FM NOVEMBER 2018 ISSUE - digital edition

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VOL 5 | ISSUE 7
PAGES 100
NOVEMBER 2018
FUTUREMEDICINEINDIA.COM
IMMUNOTHERAPY FOR
LUNG
CANCER
WILL CHECKPOINT BLOCKERS ALTER
WELL-ENTRENCHED TREATMENT ALGORITHMS?
COPD REGULATORY DRUG RESISTANCE CASE REPORT
EBV INTERVENTION
IN EMPHYSEMA
MCI IN DIRE
STRAITS
TACKLING
EMERGING
PATHOGENS
ABERNETHY -
AN UNUSUAL
SUSPECT

editor’s note
NOVEMBER AUGUST 2018 2018 / Vol: / Vol. 5 5 / Issue: / Issue 4 7
Founder & & Editor Editor
CH Unnikrishnan
Executive Editor Editor
S Harachand
Harachand
Science Editor
Science Editor
Dr Rajanikant Vangala
Dr Rajanikant Vangala
Consulting Editors
Dr Copy Shivanee Editor Shah
Jeetha Sreejiraj D’Silva Eluvangal
Dr Consulting Sumit Ghoshal Editors
Copy Dr Shivanee Editor Shah
Sreejiraj Dr Sumit Ghoshal Eluvangal
Curator-cum-Correspondent
Photo Editor
Divya
Umesh
Choyikutty
Goswami
Photo Editor
Illustrator
Umesh Goswami
Mathewkutty J Mattam
Design Editor
Gopakumar Advisory BoardK
Dr Devi Shetty
Illustrator
Mathewkutty
Dr B S Ajaikumar
J Mattam
Dr Shashank Joshi
Advisory
Dr Prof. Arumugam
Board
S
Dr Devi Shetty
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Dr B S Ajaikumar
Dr Dr N Shashank K Warrier Joshi
Dr Sekar Prof. Seshagiri Arumugam S
Dr Knowledge I C Verma Partner
Dr SGRF N K Warrier
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Partner
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Dear Doctor,
Dear Doctor
Oncology is again in focus for us, which should not come as a surprise given
the
We
extent
know you
of the
are
problem.
busy. It is
When
always
the
reassuring
entire world
that
of
the
medical
trust and
research
faith of
is
firefighting to counter this monster, it will remain in our focus till we can be
hundreds of patients in your healing touch keeps you busy in this noble
sure that we have brought you the very last bit of technological breakthrough
profession. In the hectic practice, it’s quite natural that you might miss
on this topic.
out on some of the latest developments in emerging medicine. In this era
After an in-depth cover on liquid biopsy — a new revolutionary tool in the
of innovation, medical science is getting redefined almost by the day. Old
hands of oncologists for cancer tracking — in August, we now bring you the
technologies are being replaced by the new in the blink of an eye. Robots
latest in lung cancer, the most complex cancer to deal with. Immunotherapy
and artificial intelligence are taking over a good part of the procedures,
and a few other novel techniques are here to break new ground in managing
while genomics and molecular science unveil the mysteries of life further.
lung cancer, which has otherwise proven to be difficult to tame.
We are fortunate to have such breakthroughs as they help specialists like
COPD has been another largely prevalent but difficult-to-treat disease in
you rise above the expectations of today’s informed patient.
India due to limitations in traditional treatments. We are also excited to tip
you about the new hope in endobronchial valve treatment in patients with
emphysema.
Similarly, it is also a time when India is witnessing revolutionary growth in
healthcare industry, especially in the private sector, wherein an increasing
I am sure you are fully aware of the other healthcare crisis that India
and
number
the world
of doctors
at large
are
are
taking
likely
up
to
multiple
face in the
roles
very
of clinician,
near future
researcher
— the fastemerging,
and
entrepreneur.
antibiotic-resistant
This requires expansion
pathogens.
of your
Our science
focus to
editor
a wider
Dr Rajanikant
canvas. In
Vangala this context, sheds it becomes light on the important urgent need how to a busy stop professional irrational antibiotic like you use can at all
four keep stages pace with of treatment these latest — diagnosis, developments prescription, in a quick dispensing and easy and way. patient
adherence.
At With Future a variety Medicine, of other which scientific is conceived as well and as crafted regulatory by a updates, team of including senior
the journalists, hot Union scientists vs IMA and debate doctors, on the our proposed aim is to NMC help Bill, you we’ve do just ensured that. We that
you are equipped have an exciting to bring and you well-packaged the latest from information the science tool of in care your from hands across this
time. the world in an interesting and convenient way, supplemented by the best
of Happy views and reading, analyses from the masters in each field. We present you this
specialised knowledge vehicle that plugs you into the emerging world of
care seamlessly. Come, let’s join hands in this information journey.
CH Unnikrishnan
editor@futuremedicineindia.com
C H Unnikrishnan
editor@futuremedicineindia.com
www.futuremedicineindia.com futuremedicineindia FutureMedIndia
AUGUST 2018/ FUTURE MEDICINE / 3

Vol 5 Issue 7
November 2018
₹ 250.00
VOL 5 | ISSUE 7
PAGES 100
NOVEMBER 2018
FUTUREMEDICINEINDIA.COM
IMMUNOTHERAPY FOR
LUNG
CANCER
38
WILL CHECKPOINT BLOCKERS ALTER
WELL-ENTRENCHED TREATMENT ALGORITHMS?
CASE REPORT DRUG RESISTANCE REGULATORY COPD
ABERNETHY - TACKLING
MCI IN DIRE EBV INTERVENTION
AN UNUSUAL EMERGING
STRAITS
IN EMPHYSEMA
SUSPECT
PATHOGENS
REGULAR FEATURES
CASE REPORT
GENE THERAPY
FOR BLINDNESS
06 Letters
08 News updates
12 Regulatory
34 Drug approvals
50 Education
56 Research snippets
66 Hospital news
68 Insurance
70 Public health
76 Research
78 Orthopaedics
82 Devices
88 Events
94 Calendar
95 Book review
98 Holy grail
Columns
20 THE CATALYST
Muralidharan Nair
58 TRIALOMICS
Dr Arun Bhatt
60
POLICY
TAKING OUT
THE STIGMA
Notwithstanding the new
mental health act, experts feel
protecting the rights of the
mentally ill will be
an uphill task
12
REGULATORY
MCI IN DIRE
STRAITS
The fate of the medical council
hangs in balance as govt
enforces a governing body
through an ordinance
14
DRUG RESISTANCE
TACKLING
EMERGING
PATHOGENS
Stopping irrational antibiotic
use in all the four stages of
treatment cycle is the
need of the hour

COPD
64
EBV INTERVENTION
IN EMPHYSEMA
Endoscopic
lung volume
reduction using
endobronchial
valves is an
emerging
option for COPD
patients
Cancer
immunotherapy
has been in the
doghouse for
decades.
54
STRAIGHT TALK
“I AM IN FAVOUR OF
OPEN ACCESS, IT’S
A GOOD MODEL”
Myles Axton
Chief editor, Nature Genetics
Dr Vishva M Dixit
Vice President
and Staff Scientist,
Physiological
Chemistry at
Genentech, San
Francisco, CA.
22
COVER STORY
IMMUNO PATH TO
LUNG CANCER
Immunotherapy comes as a silver lining
for the sufferers of a malignancy which
has the highest incidence and the
bleakest prognosis

REGULATORY DIAGNOSTICS HEAD & NECK CANCER CASE REPORT
letters to the editor
COMBO-DRUGS
ON THEIR
WAY OUT?
MICRODELETION:
LOST IN
TRANSLATION
EXCITING FRONTIERS
KNOWING
ORAL CANCER
STAGING BY
DEPTH OF INVASION
Roll of ECG in
epilepsy diagnosis
₹ 250.00
VOL 5 | ISSUE 6
PAGES 100
OCTOBER 2018
FUTUREMEDICINEINDIA.COM
NON-INVASIVE PRENATAL
SCREENING ENTERS
THE UNBORN
HOW SHE
REGAINED
HER LOST TASTE
The Editor
We were pleased to read the
article titled “Heart rhythm
disorders mimicking epilepsy”
by Dr. Shivanee Shah in Vol.
5, Issue 5, bringing this issue
to the notice of the readers.
The article failed to mention
that these patients have the
“Long QT syndrome”. Such
families have an abnormality
in the ECG, which gives a clue
to the presence of the Long
QT syndrome. Prolongation
of QTc more than 440ms
(milli seconds) points to this
diagnosis. We have seen
more than 100 families of
this syndrome at our Institute
over a period of 7 years.
The patients present with
a history of sudden loss of
consciousness, truly a syncopy,
but often misdiagnosed as
epilepsy. These defects arise
due to defects in cardiac
channels that control the
rhythm of the heart. In cases
with rhythm disturbances of
the heart, ECG should always
be done in patients and the
parents. Commonly, Long
QT and Brugada syndromes
(BrS) show specific types of
abnormalities on the ECG.
They also have different
triggers. For example,
symptoms in patients with
LQT1 occur due to exercise/
stress, while in LQT2 patients
due to sudden noises/
emotions and patients with
LQT3 and BrS have symptoms
during sleep. Occasionally,
these patients may have a
normal QTc/ECG but still have
defect in the gene. The most
definite test for diagnosis in
these patients is to sequence
the channelopathy genes.
Of 100 patients we studied,
mutations were identified
in 45. This not only helps to
confirm the clinical diagnosis,
but aids in detecting
asymptomatic mutation
carriers among relatives by
cascade screening, counseling
for prenatal diagnosis, and
making effective treatment
plan. We carried out cascade
screening in 42 families, and
mutations were identified
in atleast one of the two
parents, most (95%) of whom
were asymptomatic. Of the
nineteen siblings screened,
sixteen were identified with
mutations (84%) of which
eleven were asymptomatic
(69%). Majority of mutations
identified were novel and
different than those reported
in the West. This was the first
molecular cohort study of
LQTS syndrome and Brugada
syndrome patients of Indian
origin. We have published
our results [Vyas B, et al.
Am J Med Genet A. 2016
Jun;170(6):1510-9; Vyas B, et
al. Indian Pacing Electrophysiol
J. 2016 Jan-Feb;16(1):8-18].
In conclusion, we would like
to emphasize that ECG should
be performed in all cases with
sudden loss of consciousness
before making the diagnosis
of epilepsy.
Bijal Vyas-Bhatia, Ratna Puri
and Ishwar Verma
Institute of Medical Genetics
and Genomics.
Sir Ganga Ram Hospital,
New Delhi
icverma@gmail.com
Very relevant
Sir
The cover-story and the
interview in the October
edition made the reader
really cognizant of the
relevant ideas, information
and existing chasms in the
field. The contents in general
provide a great informational
platform for medical students,
practitioners and basically any
science readers.
Arundhati
Bangalore
Exhilarating
Hi
Having read the previous
editions of Future Medicine,
I feel privileged to mention it
“exhilarating”. The magazine
seems to be a pioneer
project and gives a fresh
feeling to the readers with
well-explored themes. The
authors offer great insight
into issues related to the
urgent medical needs and
ongoing developments, with
well outlined case-study and
interviews. My best wishes to
the future endeavors of the
magazine.
Dr Preeti Kamal
Ghaziabad
Cheap robotic surgery
Dear Sir
I would like to comment
on Prof. Liselotte Mettler’s
optimism that India is about
to make the big revolution
in cheaper robotic surgery.
It’s really wonderful to hear
this from one of the highly
reputed experts in the field of
gynaecology.
Congrats on your initiative
of Future Medicine, intended
on converging relevant
advancements and chasms in
the medical field. Experienced
a reader friendly approach,
and appreciate the well
written, precise quality of
the contents put forward.
Expecting more from the
magazine in its subsequent
edition. Best wishes.
Sunesh Waghmare
Pune
Excellent work
Hello
It is a great magazine
with well framed contents
including exclusive interview
with renowned doctors
and latest news on the
progressing fields of medical
science. The magazine shows
its excellence in being up-todate
promoting the readers to
be aware of the on goings in
the field. Excellent work.
Jina Bodhisatwa
Raipur

