foreign

body aspiration, radiologists often look for

an area of focal over-inflation or an area

of atelectasis, depending on the extent of

the airway blocking. In case of a normal

chest X-ray, other imaging techniques such

as computed tomography and magnetic

imaging may be explored to determine the

position of the foreign body. Non-invasive

methods such as computed tomography

with virtual bronchoscopy can be performed

IN CASE OF SUSPICION OF

FOREIGN BODY ASPIRATION,

RADIOLOGISTS OFTEN LOOK

FOR AN AREA OF FOCAL

OVER-INFLATION

in cases of sharp objects that have a high risk

of damaging the lung.

Once the location is identified, it is

imperative to remove the foreign object

to avoid further complications. Rigid

bronchoscopy under general anaesthesia is

the procedure of choice for removing objects.

Bronchoscopic removal may fail in case of

peripheral location or technical difficulties.

In such cases when the foreign body

cannot be grasped by endoscopic forceps,

bronchoscopy should be abandoned, and

an open surgical procedure or thoracotomy

should be considered.

Here is a case of a 5-year-old female

child who had swallowed an LED bulb with

two small, sharp metal prongs. She was

immediately taken to a local hospital where

a chest X-ray revealed the position of the

bulb in the left thoracic cavity. No foreign

body was found in an upper gastrointestinal

44 / FUTURE MEDICINE / FEBRUARY 2019


endoscopy. A bronchoscopy under general anaesthesia was

attempted to remove the bulb. However, this procedure

had to be abandoned due to

bleeding. Post bronchoscopy,

the child went into asystole

and required cardiopulmonary

resuscitation. She was kept

on mechanical ventilation and

inotropic support overnight in

a cardiac intensive care unit for

12 hours until she stabilized.

She was then transferred

to a specialized center for

further management and

referred to Dr Rajeev Redkar,

THE LED BULB APPEARED

TO BE EMBEDDED IN

THE LUNG PARENCHYMA

AND THE PATIENT

WAS PREPARED FOR A

THORACOTOMY

consulting paediatric surgeon. A chest computed tomography

with virtual bronchoscopy was done to visualize the foreign

body and the location was confirmed to be in the left lower

bronchus. The LED bulb appeared to be embedded in the

lung parenchyma with the prongs only partially in the airway

and the patient was prepared for a thoracotomy. Due to

its close proximity to the heart and major vessels, General

Dr V Ravishankar, a cardiothoracic surgeon, was consulted.

Dr Minhaj Sheikh, a consultant paediatric intensivist, was

also part of the medical team. Left lower bronchus was

identified and opened minimally. The foreign body was

carefully removed and the incision closed

with interrupted non-absorbable sutures.

The procedure was completed without any

bleeding and complete expansion of the

left lower lobe was confirmed post foreignbody

removal. An intercostal drain was

kept in place for 2 days post surgery. The

patient was kept on orals for 24 hours and

discharged within 4 days.

It was a harrowing experience for the

child and her family.

This is the primary reason for the alert

on toys with small parts: “Not suitable for

children under 3”. However, 3 is not a magic

age and older children also put objects in

the mouth with devastating consequences.

Aspirated foreign bodies should be

considered as a differential in any young child

with an unexplained cough, and Dr Redkar

cautions that the medical team should

also consider the potential risks involved

during and after bronchoscopy in case of

tracheobronchial foreign body aspirations.

DR SHIVANEE SHAH

FEBRUARY 2019 / FUTURE MEDICINE / 45


case reports

WOLFRAM AND A DEVICE

How continuous glucose monitoring tech came to the rescue of

a complicated genetic condition

A

25-year-old male patient presented with repeated

episodes of loss of consciousness and seizures. These

episodes were associated with hypoglycemic events,

especially at night. The patient and his family were extremely

worried and consulted with Dr Arun Menon, Endocrinologist,

Amrita Institute of Medical Sciences, Kochi. The patient had

type 1 diabetes since childhood, progressive deafness, and

was visually impaired. He had been previously diagnosed with

Wolfram syndrome type 1.

Wolfram syndrome is characterized by juvenile onset

diabetes mellitus and optic atrophy. It is primarily an

autosomal recessive inherited disorder that affects 1 out

of 100,000 to 1 out of 770,000 individuals worldwide.

Because of the associated neurodegenerative presentation,

it is also referred to by the acronym, DIDMOAD (diabetes

insipidus, diabetes mellitus, optic atrophy and deafness).

Often, a variety of other symptoms may

also be associated, such as ataxia, seizures,

depression, gastrointestinal problems, sleep

conditions, autonomic neuropathy etc..

Depending on the genetic mutation,

Wolfram syndrome can be type 1, caused

due to mutations in the WFS1 gene, or type

2, caused due to mutations in the WFS2

or CISD2 gene. WFS1 gene encodes for the

protein wolframin, which plays a role in

protein folding by regulating calcium levels

in the endoplasmic reticulum of cells. In

the pancreas, it is specifically important for

folding of the proinsulin protein. In the inner

ear, it is required for maintaining calcium

levels essential for hearing. Mutations in

46 / FUTURE MEDICINE / FEBRUARY 2019


adapted exceptionally well and managed to

regularize his life style as well as his glucose

levels with the help of the pump. This HbA1c

levels improved from 13% to 8.2% between

June 2017 to February 2018.

To ensure appropriate glucose monitoring

in addition to insulin delivery, the patient was

started on a continuous glucose monitoring

system. This is a cell phone app based realtime

glucose monitoring system that provides

continuous interstitial glucose profiles

directly on the cell phone. This system sends

regular alerts on the cell phones based

app, effectively preventing hyperglycemic or

hypoglycemic episodes and allowing for even

better glucose level control. Other benefits of

using such a continuous monitoring system

include a reduction in checking interstitial

glucose to twice a day only, and that too only

wolframin result in improper functioning of the endoplasmic

reticulum, and consequently, cell death. Prominently, insulinproducing

beta cells are affected, which results in diabetes

mellitus; and a gradual loss of the cells and the optical nerve

eventually results in blindness. Cell death in other organs may

cause a variety of other signs and symptoms associated with

Wolfram syndrome.

Currently, there is no cure for this syndrome and longterm

prognosis is completely dependent on the affected

organs. Several therapeutic options, including drugs that can

balance calcium levels in the ER or improve protein folding

and trafficking in the ER, and stem cell therapy to regenerate

the destroyed cells are being explored. However, as of now,

treatment is only supportive and based on the symptoms in

each individual. Most individuals with Wolfram syndrome have

an average lifespan of only 30-40 years.

The patient and his parents were extremely worried

because of the nocturnal hypos which significantly affected

their quality of life. The patient was already being treated with

multiple daily injections of insulin. However, this treatment

was not effective and resulted in unpredictable episodes of

hyperglycemia and hypoglycemic without any recognizable

warning signs. The patient was consequently afraid of taking

the insulin as the effect was unpredictable and even small

doses could result in dangerous hypos. To provide a more

continuous treatment strategy, Dr Menon started him on an

insulin pump. The continuous subcutaneous insulin infusion

(CSII) allows for constant, continuous infusion of insulin under

the skin. The insulin pump was effective in immediately

stabilising the glucose levels. However, a major concern was

whether the patient would be able to manage the pump with

his visual and hearing impairment. Surprisingly, the patient

THE PATIENT WAS AFRAID OF

TAKING THE INSULIN AS THE

EFFECT WAS UNPREDICTABLE

AND EVEN SMALL DOSES COULD

RESULT IN DANGEROUS HYPOS

for calibration purposes. As of September

2018, the patients HbA1c levels were at 7.3%.

While these are still higher than normal,

they are much improved compared to a year

ago, and the patient is able to manage his

glucose levels much more effectively and is

witnessing far fewer hypoglycemic episodes.

While diabetes and related conditions

are dramatically increasing worldwide,

technology is also advancing by leaps and

bounds. Several monitoring and drug delivery

devices are available now, even as others are

in the pipeline, to make it simpler to control

diabetes and continue retaining good quality

of life. Dr Menon is optimistic for the future:

“With the technological advances, it is now

possible to get real-time glucose profiles for

a better understanding of how glucose levels

fluctuate in each individual, and treatment

should be tailored accordingly.”

DR SHIVANEE SHAH

FEBRUARY 2019 / FUTURE MEDICINE / 47


esearch snippets

Light-emitting

implant to control

overactive bladder

Aaron D. Mickle et al have developed

a miniaturized, implantable device

that could potentially help people with

bladder problems in providing chronic

stability by stimulating specific cell types.

The soft bio-optoelectronic implant can

detect overactivity in the bladder and

use light from tiny bio integrated LEDs

to tamp down the urge to urinate. The

researchers had conducted the study

on a rat model where the soft stretchy

belt-like device was implanted around

the bladder. Light-sensitive protein,

opsins, were injected into the bladder.

The opsins were carried by a virus that

binds to nerve cells in the bladder,

making them sensitive to light signals.

The activity of the bladder could be

controlled using an external hand-held

Bluetooth device. During abnormally

frequent emptying of bladder, the

external device can send a signal that

activates the micro-LEDs on the device,

which activates the sensory neurons

in the bladder, thus restoring normal

bladder activity. Unlike conventional

continuous stimulation protocols,

this integrated closed loop operation

essentially delivers therapy only when a

problem is detected, avoiding discomfort

and pain. Though the stable expression

of opsin using the viral approach is still

a concerning issue, researchers hope

to soon develop it to help people who

suffer from severe bladder problems.

Source: Nature volume 565, pages361–365 (2019)

Published: 02 January 2019 https://www.nature.

com/articles/s41586-018-0823-6

Sexism among brain

tumours

Yang et al. showed a significant

role for sex difference among

patients of aggressive brain tumour

glioblastoma, marking the need to

optimise the therapeutic regimen for

each patient. The research identified

a remarkable distinction in molecular

subtyping among glioblastoma of

male and female patients, indicating

the need to stratify the tumours for

effectiveness of treatment in a sexspecific

manner. The researchers

performed a quantitative imagingbased

measure of response among

the patients using MRI scans

and survival data from a cancer

research database. The cohort of

63 patients involved 40 males and

23 females who received standard

chemotherapy. While initial tumour

Candida infections

in brain may impair

memory

Yifan Wu et al reported that the

common yeast Candida albicans

could cross the blood-brain barrier to

trigger inflammatory response leading

to the formation of granulomatous

growth velocities were the same, only

female patients showed a steady and

significant decline in tumour growth.

On the application of sophisticated

statistical algorithms, the difference

in molecular subtypes among males

and females were identified, revealing

that their survival was driven by very

different molecular pathways. The

study thus suggests that greater

precision in glioblastoma molecular

subtyping can be achieved through

sex-specific analyses. The researchers

suggest that a personalised approach

in treatment would greatly improve

outcome for the patients in the future.

Source: Science Translational Medicine 02

Jan 2019: Vol. 11, Issue 473, eaao5253

DOI:10.1126/scitranslmed.aao5253 http://stm.

sciencemag.org/content/11/473/eaao5253

structures and mild memory impairment.

The study reveals a resemblance

between the granuloma-type structures

with plaques found in Alzheimer’s

disease. The researchers injected a

dose of 25,000 C. albican cells into a

mouse model. The yeasts showed to

cross the blood-brain barrier triggering

the microglia. They also produced a

number of molecules that mediated

inflammatory response. This led to

48 / FUTURE MEDICINE / FEBRUARY 2019


capture of yeasts within a granule-type

structure in the brain called fungusinduced

glial granuloma (FIGG). Resultant

accumulation of amyloid precursor

protein within the periphery of the

granuloma revealed the possibility for

fungal involvement in the development

of neurodegenerative diseases. The

mice cleared the infection in 10 days

leaving active microglia and FIGG for

about 21 days. They also displayed mild

memory impairment that resolved with

fungal clearance. The research supports

a need for future studies on long-term

neurological consequences of sustained

C. albican infection.

Source: Nature Communications, Volume 10,

Article number: 58 (2019) Published: 04 January

2019 https://www.nature.com/articles/s41467-

018-07991-4

Inhalable mRNA offers

new therapeutic

delivery to lungs

Asha Kumari Patel et al developed

an effective method for nebulized

delivery of in vitro mRNA providing

a clinically relevant delivery system

to lung epithelium. The delivery was

facilitated by hyperbranched poly

beta-amino esters (hPBAEs) vectors.

Unlike previously used carriers, hPBAEs

are positively charged biodegradable

polymers. hPBAE protects the mRNA

from degradation during inhalation

and ensures their proper entry into

the lungs. The researchers produced

protein encoding inhalable mRNA in a

suspension from within nanoparticle

spheres. The mice used in the study

were allowed to inhale the droplet

suspension as mist via nebulizer. It

induces the production of luciferase

protein 24 hours after inhalation of

hPBAE. Repeated inhalations helped

maintain a steady concentration of the

bioluminescent protein within the lungs.

The study reveals the therapeutic utility

of the innovation which could help treat

a range of lung diseases.

Source: Advanced Materials 2019, 180511604

January 2019 https://doi.org/10.1002/

adma.201805116

—Compiled by Divya Choyikutty

Closed-loop neuromodulation

device to stimulate brain

Andy Zhou et al demonstrated a wireless artefactfree

neuromodulation device -WAND that could help

treat various neurological disorders. Using a closed-loop

neuromodulation system WAND can record as well as

stimulate over 128 channels in the brain with the ability

to fully cancel the stimulation. The device is currently

experimented in a rhesus macaque in delaying specific arm

movements. WAND can record abnormal electrical activity

in diseases such as epilepsy and regulate the stimulation

to counteract the electrical signals of the brain. This could

help patients overcome tremors and other movement

disorders. Researchers suggest that the ability to actually

stimulate and record in the same brain region could

help provide effective therapy in a variety of neurological

conditions in the future. WAND can be used as a generalpurpose

research tool for preclinical investigations of

stimulation-based therapeutic interventions and variety of

other applications with minor modifications.

Source:Nature Biomedical Engineering Volume 3, pages15–26 (2019) 31

December 2018 https://www.nature.com/articles/s41551-018-0323-x

50 / FUTURE MEDICINE / FEBRUARY 2019


column

the cellview

Need for alternative

technologies

Why reducing sequencing costs may not be a complete

answer to increasing genome-wide studies

DR RAJANI KANTH

VANGALA

The author is medical

scientist and former

director of SGRF,

Bangalore

There has been a significant

advancement in genomic sequencing

technologies with the inception of

NextGen Sequencing. However, in India

and South Asia, there is a lack of largescale

studies with long-term follow up to

understand if there are any South Asian

or India-specific genetic markers. The

biomarker discovery is largely dependent

on biospecimen collection and storage.

Even though sequencing costs are

coming down, the biospecimen collection,

processing, transport and storage systems

have remained very complex and costly.

The present-day collection systems are not

aimed at a single collection plus storage;

therefore, processing the collected samples

is a necessary step. In many studies which

involve collecting samples from different

centres, it will involve transportation of the

samples on dry ice. Furthermore, after the

samples are received, they need immediate

transfer into liquid nitrogen tanks or into

deep freezers. Long term maintenance of

these storage systems is a costly affair.

Therefore, a long-term accessible

biorepository is a major bottleneck for

such important studies as all biomarkers

will need careful evaluation and validation

before translating them into clinical practice.

I have been in the field of biomedical and

biomarker translational research for more

than two decades. In my experience, apart

from other factors, a proper biorepository

with low-cost maintenance is of high

importance, with special emphasis on low

cost. In my previous organization, a largescale

clinical biomarker study was started.

With a lot of effort from several clinical

and scientific groups, more than 12,000

biospecimens were collected over a decade.

However, these samples were extremely

difficult to maintain due to the spiraling costs

of maintenance of freezers, manpower and

power. Therefore, it became very evident

that if we were to conduct any meaningful

genomic studies, we need alternative

technologies which can truly help research

and reduce the costs.

The molecular diagnostics market is

expanding at a good pace, but if we are to

make the genome more amenable for regular

diagnostics, it is very important to reduce

costs and develop technologies for the

Indian community. At the same time, these

technologies should always be compared

to existing methods and must be validated

for several downstream applications. Apart

from different applications, the suitability to

different tissue types is also very important

as specific tissues need preservation. An ideal

technology will be that which can be used

to collect the biospecimens, and without any

major processing, can be used for long-term

storage at room temperature or ambient

temperature. This technology can truly bring

a revolution in the progress in genomic

studies in India and enable sequencing

research and diagnostics to be carried out

more robustly. Our new institute, Institute for

Applied Research and Innovation (InARI), has

been working on such a technology called

“Insta-Preserve RT”, which we are now ready

to bring into the market.

52 / FUTURE MEDICINE / FEBRUARY 2019


disease

INDIA’S CANCER

BURDEN

Cancers contributed 5% of the total

disabilities and 8.3% of all deaths in

India in 2016, shows a state-wise study

The number of cancer-related

deaths in India more than doubled

between the years 1990 and 2016,

according to a paper titled “The Burden

of Cancers and Their Variations Across

the States of India: The Global Burden

of Disease Study 1990–2016” published

in the October 2018 edition of Lancet

Oncology.

The paper gives a comprehensive

summary of the patterns and time

trends of the total cancer burden as

well as specific cancer types

in each state of India

estimated as a

The crude cancer

incidence rate in

India increased by

28.2%

part of the Global Burden of Diseases,

Injuries, and Risk Factors Study (GBD)

2016. The article was authored by a

group called ‘India State-Level Disease

Burden Initiative Cancer Collaborators’.

Setting

Though there have been previous

attempts to review the estimates of

cancer incidence and mortality in India

and its different regions, the present

article presents a comprehensive report

of the patterns and time trends.

54 / FUTURE MEDICINE / FEBRUARY 2019


Methodology of the study

Data from multiple sources, including 42

population-based cancer registries and

the national sample registration system

of India was used. The study presents

data on:

1 The incidence of 28 types of cancer

in every state of India from 1990 to

2016

2. Death rates and trends of all

types of cancers

3. Disability-adjusted life years

(DALYs) for each type of

cancer

4. The contribution of

major risk factors

to the cancer

DALYs in

India

Rajasthan

58.8

72.6

Haryana

71.0

103.3

Himachal

Pradesh

69.8

91.6

Punjab

58.0

85.5

Jammu &

Kashmir

69.1

79.2

Delhi

64.6

102.9

Uttarakhand

69.3

91.0

Uttar Pradesh

72.0

79.0

Bihar

44.9

53.9

RISING NUMBERS

Crude annual incidence

rate of all cancers together

in the states of India,

1990 and 2016

1990 2016

Jharkand

58.0

64.3

Arunachal

Pradesh

75.9

78.5

Meghalaya

69.0

81.4

Sikkim

67.8

74.4

Tripura

52.9

69.0

Assam

68.7

90.2

Nagaland

63.1

70.3

DALY (Disability Adjusted

Life Years)

Madhya

Pradesh

69.4

83.1

Gujarat

55.5

75.8

It is a metric for reporting the

disease burden due to mortality

and morbidity caused by a disease.

It is the measure recommended by

the National Health Policy of India for

tracking disease burden. Disability for

each cancer was estimated by splitting

the prevalence into four sequelae:

diagnosis and primary treatment,

controlled phase, metastatic phase and

the terminal phase. Each prevalence

sequelae were then multiplied with

specific disability weights to see the

‘years lived with disability’ (YLDs). The

years of life lost (YLLs) was calculated

from the age-specific mortality estimates

and the reference life expectancy for

that age group. DALYs were computed

Maharashtra

62.0

80.2

Goa

52.5

97.0

Karnataka

76.2

101.6

Kerala

74.1

135.3

Andhra

Pradesh

58.1

76.6

Tamil Nadu

58.9

82.9

Telengana

54.9

72.6

W Bengal

63.9

85.4

Chhattisgarh

58.8

82.0

Odisha

68.6

83.6

Incidence

rate per

100,000

Mizoram

89.1

121.7

Manipur

48.1

64.3

> 105

90-104.9

75-89.0

60-74.9

45-59.9

SOURCE: thelancet.com

FEBRUARY 2019 / FUTURE MEDICINE / 55


as the sum of YLLs and YLDs, for each

type of cancer for the location, year, age

and sex.

The data is reported for 31

geographical units in India, including 29

states, Delhi and union territories other

than Delhi.

Summary of the Results: The

article states that all cancers together

contributed 5.0% of the total DALYs

and 8.3% of the total deaths in India in

2016, an increase of 90.9% and 112.8%

respectively from 1990. The highest crude

cancer DALY rates in 2016 were in the

states of Mizoram, Kerala, Assam, Haryana

and Meghalaya. The estimated number of

incident cancer cases in India increased

from 548,000 in 1990 to 1,069,000 in

2016. The crude cancer incidence rate in

India increased by 28.2% from 63.4 per

THE CRUDE CANCER

INCIDENCE RATE WAS THE

HIGHEST IN KERALA AND

MIZORAM

100,000 in 1990 to 81.2 per 100,000 in

2016. The crude cancer incidence rate

was the highest in Kerala and Mizoram,

followed by Haryana, Delhi, Karnataka,

Goa, Himachal Pradesh, Uttarakhand and

Assam.

The number of deaths due to cancer

in India increased from 382000 in 1990

to 813000 in 2016. The crude cancer

death rate in India in 2016 was 61.8 per

100,000, as compared with 44.2 in 1990.

The cancer types responsible for

more than 5% of the total cancer DALYs

among both sexes combined in 2016

were stomach cancer (9.0%), breast

cancer (8.2%), lung cancer (7.5%), lip

and oral cavity cancer (7.2%), pharynx

cancer other than nasopharynx (6.8%),

colon and rectum cancer (5.8%), leukemia

(5.2%), and cervical cancer (5.2%).

Stomach cancer was responsible for the

highest DALYs among all cancers in India

in both 1990 and 2016. Among females,

CHANGE IN DALYS FOR DIFFERENT TYPES OF CANCERS IN INDIA,

1990–2016

Type of cancer 2016 1990 Change

Stomach cancer

Breast cancer

Lung cancer

Lip and oral cavity cancer

Pharynx cancer other than nasopharynx

Colon and rectum cancer

Leukaemia

Cervical cancer

Oesophageal cancer

Brain and nervous system cancer

Liver cancer

Non-Hodgkin’s lymphoma

Gallbladder and biliary tract cancer

Larynx cancer

Pancreatic cancer

Ovarian cancer

Prostate cancer

Bladder cancer

Nasopharynx cancer

Thyroid cancer

Myeloma

Hodgkin’s lymphoma

Uterine cancer

Kidney cancer

Mesothelioma

Malignant skin melanoma

Testicular cancer

Non-melanoma skin cancer

SOURCE: thelancet.com

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

21

22

23

24

25

26

27

28

1

4

7

5

6

8

3

2

9

11

15

12

14

10

16

17

20

22

18

19

23

13

21

25

26

27

24

28

36.2%

114.9%

136%

102.9%

106.1%

109.6%

35%

21.6%

59.3%

85.2%

206.1%

133.9%

169.4%

40.5%

122.6%

157.2%

140.3%

104%

29.1%

36.8%

158.5%

-30.3%

37.5%

124%

126.6%

110.7%

-29.8%

90.2%

56 / FUTURE MEDICINE / FEBRUARY 2019


CHANGE IN INCIDENCE RATE

Type of cancer 2016 1990 Change

Breast cancer

1 4 188.3% 89.2%

Lip and oral cavity cancer

2 3 95.9% 28.5%

Cervical cancer

3 1 19.7% -21.4%

Stomach cancer

4 2 23.7% -18.8%

Lung cancer

5 6 116% 41.8%

Pharynx cancer other than nasopharynx 6 5 104.8% 34.4%

Colon and rectum cancer

7 7 128.6% 50%

Oesophageal cancer

8 8 43.9% -5.5%

Leukaemia

9 9 33% -12.7%

Prostate cancer

10 17 221.2% 110.8%

Larynx cancer

11 10 45.6% -4.5%

Liver cancer

12 15 178.6% 82.9%

Gallbladder and biliary tract cancer 13 14 138.7% 56.7%

Ovarian cancer

14 18 165.5% 74.2%

Non-Hodgkin’s lymphoma

15 16 138.5% 56.5%

Brain and nervous system cancer 16 11 76% 15.5%

Pancreatic cancer

17 13 99.1% 30.6%

Non-melanoma skin cancer

18 12 89.8% 24.6%

Thyroid cancer

19 21 171.7% 78.4%

Bladder cancer

20 22 153.7% 66.5%

Uterine cancer

21 23 121.6% 45.5%

Kidney cancer

22 24 160.8% 71.2%

Nasopharynx cancer

23 20 25% -17.9%

Mutiple Myeloma

24 25 148.9% 63.4%

Hodgkin’s lymphoma

25 19 -26.1% -51.5%

Malignant skin melanoma

26 28 175.9% 81.1%

Testicular cancer

27 26 20.4% -21%

Mesothelioma

28 27 101.5% 32.2%

breast, cervical, and stomach cancer were

responsible for the highest DALYs in 2016.

The highest cancer DALYs among males in

India in 2016 were lung cancer, followed

by lip and oral cavity cancer, other pharynx

cancer and stomach cancer.

Among these cancers, the agestandardised

incidence rate of breast

cancer increased significantly by 40.7%

from 1990 to 2016, whereas it decreased

for stomach (39.7%), lip and oral cavity

cancer (6.4%), cervical cancer (39.7%),

oesophageal cancer (31.2%) and leukaemia

(16.1%). The study found substantial

inter-state heterogeneity in the agestandardised

incidence rate of different

types of cancers in 2016, with 3.3 times

to 11.6 times variation for the four most

frequent cancers (lip and oral, breast, lung,

and stomach).

Tobacco use, alcohol use and dietary

risks were estimated by GBD to contribute

to the highest cancer DALYs in 2016: They

were responsible for 10.9%, 6.6% and 6.0%

of the total cancer DALYs, respectively.

Tobacco use was the leading factor.

Summary

The authors interpret the study finding

by concluding that the data should be

used to strengthen the infrastructure and

human resources for cancer prevention and

control at both the national and state levels.

Efforts should focus on the ten cancers

contributing the highest DALYs in India,

including cancers of the stomach, lung,

pharynx other than nasopharynx, colon and

rectum, leukaemia, oesophageal, and brain

and nervous system, in addition to those

of the breast, lip and oral cavity and

cervical cancer, which are currently the

focus of screening and early detection

programmes.

Source: https://www.thelancet.com/journals/

lanonc/article/PIIS1470-2045(18)30447-9/

fulltext

Reviewed by Dr Krishnakumar

Thankappan, Professor, Dept

of Head & Neck Surgery and

Oncology, Amrita Institute of

Medical Sciences, Kochi

drkrishnakumart@gmail.com

FEBRUARY 2019 / FUTURE MEDICINE / 57


onco surgery

NOVEL

58 / FUTURE MEDICINE / FEBRUARY 2019


SURGICAL OPTIONS

IN BREAST CANCER

Oncoplastic techniques like nipple sparing surgery and procedures to reduce

lymphedema are being explored currently in breast cancer surgery

DIANE M RADFORD

Nipple-sparing mastectomy

(NSM) in the United States was

first described by Drs.