A medical science and news magazine for every new-age
clinician. It empowers doctors with the most relevant updates,
trends, case studies, expert views, knowledge exchange,
hospital management and latest breakthroughs in medical
science. To be relevant in the future of care, subscribe today.
AUGUST 2018/ FUTURE MEDICINE / 59

news updates
Labels on fluoroquinolones should
alert on mental health risk: DCGI
India’s drug regulator has
directed safety labelling
changes for antibiotics
belonging to the class of
fluoroquinolones to strengthen
warnings about risks of mental
health side effects and serious
blood sugar disturbances.
The Drugs Controller
General of India (DCGI) made
the labelling regulations for
these antibiotics stricter after
the recommendation of its
Antimicrobial and Antiviral
Subject Expert Committee.
Through an order, the
DCGI has directed all state
drug controllers to ensure
immediate implementation of
the new labelling norms on
all fluoroquinolone antibiotics
such as levofloxacin,
ciprofloxacin, moxifloxacin,
ofloxacin and gemifloxacin.
Apart from the cautionary
note on the label saying
the drug “may cause low
blood sugar and mental
health-related side effects”,
the package insert and
promotional literature
should mention: “The drug
may cause low blood sugar
and mental health-related
side effects. Low bloodsugar
levels, also called
hypoglycemia, can lead to
coma. The mental health side
effects are more prominent
and more consistent across
the systemic fluoroquinolone
drug class”.
In July, USFDA mandated
a new class-wide labelling
change requiring that mental
health side effects be listed
separately from other central
nervous system side effects
across fluoroquinolone
antibiotics.
Mental health side effects
to be included in the labeling
across all fluoroquinolones
are disturbances in attention,
disorientation, agitation,
nervousness, memory
impairment and delirium.
Additionally, the FDA
required new labelling for all
systemic fluoroquinolones
to explicitly reflect the
potential risk of coma with
hypoglycemia.
LifeCell
introduces DNA
screening test
for newborns
LifeCell International, a stem
cell bank and a mother &
baby diagnostics company,
launched RightStart - an
integrated DNA test for
newborns to detect over 50
medical conditions.
The technology has been
found to drastically reduce
false-positive reporting,
thereby avoiding unnecessary
follow-up tests, LifeCell said.
The current process
of newborn screening for
abnormal metabolic profile
warrant further testing for
confirmation.
RightStart newborn
screening does not require
an additional sample since
Netmeds buys telemedicine portal JustDoc.com
Netmeds.com, India’s leading online
pharmacy, announced that the
company has acquired telemedicine
portal JustDoc.com in a cash and stock
transaction.
Founded in 2015, JustDoc.com is an
online consulting portal that connects
patients with clinicians via a technology
platform. JustDoc has served thousands
of patients throughout India through
their website and app, according to the
company.
Netmeds.com provides prescription
medicine and healthcare products to
more than 3,000,000 patients across
India and serves over 19,000 pin codes.
JustDoc.com offers video medical
consultation in the country by connecting
users to doctors. Netmeds will leverage
the combined strengths of both
companies. JustDoc technology will be
integrated with Netmeds.com.
Netmeds.com’s e-pharma portal
offers prescription and over-the-counter
(OTC) medicine along with other health
products.
8 / FUTURE MEDICINE / NOVEMBER 2018

a portion of the sample
collected initially can be used.
Also, no additional costs
would need to be incurred by
the parents.
LifeCell had tied up with
Dr Mary Seeterlin, who has
a decade of experience
in newborn screening
programme at Department
of Public Health in Michigan
and is the co-author of
several guidelines and
publications on the subject,
to serve as a consultant to
the programme.
In India, adoption of
newborn screening has been
weak, largely due to low
awareness and also due to
the lack of reliability of test
results, according to the
company.
iGenetic
launches
TruTest labs
iGenetic Diagnostics, a
pathology labs chain, has
launched TruTest Laboratories
with an aim to provide
advanced diagnostics.
TruTest Laboratories is
operational pan-India, with
centres located in Mumbai,
Delhi, Bengaluru, Hyderabad,
Indore, Nagpur, and Kochi.
The lab network will offer
tests ranging from routine
biochemistry to molecular
pathology.
“There is a huge demand
for accurate diagnostic
solutions, which can provide
faster results and are
affordable for the masses.
The growing threat of various
communicable and noncommunicable
diseases
has made it mandatory for
people to go for regular
health check-ups,” said
Arunima Patel, founder, and
managing director, iGenetic
Diagnostics.
Many diseases are
asymptomatic initially and
show symptoms at later
stages, while many infections
share common or similar
symptoms. Regular testing
has become the need
of the hour for early
diagnosis and treatment, she
added.
Metropolis
plans to enter
capital market
M
etropolis Healthcare
Ltd, one of the leading
diagnostics companies in
India, has filed an offer
document with the SEBI,
proposing an Initial
Public Offering (IPO) of
its equity shares.
The Equity Shares
offered through
the Red Herring
Prospectus are
proposed to be listed
on BSE and NSE.
The company’s IPO
comprises up to 15.3 mln
equity shares, consisting
of an Offer for Sale of up to
Handbook on benefits
of vitamin E launched
Merck Consumer Health India has launched a
handbook that highlights the benefits and
widespread utility of vitamin E. Titled “Vitamin E:
Clinical Applications and Evidences”, the book has
been edited by Dr YK Gupta and Dr AC Anand, leading
health experts.
The book focuses on the manifold uses of vitamin E
as a supplement.
According to Merck, People in India are not entirely
aware of the extensive benefits offered by vitamin E
and the book is a step toward increasing awareness
about the benefits of vitamin E, backed by scientific
data and clinical evidence.
More than 90 percent of India is unaware of
vitamin E applications and advantages. Educational
initiatives like these have become the need of the hour,
the company said. Extensive knowledge about vitamin
E in the book underlines Merck’s efforts towards
keeping Indian medical practitioners abreast of latest
medical knowledge, thus giving way to a healthier
future for the general population, the company said.
5 mln shares by promoter
Dr. Sushil Kanubhai Shah
and up to 10.3 mln equity
shares by investor CA Lotus
Investments. The offer
includes a reservation of
up to 3 lakh equity shares
for subscription by eligible
employees.
The Book Running Lead
Managers (BRLMs) are JM
Financial Limited, Credit
Suisse Securities (India)
Private Limited, Goldman
Sachs (India) Securities
Private Limited, HDFC
Bank Limited and Kotak
Mahindra Capital Company
Limited.
Metropolis conducts
operations through a
laboratory and service
network which covers
173 cities in India. During
NOVEMBER 2018 / FUTURE MEDICINE / 9

the financial year 2018, it
conducted approximately
16 million tests from
approximately 7.7 million
patient visits, as per company
data.
MedGenome
launches gene
test for CLL
MedGenome has
introduced the IGHV
(immunoglobulin heavy
chain) gene mutation
testing for chronic
lymphocytic leukemia (CLL)
diagnosis.
Current guidelines for
CLL management involves
a comprehensive molecular
workup that includes some
genetic tests performed on
the patient’s blood or bone
marrow sample. The tests
enable oncologists to assess
the prognosis of the disease
subtype and further manage
the disease by personalized
therapy.
Four of the important
biomarker tests includes
those for somatic
hypermutations (SHM) of the
immunoglobulin heavy chain
variable region genes (IGHV)
and somatic mutations of
genes such as TP53, NOTCH1
and SF3B1.
Based on the SHM value,
the disease is classified
Mutated CLL (M-CLL) and
Unmutated CLL (U-CLL).
The status of SHM has a
clear influence on the median
survival of CLL patients.
Presence of SHM of the IGHV
region is strongly predictive
of a good prognosis, while a
lack of SHM predicts a poorer
prognosis. Patients with an
unmutated IGHV gene
usually have a more
aggressive disease and
shorter overall survival.
Patients with a mutated
IGHV gene usually have a
less aggressive disease, with
longer overall survival, said
the company.
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Cardiologist invests US$60 m
in DEB device firm
An Indian-American
cardiologist and
entrepreneur, Dr Kiran Patel,
has invested $60 million
in a medical company that
develops sirolimus-coated
balloons as an alternative
to stents used in coronary
angioplasty.
Concept Medical Inc, a
Florida-based medical device
company, has approached
USFDA for an Investigational
Device Exemption (IDE) for the
world’s first sirolimus-coated
balloon.
The company can
commence clinical studies
to determine the safety and
efficacy of the device after
obtaining IDE from the US
drug regulatory agency.
According to the company,
the investment by Dr Kiran
Patel will pave way for clinical
studies using the device.
The fund will be utilised
to augment clinical data and
clinical registries to qualify
for re imbursement in the
European markets, where the
company has commercially
launched the product, said
Concept Medical Inc.
MagicTouch-DEB, the
sirolimus -coated balloon with
application in coronary and
peripheral artery disease, is
currently available in many
parts of the world.
Extended applications
of MagicTouch-DEB in renal
transplant, erectile dysfunction
and Arteriovenous Fistula/
Arteriovenous Graft (AVG)
for renal dialysis patients are
under ongoing clinical trials.
The company has initiated
a series of global clinical
programmes for MagicTouch-
DEB including Nanolute,
Eastbourne, Transform-I,
Transform-II. They are also
pursuing regulatory pathways
in Japan and China.
Concept Medical has a
manufacturing subsidiary in
India, Envision Scientific Pvt.
Ltd., where all their products
are made. A portion of the
funds will also be utilized to
bolster the manufacturing
operations. The company’s
global distribution and
marketing network is operated
from offices in India, Singapore,
Netherlands and Brazil. ESPL
also has an India-focused,
marketing and distribution
business.
A Board-certified
cardiologist, Dr. Patel
completed his residency
in Internal Medicine in
New Jersey after obtaining
a medical degree from
Gujarat University in India
and an internship in Africa.
In 1982, he completed his
fellowship in Cardiology from
a Columbia University-affiliated
programme.
Dr. Patel subsequently
entered the managed care
industry and was the chairman
of WellCare of Florida till 2002.
Chan Zuckerberg and Gates
Foundation partner to track
infectious diseases
The Chan Zuckerberg
Biohub (Biohub) and
the Chan Zuckerberg
Initiative (CZI) have
launched IDseq, an open
source cloud-based
analysis platform to detect
and respond to infectious
disease outbreaks around
the world.
The tool works by
rapidly combing through
terabytes of metagenomic
data for pathogens
in a given sample. By
identifying diseasecausing
pathogens,
IDseq can provide an
actionable report of what
is happening on the
ground in labs and clinics
anywhere in the world.
In a recent pilot
project, IDseq has been
employed to identify
the presence of the
mosquito-borne viral
chikungunya disease in
the spinal fluid of patients
at Dhaka Shishu Hospital,
the largest paediatric
hospital in Bangladesh.
Based on this information,
follow-up testing
identified additional
cases of neuroinvasive
chikungunya from the
same time period that
were previously labeled
“mystery cases.”
To enable broader
access to IDseq and
valuable on-the-ground
feedback, the Bill &
Melinda Gates Foundation
announced a new
funding opportunity for
global health workers
via the Bill & Melinda
Gates Foundation Grand
Challenges Explorations
Initiative. Awardees will
receive molecular biology
and bioinformatics
training and free access
and compute on the
IDseq platform supported
by CZI, along with the
necessary equipment
and supplies immediately
needed to begin work in
their own countries.
The Biohub and
CZI plan to make IDseq
available within the
next year to partner
organizations, and then
more broadly afterward.
The software itself is
open-source and freely
available.
The CZ Biohub is
a non-profit medical
research organization
collaborating with the
University of California,
Berkeley, Stanford
University and the
University of California,
San Francisco.
The Chan Zuckerberg
Initiative, founded by Mark
Zuckerberg and Priscilla
Chan is a philanthropic
organization.
NOVEMBER 2018 / FUTURE MEDICINE / 11