Joseph Crowe and Randall Yetman of

the Cleveland Clinic (CCF) in

2004. Incision placement for the

procedure can be inframammary,

periareolar, lateral, upper outer

quadrant, lateral with a periareolar

extension, medial, and transareolar.

When the tumour is superficial in

location, preserving the skin anterior

to the tumor can compromise the

oncologic goal of clear margins. The

technique of Tumour Ultrasoundguided

Incision (TUGI) for NSM

developed by Dr Stephen Grobmyer

and colleagues at CCF overcomes this

problem.

The technique employs

intraoperative ultrasound to locate

the tumour and delineate the skin

overlying it. The incision is then based

on the tumour location, removing the

skin anterior to the tumour en bloc

with the NSM. This approach balances

oncologic safety and technical

outcomes.

Lymphedema is the nemesis of

axillary nodal surgery for breast cancer,

impacting patient quality of life and

resulting in significant functional,

Round

periareolar

Elliptical

periareolar

LYMPHEDEMA IS THE NEMESIS

OF AXILLARY NODAL

SURGERY FOR BREAST

CANCER, IMPACTING PATIENT

QUALITY OF LIFE AND

RESULTING IN SIGNIFICANT

MORBIDITY

psychological, and social morbidity.

Although the increased use of sentinel

node biopsy, either when nodes are

clinically negative, or following neoadjuvant

therapy (NAC), has resulted

in lower lymphedema rates, the rates

following full axillary dissection can be

up to 77%.

Techniques to reduce lymphedema

Inferior

extension

Lateral

extension

include axillary reverse mapping

(ARM), meticulous dissection of arm

lymphatics with loupe magnification,

microsurgical lymphaticovenous

bypass, and a triple mapping

technique following NAC which

incorporates Indocyanine Green (ICG)

fluorescence for sentinel node bypass.

Slides illustrating these techniques

were shown.

Dr Diane M Radford

MD, FACS, FRCSEd is

with Cleveland Clinic

Foundation, Ohio, USA.

She discussed the

advances in oncoplastic

surgery techniques

for breast cancer, and

surgical methods to

reduce lymphedema

in her presentation at

MVRCanCon, Kozhikode,

India, recently.

FEBRUARY 2019 / FUTURE MEDICINE / 59


hospital news

FICCI lauds move to accord

‘industry status’ to hospitals

The Federation of Indian Chambers

of Commerce and Industry (FICCI),

the largest business organisation

in the country, has welcomed the

government’s announcement of

according ‘industry status’ and support

for land acquisition, clearances and

funding to private hospitals to boost

expansion of healthcare infrastructure in

tier 2 and 3 cities.

“In India, a skewed distribution

of hospital beds, with their heavy

concentration in the metros, has long

been a challenge in reaching the last

mile with quality healthcare provision.

This opportune step by the government

strongly reinforces private healthcare

providers’ commitment towards

improving access to quality care,” said

Sangita Reddy, Senior VP, FICCI, and

Joint MD, Apollo Hospitals Enterprise Ltd,

in a media release.

In the last decade, 70% of the

new bed capacity additions were in

the private sector, which also caters to

70% of the in-patient and 60% of the

outpatient healthcare demand in the

country.

“The key to engage more private

healthcare organisations will be a viable

model for their sustainability,” said Brig

Dr Arvind Lal, Chair, FICCI Health Services

Sangita Reddy

Committee and CMD, Dr Lal Path Labs

Ltd. The new hospitals, which would

be mandated to be empaneled under

Pradhan Mantri Jan Arogya Yojana

(PMJAY), or Ayushman Bharat, should

be allowed to charge other patients

who can afford to pay as per market

rates, as the current PMJAY package

rates may not be sustainable to set up

and run operations in such locations, he

said.

Apart from aiding the expansion

of bed capacity, the new hospitals will

open avenues for employment in tier

2 and 3 cities in the healthcare sector,

FICCI said in the statement.

Paras opens

multi-specialty

hospital at Panchkula

Paras Healthcare has inaugurated a new,

232-bed multi-super-specialty hospital

in Panchkula, Haryana.

Paras Hospitals Panchkula will

provide comprehensive cancer care

facilities ranging from chemotherapy,

surgical oncology, radiation therapy and

nuclear medicine. Equipped with a PET

CT scan centre, radiation oncology

will include the latest third generation

technology of LINAC along with VMAT,

IGRT and IMRT.

The hospital will have 44 specialties,

including cardiology, cardiac surgery,

orthopaedics and joint replacement,

nephrology and kidney transplant, cancer

care, gastroenterology and GI surgery,

urology, neurology and neurosurgery.

Located near Nada Sahib Gurudwara,

this is Paras Healthcare’s second hospital

in the city after Paras Bliss which has been

providing specialized mother and child

care, reports said.

Manipal Hospitals launches lifesaving

care training for public

Aimed at creating awareness

and training people with lifesaving

techniques, Manipal Hospitals

Bengaluru organized ‘You can save life

anywhere’ campaign coinciding with

World Ambulance Day.

The campaign kicked off with

Manipal Ambulance Response

Services (MARS) ambulance rally to

spread the message of ‘Give Way

Save a Life’ to the public. The training

programmes for the public included

cardiopulmonary resuscitation (CPR)

and automated external defibrillator

(AED).

People can further avail these

training programmes across all the

hospitals of Manipal by booking via

the hospital’s website. The training will

be available every second Saturday of

the month. Initially, the hospital aims

to train people in batches starting

with admin staff of metro and malls

in Bengaluru, police, students and the

general public.

GPS-enabled MARS vehicles

are equipped with critical lifesaving

systems. Manipal’s fleet of ambulance

also has Central Monitoring System,

which relays images of patient

condition direct to Emergency

Response Centre.

60 / FUTURE MEDICINE / FEBRUARY 2019


policy

LOOPHOLES

IN THE LAW

Though a good initiative,

the Surrogacy Bill that was

passed in the lower house

of the Indian parliament is

lacking in many respects,

say experts

In a significant development, Lok

Sabha recently passed the muchawaited

Surrogacy (Regulation)

Bill 2016, which bans commercial

surrogacy in the country. The

Surrogacy Bill was introduced in

Lok Sabha in 2016 with an aim

to regulate surrogacy in India and

protect women from exploitation. The

bill is now in the Rajya Sabha for its

ratification. The government move

to ban commercial surrogacy in the

country came after reports of misuse

of women and campaigns against

commercial surrogacy by various

organizations.

India emerged as a favourite

surrogacy hub for couples across

the world over the years. There

were several incidents of unethical

practices, exploitation of surrogate

mothers, abandonment of children

born out of surrogacy and import

of human embryos and gametes.

The Law Commission of India had

also recommended the prohibition

of commercial surrogacy through

legislation as lack of legislation

had resulted in a huge increase in

commercial surrogacy and widespread

unethical practices in the area of

surrogacy. The bill, which proposed

62 / FUTURE MEDICINE / FEBRUARY 2019


AUGUST 2018/ FUTURE MEDICINE / 85


anning of commercial surrogacy,

however, allowed altruistic surrogacy.

Who is a ‘close relative’?

Dr Ranjana Kumari, Director, Centre

for Social Research, said, “A few

years ago we conducted researches

in places such as Jamnagar, Surat,

Bombay, Delhi and Hyderabad, where

commercial surrogacy is prevalent.

As part of the study, we consulted

stakeholders, including surrogate

mothers, and it was found that

women are indiscriminately exploited.

In the report we submitted to the

Union government, we suggested

the regulation of surrogacy and not a

total ban on surrogacy. However, the

present legislation banned commercial

surrogacy.”

The Surrogacy Bill proposes that

the intending couple must be Indian

citizens and married for at least five

years, and either or both members of

the couple should be infertile. As per

the bill, the intending couple should

THE BILL IS NOT CLEAR IN

THE CASE OF EMBRYOS AND

GAMETES IN CRYOSTORAGES

IN THE COUNTRY. THE

CURRENT SITUATION DOES

NOT ALLOW THEIR EXPORT

not have any surviving child biologically

or through adoption or surrogacy

earlier. The bill also states that the

surrogate mother should be a close

relative, who is married and having a

child of her own. However, it did not

define close relative. As per the bill, the

child born out of surrogacy procedure

shall be deemed to be a biological

child of the intending couple and the

child shall be entitled to all the rights

and privileges available to a natural

child.

Under the bill, central and state

governments will appoint appropriate

authorities to grant eligibility

certificates to the intending couple

and the surrogate mother. The bill

proposes imprisonment for a period of

10 years and a fine of up to Rs 10 lakh

if surrogacy is undertaken for a fee,

advertised or the surrogate mother is

exploited.

Silent on cryostorage

Commenting on the bill, Dr Alex C.

Varghese, Former President, Academy

of Clinical Embryologists, said: “The

surrogacy bill is a good initiative. There

should be some kind of checks as

there can be lots of practices which are

not ethical. Commercial surrogacy also

puts a question mark on womanhood.

In India, there are more chances of

unethical practices, and based on that,

this kind of law is very valid.” He added

that there may be some loopholes in

the bill and more discussions may be

required to check those loopholes.

The bill proposed that the intending

couple and the surrogate mother need

eligibility certificate, but it does not

specify a time limit for granting the

certificates. Though the bill states that

the surrogate mother should be a close

relative, it also does not define close

relative. As per the bill, the approval

of the appropriate authority and the

consent of the surrogate mother are

required for an abortion. However, it

does not give any role for the intending

couple in the decision for abortion.

The bill has also proposed banning

the storage of embryos and gametes

for surrogacy purpose in contrast to

the existing ICMR guidelines, which

allow storage of embryos for a period

of five years. “The bill is not clear in

the case of embryos and gametes

in cryostorages in the country. The

current situation does not allow their

export. As they are a form of life, they

cannot be destroyed,” said Dr Alex C.

Varghese.

As per the bill, no person shall

establish surrogacy clinics for

undertaking surrogacy unless they are

duly registered under the Act.

64 / FUTURE MEDICINE / FEBRUARY 2019


exotica

THE MIND-BODY

CONNECTION IN CANCER

Currently, there is not enough scientific evidence to support the theory that

one’s attitude alone can directly impact cancer progression

DR SUMIT GHOSHAL

Most doctors know that every

patient responds differently to

treatment. Often two patients

with the same clinical condition,

receiving the same treatment, will show

a very different clinical course. While

one recovers faster or better than

expected, the other appears refractory

to treatment. This phenomenon,

which involves the interplay of several

factors such as the patient’s mental

strength, the incentive and motivation

to recover and the determination to

fight the disease, is often as crucial as

the treatment and intervention by the

doctors.

While healthcare professionals such

as doctors and nurses have known

this for generations, the reasons are

becoming clear only in recent years. In

the context of cancer, it has to be viewed

as the coming together of three separate

trains of thought: One, that human

feelings and emotions are expressed in

terms of neuro-chemical substances;

two, that these neuro-chemicals exert

an impact on the immune system (both

cell-mediated and humoral); and three,

that cancer cells can be combated and

even controlled by strengthening the

immune system. A combination of these

three ideas has given birth to a new

discipline of medical research, known as

Psycho-Neuro-Immunology or PNI.

In recent years, more and more

cancer specialists have started to believe

that the human immune system can be

an invaluable ally in the battle against

malignancy. “One reason that cancer

cells thrive is that they are able to hide

from your immune system. Certain

immunotherapies can mark cancer

cells, so that it is easier for the body’s

immune system to find and destroy

them,” says a recent article published by

the National Cancer Institute, a member

of the National Institutes of Health (NIH)

network. Immune therapies can be

THE EXISTING RESEARCH

FOCUS ON THE IMPACT OF

EMOTIONS AND BEHAVIOR

ON THE CLINICAL COURSE OF

CANCER AFTER IT HAS BEEN

DIAGNOSED

of many types: cytokines, monoclonal

antibodies, treatment vaccines and

even BCG (originally discovered as a

preventive against tuberculosis).

Impact of emotions

On the other hand, we also know

that emotions are chemical reactions

mediated by hormones and other

biochemical such as serotonin,

dopamine, oxytocin, endorphins, etc.

Numerous scientific articles published

globally in the past few years have

expounded the concept that these

same chemicals also affect the immune

system – both cell mediated and

humoral. In an article in Frontiers in

Behavioural Neuroscience published last

year (doi: 10.3389/fnbeh/.2018.00056),

Aki Takahashi et al, have written that

“individuals with high aggression display

heightened inflammatory cytokine

activity and dysregulated immune

responses such as slower wound

healing. Similar findings have been

observed in patients with depression,

and comorbidity of depression and

aggression was correlated with stronger

human dysregulation.”

So, when we put these two concepts

together, what do we get? The perfectly

conceivable idea that anger, depression

and other negative emotions are

capable of slowing down the immune

response to cancer and retard the

effectiveness of traditional cancer

therapies! While this appears quite

logical and obvious, we still have to see

if it is supported by experimental and

scientific evidence.

Much of the existing research, both

in India and abroad, focuses on the

impact of emotions and behavior

on the clinical course of cancer

after it has been diagnosed.