egulatory
MCI IN DIRE STRAITS
The fate of the medical council hangs in balance as govt enforces a governing
body through an ordinance
DR SUMIT GHOSHAL
Nearly two months after the Union
Government promulgated an
ordinance replacing the existing
Executive Committee of the Medical
Council of India (MCI) with a nominated
board of governors, nobody is sure what
is going to happen next. The Sept 26
notification, titled Indian Medical Council
(Amendment) Ordinance 2018, has
effectively placed the MCI in suspended
animation and blocked the process of
election or nomination of its executive
members until further notice.
“Whereas Parliament is not in
session and the President is satisfied
that circumstances exist which render
it necessary for him to take immediate
action…” the text of the ordinance says
by way of introduction. In addition, the
ordinance mentions that the Board
of Governors would be assisted by a
Secretary General who may be deputed
from among the government’s own
cadres or appointed from outside on a
one-year contract.
While the ordinance does not spell
out the ‘circumstances’ which impelled
President Ramnath Kovind to take
this decision, independent reports in
the media suggest that an Oversight
Committee appointed by the Supreme
Court to look after the affairs of the MCI
was being ignored by those in charge.
The Supreme Court committee had been
formed after repeated allegations of
corruption against some members of the
MCI Executive Committee.
In the past few years, the MCI had
come under stringent criticism from
IN THE PAST FEW YEARS,
THE MCI HAS COME UNDER
STRINGENT CRITICISM
FROM THE SUPREME
COURT AS WELL AS THE
PARLIAMENTARY STANDING
COMMITTEE.
the Supreme Court as well as the
Parliamentary Standing Committee for
Health and Family Welfare. In its 92nd
report, the Standing Committee wrote
in September 2015: “The situation
has gone far beyond the point where
incremental tweaking of the existing
system or a piecemeal approach can
give the contemplated dividends. That
is why the committee is convinced that
the MCI cannot be remedied according
to the existing provisions of the Indian
Medical Council Act, 1956 which is
certainly outdated.”
The latest ordinance has to be
ratified through suitable legislation
within six months from the date of
promulgation, or by the end of March
2019. Meanwhile it has evoked strong
criticism from the Indian Medical
Association (IMA) and other professional
bodies.
“My main point of opposition
is that the Board of Governors is a
nominated body which has replaced
a democratically elected body; that
is, the MCI Executive Committee,” says
Dr K K Agrawal, IMA’s immediate past
president and the president-elect of the
Confederation of Medical Associations
of Asia and Oceania as well as the
president of the Heart Care Foundation
of India. “Hence, by its very nature, the
government action is undemocratic.”
Besides, Dr Agrawal adds, the Board
comprises entirely of doctors belonging
to the government cadres, while private
doctors are nowhere in the picture.
“Who will deal with the problems of the
private doctors?” he asks rhetorically.
Also, there are no representatives from
12 / FUTURE MEDICINE / NOVEMBER 2018

any of the universities, nor anybody to
represent state-level issues.
A larger issue which could render
the latest ordinance unnecessary and
obsolete is that of the National Medical
Commission (NMC). The draft NMC bill
has been pending since 2016, after
undergoing several modifications during
these two years, and is likely to come up
for discussion in the winter session of
Parliament which is scheduled to begin
in late November or early December.
It will most probably be the last
opportunity for a discussion on the Bill in
the current Lok Sabha, whose term ends
in June 2019.
Under the NMC Bill, which was
cleared by the Union Cabinet as far back
as August-September 2016, the Medical
Council will be replaced by the NMC.
The new body would comprise four
subordinate bodies: the Undergraduate
Medical Education Board, Postgraduate
Medical Education Board, the Medical
College Assessment and Ratings Board
and the Board of Medical Registration.
Thus the NMC would take over all the
important functions of the MCI.
Senior medical teachers also point
out that the NMC Bill could transform
the state of medical education in the
country, perhaps for the better. One of its
proposals is to introduce a common final
MBBS examination for all the medical
colleges in the entire country. This would
surely be an unprecedented innovation
for medical education. The problem of
varying standards of medical training
imparted in various parts of the country
would thus become a thing of the past.
The IMA has been conducting a
fierce campaign against the NMC Bill
ever since it was made public two years
ago on the grounds that the new body
would almost entirely be composed of
bureaucrats and government doctors,
with no elected representatives.
In addition, the IMA website
describes the NMC Bill as anti-poor
and anti-people, while alleging that “all
the state health universities have been
marginalized into an advisory role.” Also,
the Parliamentary Standing Committee,
to which the Bill had been sent for
consideration, had recommended as
many as 24 amendments. Of these, the
government has accepted just one in full,
and three in part, IMA sources said.
My main point of opposition is that the Board
of Governors is a nominated body which
has replaced a democratically elected body;
that is, the MCI Executive Committee.
Dr K K Agrawal,
IMA’s immediate past president
Sabotaging
democratic
process: IMA
The Indian Medical Association
(IMA) said in a statement that the
“supersession” of the MCI is only a
smokescreen and a ploy to prepare
the ground for the NMC and sabotage
the democratic process of the Council.
The Board of Governors (BOG)
should conform to the basic tenets
of the IMC Act and refrain from
tinkering with its fundamental
structure, the IMA said. The Board
should refrain from taking major
policy decisions or passing any
amendment changing the character
of the IMC Act. The election process
of the MCI should be allowed to
continue, it added.
Crosspathy, registration of nonmedical
persons, bridge courses
and the mixing of syllabi are core
concerns of the outgoing team. 184
private medical colleges are awaiting
recognition due to the strict norms
of the outgoing MCI team, it said. By
removing the democratically elected
MCI, checks and balances have been
removed and the chances of arbitrary
action have increased. A generation
of substandard doctors will be the
legacy of this action, according to the
statement.
Maintaining that the composition
of the Board itself was unacceptable,
the team pointed out that there is
no representation to women and
registered medical practitioners.
Directors of major institutions would
scarcely find time to administer more
than 450 medical colleges and their
undergraduate and postgraduate
courses, it alleged.
NOVEMBER 2018 / FUTURE MEDICINE / 13

drug resistance
TACKLING
EMERGING
Stopping irrational antibiotic use in all the four stages
of treatment cycle is the need of the hour
14 / FUTURE MEDICINE / NOVEMBER 2018

DR RAJANI KANTH VANGALA
In India, the largest therapeutic
group — which accounts for 15.7% of
the drugs market — are antibiotics.
This suggests not only that antibiotics
are now available to a larger segment
of needed people, but also irrational
use, leading to antibiotic resistance
in bugs. India and the world at large
are on the verge of facing their worst
healthcare crisis due to fast-emerging
antibiotic-resistant pathogens. This
multifaceted problem arises due to
several aspects, such as non-prescription
self-medication, unwarranted dosages
to patients by clinics, and the lack of
knowledge translation to the public.
According to the World Health
Organization (WHO) definition,
medicines are used ‘rationally’ (i.e.,
responsibly, appropriately, correctly and
properly) when patients receive the
medicines from responsible clinicians in
appropriate doses for correct indications
and meet the individual need for an
adequate period of time with proper
knowledge. However, these aspects
are seldom practiced, leading to high
expenditure on buying medicines and
the ever-growing problem of resistant
bacteria. The development and
implementation of certain guidelines
by regulatory authorities may, to some
extent, help in curbing this problem.
Due to patients’ demand for instant
gratification and other market issues,
clinicians are forced to prescribe more
than the required amount of antibiotics.
It is important to note that bacteria
can develop resistance in different
ways, like de novo gene mutations
and the import of resistance-related
genetic information from other bacteria
due to selective pressure on them by
an overdose of antibiotics. With less
antibiotic use, antibiotic effectiveness
is maintained for a longer period and
the chances of developing resistant
bacteria are reduced.
EML for better outcomes
The inappropriate use of antibiotics
can start at any of the four stages of
treatment cycle, namely diagnosis,
prescribing, dispensing and patient
adherence. In the first stage, a wrong
diagnosis can lead to the use of drugs
which will be ineffective. It is very
important to practice proper diagnosis
and look at the possibility of using nondrug
based therapies that may relieve
the patient before prescribing drugs.
Every country has an Essential
Medicines List (EML) based on the
needs of the populations. The concept
of the EML is based on the notion that
limited use of well-known and cost-
PATHOGENS
ANTIBIOTICS
FOUR STAGES OF TREATMENT CYCLE
The inappropriate use of antibiotics
can start at any of the four stages
DIAGNOSIS PRESCRIPTION DISPENSING PATIENT
ADHERENCE
NOVEMBER 2018 / FUTURE MEDICINE / 15

Three million surgeries and cancer
treatments may turn life-threatening
Public Health England’s (PHE’s)
English Surveillance Programme for
Antimicrobial Utilisation and Resistance
(ESPAUR) report published in October
highlights how more than 3 million
common procedures such as cesarean
sections and hip replacements could
become life-threatening without
antibiotics.
Without antibiotics, infections related
to surgery could double, putting people at
risk of dangerous complications. Cancer
patients are also much more vulnerable
if antibiotics don’t work; both cancer and
the treatment (chemotherapy) reduce
the ability of the immune system to fight
infections. Antibiotics are critical to prevent
and treat infections in these patients.
The threat of antibiotic resistance
continues to grow. Bloodstream infections
have increased, and the report shows that
antibiotic-resistant bloodstream infections
rose by an estimated 35% between 2013
and 2017.
Despite the risks of antibiotic
resistance, research shows that 38%
of people still expect an antibiotic
from a doctor’s surgery, NHS walk-in
centre or ‘GP out-of-hours’ service when
they visited with a cough, flu or a throat,
ear, sinus or chest infection in 2017.
The ‘Keep Antibiotics Working’
campaign educates the public about the
risks of antibiotic resistance, urging people
to always take healthcare professionals’
advice as to when they need antibiotics.
The campaign also provides effective
self-care advice to help individuals and
their families to feel better if they are not
prescribed antibiotics.
The Ipsos MORI Capibus Survey,
‘Attitudes towards antibiotics, 2017’ was
conducted between 24 January to 5
February 2017 with a representative
sample size of 1,691 adults (aged 15+) in
England only.
effective medicines can result in better
healthcare outcomes, enhanced longterm
supply and sustainable access to
medicines.
Prescribing is a complex process for
doctors and begins with establishing
the goal(s) of the therapy. Meeting the
patient expectation, arriving at benefitrisk
balance, availability and cost are the
important considerations for clinicians.
This daunting process of prescribing
needs openness in engaging with the
patient, which is important as it is the
patient who is the ultimate recipient of
any benefits of taking the medication.
For most patients, transitioning into
a role of someone who has to take
medicines is often difficult. This is more
so in cases where the benefits of the
medication are not immediate and the
mere presentation of the diagnosis
may not be a motivator. There is an
urgent need to understand this and
develop better methodologies in patient
adherence and reduce the irrational use
of antibiotics.
Threat to progress
In the event of no proper diagnosis,
incorrect or general antibiotic
prescription can lead to complex and
unwanted clinical outcomes. In such
cases, it is important to evaluate the
patient’s co-existing medical, genetic
and environmental conditions. Beyond
the prescription, dispensing and patient
adherence are even more difficult to
follow and improve. Especially in rural
areas, the pharmacists almost become
non-prescribing doctors in giving
medicines and advice, which may not
be effective. This aspect also leads
to patient non-adherence in taking
medications. Essential cross-checks
and patient knowledge translation,
empowering them for better adherence
to therapy protocols, are needed.
Antibiotic development is now
considered to be a global health
emergency, with the average time
needed to receive regulatory approvals
16 / FUTURE MEDICINE / NOVEMBER 2018

eing 7.2 years, with a very low clinical
success rate of 16%. There is a need
for a national-level plan to combat
antibiotic resistance by driving more
inter-sectoral partnerships among
scientists and medical, epidemiological
and diagnostic personnel. Ever since
penicillin ushered in the modern era
of antibiotic development, they have
become the cornerstone of human
lives by changing the way we live. In
this post-antibiotic era, evaluation of
epidemiological aspects and tailoring
the use of antibiotics by proper use of
scientific methods can lower the threat
THE EMERGENCE OF
NEW PATHOGENS
WITH ANTIMICROBIAL
RESISTANCE CAN MAKE
HUMANITY GO BACK TO
THE PRE-ANTIBIOTIC ERA.
of ever-growing, drug-resistant bacteria.
The impact of the irrational use of
antibiotics can be more far-reaching
than perceived, as suggested by the
Nobel Laureate Joshua Lederberg: “The
future of humanity and microbes will
evolve as episodes...of our wits versus
their genes”. The emergence of new
pathogens with antimicrobial resistance
can not only be seen as a threat to the
progress made in healthcare, but also
as something that can make humanity
go back to the pre-antibiotic era where
the masses suffered and died due to
untreatable infections. It is now in our
hands to embrace the most logical step
of stopping irrational antibiotic use at
each and every step of therapy.
PIL questions unchecked
antibiotics sale
public interest litigation (PIL) has
A been registered in Bombay High
Court demanding action to address
unchecked sales of high potency
antibiotics without prescriptions. It was
filed by a city-based lawyer against
the Union of India, Government of
Maharashtra, Central Drugs Standard
Control and the Drug Controller.
The PIL outlined mainly four
aspects, including the unchecked sale
and consumption of antibiotics as an
OTC product, drug resistance and the
impact on disease-control measures,
increased cost of healthcare, insurance
and research, and the unchecked
sale and access to H and H1 category
antibiotics.
The petition, filed by Bharat Kothari,
a Mumbai-based lawyer, followed
findings of a survey conducted across
500 pharmacies in Maharashtra.
In the survey, Bharat Sarge, an
activist, discovered that antibiotics
belonging to H and H1 categories were
freely available across pharmacies.
Listing the critical issues that surfaced
due to unchecked consumption
of high-potency antibiotics, such
as serious drug resistance among
infectious diseases and unauthorised
sale, the lawyer felt there was great
merit in a PIL.
According to Kothari, over 118
different antibiotic formulations are sold
in India. Out of such a large number of
antibiotic formulations — as against just
five in the United Kingdom and the US
— 64% are apparently not approved by
the national drug regulator, the Central
Drugs Standard Control Organisation.
Presently, India is the largest consumer
of antibiotics in the world, he added.
“Temporary suspension of licenses
of local pharmacies have failed to
control rising concerns and medicines
continue to be dispensed irresponsibly
by shop owners. It’s about time there
is a system in place to control these
irregularities effectively, and severe
punishment should be levied against
such defaulters,” says Bharat Serge
of Venkateshwar Seva Sanstha, which
conducted the survey.
The petition has outlined citizens’
rights to health, stated to have been
compromised due to the indiscriminate
OTC sale and unchecked use of
prescription medication. It draws
attention to the duty of the state to
assess and monitor any dependency
or addiction to antibiotics and other
high-potency drugs and ensure that
there is no damage to the consumers’
health by uncontrolled, unchecked selfmedication.
Since it has been a strategic goal
of WHO and many countries to limit
antimicrobial resistance, most countries
are taking brisk measures to prevent
production and sale of illegal and
unapproved medication.
The author is medical
scientist and former
director of SGRF,
Bangalore
18 / FUTURE MEDICINE / NOVEMBER 2018

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column
the catalyst
Dichotomy of price
control
Unless fortified by quality standards, price control on
medical products could prove counterproductive
MURALIDHARAN NAIR
India has followed a policy of price control
of pharmaceutical products for long,
and in recent times it has extended the
ambit to include certain devices as well.
Now, there is an imminent possibility of it
expanding further to include more medical
products and even medical services.
The policy of price control on healthcare
products and services has been a subject
of debate for long. It has intensified in
the recent past owing to the twin factors
of India’s high dependence on private
sector health care facilities (more than 60
percent of the surrendered care is through
the private sector) and the increasing
unaffordability of the same.
The proponents of price control have
often to contend with stiff opposition
from market players who argue that it
impairs the industry’s ability to invest
sufficiently in innovation, and as long as
there are competitive forces at play in
the form of multiple providers/vendors,
prices will find a fair equilibrium. I have
never been convinced by this argument
of the opponents of price control, based
on my observations of the realities in the
market for more than two decades now.
A careful analysis of the market prices will
reveal that the burden of an inefficient
research and development process and
an aggressive commercialization agenda
have contributed to market prices that are
not fair to the consumer. This is further
compounded by the fact that consumer
choice is highly influenced by care providers,
and as such, it is not a free market. Let me
try and elucidate this through the events
leading to, and following, the imposition of
price control on cardiac stents more than
a year back. The cardiac stent market in
India is characterized by a mix of Indian
(~15 players), MNC (5 players) and some
emerging Chinese players. There are two
types of stents prevalent in the market, viz.
Drug Eluting (DES) and Bare Metal, with the
DES having a share of ~ 90%.
It is evident from the data that any
claim of the MNC players seeking to
justify the price to patient / MRP as a
legitimate cost for sustaining research and
innovation is untenable since the post
manufacturer “value addition” far exceeds
the manufacturer’s (innovator’s) margins.
It is essentially the cost of aggressive
commercialization that the poor customer
is paying in the name of innovation
and quality, despite the market having
reasonable competitive intensity. What
happened subsequent to the price control,
which essentially equalized the MRPs of
Indian and MNC innovator players, is a great
example of how little control the customer
exercises in making the choice of healthcare
products. Despite the price equalization,
which should have effectively given a fillip to
20 / FUTURE MEDICINE / NOVEMBER 2018

PRICE CONTROL SCENARIO
1,30,000+
2016
PRE-PRICE
CONTROL
2017
POST-PRICE
CONTROL
2016
PRE-PRICE
CONTROL
2017
POST-PRICE
CONTROL
PRICE (INR)
1,00,000+
57% 43% 61%
39%
30%
70%
45% 55%
2016 2017
29,284
MARKET SHARE
(ENTIRE COUNTRY)
MARKET SHARE
(METRO CITIES)
INDIAN MNC
Prices inclusive of GST
Marketshare by volume
SOURCE: NPPA, EY ANALYSIS
MNC
INDIAN
TRANSFER PRICE/MANUFACTURING COST
15,000-17,500 2,500-5,000
PATIENT CHARGING PRICE
1,20,000 60,000-70,000
MRP (PRE-PRICE CONTROL)
1,30,000+ 1,00,000+
DESPITE THE PRICE
EQUALIZATION, WHICH
SHOULD HAVE EFFECTIVELY
GIVEN A FILLIP TO THE MNC
SHARE WITH ITS PERCEIVED
SUPERIORITY OF AN
ORIGINATOR, MNC’S
MARKET SHARE FELL.
the MNC share with its perceived superiority
of an originator, MNC’s market share fell.
Even if the domestic players could offer little
price advantage post price control, it was
not material enough to affect a decision
change by a consumer in the context of the
overall cost of angioplasty and criticality
of the product in the scheme of things.
Importantly, despite the massive reduction
in the price of stent, which was a critical
cost driver for angioplasty, the procedure
cost did not come down materially (less
than 15 percent).
No less than the Prime Minister himself
has spoken of stent price rationalization
as one of the major successes of his
government. But in reality, the intended
beneficiaries are not really better off.
This exposes the complexity involved
in matters of healthcare delivery. What
may offer great optics from a political
perspective is not necessarily a measure
of the true effectiveness of the policy.
It is imperative that the policy makers
understand the complexity around the
issues before formulating a policy, to
ensure that the intended benefit reaches
the last mile. This is another important
lesson for us to learn: Price control is an
important tool and is also an attractive
proposition as a populist measure, but
price control alone, without accompanying
measures for fortifying quality standards,
may be counterproductive in the long
run. More on this in the subsequent
columns.
The author has long-standing association with
EY India but the views are strictly personal.
NOVEMBER 2018 / FUTURE MEDICINE / 21

cover story
IMMUNO
TO
LUNG CANCER
Immunotherapy comes as a silver
lining for the sufferers of a malignancy
which has the highest incidence and
the bleakest prognosis
22 / FUTURE MEDICINE / NOVEMBER 2018