Thus Dr Raghavendra Mohan

Rao and his colleagues in

the Centre for Academic

Research, HCG Foundation,

Bangalore, writing in Indian

Journal of Palliative Care (Indian J

Palliat Care 2017; 23-225-30) point out:

“Treatment-related distress can manifest

as anxiety or depressive disorders in

some cancer patients, leading to a

heightened feeling of hopelessness, a

66 / FUTURE MEDICINE / FEBRUARY 2019


lack of will to survive, a loss of control

over one’s life, low self-esteem and other

indicators. Studies have also shown that

such a state of mind can lead to sleep

disturbances, aberrant cortisol rhythms,

poor anti-tumor immune response, a

decrease in overall and disease-free

survival with early relapse/recurrence,

and heightened distress.”

Likewise, in a 2013 review article

published in Brain, Behaviour and

Immunity, Paige Green MacDonald et

al. write that stressful experiences in

life and a state of depression have

been linked with poorer survival rates

and greater frequency of death in a

wide range of cancers, including those

originating in the breast, lung, head and

neck, hepatobiliary system and blood.

The article (http://dx.doi.

org/10/1016/j.bbi.2013.01.003 ) also

points out that symptoms of depression

have an adverse impact on the survival

of patients with metastatic kidney

cancer. On the other hand, amelioration

of depressive symptoms was clearly

linked with better clinical outcomes in

advanced cases of breast cancer. In

addition, the potential for damage on

account of unsatisfactory or unfulfilling

social relationships was as serious as the

risk conferred by excessive alcohol and

tobacco use!

“People under stress have a lower

level of T-cell mediated immunity,”

says Dr Navin Salins, a palliative care

AMELIORATION OF

DEPRESSIVE SYMPTOMS

WAS CLEARLY LINKED WITH

BETTER CLINICAL OUTCOMES

IN ADVANCED CASES OF

BREAST CANCER

physician with Kasturba Medical College,

Manipal. He also mentions other studies

conducted in HCG, Bangalore that have

revealed that “mind-body intervention”

such as yoga have a definite role in

controlling the nausea, vomiting and

other symptoms of anti-cancer therapy.

Insufficient evidence

But can this set of ideas be taken

one step further, and be used for the

prevention of cancer? Perhaps not in the

near future, because a number of Indian

scientists have pointed out that the

evidence on this aspect is insufficient at

the present time.

“I have done one retrospective study

about five years ago where I found

some correlation ‘Fear of Cancer’ and

‘Cancer Recurrence’, keeping in mind

this concept that anxiety and stress can

compromise our immune system and

help cancer to recur,” says Dr Suchitra

Mehta, Director and Head, Psycho-

Oncology, HCG NCHRI Cancer Centre,

Nagpur.

Speaking on similar lines, Bincy

Mathew, a psycho-oncologist with

Manipal Hospitals, New Delhi and

founder of non-profit organization

www.psycho-oncology.in, says: “One’s

attitude and its influence on cancer is

still a big debate in cancer circles. In

my experience, I have not found

strong enough scientific

evidence that one’s attitude

alone can directly impact

cancer progression or

the immune system. But

many studies have proven

that one’s emotions may

contribute to stronger,

better immunity during

cancer treatment.”

The jury is therefore out

on exactly how much impact

psychological factors can have on

individual cancer patients and how

these findings can be put to use.

However, these developments hold out

the hope that before too long, mental

and psychological training would

play a significant part in cancer therapy

as a whole.

FEBRUARY 2019 / FUTURE MEDICINE / 67


devices&gadgets

Hemoblast Bellows to control

bleeding in laparo surgery

Biom’up’s Hemoblast

Bellows Laparoscopic

Applicator has received

marketing approval from

US FDA for all minimallyinvasive

procedures.

The new approval

expands the indications

of the Hemoblast Bellows

device and enables

surgeons to use the

haemostatic powder

for both traditional and

laparoscopic surgeries with

the same patient.

The 35cm long

polycarbonate applicator

fits easily into the existing

applicator and delivers

Hemoblast powder to

minimally invasive bleeding

sites in under one minute.

Hemoblast Bellows

is the only surgical

haemostatic agent

approved by the FDA based

on the validated Spot

Grade Surface Bleeding

Severity Scale (SBSS), which

demonstrates its ability to

control a range of bleeding

from minimal (oozing), mild

(pooling) and moderate

(flowing) bleeding.

Hemoblast Bellows is

proven to control bleeding

with flow rates up to 117

mL per minute, Biom’up

said.

Hemoblast Bellows can

be used to control bleeding

in a broad range of

procedures, such as cardiac,

general and orthopaedic

surgeries.

patients treated with the

device under a continued

access protocol.

Bioventus

launches

biphasic

bone graft

Amplatzer device

to treat heart

defect in infants

The US FDA approved

Amplatzer Piccolo

Occluder, a device to treat

the congenital patent

ductus arteriosus (PDA)

announced Abbott

Pharmaceuticals.

The device is intended for

use in infants >3 days old at

the time of procedure who

may be nonresponsive to

medical management

and who may not be

able to undergo corrective

surgery.

The pea-sized device is a

self-expanding wire mesh

that is inserted through an

incision in the leg and guided

through vessels to the heart,

where it is placed to seal the

opening.

The approval was

supported by the ADO II AS

study which included 50

patients with a PDA, with

additional safety and

efficacy data obtained from

Bioventus has launched

Osteomatrix+, a biphasic

bone graft for use in bone

remodelling in a variety

of orthopaedic and spine

applications.

Osteomatrix+ is a

moldable bone graft

substitute consisting of

bovine collagen and biphasic

hydroxyapatite/ß-tricalcium

phosphate granules

designed to produce a

reliable, porous scaffold and

sustained osteoconductivity

throughout the bone

remodeling process.

Osteomatrix+ has more

unique handling properties,

including improved

moldability, flexibility

and versatility, than its

predecessor, according to the

company.

Bioventus’ portfolio

includes offerings for

osteoarthritis, surgical and

non-surgical bone healing.

68 / FUTURE MEDICINE / FEBRUARY 2019


New ablation

catheter to

treat AFib

TactiCath Contact Force

Ablation Catheter, a new

ablation catheter designed

to help physicians treat atrial

fibrillation (AFib), has been

granted approval by US FDA.

The sensor-enabled

TactiCath SE delivers more

precise images of the heart

overlaid with real-time

electrical activity information.

The catheter also utilises

the advanced ergonomic

design for better reach and

manoeuvrability during

cardiac ablation procedures.

Physicians have begun

exploring the use of new

tools such as “contact force”

technology during ablation

procedures to help them

avoid applying too much

pressure to heart tissue or

insufficient pressure, Abbot

said.

Perflow wins

4 patents for

neurovascular

technology

Perflow Medical has been

issued four international

patents that for the novel

Stream Dynamic Neuro-

Thrombectomy Net and

Cascade Non-Occlusive

Remodeling Net.

Perflow’s global portfolio

of eight issued patents

includes two new patents

from the European Patent

Office (EPO), one from the

Medtronic launches mobile

app to support pacemakers

Medtronic plc has

launched MyCareLink

Heart mobile app to

support the portfolio of

pacemakers that can

communicate directly with

patients’ smartphones and

tablets.

Compatible with

Medtronic BlueSync

technology-enabled

pacemakers, the

MyCareLink Heart mobile

app is designed to securely

and wirelessly send device

data to the Medtronic

CareLink network via smart

technology, eliminating

the need for a dedicated

bedside monitor or

other remote monitoring

hardware.

BlueSync technologyenabled

pacemakers

include the Azure

pacemaker and Percepta,

Serena and Solara

quadripolar cardiac

resynchronization therapy

pacemakers (CRT-Ps).

Data collected by these

devices is encrypted

and sent to the CareLink

network through the

MyCareLink Heart mobile

app, providing physicians

with timely alerts on

clinically-relevant patient

events. The app also makes

select pacemaker data

easily accessible to patients

including transmission

success history, pacemaker

battery information,

answers to common

questions about living with

a pacemaker, and updates

on physical activity.

MyCareLink Heart

Mobile App provides

patients with information

about transmissions

that have been sent to

their doctors, as well

as confirmation when

transmissions are received

by physicians. It also allows

patients to record weight,

blood pressure and heart

rate in the app, and to

track these measurements

over time to help better

understand health status.

This information is only

stored on their mobile

device; it is not sent to the

clinic.

Further. the

app allows patients

to catalogue symptomatic

events which can be

reviewed with their

physicians during in-person

clinic visits.

China National Intellectual

Property Administration

(CNIPA), and one from the

Japanese Patent Office (JPO).

Perflow’s Cerebral Net

technology platform is

designed to expand treatment

options with real-time control

and overall improved device

performance. The company

currently has two commercial

products with CE Mark

available for use in Europe,

with a third product in latestage

development. The

Stream Net, the company’s

first product, has been used

across Europe and provides

full control and dynamic

wall apposition during the

treatment of acute ischemic

stroke. The Cascade Net,

which was launched last

year, is a device that allows

blood flow without the risk

of coil entanglement during

embolization of intracranial

aneurysms.

Both devices allow the

physician to manipulate

the net diameter, length,

and radial force to optimize

contact with the vessel wall

and improve control through

tortuous anatomy during

neurovascular procedures.

Fujifilm launches

Apollo X

mammalian

expression system

Fujifilm Diosynth

Biotechnologies has

FEBRUARY 2019 / FUTURE MEDICINE / 69


introduced Apollo mammalian

expression system, Apollo X.

The Apollo X advanced

mammalian expression system

is capable of delivering titres

in excess of 10 g/L.

CHO-DG44-derived host

cell line selected through a

directed evolution approach

to control and manage

cellular heterogeneity, is

one of the key components

of the system. The selected

cell line has been fully

sequenced and analysed,

a novel expression vector

with a proprietary leader

sequence developed for

efficient secretion and high

productivities without the

need for amplification.

Its cell culture medium

is specifically screened for

achieving high titres by

monitoring initial cell

growth, controlling peak

cell density and maintaining

high cell viability, streamlined

units of operations

for efficient process

implementation.

Apollo X cell line

development timelines

have been reduced by 30%,

from gene to clonal cell line

compared to the original

Apollo expression system.

Digital laparoscopic system gets

510(k) clearance

TransEnterix, Inc

announced the

company received FDA

510(k) clearance for its

Senhance Ultrasonic

System.

The Senhance System

is a new abdominal

robotic surgery platform

to receive FDA clearance

since 2000 and is the

first digital laparoscopic

surgical platform to offer

the security of haptic

force feedback that allows

surgeons to feel the forces

the instruments generate

when handling delicate

tissue.

It uses reusable

instruments that help

keep per-procedure costs

similar to that of traditional

laparoscopic surgeries, as

well as 3 mm instruments

for microlaparoscopic

procedures that enable

virtually scarless incisions

for patients.

Advanced energy

devices, including

ultrasonic devices,

represent some of the

most versatile and critical

tools for surgeons in

minimally invasive surgery.

These instruments

deliver controlled energy

to effectively ligate

and divide tissue and

minimize thermal injury to

surrounding structures.

In the US, the

Senhance System is

cleared for laparoscopic

colorectal, gynaecological,

inguinal hernia and

cholecystectomy surgery.

Wearable BP

monitor

HeartGuide

launched in US

H

eartGuide,

a wearable

oscillometric blood

pressure monitor in the

design of a wristwatch

recently received 510K

FDA clearance as a medical

device.

HeartGuide is launching

with a new mobile app,

HeartAdvisor – a digital health

service from Omron with

insights and coaching to

help users.

HeartGuide can

hold up to 100

readings in memory

and all readings can

be transferred to a

new corresponding

mobile app,

HeartAdvisor, for

review, comparison

and treatment

optimisation.

HeartAdvisor is now

available through Apple

iTunes and Google

Play stores and will be

upgraded with additional

features throughout 2019.

Omron is initially launching

HeartGuide in the US with

plans to roll out the product

in Europe and Asia later this

year.

Neuro aspiration

device for MRI

procedures

approved in US

The US FDA approved

ClearPoint Pursuit, a neuro

aspiration device for MRI

Interventions.

The new neuro aspiration

70 / FUTURE MEDICINE / FEBRUARY 2019


Benchtop blood analyser

Erytra Eflexis get USFDA ok

Grifols received US FDA

approval of Erytra Eflexis,

a fully automated, benchtop

analyzer. The system performs

pretransfusion compatibility

testing using DG gel

technology.

The blood typing analyser

facilitates multiple lab

configurations and requires

minimal laboratory technician

interaction.

Erytra Eflexis incorporates

two lab configurations

in a single instrument so

laboratories can select

the solution best suited to

various workflow needs and

capacities. This smart,

flexible and intuitive

system optimises workflow

efficiency and improves

daily workloads, providing

laboratories with a high

level of flexibility and

adaptability, the company

said.

Interchangeable sample

and reagent linear racks allow

easy, continuous loading

of cards, reagents and

samples. The device features

real random access with a

capacity of up to 200 cards,

72 samples and 46 liquid

reagents.

device is indicated for the

controlled aspiration of

blood, clotted blood, cystic

components of tumours,

abscesses, colloid cysts, and

cerebral spinal fluid using a

manual syringe during the

surgery of the ventricular

system or cerebrum.

It leverages the ClearPoint

navigation system from MRI

interventions and is designed

to be used under MRI

guidance.

The Pursuit device was

designed in collaboration with

the Mayo Clinic. It is being

placed under a limited market

release at a select number of

U.S. hospitals.

The company expects to

launch Pursuit commercially in

the first half of 2019.

Non-invasive

test for

concussion

wins FDA nod

Marketing permission has

been granted by US FDA

for EyeBOX, a non-invasive,

baseline-free aid in diagnosis

of concussion.