LUNG CARCINOMA:
THE COMMONEST CANCER
WORLD OVER
Lung cancer is now the most common cancer
worldwide, with 2·1 million people diagnosed
in 2018 and 1·8 million deaths, influenced
strongly by the tobacco epidemic.
WORLD
INDIA
11.6%
incidence of
lung cancer
among
all new
cancer cases
18.4%
lung cancer
accounts for all
cancer related incidence
6.3%
of lung
deaths cancer among
all new
cancer cases
9.1%
PATH
INCIDENCE OF NSCLC AS
COMPARED TO SCLC
Adenocarcinoma accounts for nearly 40% of lung
cancers and is the most common form of cancer
among smokers
5%+
Large Cell
6.7%
1.Carcinoma
1.0%+
15.7%
lung cancer
accounts for all
cancer related
deaths
Squamous Cell Carcinoma
S HARACHAND
Immunotherapy stepped onto the hall of fame by winning
the 2018 Nobel prize for medicine. Through their landmark
discovery, Professor James P Allison from the US and
Professor Tasuku Honjo from Japan have outlined how
immune checkpoints can be effectively targeted to deal with
the toughest of cancers.
Their seminal work on cytotoxic T-lymphocyte associated
protein 4 (CTLA-4) and programmed cell death receptor-1 (PD-
1) mechanism led to a new class of therapeutics called immune
checkpoint inhibitors. These drugs have brought remarkable
outcomes by radically changing the treatment approach to
38.9%
Adenocarcinoma
11.6%+
Other or unspecified 0.4%
Small Cell Carcinoma
24.0%
0.3%+
Non-smoker
Smoker
NOVEMBER 2018 / FUTURE MEDICINE / 23

cancer and made immunotherapy one of the
hottest areas of cancer research.
“If you really want to do something
paradigm shifting, then you really have to probe
basic mechanisms,” says Dr Vishva M Dixit,
Vice President and Staff Scientist, Physiological
Chemistry at Genentech, San Francisco, CA,
commenting on the Nobel-winning work in
basic science.
Unlike conventional therapeutic modalities
that directly target cancer cells, these drugs
block the checkpoints of the host immune
systems to unleash an outright attack on cancer
cells.
Since the approval of ipilimumab, a CTLA-4
blocker, for melanoma by the USFDA in 2011,
checkpoint inhibitors have fundamentally
changed the outcome for certain subsets of
patients with advanced forms of cancers, which
were hitherto considered largely untreatable.
This paved the way for US regulatory approval
of checkpoint inhibitors with a broader range -
PD-1 and PD-L1 - to treat over a dozen cancers.
Of the two treatment strategies, checkpoint
therapy against PD-1 has proven to be more
effective for the carcinoma of the lung. As
a group of malignancies, lung cancer offers
the lowest survival rates. Lung cancer has an
incidence rate of 11.6% - the highest among all
cancers — and a mortality rate of 18.4%, the
highest of all cancer-specific deaths, according
to the Globocan 2018 report.
Immune checkpoint inhibitors that block
the PD-1/PD-L1 pathway, such as nivolumab,
pembrolizumab and atezolizumab, have been
rapidly adopted into clinical practice as a
We are continuing
to explore
the potential
of nivolumab
through our broad
development
programme
in thoracic
malignancies,
including early
and late-stage
NSCLC, SCLC and
malignant pleural
mesothelioma.
Sabine Maier,
M D, Development Lead,
Thoracic Cancers,
Bristol-Myers Squibb.
standard treatment option for patients with
advanced non-small-cell lung cancer (NSCLC).
Exploring PD-1/PD-L1 pathways
Nivolumab, a fully human monoclonal
immunoglobulin G4 antibody to PD-1 intended
for the treatment of squamous cell lung cancer,
won US FDA approval in March 2015. Marketed
by Bristol-Myers Squibb under the brand name
Opdivo, its efficacy to treat squamous NSCLC
was established in a randomized trial of 272
participants, 135 of whom received nivolumab
and 137 received docetaxel.
In October 2015, FDA expanded
nivolumab’s approval to advanced (metastatic)
nonsquamous non-small cell lung cancer
patients whose disease progressed during or
after platinum-based chemotherapy.
“We are continuing to explore the potential
of nivolumab through our broad development
programme in thoracic malignancies, including
early and late-stage NSCLC, SCLC and malignant
pleural mesothelioma,” says Sabine Maier, M D,
Development Lead, Thoracic Cancers at Bristol-
Myers Squibb.
Pembrolizumab is an alternative, highly
selective IgG4-kappa humanized monoclonal
antibody against PD-1 receptor.
Pembrolizumab got approval from the US
FDA on October 2015 for the treatment of
metastatic NSCLC in patients whose tumours
express PD-L1 and who have failed treatment
with other chemotherapeutic agents.
Merck sells the drug under the brand name
Keytruda.
Merck is evaluating pembrolizumab in
LUNG CANCER
THE WORLDWIDE SCENARIO
Age standardized (World) incidence
rates, lung, females, all ages
≥ 18.0
10.0–18.0
6.3–10.0
3.9–6.3
1.9–3.9
< 1.9
24 / FUTURE MEDICINE / NOVEMBER 2018

oth neoadjuvant and adjuvant settings; for example, in
Keynote-091 (adjuvant) and Keynote-671 (neoadjuvant and
adjuvant), which are currently recruiting patients, said a Merck
spokesperson.
Cemiplimab (Libtayo) is another PD-1 blocker, developed by
Regeneron and Sanofi. The drug is being investigated presently
for NSCLC as a monotherapy and in combination in first-line
patients in different trial settings.
Atezolizumab, marketed as Tecentriq by F Hoffmann-La
Roche/Genentech, works through the PD-L1 pathway. The drug
is approved in Europe and the USA for second-line treatment
of NSCLC following platinum-based chemotherapy.
Currently, Roche has eight Phase III lung cancer studies
underway, evaluating atezolizumab alone or in combination
with other medicines.
Other PD-L1 inhibitors in late-stage development for NSCLC
include durvalumab (Imfinzi, AstraZeneca) and avelumab
(Bavencio, EMD Serono and Pfizer).
LUNG TOPS CHART
IN INDIA
Lung cancer remains the
leading type of malignancy in
men in India, according to a new
study conducted on data from
28 population-based cancer
registries (PBCR) across the
country.
The highest incidence of
cancer was seen in the East and
the Northeast regions and the
lowest was in rural areas for all
age groups in both men and
women.
The lung topped as the
leading site for all the registries.
In the Bengaluru registry,
the leading cancer sites
were the stomach and the
lung. In Bhopal, Mumbai and
Aurangabad, they were the lung
and the mouth and in Kolkata
and Tripura, it was the lung.
Prepared by researchers
from the Indian Council of
Medical Research and the Delhibased
Dharamshila Narayana
Superspecialty Hospital, the
paper compared data for all
registries and reviewed the
change in cancer pattern among
different age groups from 2005
to 2014.
Checkpoint concerns
Checkpoint therapy has really worked wonders. It brought
SOURCE: GLOBOCAN 2018
54.1
24.0
52.0
24.5
49.3
11.9
ASR (World) per
CARCINOMA OF LUNG
MALE FEMALE RATIO
Age standardized (World)
incidence rates, lung, by sex
Male
Female
Micronesia
Polynesia
Central and
Eastern
Europe
Eastern
Asia
Western
Europe
Southern
Europe
North
America
Western
Asia
Northern
Europe
World
Australia/
New
Zealand
South-
Eastern
Asia
Southern
Africa
Caribbean
Melanesia
Northern
Africa
South
America
South-
Central Asia
Central
America
Middle
Africa
Eastern
Africa
Western
Africa
47.2
21.9
43.3
25.7
43.1
15.7
39.1
30.7
38.8
7.8
34.0
26.9
31.5
14.6
28.4
24.0
26.3
9.6
100,000
26.0
8.9
23.5
14.2
17.1
8.9
16.9
3.4
16.8
10.2
9.4
3.4
7.2
4.5
3.8
2.3
3.4
2.2
2.4
1.2
NOVEMBER 2018 / FUTURE MEDICINE / 25

IMMUNE CHECKPOINT
BLOCKADE: THE NEW RAGE
Drugs that inhibit PD-1/PD-L1 pathway have been
rapidly getting adopted into clinical practice
NSCLC tumours overexpress the
immunosuppressive checkpoint
protein programmed death ligand 1
(PD-L1) to evade detection and attack
by immune cells. Inhibiting the PD-1/
PD-L1 axis with monoclonal antibodies
has significantly changed the treatment
approach in lung cancer during the last
5 years.
Immune checkpoint inhibitors that
block the PD-1/PD-L1 pathway, such
as nivolumab, pembrolizumab and
atezolizumab, have become a standard
treatment option for patients with
advanced non-small-cell lung cancer
(NSCLC).
NIVOLUMAB
Nivolumab is a fully human monoclonal
immunoglobulin G4 antibody targetting
PD-1. The treatment won US FDA
approval in March 2015 for the treatment
of squamous cell lung cancer. Marketed
by Bristol-Myers Squibb under the
brand name Opdivo, its efficacy to treat
squamous NSCLC was established in a
randomized trial of 272
participants of whom
135 received nivolumab
and 137 received
docetaxel.
In October 2015,
FDA expanded
nivolumab's approval to
advanced (metastatic)
nonsquamous nonsmall
cell lung cancer in
cases where the disease
progressed during or
after platinum-based chemotherapy.
Patients who received nivolumab
lived longer than those who received
docetaxel in the study. However, it was
found that the level of PD-L1 expression
in NSCLC tumours may help identify
the patients who are more likely to
live longer with the help of nivolumab
treatment. Therefore, the FDA also
approved the PD-L1 IHC 28-8 pharmDx
test to detect PD-L1 protein expression
levels and help physicians determine
which patients may benefit most from
treatment with nivolumab.
Currently, several studies are
underway to determine whether
nivolumab, in combination with other
therapies, is effective in patients with
advanced NSCLC. Among them are
Biomarker-Targeted Second-Line Therapy
in Treating Patients with Recurrent Stage
IV Squamous Cell Lung Cancer (The
Lung-MAP Screening Trial) and Alchemist
treatment trial. Studies using nivolumab
in NSCLC patients are ongoing in India as
well, according to ClinicalTrials.gov
“We are continuing to
explore the potential of
Opdivo through our broad
development programme in
thoracic malignancies, including
early- and late-stage NSCLC,
SCLC and malignant pleural
mesothelioma,'' says Sabine
Maier, M D, Development
Lead, Thoracic Cancers,
Bristol-Myers Squibb.
In October, BMS
announced topline results
from the Phase 3 CheckMate-331 study
evaluating nivolumab versus the current
standard of care, topotecan or amrubicin,
in patients with SCLC who relapsed
following platinum-based chemotherapy
did not meet its primary endpoint of
overall survival.
Earlier, in 2016, BMS said nivolumab
failed to achieve its endpoint in a study
and was no better than traditional
chemotherapy at treating newly
diagnosed lung cancer.
Nivolumab has been approved for
second-line NSCLC in more than 65
countries, including the US, Europe,
Japan and China.
PEMBROLIZUMAB
Pembrolizumab is a highly selective IgG4-
kappa humanized monoclonal antibody
against PD-1 receptor.
Pembrolizumab was approved
by the US FDA on October 2015 for
the treatment of metastatic NSCLC in
patients whose tumours express PD-L1
and who have failed treatment with
other chemotherapeutic agents.
Merck sells the drug under the brand
name Keytruda.
Following the results of Keynote
024 trial, the initial approval of
pembrolizumab as a second-line
treatment was extended to first-line
treatment in NSCLC patients with high
PD-L1-expressing tumours (PD-L1 >50%)
with no EGFR or ALK mutations.
The study found treatment with
pembrolizumab prolonged progressionfree
survival (PFS) and overall survival
(OS) and improved objective response
remarkable results in patients who are deemed untreatable
otherwise. It resulted in the complete remission of disease
even in cases of melanoma which has metastasised. However,
it fails to do the trick in all patients with the same condition.
PD-1/PD-L1 inhibitors also share some of the debilitating
adverse effects which are common to this class of
immunotherapies.
“There’s a substantial toxicity because when we remove
the brakes, the immune system will also attack normal tissue.
There is, especially with the anti-CTLA4 therapy, a tendency to
get autoimmune diseases like thyroiditis and hypopituitarism,”
points out Dr Dixit. But that, fortunately, has been largely
managed by dose alterations and other supportive care, he
adds.
26 / FUTURE MEDICINE / NOVEMBER 2018