EyeBOX is easy to use test

that collects and analyses

over 100,000 data

points to generate an

objective assessment

that is unique to

each patient. It can

be used as aids in

the diagnosis of

concussion in patients

5 to 67 years of

age, Oculogica said.

EyeBOX uses

eye-tracking to

provide objective

information to aid in the

assessment of patients with

suspected concussion via an

easy to take, 4-minute test.

A binocular camera then

tracks each eye and gathers

data that ultimately leads to

a score that rates the severity

of brain injury; a score =10

is Oculogica’s threshold for a

concussion.

The FDA approval was

supported by results from the

DETECT clinical study which

included 282 patients with

suspected traumatic brain

injury.

Results showed that

compared with a clinical

reference standard for a

concussion, EyeBox had high

sensitivity to the presence of

concussion; a negative result

was consistent with a lack of

concussion.

The company plans to

market the device for use in

paediatrics ages 5 and older

and adults up to 67 years of

age, starting with a pilot launch

for select, qualified sites.

72 / FUTURE MEDICINE / FEBRUARY 2019


Bioelectronic

device for

sinus pain

The US FDA has approved

ClearUP Sinus Pain Relief

for the treatment of sinus

pain due to allergic rhinitis in

adults.

The device is a

bioelectronic treatment and

a new way to treat allergyrelated

sinus pain from

environmental allergies like

mould, dust, pollen, dander

as well as food allergies. The

advanced neuromodulation

technology uses gentle

microcurrent.

The handheld device

measures the user’s skin

properties to target the

optimal treatment points.

As the user glides the

device along the outer nasal

passage, gentle microcurrent

waveforms stimulate the

nerves under the skin to

relieve sinus pain. Each

5-minute treatment can be

personalised at 3 intensity

levels and can be used up to

4 times a day.

As the device glides along

the cheek, nose, and brow

bone, it locates areas of the

skin with low impedance,

where current can pass most

easily. At these treatment

points, the device emits lowcurrent

electrical stimulation,

called Microcurrent, to

stimulate underlying nerve

fibres.

Electrical stimulation

of nerves has been used

to reduce the sensory

perception of pain. Research

has also shown that electrical

stimulation can activate

sympathetic nerve fibres and

promote constriction of blood

vessels, which can result in the

shrinking swollen tissue.

Smartwatch for

monitoring seizure in kids

Embrace smartwatch

for tracking seizures

in children as young as

age 6 has been granted

marketing approval by

USFDA.

The watch uses an

electrodermal activity

sensor to measure

sympathetic nervous system

activity. The latest approval

has made it the first non-

EEG based physiology

signal seizure monitor to be

cleared for use in paediatric

patients. The Embrace

was previously approved

in January 2018 for adults

aged =21 years.

The smartwatch

identifies certain motion

and physiological signals

associated with generalized

tonic-clonic seizures and

promptly alerts caregivers.

The Alert App immediately

sends a call and SMS to

your caregivers when

Embrace detects patterns

that may be associated

with a convulsive seizure.

Embrace bagged the

marketing rights after the

positive results of a clinical

test which was conducted

among 141 epilepsy

patients, out of which 80

patients were aged 6 to 21

years and 61 patients were

aged >21 years. The data

demonstrated an accuracy

rate of 98% for detecting

generalized tonic-clonic

seizures. The overall false

alarm rate (FAR) for adults

was 0.67 and 1.35 for

paediatrics, Empatica Inc

said.

FEBRUARY 2019 / FUTURE MEDICINE / 73


MERIL’S

MYVAL

Indigenous transcatheter aortic valve replacement

technology makes India proud

Vapi never figured in India’s

science hotspots until now.

But this small industrial town

in Gujarat—predominantly a chemical

manufacturing hub on the Maharashtra

border, has started attracting young

scientific talent in the biomedical

engineering field, thanks to the

unrelenting medical technology research

and development efforts of a company

that made India proud of late.

The country’s first indigenous

Transcatheter Aortic Heart Valve

MILESTONES

2006 2009

Thought

of Meril

2008

State-of-the-art

manufacturing facility

at Vapi, Gujarat, India.

Launched flagship

product, BioMime,

Nexgen, Crypton &

Haiku

74 / FUTURE MEDICINE / FEBRUARY 2019


Replacement (TAVR) device, an

important milestone that made the

Indian med-tech industry proud, was

successfully developed in this tiny town.

Meril Life Sciences, the Vapibased

med-tech company received

approval for launching its indigenous

TAVR technology— Myval THV—from

the Central Drugs Standard Control

Organisation (CDSCO) in October. With

this, Meril has become the first Indian

company in the world to make this

technology commercially available,

MERIL LIFE SCIENCES

RECEIVED APPROVAL FOR ITS

TAVR TECHNOLOGY— MYVAL

THV—FROM THE CDSCO IN

OCTOBER 2018

promising to give long-established

multinational brands tough competition.

TAVR, an established treatment

modality for patients who are at a

high risk or unwilling to undergo open

heart valve replacement surgery, is a

minimally invasive procedure in which

the doctor inserts a replacement valve

into the patient’s native diseased valve

via a catheter inserted through the

femoral artery. This is an alternative

way to replace diseased valves without

undergoing the traditional open heart

procedure, which some patients may not

tolerate. The market for transcatheter

aortic valve implantation (TAVI), which

is growing rapidly with the increasing

cases of aortic valve stenosis, has so

far been catered to by multinational

med-tech giants such as the US-based

Edwards Lifesciences and Medtronic,

Ireland.

Long and passionate effort

Meril has been working on this project

for the last six years. Though its 150

strong R&D team at the Vapi campus

has had several other firsts to their

credit, including a completely indigenous

ultra-thin strut bio-degradable polymerbased

Sirolimus DES—BioMime in

2010, a thin-strut Sirolimus eluting

bioresorbable vascular scaffold — MeRes

100 in 2016, Myval is one of their most

prestigious projects.

“Since its inception, Meril has

played a leading role in developing

and introducing innovative medical

technologies. The TAVR technology

has been developed after 6 years of

extensive research and is backed by

robust bench testing, pre-clinical and

clinical data. We are committed to take

this technology to over 100 countries

and benefit thousands of patients

2010

2011

Established direct presence through

subsidies in Germany and Brazil and

grew international presence to over

60 countries.

Established International presence over

30 countires and got validation from

European Commission through CE mark

BioMime became

preferred brand

in south asian

countries.

Launched a

completely indigenous

PTCA balloon catheter,

MOZEC.

Demonstrated Meril’s

Innovation by introducing

BioMime Aura

2012

2013

Presented at EuroPCR, first

animal studies of MeRes

Bioresorbable Vascualar Scaffold

and Myval Transcatheter Aortic

Valve (TAVI) System

Expanded presence in more

than 100 countries through strong

partnerships across regions

FEBRUARY 2019 / FUTURE MEDICINE / 75


The innovation that

we could bring in

Myval’s design is

clinically significant

as compared

to all existing

technologies.

Sanjeev Bhatt

Vice President

Corporate Strategy

Meril Life Sciences

across the globe,” says Dr P K Minocha,

director, Research & Development, Meril

Life Sciences.

The launch of the indigenously

developed transcatheter heart valve

is an assertion of the company’s

fundamental belief that it will focus on

novel, clinically relevant and best-in-class

devices to alleviate human suffering

and improve quality of life, according to

Meril’s senior management.

Clinically differentiated

“Meril has always been dedicated

towards design and development

of novel, clinically relevant and bestin-class

devices to alleviate human

suffering and improve quality of life.

For us, it is a proud moment to be the

first Indian company to commercially

make this therapy available in the

country,” says Sanjeev Bhatt, vice

president, Corporate Strategy, Meril Life

Sciences.

The regulatory approval for Myval

came after successful completion of

extensive clinical studies in India.

“All the patients are doing well post

Myval procedure and during follow-up,”

says a confident Bhatt.

The product demonstrates that it

is possible to develop such a complex

medical device completely in India by

Indian scientists.

“We have not outsourced the

technology and it’s fully developed

here in this campus and within our

own means. And more importantly,

the innovation that we could bring

in its design is clinically significant as

compared to all existing technologies,”

Bhatt said in an interview with Future

Medicine.

Because of its unique design,

the product sits at the annulus in

a precise manner, Bhatt said. It

therefore prevents leakage, known as

paravalvular leakage (PVL), associated

with the implantation of a prosthetic

heart valve, whether using a traditional

76 / FUTURE MEDICINE / FEBRUARY 2019


(surgical) or transcatheter (TAVI)

approach.

Secondly, this design is also

associated with zero new pacemaker

implantation rates post procedure,

which is an important benefit for

the patient already treated for valve

replacement. This is because its

precise placement mechanism doesn’t

excite the conduction system. Since

the tolerance at this zone is minimum,

only a precise deployment of the

device can avoid exciting the system.

In the current genre of devices, usually

there are upto double digit rates of

needing new permanent pacemakers.

A study published in the Journal

of American College Cardiology

(JACC) in 2016 found that patients

who undergo minimally invasive

heart valve replacement, typically

a TAVR, sometimes develop heart

rhythm problems that necessitate the

placement of a permanent pacemaker.

However, when a new pacemaker is

needed soon after TAVR procedure,

patients often have worse outcomes

than those who do not need a

pacemaker. The study, based for the

JACC report, also showed that such

risks are both short- and long-term and

include lengthier stays at hospital and

intensive care units as well as a greater

risk of death.

Proud moment

“For us, it is a proud moment to be the

first Indian company to commercially

make this therapy available in the

country. Through the commercialisation

of this technology, Meril will soon bring

a next-generation treatment modality to

THE ULTIMATE MERIT OF THIS

INDIGENOUS TECHNOLOGY

DEPENDS ON THE RESPONSE

THAT IT RECEIVES FROM THE

CARDIAC SURGEONS IN THE

COUNTRY

thousands of patients globally, making

India proud of this achievement,” claims

Bhatt.

According to him, Meril realises that

if it has to do very complex science in

areas where no alternatives exist at the

moment, it has to be in keeping with

its primary philosophy of identifying

an unmet need and then providing its

whole infrastructure, knowhow, talent

and even the training for doctors by

becoming a perfect facilitator of that

new concept and technology.

Although the critics say that the

Indian devise was built on the existing

technology platform that is already

available in the market, Meril argues that

every novel design has been developed

by improvising existing platforms, which

is a fact everywhere in the world and

India is not an exception.

But the ultimate merit of this

indigenous technology depends on

the response that it receives from the

cardiac surgeons in the country.

“We have found Myval to be safe

and easy to use in the initial series of

procedures. But a longer follow up data

will be needed to study the long term

durability and cardiovascular outcomes,

though the cost has been proved

advantageous,” said Dr Hisham Ahmed,

a senior cardiac surgeon at Amrutha

Institute of Medical Sciences, Kochi,

whose team has implanted Myval in four

patients so far.

Aortic valve stenosis is one of the

most prevalent heart diseases globally

and the number of cases at any

conservative estimate would cross 3 to

3.5 per cent of the elderly population.

Currently available estimates show

that more than 1 million cases of aortic

stenosis are diagnosed per year in

India alone, mainly due to age related

degradation of the aortic valve—an

important cause not only in India but

in other parts of the world as well.

Although less invasive procedure to

replace the valve is the much sought

after treatment today, the number of

such procedures is comparatively less

in India due to cost and access issues.

Indigenous technology and more

awareness can bring in more volumes

and counter pricing and affordability

issues.

This is part of a series that features India’s

First & Most Unique institutions, facilities,

technologies, products etc in the medical

and healthcare space.

FEBRUARY 2019 / FUTURE MEDICINE / 77


guidelines

MANAGEMENT OF

UTERINE CANCER

Consensus document for the management of endometrial carcinoma by

Indian Council of Medical Research 2018

Carcinoma endometrium is the

most common gynecological

malignancy in the developed

countries with age standardized

incidence rate of 2.3 per 100,000. In

developing countries, cervical cancer

still remains the leading cause of

gynecological cancers, but there is a

recent increase in the incidence of

endometrial cancer. In India, the total

number of estimated new cases of

endometrial cancer in 2018is 13,328

with an estimated 5010 deaths. The

age standardized incidence rate (ASIR)

of endometrial cancer in India is

2.1/100,000 women. The rise is mainly

attributed to the changing trends in

the lifestyle and reproductive profile of

women especially in urban areas. The

majority of cases present in 6th and

7th decade of life with the mean age of

diagnosis being 60 years.

HISTOPATHOLOGIC VARIANTS

Endometrial adenocarcinoma is the

most common histology of uterine

cancer. There are two distinct subtypes,

which have different incidence,

clinical picture, molecular pattern and

biological behavior.

Type 1 Endometrial Carcinoma:

Type 1 endometrial cancers comprise

approximately 80% of uterine

cancers. These tumours are estrogen

responsive and are seen in pre- or perimenopausal

age group. They are of

endometrioid histology and are usually

well differentiated. Type 1 endometrial

carcinomas are usually associated with

prolonged and unopposed estrogen

exposure as seen in women with

obesity, anovulatory cycles, infertility,

78 / FUTURE MEDICINE / FEBRUARY 2019


and estrogen-secreting tumours. These

tumours usually have a favorable

prognosis with >90% 5-year survival

rate. They are characterized by K-ras

overexpression, PTEN, PIK3CA, KRAS

mutations, and microsatellite instability.

Type 2 Endometrial Carcinoma:

Type 2 endometrial cancers comprise

the remaining 10-20% of cases. They

are estrogen independent and usually

arise from an atrophic endometrial

background. They occur in women

who are older, postmenopausal,

multiparous, non-obese, smokers, and

tamoxifen users. They include grade 3

endometrioid adenocarcinoma, serous,

clear cell, mucinous and squamous

variety. They are aggressive tumours

and often show deep myometrial

invasion and extrauterine spread. Type

2 tumours are associated with worse

prognosis with a recurrence rate of

50% and overall survival (OS) of 35%.