ates (45% vs 28%, respectively)
compared with chemotherapy in a firstline
setting.
The drug was granted accelerated
approval by the US regulator in May
2017 as a first-line combination therapy
for metastatic non-squamous NSCLC
regardless of PD-L1 status, based on the
results of the Keynote-021 Phase 1/2
clinical trial.
"With Keynote-407 and Keynote-042,
there are now five Phase 3 studies
in patients with advanced NSCLC
across common histologies where
pembrolizumab, in combination or as
a monotherapy, has demonstrated an
improved OS benefit over chemotherapy,''
said a Merck spokesperson.
In a first-line setting, pembrolizumab
has shown an OS benefit in around 80%
of all NSCLC patients. In Keynote-189,
pembrolizumab in combination with
pemetrexed and platinum chemotherapy
reduced the risk of death by half
compared to chemotherapy alone as
a first-line treatment for metastatic
nonsquamous NSCLC, regardless of PD-
L1 expression.
In Keynote-407, pembrolizumab, in
combination with carboplatin-paclitaxel
or nab-paclitaxel, significantly improved
OS and PFS as a first-line treatment
in patients with metastatic squamous
NSCLC, regardless of PD-L1 expression.
As a monotherapy, in Keynote-024,
pembrolizumab more than doubled
median OS compared to chemotherapy
in first-line treatment of patients with
metastatic NSCLC whose tumours
expressed PD-L1 with a TPS =50%.
Keynote-042 showed that
pembrolizumab monotherapy
significantly improved OS as the firstline
treatment in patients with locally
advanced or metastatic nonsquamous
or squamous NSCLC whose tumors
expressed PD-L1 (TPS =1%).
In a second-line setting, in
Keynote-010, pembrolizumab significantly
improved OS compared to chemotherapy
in patients whose tumours express PD-L1
(TPS of one percent or more).
According to the Merck spokesperson,
the company has an extensive clinical
development programme in lung cancer
and is advancing multiple registrationenabling
studies with pembrolizumab in
combination with other treatments, as
well as in the form of a monotherapy.
The programme, which comprises nearly
9,000 patients across 15 clinical studies,
is evaluating pembrolizumab across
multiple settings and stages of the
disease. Some of the subsets include:
Pembrolizumab in patients
IN A FIRST-LINE SETTING,
PEMBROLIZUMAB HAS
SHOWN AN OS BENEFIT
IN AROUND 80% OF ALL
NSCLC PATIENTS.
with EGFR mutations (Keynote-789)
or ALK translocations; and
pembrolizumab for the treatment of
SCLC as monotherapy (Keynote-158)
and in combination with chemotherapy
(Keynote-604).
"Merck has more than 20
early phase molecules that we are
exploring as monotherapy or for
potential combination activity with
pembrolizumab, including STING, LAG-
3, TIGIT, RIG-I and an oncolytic virus
CAVATAK. All these agents have the
potential to add significantly
to the effectiveness of
pembrolizumab," she
added.
ATEZOLIZUMAB
Atezolizumab,
marketed as Tecentriq
by F Hoffmann-La
Roche/Genentech is
approved in Europe
and the USA for
second-line treatment of NSCLC following
platinum-based chemotherapy. A
Phase 3 study compared atezolizumab
with docetaxel in unselected patients
who had received up to two previous
chemotherapy regimens, including
at least one platinum-based therapy.
The data showed that the regimen
significantly improved OS in the
atezolizumab treatment group compared
with the docetaxel group. This benefit
was independent of the level of PD-L1
expression, with the patients with low
or undetectable PD-L1 expression also
demonstrating a prolonged OS with
atezolizumab versus docetaxel (12.6 vs
8.9 months).
In March 2018, Phase III IMpower150
study showed that atezolizumab and
bevacizumab plus carboplatin and
paclitaxel helped people with advanced
lung cancer live longer compared to
bevacizumab plus carboplatin and
paclitaxel.
Currently, Roche has eight Phase III
lung cancer studies underway, evaluating
atezolizumab alone or in combination
with other medicines.
DURVALUMAB, AVELUMAB
Other PD-L1 inhibitors in late-stage
development for NSCLC include
durvalumab (Imfinzi, AstraZeneca) and
avelumab (Bavencio, EMD Serona and
Pfizer). Data for both have recently been
reported.
Data from Pacific Phase 3 trial
involving durvalumab showed that
the drug reduced the risk of death by
32% for patients with unresectable,
stage III NSCLC following chemoradiation
therapy.
Avelumab failed to outdo docetaxel in
second-line NSCLC patients with PD-L1-
positive tumours that cannot be removed
surgically.
Uncertainty about which patients with NSCLC are most
likely to benefit from anti-PD-1/PD-L1 therapy, however,
continues to be the biggest concern for oncologists treating
lung carcinoma.
Researchers point to the many limitations of using the
PD-L1 expression as a biomarker. Anti-PD-1/PD-L1 drugs
do not inhibit every co-inhibitory interaction that may play
a role in anti-tumour T-cell responses. This could be a
contributing factor to the failure of PD-L1 expression to fully
differentiate responders and nonresponders, they opine. The
anti-PD-1/PD-L1 drug is co-developed with its own PD-L1
immunohistochemistry (IHC) diagnostic assay. The US FDA has
mandated that pembrolizumab be used only in conjunction
with its companion PD-L1 test, while the assays for nivolumab
NOVEMBER 2018 / FUTURE MEDICINE / 27

"Immunotherapy
is going to be
routinely used
in NSCLC"
The tumour cells
have a blanket
to prevent the
immune system
from working.
With the help
of these drugs
[immunotherapy],
we can take out the
blanket and make
the immune system
work.
Dr K Govind Babu
Professor of Medical
Oncology, Kidwai
Memorial Institute of
Oncology, Bengaluru.
and atezolizumab are considered complementary.
Too many subsets
Sub-typing is
better because
now oncologists
can understand
the biology and
treat the patients
accordingly. But, it
is also bad because
it gets the diagnosis
complicated,
requiring many
different approaches
and resources.
Dr Kurt A Schalper,
Assistant Professor of
Pathology and Medicine
(Medical Oncology), Yale
School of Medicine, USA
The carcinoma of the lung has high mutational burden.
Mutations in EGFR and ALK genes are considered key to
the development of NSCLC. These driver mutations are
seen to occur in approximately 10%–35% and 3%–7% of
patients respectively. KRAS mutations are found in around
30% of NSCLC cases. They are more common in patients
with adenocarcinomas and smokers. At present, there is no
approved targeted treatment for KRAS mutant NSCLC. Trials
are underway to determine the efficacy of anti-PD-1/PD-L1
therapy according to KRAS mutation status in a subgroup.
It has also been found that high-level MET (exon 14
skipping mutations) amplification and BRAF and ROS1
mutations are driving events in NSCLC. They occur in 1%–3%
of lung cancers.
Carcinoma of the lung, which appears as a single disease
entity at the outset, is actually a composite of several
pathologies, avers Dr K Govind Babu, Professor of Medical
Oncology, Kidwai Memorial Institute of Oncology, Bengaluru.
“If a cell has a very high number of mutations, we call it
a hot tumour. These cells can initiate a response from our
immune system. But the tumour cells have a blanket to
prevent the immune system from working. With the help
Dr Vishva M Dixit is Vice President and
Staff Scientist, Physiological Chemistry at
Genentech, San Francisco, CA. After heading
Molecular Oncology for 10 years, Dr Dixit
has now turned his efforts to basic research
to study the biochemistry of components
of signaling pathways that often go awry
in disease. Author of over 166 publications
in various journals, he is the winner of
several awards and honours including AHA
Investigatorship Award – 1989-1994; Dawson
Prize in Genetics – 2015 and Gutenberg
Research Award – 2016, among others.
"My mission is to further our knowledge
of disease-related cellular signaling and to
develop novel, high-impact therapeutics,"
says Dr Dixit. Edited excerpts from his
conversation with FM.
A discovery on cancer immunotherapy
won this year's Nobel Prize for medicine.
How exactly does the discovery help in
understanding malignancies?
Cancer immunotherapy has been in
the doghouse for decades. The work of
the two investigators, James P. Allison
and Tasuku Honjo, resurrected it so that it
plays a prominent role in the therapeutic
armamentarium in future.
Immunotherapy held a lot of promise.
But there weren't any successes. The reason
is that people were trying to activate the
immune system. And a number of immune
activators were tried and they invariably
failed. The realization of Allison and Honjo
was that the cells have a brake on them. You
can put as much fuel in the system as you
want, as much accelerator as you can press
on: The car is not going to go. The cell is not
going to proliferate or rejuvenate unless you
remove the brakes. That was their realisation.
They said, you have been trying to activate
the immune system in a tumour without
28 / FUTURE MEDICINE / NOVEMBER 2018

PHOTO: UMESH GOSWAMI
Cancer immunotherapy has been in the doghouse for decades.
The work of the two investigators, James P. Allison and Tasuku
Honjo, resurrected it so that it plays a prominent role in the
therapeutic armamentarium in future.
Dr Vishva M Dixit
realising the fact that a brake has been
put on it in the tumour environment.
And the immune system is sitting there
paralysed. It can't do anything unless
you remove the brakes. The molecules
CTLA4 and CD-1 are essentially the
brakes of the immune system. Now they
have developed antibodies to neutralize
the brakes and get the immune system
work. Now the immune system is able to
eradicate tumour cells in many cases.
In what way is immunotherapy
going to change the treatment
paradigms in cancer?
The potential of immunotherapy has
already been validated in melanoma
and NSCLC. Treatment with the immune
activators — which activate the immune
system against cancer cells — has proved
to be immensely beneficial. In many
cases, people who would have ordinarily
been dead are still alive...
Does immunotherapy work for
all cancers?
No. There are many cancers that
don't respond to immunotherapy. That is
an area of active research today. It works
only for malignancies that have a very
high mutational burden. NSCLC has the
highest mutation because of smokers.
Smoking generates a lot of mutagens.
What are the possible adverse
effects?
There's substantial toxicity, because
when we remove the brakes, the
immune system will also start to attack
normal tissue. There is, especially with
the anti-CTLA4 therapy, a tendency
to get autoimmune diseases like
thyroiditis and hypopituitarism. But that,
fortunately, has been, largely managed
now by dose alterations and other
supportive care.
How do you compare the benefit of
immunotherapy with other standard
therapies?
These drugs are used in combination.
In melanoma, metastatic melanoma, I
never thought, in my lifetime, the
disease could be cured. Now, it has
been cured: Cured in 10% of the patients
with twelve years out. There's no relapse.
It's a small fraction. But still, it has been
cured. I think it is an amazing step
forward.
What is the potential of
immunotherapy in lung cancer?
Trials are going on. NSCLC has been
a heterogeneously aggressive disease.
Maybe in the adjuvant setting, one may
see a substantial benefit. We may get to
a day when we have targeted biologics,
or we have an inhibitor for an oncogene
like the EGF receptor inhibitor. Then, we
won't need chemotherapy. We are not
there yet.
The future of immunotherapy?
I think it is going to be bright. That's
why they gave the Nobel. It is going to
be routinely used in melanoma, NSCLC,
renal cancer and subsets of prominent
malignancies. But it is not effective in
colon cancer unless you have something
called a mutated phenotype, which is
found only in a small percent of colon
cancers. But it is going to open the door
for more immunotherapies.
NOVEMBER 2018 / FUTURE MEDICINE / 29