They are associated with genetic

alteration in E-cadherin, p53 and HER2/

neu expression.

DIAGNOSTIC WORKUP

Detailed history: The usual presenting

complaints are abnormal uterine

bleeding and postmenopausal bleeding.

Risk of carcinoma endometrium in a

woman with postmenopausal bleeding

is approximately 10%.

Clinical presentation with

advanced disease includes urinary

or rectal bleeding, constipation,

pain, lower extremity lymphedema,

abdominal distention due to ascites,

hepatomegaly, jaundice, cough and/or

hemoptysis.

History of use of hormones,

diabetes, hypertension, and tamoxifen

use should be elicited.

Previous menstrual and obstetric

history: History of early menarche

or late menopause, history of

prolonged and heavy periods and

history of menstrual abnormalities in

perimenopausal transition.

Family history of uterus and

colorectal cancer, especially if

endometrial cancer is diagnosed

TYPE 2 TUMOURS ARE

ASSOCIATED WITH GENETIC

ALTERATION IN E-CADHERIN,

P53 AND HER2/NEU

EXPRESSION

at age


outcome (disease specific survival or

recurrence).

FURTHER EVALUATION

After confirming the diagnosis, further

laboratory investigations and detailed

imaging is done to assess the surgical

risk, extent of disease, and to plan the

appropriate surgical treatment.

Advanced imaging

MRI abdomen and pelvis with

contrast: MRI is the most accurate

modality for assessing the size and

extent of tumour, myometrial invasion,

extension to cervix and adnexal

pathology. Contrast enhanced MRI

to exclude myometrial invasion and

cervical extension is mandatory,

when planning for fertility preserving

options.

CT abdomen with pelvis (contrast):

Poor soft tissue differentiation of CT

scan limits its use to assess the local

extent of disease. The sensitivity and

specificity of CT in assessing the extent

of myometrial invasion range from

40% to 83% and from 42% to 75%,

respectively. CT scan is mainly utilized

for assessing extra pelvic disease and

lymph node involvement.

Positron emission tomography/

computed tomography (PET/CT): This

has little benefit in assessing primary

tumour extension. PET/CT has sensitivity

of 50% to 100% and specificity of 87%

to 100% in detecting regional lymph

node metastasis. Routine use of PET CT

is not indicated for preoperative staging

purpose. PET/CT is highly sensitive and

specific for detecting positive pelvic

and/or paraaortic lymphadenopathy as

well as distant metastases in selected

high-risk patients and also those with

recurrent disease.

PET/MR imaging systems have

recently been developed to take

advantage of MRI’s high soft tissue

resolution and improve the anatomic

assessment.

Other preoperative work up

Complete blood count, renal and liver

functional tests, serum electrolytes,

urinalysis, blood glucose and viral

markers.

Cancer Antigen 125 (CA 125): The

preoperative serum levels of CA 125

could be elevated in patients with

extrauterine spread of the disease

and can be utilized for monitoring

the clinical response after therapy in

selected patients.

Chest X-ray to rule out lung metastasis

should be done. If the chest X-ray

is suspicious of metastasis, CT chest

without contrast is advised.

– Patients diagnosed with

endometrial malignancy prior to 50

THE SENSITIVITY AND

SPECIFICITY OF CT IN

ASSESSING THE EXTENT

OF MYOMETRIAL INVASION

RANGE FROM 40% TO 83%

AND FROM 42% TO 75%,

RESPECTIVELY

years and those with significant family

history of endometrial and colorectal

cancers should undergo genetic

evaluation.

Histological Classification of

Endometrial Carcinoma (2014

WHO)

Endometrioid adenocarcinoma

Endometrioid adenocarcinoma variants

• With squamous differentiation

• Secretory variant

• Ciliated cell variant

Mucinous adenocarcinoma

Serous endometrioid intraepithelial

carcinoma

Serous adenocarcinoma

Clear cell carcinoma

Mixed cell carcinoma

Undifferentiated carcinoma

• Monomorphic type

• De-differentiated type

Neuroendocrine tumours

• Well differentiated neuro endocrine

tumour (carcinoid tumour)

• Poorly differentiated small cell

neuroendocrine tumour

• Poorly differentiated large cell

neuroendocrine tumour

Staging of Carcinoma

Endometrium

Endometrial cancer should be surgically

staged with histological assessment of

grading and extent of disease. AJCC-

(American Joint Cancer Committee)

Tumour-Node-Metastasis (TNM) and

FIGO 2009 staging for carcinoma

endometrium is depicted in Table A.

Cases should also be stratified

based on degree of differentiation

• G1- 5% or less of a non-squamous

or non-morular solid growth pattern.

• G2- 6%-50% of a non-squamous or

non-morular solid growth pattern.

• G3- more than 50% of a nonsquamous

or non-morular solid

growth pattern.

PROGNOSTIC FACTORS

The following prognostic variables have

been identified (3,19)

FIGO stage

Age

Histological type

Histological grade

Nuclear grade

Myometrial invasion

Cervical stromal invasion

Lymphovascular space invasion

Tumour size >2 cm

Positive peritoneal cytology

Hormone receptor status

DNA ploidy and other biological

markers

Type of primary therapy - Surgery or

Radiation

TREATMENT

Surgical treatment remains the

mainstay of therapy for both early as

well as advanced disease. Complete

surgical staging involving examination

of the bowel, peritoneal, liver and

splenic surface should be done.

Biopsy(s) from suspicious areas should

be taken.

80 / FUTURE MEDICINE / FEBRUARY 2019


TABLE A

STAGING OF ENDOMETRIAL CARCINOMA AND CARCINOSARCOMA

TNM

STAGING

Tx

T0

Tis

FIGO

STAGING

Primary Tumour (T)

SURGICO- PATHOLOGICAL FACTORS

Primary tumour cannot be assessed

No evidence of primary tumour

Carcinoma in situ (Preinvasive carcinoma)

T1 I Tumour confined to corpus uteri

T1b IA Tumour limited to endometrium or invades less

than one half of myometrium

T1b IB Tumour invades one half or more than one half of

myometrium

T2 II Tumour invades stromal connective tissue of the

cervix but not extend beyond the uterus

T3a IIIA Tumour involves serosa and/ or adnexa (direct

extension or metastasis)

T3b IIIB Vaginal involvement (direct extension or metastasis)

or parametrial involvement

IIIC

IV

Metastasis to pelvic and/ or paraaortic nodes

Tumour invades bladder and/ or bowel mucosa

and/or distant metastases

T4 IVA Tumour invades bladder mucosa and/ or bowel

Nx

N0

Lymph nodes (N):

Regional lymph nodes cannot be assessed

No evidence of regional lymph nodes

N1 IIIC1 Regional lymph node metastasis to pelvic lymph

nodes (Positive pelvic nodes)

N2 IIIC2 Regional lymph node metastasis to para- aortic

nodes, with or without positive pelvic lymph nodes

Metastasis (M):

M0 No distant metastasis

M1 IV B Metastasis to inguinal lymph nodes, intraperitoneal

disease, liver, lung or bone.

Though peritoneal cytology does

not change staging, it is recommended

to collect peritoneal fluid for cytology

by both FIGO and TNM.

Omental biopsy or omentectomy

is indicated in patients with

non-endometrioid histology,

G3 endometrioid tumour and

carcinosarcomas.

The standard surgical management

for uterine cancer is extra fascial total

hysterectomy with bilateral salpingooophorectomy

with or without lymph

node assessment. For younger

women who are desirous of future

child bearing, fertility preserving

management can be advised after

thorough evaluation and detailed

counselling.

The route of surgery can be open

or minimally invasive (laparoscopic

or robotic). Several studies have

proved the feasibility, safety, efficacy

of minimally invasive approach

with comparable survival rates.

However, during laparoscopic surgery

morcellation or tumour fragmentation

is not permissible in patients with

endometrial carcinoma.

Lymphadenectomy

Supporting Evidence review:

The extent of lymphadenectomy

has been a matter of debate and

has been extensively investigated in

several studies. The baseline rate of

nodal disease in endometrial cancer

is approximately 9%. The extent of

lymphadenectomy is important to

decide the need to administer adjuvant

therapy but may also impart some

therapeutic benefit. The overall surgical

complication rate of lymphadenectomy

varies from 6% to 20% depending

mainly on the surgical expertise. In

order to determine which patients

are at low risk of nodal metastasis, so

that lymphadenectomy can be safely

omitted, several risk stratification

systems have been developed.

1. In 2000, a model was suggested

by Mayo Clinic that could help in

identifying cases with low risk of

nodal spread and high disease-free

FEBRUARY 2019 / FUTURE MEDICINE / 81


survival (DFS) based on frozen section

evaluation of uterus. They found that

women with Grade 1 to 2 endometrioid

tumours, inner 50% myometrial

invasion and tumour size


location of pelvic SLN being medial

to the external iliac, ventral to the

hypogastric, or in the superior part of

the obturator region. Occasionally the

lymphatic trunks do not cross over

the obliterated umbilical and move

upwards following the mesoureter and

seen in the common iliac presacral

region also. Considering the low

volume nodal metastasis ultra-staging

is recommended to detect the

disease. A side-specific nodal

dissection should be performed in

cases of failed mapping and any

suspicious or grossly enlarged nodes

should be removed regardless of

mapping.

SLN mapping should be undertaken

for the surgical staging of uterineconfined

disease with no obvious

factors, stage 1 can be further subdivided

into three risk categories. This

stratification is useful to plan adjuvant

therapy.

Adjuvant treatment according to

FIGO Stage and Grade of tumour

Radiotherapy plays an important role

in the management of endometrial

cancer.

STAGE I A

G1–G2: Observation

The risk of pelvic node positivity is

as low as 50%, LVSI, lymph

node metastasis and tumour diameter

>2 cm. Based on the presence of these

RISK STRATIFICATION OF

ENDOMETRIAL CARCINOMA

Low risk

Intermediate

risk

High risk

IB G3: external beam radiation therapy

(EBRT) and vaginal brachytherapy

STAGE II

Stage 1A (G1,2),

endometrioid disease

Stage 1A (G 3),

endometrioid type,

stage 1B (G1,2),

endometrioid type

Stage 1B (G3),

endometrioid type

All stages, nonendometrioid

type

Surgical treatment

Radical hysterectomy with bilateral

salpingo-oophorectomy and bilateral

pelvic ± para-aortic lymphadenectomy

When surgery is not feasible due to

medical contraindications (in ~5%–10%

of patients), or because of irresectable

disease, external beam radiation

therapy with or without intracavitary

brachytherapy can be considered.

Surgical treatment

Maximal surgical cytoreduction is

indicated in patients with a good

performance status and resectable

tumour.

STAGE III B

Vaginal involvement is usually treated

with a combination of external radiation

and intracavitary / interstitial radiation,

tailored according to the disease extent.

Adjuvant treatment

Chemotherapy

If positive nodes are detected

concurrent chemoradiotherapy

consisting of EBRT with platinum and

taxane based chemotherapy can be

considered. If paraaortic nodes are

involved, extended field radiation

should be considered.

STAGE IV

Systemic therapy + pelvic radiotherapy

If positive nodes are detected,

radiotherapy can be considered.

Recurrent endometrial cancer

Recurrent endometrial cancer is

treatable but not curable unless it is

confined to the vaginal cuff or pelvis.

Widely metastatic recurrence carries

poor prognosis. The treatment for

84 / FUTURE MEDICINE / FEBRUARY 2019


ecurrent endometrial cancer depends

on the anatomic location of the

recurrence.

TREATMENT FOR LOCAL

RECURRENCE

Distant metastasis should be ruled out

by imaging with PET-CT/ contrast CT.

Treatment should be individualized

based on the following factors (3,32):

• Whether recurred in previously

irradiated area

• Whether complete resection is

possible

• Disease free interval

• Grade of disease

These patients experience a 5-year

local control rate of 42%–65% and a

5-year overall survival rate of 31%–53%.

(43)

While this treatment approach has

a good response rate, it is not without

side effects. Indeed, the rate of grade

4 complications has been reported to

be as high as 9%, and many patients

who receive radiation to the pelvis

experience vaginal stenosis, cystitis,

THE RATE OF GRADE 4

COMPLICATIONS HAS BEEN

REPORTED TO BE AS HIGH

AS 9%, AND MANY PATIENTS

WHO RECEIVE RADIATION

TO THE PELVIS EXPERIENCE

VAGINAL STENOSIS, CYSTITIS,

PROCTITIS, AND CHRONIC

DIARRHOEA

proctitis, and chronic diarrhoea, which

significantly impacts their life.

Surgery

In cases where complete surgical

resection appears possible, surgical

exploration and resection with negative

free margins and intraoperative

radiotherapy if available.

Radiotherapy

Isolated vaginal recurrence - Surgical

excision and Pelvic radiation +

brachytherapy.

Inoperable pelvic recurrence - consider

palliative pelvic radiation.

Chemotherapy

If previously irradiated and inoperable,

palliative chemotherapy is to be

considered. Platinum and taxane based

chemotherapy regimens are used.

Treatment for nodal recurrence:

If not irradiated previously – External

beam radiotherapy + Chemotherapy

TREATMENT FOR METASTATIC

DISEASE

Palliative chemotherapy

Palliative chemotherapy is

recommended if previously not

exposed to chemotherapy or there

has been a long disease-free interval

after previous chemotherapy. Single

cytotoxic agents have been reported

to achieve a response rate up to 40%

in chemotherapy-naïve patients with

metastatic endometrial cancer.)