RESPIRATION-GATED
RADIATION THERAPY
PHOTOS: UMESH GOSWAMI
According to Dr Manish Chandra, Chief Radio
Oncologist at Jupiter Hospital, Thane, gated radiation
therapy is an exciting and comparatively new option for
treating lung cancer.
“Though the cost is almost 30% more compared to
traditional radiation, the local control achieved through
this method is much better,” he added.
The higher cost is because of more time spent per
patient on the machine for gated radiation. The machine
tries to ensure that the tumour is always within the
radiation beam even as the tumor moves constantly
during the treatment. It takes longer as the procedure is
done after preparing the patient using a kind of breath
control technique.
Radiation treatment for lung cancer has always been
a challenge to radiation oncologists as the target tumour
is usually on the move during the treatment as the lung
is a constantly moving organ.
Traditionally, a larger area of the lung than strictly
required is irradiated to ensure that the tumour is within
the radiation beam, affecting the nearby healthy cells.
With the respiration-gated approach, the radiation
beam is targeted to a specific point in real time in
keeping with the cycle of respiration. Radiation gating
helps to reduce the amount of healthy tissues in the
lung receiving radiation. Thus a higher dose of radiation
can be used at the targeted location. It can also reduce
the length of the treatment from as many as six weeks
to just two or four.
Chandra added that this method, which is practised
by many experienced radio-oncologists in India today,
brings new hope to lung cancer patients who are
untreatable through surgery or traditional radiation
therapy.
Respiration-gated radiation therapy is also being
considered for treating other difficult areas such as
pancreas cancer or tumours close to the kidneys etc..
The studies for such expansion are underway.
of these drugs [immunotherapy], we can take out the
blanket and make the immune system work,” Dr Babu
elaborates.
Newer sub-types of lung cancer are getting identified
as genomic information helps to reclassify tumours. “There
are many [subsets in lung carcinoma], more than we can
count,” says Dr Kurt A Schalper, Assistant Professor of
Pathology and Medicine (Medical Oncology), Yale School
of Medicine, USA. Even as sub-typing helps re-group
tumours more specifically, the deluge of information can
also complicate the diagnosis process at times.
“It is better because now oncologists can understand
the biology and treat the patients accordingly. But, it
is also bad because it gets the diagnosis complicated,
requiring many different approaches and resources,” says
Schalper.
What makes immunotherapy a better option for
lung cancer are certain features characteristic of this
carcinoma. Tumours in the lung tissue, as in case
of melanoma, are very good at invading immunity.
Therefore, the stimulation and the restoration of
the body’s immunity generates a lot of anti-tumour
effects. Conventional treatments, when combined with
immunostimulatory agents, have been shown to be more
effective than either used alone. For example, advanced
carcinoma of the lung, which used to be treated with
standard platinum-based chemotherapy, now depends
on the expression of PD-1 marker. This can improve the
outcome.
Immunotherapy is very a dynamic field and it has a
very well-established role in lung cancer. Investigations
are going on to see the effect of PD-1/PD-L1 blockers
in earlier stages as well as in second and third-degree
lesions, informs Dr Schalper.
Prolonging survival
In personalised medicine, oncologists can select drugs
which works best for the individual by assessing the
genetic makeup of a particular tumour. This concept
of personalised medicine has greater relevance to the
treatment of lung cancer. Earlier, chemotherapy used to
be the only option to kill cancer cells. Then came targeted
therapy where the tumour tissue is first sequenced and
then specifically targeted by drugs. Now, immunotherapy
shows that it is possible to enhance immunity with the
help of some medications so that the body itself can
attack the cancer cells. Here, all one has to do is to check
for relevant biomarkers. “For lung cancers, biomarkers like
PD-1 are currently available. If it is strongly positive, we
can avoid chemo and go ahead with immune therapy,”
comments Dr Rejiv Rajendranath, Consultant Oncologist,
Apollo Specialty Hospital, Chennai, India.
The identification of the right kind of treatment is
better than exposing patients to tedious chemo regimens
without being sure of their efficacy.
30 / FUTURE MEDICINE / NOVEMBER 2018

Oncologists, according to Dr Rajendranath, are trying to
lessen the use of chemo and radiation in case of lung cancer
and stratify the patients to check the feasibility of various
therapeutic regimes like targeted therapy, immunotherapy
or chemotherapy. “Only if all the targets fail, will we go
back to chemotherapy, unlike earlier days where we treated
everybody with chemo,” he says, explaining how targeted and
immunotherapies have brought about a shift in treatment
approaches.
Clearly, NSCLC has a lot of druggable targets. But SCLC
is a different story altogether. SCLC has, largely, been an
orphan disease. Cisplatin chemotherapy for lung carcinoma
is now almost 20-30 years old. Hardly any trials are taking
place in this direction. Most recently, some breakthrough
studies have come up with data showing that if we add an
immunetherapy agent along with chemo in advanced stage
SCLC, the survival of the patient can be improved. Survival
rates are still modest. But such an advancement is really
practice-changing, because clinicians now have one more
drug to use on patients left with no option after all available
drugs failed, contends Dr Rejindranath.
Several oncologists in India, however, prefer a wait-andwatch
approach to immunotherapy. They believe that the
concept is still in its infancy. Moreover, immunotherapy it is
not curative. “We always tell patients that immunotherapy
is not curative. But it is a better option for elderly patients,
who cannot stand chemo,” says Dr Arun Warrier, Consultant
ADENOCARCINOMA:
CHANGING PROFILE
People change. Lifestyles
change. So do disease
profiles. Earlier, squamous
cell carcinoma and small cell
carcinoma were common in
the Indian population because
of smoking and high tobacco
consumption. But interestingly,
lung carcinoma has given way
to adenocarcinoma of late.
“Adenocarcinoma is something
which is more common in the
West. Maybe, because of the
higher use of filter cigarettes
and the western style of life,
adenocarcinoma has become
the most common lung cancer
in India also, according to Dr
Rejiv Rajendranath.
Recent trends indicate that
the incidence of SCLC is coming
down in India. But the numbers
related to NSCLC are going
up. “This increase in NSCLC is
due to genetic aberrations. All
these existed earlier too, but
we’ve started to identify them
only now, that’s all,” says Dr
Anand Babu, Consultant Medical
Oncologist, HCG, Bangalore.
For lung cancers,
biomarkers like
PD-1 are currently
available. If it is
strongly positive,
we can avoid
chemo and go
ahead with immune
therapy.
Dr Rejiv
Rajendranath,
Consultant Oncologist,
Apollo Specialty Hospital,
Chennai.
We always tell
patients that
immunotherapy is
not curative. But it
is a better option
for elderly patients,
who cannot stand
chemo.
Dr Arun Warrier,
Consultant Oncologist at
Aster Medcity, Cochin.
NOVEMBER 2018 / FUTURE MEDICINE / 31

Oncologist at Aster Medcity, Kochi,
Kerala. Overall, immunotherapy benefits
only 10%-15% of the patients with
lung cancer, although it is easier on the
patients. The survival benefits are also
not quite significant vis-a-vis the cost,
he adds.
Immunotherapy, as a breakthrough
treatment modality, comes with a
hefty price tag. Most Indian patients
consider it unaffordable. Now, the effort
is to combine the benefits of different
therapies with checkpoint drugs.
“But all these come at a financial cost
that we like to call financial toxicity,”
comments Dr Govind Babu.
Cost is an issue but it might also
come down over time, believes Dr
Rejindranath. But the survival rate in
lung cancer, which otherwise has the
poorest prognosis among malignancies,
LUNG CANCER: TARG
Immuno-oncology landscape has many
promising vaccine candidates against NSCLC
Efforts to develop vaccines
against lung cancer always
stalled in the face of
challenges and several previous
attempts have proved ineffective.
It is now recognised that immunesuppressive
factors exist in the
microenvironment of tumour cells.
The local immunosuppression arises
from the interplay of cellular and
metabolic functions to regulate
inflammation. Understanding the
fundamental basis of the cancerimmunity
cycle has significantly
boosted vaccine efforts.
A recent analysis of the global
immune-oncology landscape that
appeared in Annals of Oncology
shows that there are more cancer
vaccines under clinical investigation
than any other class of therapeutic
agents. There are more than 340
agents under clinical trials and
another estimated 260 candidates
SURVIVAL BENEFITS, FOR
CERTAIN SUBSETS OF LUNG
CANCER, ARE TEN TIMES
HIGHER THAN THOSE OF
DECADES PAST. MOST OF
THE TIME, PATIENTS WITH
LUNG CARCINOMA COME
FOR DIAGNOSIS AT VERY
LATE STAGES OF THEIR
DISEASE.
has changed dramatically with the
targeted therapies. Survival benefits,
for certain subsets of lung cancer, are
ten times higher than those of decades
past. Most of the time, patients with
lung carcinoma come for diagnosis at
very late stages of their disease. “Here
we can only prolong their survival
and give a meaningful quality of life;
instead of 5-6 months to 24-28-40
months, slowly but steadily,” opines Dr
Rejindranath. Surely, it does make a
difference, all the more.
Divya Choyikutty from Kochi contributed
reporting to this article
32 / FUTURE MEDICINE / NOVEMBER 2018