FEBRUARY 2019 / FUTURE MEDICINE / 85


Platinum based compounds,

anthracyclines and taxane are the

commonly used agents. Paclitaxelbased

combination regimens are

preferred for first-line chemotherapy of

advanced and recurrent endometrial

cancer.

Endometrial cancer recurring

after first-line chemotherapy is largely

a chemo resistant disease. Various

agents have been tested in a number

of small phase II trials in patients

previously exposed to chemotherapy.

Only paclitaxel has consistently shown a

response rate >20%.

In the case of systemic metastases,

chemotherapy has a poor track record

in improving survival, with most trials

reporting response rates of less than

20%, progression-free survival of 3–6

months, and overall survival of less than

12 months when using chemotherapy

in the recurrent setting.

Hormonal therapy:

• For endometrioid histology only.

• Progestational agents: Tamoxifen

and aromatase inhibitors are also

used.

• Predictors of response: welldifferentiated

tumours, a long

disease-free interval and the

location and extent of extra pelvic

(particularly pulmonary) metastases.

• The overall response to progestins

is ~25%.

Palliative radiation can be

considered for bone metastasis and for

control of vaginal bleeding.

PRICIPLES OF RADIOTHERAPY IN

THE MANAGEMENT OF UTERINE

CANCER

Pelvic Radiotherapy

Should include gross disease

(if present), parametria, vagina

(depending on extent of involvement),

paravaginal tissues, iliac nodes (internal,

external, lower common iliac), presacral

nodes (if cervix is infiltrated).

Extended field radiotherapy should

include the pelvic and entire common

iliac and paraaortic lymph node region

ideally up to the level of renal vessels.

External beam radiotherapy dose

for microscopic disease 45-50 Gy

preferably with CT based planning and

conformal therapy.

Brachytherapy

Brachytherapy should be administered

4-6 weeks from the time of surgery /

when the vaginal cuff has healed well

but not beyond 12 weeks.

Treatment volume should include

the vault and upper two thirds of the

vagina.

SEVERAL HORMONAL AGENTS

HAVE BEEN INVESTIGATED

INCLUDING MEGESTROL

ACETATE ALTERNATING WITH

TAMOXIFEN, PROGESTATIONAL

AGENTS ALONE, AROMATASE

INHIBITORS, TAMOXIFEN

ALONE OR FULVESTRANT

WITH VARIABLE RESPONSE

For High Dose Rate brachytherapy

7Gy x 3 fractions, calculated at 0.5 cm

depth from vaginal surface or 6Gy x 5

fractions, calculated at vaginal mucosal

surface.

For High Dose Rate brachytherapy

after external beam therapy a dose of

6Gy x 2 or 3 fractions prescribed to

vaginal mucosal surface.

Palliative Radiation

Palliative radiation should depend upon

patient’s performance status and needs

to be tailored as per need / extent of

disease.

Medically inoperable Stage I / II

Intracavitary application with or without

pelvic RT

Intracavitary application 70-75Gy

point A, when pelvic RT is combined

45-50 Gy and intracavitary 30-35 Gy.

Whole body irradiation was

compared with systemic therapy and

was found to have more side effects

than systemic therapy hence not

preferred.

Role of systemic therapy

Adjuvant systemic therapy plays an

important role in extrauterine disease.

Paclitaxel with carboplatin has been

used in systemic therapy. In patients

with high grade deeply invading

tumours of the uterine endometrium,

systemic therapy is used to prevent

distant metastasis.PFS is shown to

improve with adjuvant sequential

chemotherapy/RT.

Hormonal Therapy

In patients with endometrioid histology

hormonal therapy has been tried.

Patients with recurrent or metastatic

endometrioid tumours who have

low grade tumour with an indolent

course should be offered hormonal

treatment. Several hormonal agents

have been investigated including

megestrol acetate alternating with

tamoxifen, progestational agents

alone, aromatase inhibitors, tamoxifen

alone or fulvestrant with variable

response. Response depends upon ER/

PR receptor positivity, long diseasefree

interval, location and extent of

metastasis. Tamoxifen, acting through

ER, would increase expression of

PR and is thus likely to enhance the

sensitivity to medroxyprogesterone

acetate (MPA) ormegestrol acetate

(MA). In a systematic review, 11%–56%

of grade 1 and 2 tumours were shown

to respond to progestins, with the

response rate generally higher for PRpositive

tumours. Importantly, toxicity

was remarkably low, with the rate of

grade 3 and 4 events being less than

5%.

Overall, progestins remain a valid

option not only for patients with

recurrent receptor-positive tumours

after chemotherapy, but also for

patients with well differentiated (low-

86 / FUTURE MEDICINE / FEBRUARY 2019


STUDIES SHOWING IMPACT OF HORMONAL THERAPY IN

TREATMENT OF ENDOMETRIAL CARCINOMA

Trial Treatment given PFS OS Response rate

GOG

81(48)

GOG

12(49)

GOG

119(50)

GOG

168(51)

Ma et al

(52)

Group 1 : MPA 1000mg

daily (n=154)

Group 2: MPA 200 mg

daily (n=145)

2.5months 7

months

15%

MA 800 mg daily 3.2 11 25%

MPA 100 mg BD on

alternating weeks

+Tamoxifen 20 mg daily

continuous

33 3 13%

Anastrozole 1 mg/day 1 6 9%

Letrozole 2.5mg daily 4 9 9.4%

grade) endometrioid adenocarcinomas

that are positive for hormone receptors

but are not suitable for chemotherapy.

Menopausal hormone therapy

(MHT) in survivors

Endometrial cancer is considered

hormonally dependent hence the

use of HRT in patients who have

undergone oophorectomy was

previously considered harmful. The use

of estrogen replacement therapy in

patients with profound hypoestrogenic

symptoms may be considered after

counseling the patient especially in

women who had early stage low grade

endometrioid disease. In advanced

stage and high-risk cases use of

FEBRUARY 2019 / FUTURE MEDICINE / 87


selective estrogen receptor modulators

(SERMs) and non-hormonal therapy

should be considered as first line.

Fertility preserving therapy

Patients who want to preserve

childbearing function may be

considered for fertility preserving

options after thorough evaluation and

after explaining the deviation from

standard therapy. A pre-operative

counseling with reproductive medicine

and genetics specialists is desirable.

Young women with stage IA grade

1 disease without myometrial or

cervical involvement can be considered

for medical management with

progestational agents. They should

be carefully evaluated for other risk

factors like breast cancer, deep vein

thrombosis, myocardial infarction,

stroke, pulmonary embolism, and

smoking. The drugs used are

medroxyprogesterone acetate (400–

600 mg/day), megestrol acetate

(160–320 mg/day), and levonorgestrel

releasing intrauterine systems, with

or without GnRH analogues, have

been tried with variable success

rates. Patients need to be on followup

3-monthly with endometrial

biopsy with or without hysteroscopy.

Treatment should be discontinued if

disease persists for more than 6-12

months, or if there is progression

of disease (proven by histology) in

patients with stable disease after 6

months of treatment. Imaging should

be repeated after 6 months to rule out

myometrial involvement or extrauterine

or ovarian involvement. Definitive

treatment should be considered

when childbearing is complete, if

there is progression of disease or if

no reversal of disease after 12 months

of treatment. Patients on high dose

progesterone should also be monitored

for the side effects of progesterone.

RESPONSE TO MEDICAL

THERAPY FOR FERTILITY

PRESERVING MANAGEMENT OF

CARCINOMA ENDOMETRIUM

Author,

Year

Qin et al,

2016 (54)

Simpson

et al,

2014(55)

Gallos et al,

2012(56)

Intervention

MPA/MA 83%

MPA/MA 55%

MPA/MA

Others 76%

Ramirez

et al,

2004(57)

FOLLOW UP

Endometrial

resection

MPA/MA 75%

Response

rate

Every 3 months up to a period of two

years, then 6 monthlies up to 5 years

thereafter annually.

At every visit the patient is asked

in detail for symptoms of potential

recurrence and complete systemic

examination and pelvic examination

is performed. The use of imaging

andserumCA-125 is advised according

to symptoms. Vault cytology has

limited significance and is reserved for

patients with no prior radiation therapy.

Mammography can be done as per

standard guidelines for breast cancer

screening. For patients at risk of colon

cancer (Lynch syndrome), colonoscopy

must be requested everyone to two

years, to start at 20-25 years or 10

years before the youngest case in the

immediate family (American Cancer

Society recommendation for colorectal

cancer early detection).

Survival: Prognosis for carcinoma

endometrium is generally favourable.

Disease stage remain the most

significant prognostic factor (59) as

seen in Table B.

SCREENING

Currently routine screening for

endometrial cancer for asymptomatic

population with average risk or with

above-mentioned risk factors including

tamoxifen intake has not proven

beneficial and is not recommended.

The American Cancer Society (ACS)

recommends that women at the onset

of menopause be informed about risks

and symptoms of endometrial cancer,

i.e., unexpected bleeding or spotting,

and should be encouraged to report

immediately if these symptoms occur.

Women who are taking tamoxifen

therapy for prevention of recurrence

or development of contralateral

breast cancer are at increased risk of

developing uterine cancer. However,

routine screening with ultrasound

or endometrial biopsy is not

recommended. These women should

be advised to report if there is any

abnormal vaginal discharge or bleeding

per vagina.

Women with family history of Lynch

syndrome are at high risk of developing

carcinoma endometrium and should be

advised to undertake regular screening.

In these women screening should start

at the age of 35 years, or 5-10 years

prior to the diagnosis of any Lynch

associated cancer in the youngest

family member and consist of annual

endometrial sampling.

—Prepared as an outcome of ICMR

Subcommittee on Uterine Cancer

TABLE B

STAGE WISE SURVIVAL RATES FOR CARCINOMA ENDOMETRIUM

STAGE I A I B II IIIA III B III C IV A IV B

SURVIVAL 88% 75% 69% 58% 50% 47% 17% 15%

88 / FUTURE MEDICINE / FEBRUARY 2019


events

Maiden neuroscience session unfolds

secrets of consciousness

Kerala Literature Festival 2019 opens an era of science debates starting from this year

DIVYA CHOYIKUTTY

The first-ever session on

neuroscience at Kerala Literature

Festival (KLF) unfolded the hidden

capabilities of the human brain at the

fourth edition of the annual literary

event.

The session highlighted the scope

and relevance of a deep understanding

of neuroscience, and its possibilities in

modern healthcare.

Thus began an era of science

debates at Asia’s second-largest

literature festival that saw an illustrious

gathering of eminent authors, artists,

philosophers and activists discussing

and sharing insights with a vibrant

audience.

The session ‘Locating consciousness

in the brain’ marked its importance

at the event as the speakers

Dr K Rajasekharan Nair, an eminent

neurologist and science author,

Dr Vishwanathan Chathoth, a well-known

rationalist, and Dr Ethiran Kathiravan, a

genetic scientist and author, explored

the deep and complex neuronal network

in the brain. The session was moderated

by CH Unnikrishnan, founder & editor,

Future Medicine, India’s premium

medical science news magazine.

“Who we are is determined by the

activity that happens within our brain,

based on what we see, touch or hear,”

said Dr K Rajasekharan Nair. That is

how our external stimuli makes us.

The activities within the hundreds of

billions of neurons that make up the

complex neuronal network in our brain

“IF A DOCTOR KNOWS THE

STORY OF A PATIENT, HE

SURELY CAN BE A GREAT

DOCTOR AND A WRITER.”

— DR B EKBAL

determines all our actions, he says.

“We become materialistic when we

realise that consciousness is a process.

It does not have individuality,” said Dr

Vishwanathan, explaining that it is never

an entity. He explains consciousness as

a process that happens within the brain,

and that it can never be independent

of it.

He also described the hyper-normal

activity of the brain in autism, which

unlocks a special ability to perceive

things more intensely, inhibited in the

normal brain.

Exploring the scientific location of

consciousness, Dr Kathiravan explained

that it happens where the complex

neuronal network works together at

the same time. “Neuronal network is

very complex. When it works together

at the same time, there [it] creates our

consciousness.” he said.

Another key scientific session

— ‘Medicine and Literature’ — was

addressed by Dr M V Pillai, an eminent

physician specialised in Internal Medicine,

Hematology and Medical Oncology,

Dr Khadija Mumtaz, a well-known

Malayalam author and a physician,

and Dr B. Ekbal, a public health activist

and a neurosurgeon. It closely analysed

the relationship between literature

and medicine and criticised the

malpractices happening around the field

of medicine.

Connecting literature and medicine,

Dr Ekbal said, “If a doctor knows the

story of a patient, he surely can be a

great doctor and a writer.”

The four day event, which had 500

speakers and 180 sessions on topics

spanning from literature, media, politics,

religion, films to socio-economic issues,

was attended by 2.7 lakh audience.

90 / FUTURE MEDICINE / FEBRUARY 2019


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Dr Chhajer passed out his MBBS from

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SAAOL introduced the US FDA approved

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Could you explain what is ECP and its

advantages?

External Counter Pulsation therapy

is a wonderful treatment that can help

preventing and healing of all forms

of disease that stem from circulatory

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such as angina, coronary disease,

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ECP system consists of three sets of

92 / FUTURE MEDICINE / FEBRUARY 2019


inflatable pressure cuffs wrapped around

the calves and the lower and upper

thighs, including the buttocks. In

synchronization with each cardiac cycle,

obtained with an integrated 3-lead

ECG, the cuffs are sequentially inflated

from the calves to the buttocks during

diastole to produce an arterial retrograde

flow towards the aortic root to increase

coronary blood flow. ECP simultaneously

increases venous return to raise the

cardiac output. The cuffs are deflated

simultaneously before the onset of systole

to provide an empty vascular space,

reducing systemic vascular resistance

in the lower extremities to receive blood

ejecting from the heart, significantly

reducing the workload and oxygen

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The patients can feel the change after

7-10 days of therapy an indication of well

being which improves the circulation due

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with improved blood flow in affected

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function.

Innumerable research papers outcomes

state that the patients with heart failure

with varying degrees of seriousness (NYHA

Classes I II III IV, with class I being less

serious and class IV being most serious)

improve in their classification and could

be classified in less severe class due to

improved exercise tolerance and overall

well being.

How does the counter pulsation

technique function in the body?

ECP therapy, which was approved by

US FDA and in practice for more than 30

years, triggers the body to create tiny blood

vessels (known as collaterals) that act like

a natural bypass, carrying blood around

larger blocked vessels. Chest pain is then

reduced because the heart is again able to

receive oxygen rich blood.

It acts by decreasing the after load

that the heart has to pump against, and

increase the preload that fills the heart,

increasing the cardiac output. In this way,

ECP is similar to the intra aortic balloon

pump (IABP). Since it increases pressure

in the aorta while the heart is relaxing

(during diastole) ECP also increases blood

flow into the coronary arteries, which also

occurs during that phase.

Another theory is that cuff inflation/

deflation increases the force of the blood

flow to the heart, causing the cells lining

the blood vessels to produce chemicals

that widen the blood vessels, allowing

blood to flow through more freely.

Are there enough clinical studies to

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Yes, there are research papers and

clinical trials to support the same.

Published in peer reviewed medical

journals, these studies have demonstrated

ECP Therapy as a non-invasive, safe, low

cost and highly effective treatment for

patients with coronary artery disease.

There are 8 randomised controlled trials

(RCT) documenting the clinical outcomes

and mechanisms of action of enhanced

ECP Therapy. The most well known

RCTs were the multicentre study of

ECP (MUST) in the treatment of patients

with angina pectoris and Prospective

Evaluation of ECP Congestive Heart

Failure (PEECH) study. There is also

subgroup study analyzing data from the

PEECH trial for heart failure patients age

65 or older.

Another multicentre study of External

Counterpulsation (MUST-EECP) in

2006 to evaluate the safety and efficacy

of ECP on exercise-induced Myocardial

Ischemia and Anginal Episodes, which

was published in the Journal of American

College of Cardiology (Rohit R. Arora,

MD, Tony M. Chou, MD,† Diwakar Jain,

MD,‡ Bruce Fleishman, MD,§ Lawrence

Crawford, MD,\ Thomas McKiernan, MD,

Richard W. Nesto, MD# New York, New

York; San Francisco, California;

New Haven, Connecticut; Columbus,

Ohio; Pittsburgh, Pennsylvania; Maywood,

Illinois; Boston, Massachusetts et. all.),

have also shown that enhanced external

counter pulsation reduces angina and

extends time to exercise-induced ischemia

in patients with symptomatic CAD.

Treatment was relatively well tolerated

and free of limiting side effects in most

patients.

How critical is the role of ECP in “nooption”

patients?

A recent study (Anil Kumar Gothwal,

Sanjay Mittal, Sound Shore Medical Centre

of Westchester, New York Medical College,

New Rochelle, USA , and Escorts Heart

Institute and Research Centre,

New Delhi) concluded that refractory

angina is growing in prevalence and

has become an increasingly challenging

problem in clinical practice. While

various forms of treatment have been

tried, results from clinical studies

suggest that ECP therapy has the most

favourable risk/cost-benefit profile.

This therapy is the only FDA-approved

non-pharmacological approach to

refractory angina that has been supported

by sham-controlled data. It is also

recommended by the American Heart

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refractory angina as a class IIb indication,

though its usefulness/efficacy is relatively

less well established. Given the rapid

development of ECP over the past few

years, it is hoped that the use of this

modality will soon receive greater priority

than at present. In the future, more

patients are expected to benefit from this

innovative treatment for angina and other

cardiovascular conditions.

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

FEBRUARY 2019 / FUTURE MEDICINE / 93


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94 / FUTURE MEDICINE / FEBRUARY 2019


calendar

Upcoming conferences

FEBRUARY

1-2 SURGERY

Basic Surgical Skills Course

Dervan

1-3 OTORHINOLARYNGOLOGY

PHONOCON 2019: 15th Annual

Conference of the Association of

Phonosurgeons

Kolkata

5-9 GYNECOLOGY

All India Congress of Obstetrics

and Gynaecology (AICOG) 2020

Lucknow

6-10 PAEDIATRICS

Illness to Wellness Pedicone

Mumbai

7-9 NEUROLOGY

Neonatal Neurology: stateof-the-art

in inborn errors of

metabolism, seizures, and

pathophysiology of brain

damage Course

Bangalore

7-9 GASTRO-ENTEROLOGY

Annual Congress of Indian

Association of Gastrointestinal

Endosurgeons (IAGES)

Bhubaneswar

8-9 CLINICAL ANATOMISTS

Society of Clinical Anatomists

Chennai

8-10 PEDIATRICS

Conference of Indian Association

of Pediatric Anaesthesiologists

(IAPA)

New Delhi

8-10 PLASTIC SURGERY

Annual Meeting of Indian

Society of Cleft Lip Palate

and Craniofacial Anomalies

(Indocleftcon)

Varanasi

ONCOLOGY

Conference of Society of

Oncologic Imaging India

New Delhi

9-10 PEDIATRICS

IAPEN Clinical Nutrition Congress

(ICNC-2019)

Mumbai

13-14 RADIOLOGY

International Conference on

Public Health, Radiology, Nuclear

Medicine & Imaging

Chennai

14-15 NEUROSURGERY

International Conference on

Conjoined Twins (ICCT)

New Delhi

14-17 ONCOLOGY

MEDINSPIRE - An International

Multidisciplinary Medical Summit

Mumbai

15-16 CLINICAL RESEARCH

ISCR Conference

New Delhi

15-17 PHYSIOTHERAPY

Society of Indian Physiotherapist

Annual Conference (Society of

Indian Physiotherapist Annual

Conference)

New Delhi

15-17 NEUROLOGY

Annual Conference of the Indian

Society of Neuroanaesthesiology

and Critical Care (ISNACC)

Gurgaon

HEPATOLOGY

Advanced Institute of Liver

& Biliary Science (AILBS)

International Conference 2019

New Delhi

21-23 ORTHOPAEDICS

Ranawat Orthopaedic

Conference

New Delhi

21-24 CARDIOLOGY

ASCVTS & IACTSCON

Chennai

22-24 CARDIOLOGY

World Congress on Cardiac

Imaging Clinical Cardiology

(WCCICC)

Mumbai

ANAESTHESIOLOGY

Conference of the Indian

Association of Cardiovascular

Thoracic Anaesthesiologists

(IACTACON)

Kolkata

NEUROLOGY AND

PSYCHIATRY

MDSICON

New Delhi

28-3 CARDIOLOGY

India Live Conference

Mumbai

MARCH

1-2 GASTROENTEROLOGY

ISTH–ILBS Symposium on

Coagulopathy in Liver Disease

2019

New Delhi

1-3 GYNECOLOGY

ISAR Conference

Mumbai

2-3 GASTROENTEROLOGY

ISTH–ILBS Symposium on

Coagulopathy in Liver Disease

2019

New Delhi

8-10 NEUROLOGY

ISAR Conference

New Delhi

8-10 DIABETES

International Diabetes Summit

(IDC)

Pune

8-10 NEUROLOGY

Joint Annual Conference of

Indian Epilepsy Society and

Indian Epilepsy Association

New Delhi

9-10 GYNECOLOGY

India Fertility Show-2019

Bangalore

9-11 IMMUNODEFICIENCY

DISEASES

International Conference on

Primary Immunodeficiency

Diseases

Mumbai

11-12 CARDIOLOGY

ICCA Stroke 2019 - Acute Stroke

Interventions and Carotid

Stenting

New Delhi

16-17 NEUROSURGERY

Indo Japan Neurosurgical

Meeting (IJNM)

Secunderabad

24-25 EDUCATION & TRAINING

International Conference on

Medical & Health Science

(ICMHS)

Pune

28-29 EDUCATION & TRAINING

International Conference on

Medical & Health Science

(ICMHS)

Panjim

The announced dates of the conferences may change

96 / FUTURE MEDICINE / FEBRUARY 2019


ook review

THE IMPORTANCE OF

BEING INFORMED

NAVIGATING LIFE

WITH MIGRAINE AND

OTHER HEADACHES

William B Young, MD,

FAAN, FANA, FAHS and

Stephen D Silberstein,

MD, FAHS, FAAN, FACP

pp241

Oxford University Press

Managing a neurologic disorder is

new territory. To effectively manage

a neurologic condition, the person

should be armed with new information and

new skill sets. Informed involvement of the

patient in the treatment programme can

lead to better care and better outcomes.

But one cannot escape the question of how

such information could help in curing the

condition.

Presenting their book, Navigating Life

with Migraine and Other Headaches, authors

William B. Young and Stephen D. Silberstein

seek to address this question, underscoring

the importance of being informed about your

condition.

Headache is one of the most common

complaints patients consult neurologists for.

It is the seventh most common symptom

for which they visit primary care providers.

Headache is such a common symptom

that it often goes overlooked, undertreated,

overtreated or untreated. Many people think

that “nothing can be really done”. While

many others, including some doctors, seem

to cherish certain notions: For example,

without aura, tingling, numbness and blurred

vision, a headache cannot truly be called

migraine. But it remains a fact that most of

the people suffering from migraine do not

experience aura or any of these symptoms.

You can avail the best new treatments

if you land up with the right expert. The

key requisite is that you should be armed

with the right kind of information about the

condition.

Spread across three sections, the book

explains migraine and other headaches

in simple terms. All the known forms of

migraine, migraine equivalents, their triggers,

symptoms, patterns as well as the hormonal

aspects of the condition are discussed at

length. Then it goes on with various drugs

as well as other alternative and behavioural

treatments for migraine. The authors point

out that migraine can occur at any age. Even

very young children are suspected of having

migraine, but it is difficult to diagnose it until

they learn to speak.

Sinus headaches and headaches related

to disorders of the neck, post-trauma,

trigeminal neuralgia etc are classified under

Secondary Headaches and Neuralgia section.

THE MORE PRECISELY YOU PIN

DOWN AND COMMUNICATE

YOUR PROBLEM, THE MORE

LIKELY YOU WALK OUT OF

YOUR DOCTOR’S OFFICE WITH

A PLAN RIGHT FOR YOU

While listing some of the headaches that

require urgent medical attention, the book

also mentions some of the unusual type of

headaches such as ice pick headaches and

sexual activity headache.

The book provides up-to-date and useful

answers to the questions that concern most

to the patients and caregivers, illustrated

with real-life experiences of patients and

families.

Physician’s decision is not “a one

shoe fits all” enterprise. The more precisely

you pin down and communicate your

problem, the more likely you walk out of your

doctor’s office with a plan right for you, says

the book.

FEBRUARY 2019 / FUTURE MEDICINE / 97


OUR DEVOTION THAT MAKES

THE DIFFERENCE

DR INDIRA HINDUJA

Senior Gynaecologist and ART Specialist

We in India often have the tendency to get

excited about a big breakthrough or a curious

discovery that has happened in the West,

expressing deep regret that our country lags far behind.

But what we do not realise is the fact that this country is

equally, if not more, capable of doing such things if we

put our real potential to work. We may have constraints

like inadequate resources and infrastructure, but these are

resolvable issues if one has the will to pursue his or her

passion with full devotion.

I don’t think that Indian brains are any less as far

as research in science and technology is concerned,

especially in the area of biomedical research. In this field,

India has got many natural advantages too, including the

diverse nature of the human race, wider genetic variations

and a broader lifestyle and disease profile, among others.

I want to tell new generation doctors and aspiring

biomedical researchers that we are not inferior to anyone

and we have the brightest brains in this country itself.

What we lack often is the commitment and the courage

to take on the challenges.

Be passionate about what you want to do in life and

have full faith in your capabilities to take that dream

forward. More importantly, try not to find faults with

others for your failures. Instead, learn from your mistakes

and take your failures as bigger steps towards success.

One should realise that blaming others for one’s own

failure is just an excuse and will never help in achieving

progress. On the contrary, failures may prove to be the

biggest opportunities for you later, if you overcome them

and proceed further.

In my journey of IVF research, I have many a time felt

terrible when I missed opportunities or faced difficulties

in pursuing my work due to sudden departures of

teammates or even accusations and non-cooperation

from organisations and senior colleagues. But now, I feel

that many such difficult situations have actually helped

me develop the courage to become more committed and

deeply involved in my work, which has ultimately helped

me achieve what I wanted.

If you are fully devoted to something that you are

passionate about, there will open a hundred other doors

even if the one in front of you is closed. Once you decide

to take the plunge and show your dedication, trust me,

everything else, including money and infrastructure, will

follow. From my own experience, I can confidently say that

nothing can stop you from your achievements if you are

determined to take the mission on. There will be people

to push you up as well as pull you down. But both these

should not affect your determination and hard work.

— As told to CH Unnikrishnan

98 / FUTURE MEDICINE / FEBRUARY 2019


RNI Number KERENG/2012/44529

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