ETED VACCINE THERAPY ON WAY
in preclinical and discovery stages as of
September 2017.
CIMAVax-EGF: Combo trials
CIMAvax-EGF is a therapeutic vaccine
being tested against advanced NSCLC,
developed by the Center of Molecular
Immunology, Havana, Cuba. It is
composed of recombinant human
EGF chemically conjugated to a
recombinant carrier protein, p64, from
Neisseria meningitidis. Results from a
randomized phase III trial conducted
in Cuba between 2006 and 2012 on
a total of 405 patients with advanced
NSCLC showed that the overall survival
(OS) was numerically higher in the
vaccine arm (receiving at least 1 dose
of vaccine) versus control. In the
analysis of per-protocol population,
consisting of patients who received at
least 4 vaccine doses, median OS was
12.4 months versus 9.4 months in the
control group. The survival effect was
even better for patients who had high
EGF concentration (serum EGF >870
pg/ml) at baseline: Median OS for
vaccinated patients in this group was
14.7 versus 8.6 months in the matched
control group.
A study (NCT02955290) to
evaluate the efficacy of CIMAvax-EGF
in combination with nivolumab as
second-line therapy for advanced
NSCLC commenced recruitment in
December 2016.
Another randomized international
phase III study of CIMAvax-EGF in
combination with first-line platinumbased
chemotherapy for patients with
stage IV NSCLC is ongoing.
Vx-001 targeting TERT
Vx-001, a peptide-based vaccine
developed by Paris-based Vaxon
Biotech, is currently in Phase II
clinical studies. It is designed to elicit
immunogenicity of the cryptic epitope
A RANDOMIZED
INTERNATIONAL PHASE III
STUDY OF CIMAVAX-EGF
IN COMBINATION WITH
FIRST-LINE PLATINUM-
BASED CHEMOTHERAPY FOR
PATIENTS WITH STAGE IV
NSCLC IS ONGOING.
derived from telomerase reverse
transcriptase (TERT), a universal
tumour antigen, in order to bind human
leukocyte antigen A2 (HLA-A2) positive
T cells. Data from a randomized,
double-blind, placebo-controlled,
phase IIb clinical trial in about 190
HLA-A2–positive patients with
metastatic or recurrent NSCLC after
platinum-based first-line chemotherapy
found no significant differences in
OS between the groups treated with
Vx-001 and placebo. However, 29%
of patients, who were able to develop
a vaccine-specific immune response,
demonstrated higher OS compared
with non-responders (21 vs 13 months,
P = .004). A subset analysis also found
better OS with vaccine, among patients
who were never-smokers or light
smokers and had non-immunogenic
tumours, with median OS of 20.2
months versus 7.9 months. Vaxon
has plans to investigate Vx-001 in
combination with immune checkpoint
inhibitors in the population of patients
with non-immunogenic NSCLC.
Racotumomab: Anti-idiotype mAb
Racotumomab (Vaxira) is a therapeutic
vaccine that is currently under clinical
development by Recombio, an
international public-private consortium,
in association with the Center of
Molecular Immunology at Havana, Cuba
(CIM) and researchers from Buenos
Aires University and the National
University of Quilmes in Argentina.
It is an anti-idiotype monoclonal
antibody (mAb) against ganglioside
containing NeuGcGM3, a Neu glycolyl
(NeuGc). NeuGcGM3 ganglioside is
expressed in NSCLC. Anti-idiotypic
antibodies are capable of eliciting
an immunogenic reaction against
the original epitope of the selected
antigen as they mimic the nominal
antigen. Final results are awaited
from a randomized phase III trial
(NCT01460472) of racotumomab in
about 1,080 patients carried out in
South America and Southeast Asia.
Tumour neoantigens approach
An alternative vaccine approach gaining
currency recently is the targeting of
tumour neoantigens that arise from
somatic mutations. These neoantigens
are tumour-specific and highly
immunogenic. They are individualized
vaccines comprising multiple RNA or
peptide-based neoepitopes identified
after whole exome sequencing of the
tumour tissue in each patient. Several
clinical trials are underway pursuing the
neoantigens approach in combination
with anti-PD1/PD-L1 drugs. Studies
such as NEO-PV-01, RO7198457,
mRNA-4157, NCT02897765,
NCT03289962 and NCT03313778 are
among them.
NOVEMBER 2018 / FUTURE MEDICINE / 33

drug approvals
Dupilumab for asthma in US
The US Food and Drug
Administration has
approved dupilumab
(Dupixent) as an add-on
maintenance therapy in
patients aged 12 years and
older with moderate-to-severe
asthma with an eosinophilic
phenotype and those with
oral corticosteroid-dependent
asthma.
Dupilumab inhibits
the overactive signaling
of interleukin-4 (IL-4) and
interleukin-13 (IL-13), two key
proteins that contribute to
the Type 2 inflammation that
may underlie moderate-tosevere
asthma. This effect is
associated with the reduction
of inflammatory biomarkers,
including fractional exhaled
nitric oxide (FeNO),
immunoglobulin E (IgE) and
eotaxin-3 (CCL26).
The pivotal trial
programme evaluated 2,888
adult and adolescent patients
with moderate-to-severe
asthma in three randomized,
placebo-controlled,
Talazoparib to
treat gBRCAm
breast cancer
Talazoparib (Talzenna) has
been cleared by US FDA
for patients with deleterious
germline BRCA-mutated
(gBRCAm), HER2-negative
metastatic breast cancer.
Developed by Pfizer,
talazoparib is a poly (ADPribose)
polymerase (PARP)
inhibitor.
The approval was based
on EMBRACA, an open-label
trial randomizing 431 patients
(2:1) with gBRCAm HER2-
negative locally advanced
or metastatic breast cancer
to receive talazoparib (1
mg) or physician’s choice of
chemotherapy (capecitabine,
eribulin, gemcitabine or
multicentre trials for six
months to one year.
In Trial 2 (the largest
trial), dupilumab reduced
exacerbations and improved
lung function in the overall
population. Benefits in
exacerbations were seen
in patients with eosinophil
counts greater than or equal
to 150 cells/microliter, which
represented 70% of the
patients enrolled. Efficacy
improved in patients with
vinorelbine).
The primary efficacy
outcome was progression-free
survival (PFS), according to
Response Evaluation Criteria
in Solid Tumours (RECIST)
1.1, as assessed by a blinded
independent central review.
Estimated median PFS was
8.6 months and 5.6
months in the talazoparib
higher eosinophil counts.
In Trial 3, which evaluated
severe, oral corticosteroiddependent
patients,
dupilumab reduced average
daily oral corticosteroid use
by 70% compared to 42%
with placebo. More than
half of patients treated
with dupilumab completely
eliminated the use of oral
corticosteroids, announced
Regeneron Pharmaceuticals,
Inc and Sanofi.
and chemotherapy arms,
respectively (HR 0.54; 95%
CI: 0.41, 0.71; p

showed that rivaroxaban
vascular dose, 2.5 mg twice
daily, plus aspirin 100 mg
once daily reduced the
risk of the composite
of stroke, CV death and
heart attack by 24 percent
compared with aspirin 100
mg once daily alone in
patients with CAD or PAD.
Rivaroxaban was
discovered by Bayer, and
is being jointly developed
with Janssen Research &
Development, LLC.
Abemaciclib
for HR+ breast
cancer in EU
EMA has cleared
abemaciclib (Verzenio) to
treat women with hormone
receptor-positive (HR+),
epidermal growth factor
receptor 2 negative (HER2-)
locally advanced or metastatic
breast cancer.
The treatment with
CDK4/6inhibitor is approved
as a first-line therapy
in combination with an
aromatase inhibitor or
fulvestrant, and as a secondline
treatment after earlier
endocrine drugs.
The approval of
abemaciclib is based on the
results of the Monarch 2
and Monarch 3 as secondline
and first-line studies. A
phase III trial called Monarch
E is currently underway to
determine the efficacy of
abemaciclibas adjuvant
therapy in early breast cancer.
Earlier, Eli Lilly suspended
the Phase 3 Juniper
programme to extend the use
of abemaciclibinto pancreatic
cancer as it failed to meet the
endpoints
Elapegademase
for ADA-SCID
US FDA has granted
approval for
elapegademase (Revcovi) for
adenosine deaminase severe
combined immune deficiency
(ADA-SCID).
Elapegademase is a longacting
drug that replaces
the missing ADA enzyme in
patients with ADA-SCID with
an engineered, recombinant
form.
The new drug comes as an
alternative to current animalderived
enzyme replacement
therapy pegademase bovine
by Leadiant.
Also known as bubble boy
disease, ADA-SCID is an ultrarare,
inherited geneticdisorder
that compromises patients’
immune systems and leaves
patients unprotected from
infections, and is fatal if
untreated.
The disease is typically
diagnosed within the first
few months of life, and
undiagnosed babies with
ADA-SCID usually die before
Breakthrough
designation for
20-valent vac
Pfizer’s 20-valent
pneumococcal
conjugate vaccine
(20vPnC) candidate,
PF-06482077, received
breakthrough therapy
designation from the US
FDA for the prevention
of pneumonia caused by
Streptococcus pneumoniae
serotypes in the vaccine in
adults.
The FDA decision is
informed by the results
of the 20vPnC Phase 2
randomized, double-blind
trial to evaluate the safety
and immunogenicity of a
multivalent pneumococcal
conjugate vaccine in adults
60 through 64 years of
age.
Anti-depressant vortioxetine
launched in India
Lundbeck launched vortioxetine
(Brintellix) in India for the
treatment of patients suffering
from major depressive disorder
(MDD), following approval from
Drug Controller General of India
(DCGI).
Vortioxetine is a novel
multimodal antidepressant which
has been specifically designed
to inhibit serotonin reuptake and
modulate serotonergic receptor
activity of the neurons in the brain
of affected patients.
It has demonstrated significant
efficacy in reducing the mood
symptoms in adult patients with
depression as measured by
traditional scales like MADRS or
HAMD.
The drug also improves
cognitive performance in adult
patients with depression, as
measured with neuropsychological
tests. Cognitive symptoms are
part of the diagnostic criteria
for depression and include the
ability to concentrate, make
decisions and the ability to
remember, said Lundbeck.
NOVEMBER 2018 / FUTURE MEDICINE / 35

they reach age two due to
infections.
Elapegademase approval
is based on two open-label
trials demonstrating the drug
increases ADA activity, reduces
concentrations of toxic
metabolites and improves
total lymphocyte counts in
ADA-SCID patients.
Cemiplimab for
skin cancer in US
Inotersen to address polyneuropathy
The US Food and Drug
Administration has
approved inotersen (Tegsedi)
for the treatment of
polyneuropathy of hereditary
transthyretin-mediated
amyloidosis in adults.
Inotersenis an RNAtargeting
therapeutic that
reduces the production
of TTR protein through a
once-weekly subcutaneous
injection offering a treatment
for people living with
polyneuropathy caused by
hATTR amyloidosis.
In hATTRamyloidosis,
transthyretin (TTR) protein
misfolds and accumulates as
amyloid deposits throughout
the body. Inotersen targets
the disease at its source by
reducing the production of
TTR protein.
The FDA looked at results
from the Phase 3 NEURO-
TTR study in patients with
hATTRamyloidosis with
symptoms of polyneuropathy.
Results from that study
demonstrated that patients
treated with inotersen
experienced significant benefit
compared to patients treated
with placebo across both coprimary
endpoints: the Norfolk
Quality of Life Questionnaire-
Diabetic Neuropathy (Norfolk
QoL-DN) and modified
Neuropathy Impairment
Score +7 (mNIS+7), a
measure of neuropathic
disease progression, Akcea
Therapeutics, Inc and
Ionis Pharmaceuticals, Inc,
announced.
Cemiplimab-rwlc(Libtayo)
injection for the treatment
of patients with metastatic
cutaneous squamous cell
carcinoma (CSCC) has been
granted approval by USFDA.
Cemiplimab works by
targeting the cellular
pathway known as PD-1. By
blocking this pathway, the
drug may help the body’s
immune system fight the
cancer cells.
The safety and efficacy
of Libtayo were studied in
two open-label clinical trials.
A total of 108 patients (75
with metastatic disease and
33 with the locally-advanced
disease) were included in the
efficacy evaluation.
The study’s primary
endpoint was objective
response rate or the
percentage of patients who
experienced partial shrinkage
or complete disappearance of
their tumor(s) after treatment.
Results showed that 47.2
per centof all patients treated
with cemiplimabhad their
tumoursshrink or disappear.
Cemiplimab is
developed by Regeneron
Pharmaceuticals, Inc.
Emicizumab for
haemophilia
without FVIII
The US FDA has
approved emicizumabkxwh(Hemlibra)
for routine
prophylaxis to reduce the
frequency of bleeding
episodes in adults and
children with haemophiliaA
without factor VIII inhibitors.
Emicizumab is now the
only prophylactic treatment
for people with haemophilia
A with and without factor
VIII inhibitors that can be
administered subcutaneously
and at multiple dosing
options, Roche said.
This approval is based
on positive results from
the phase III Haven 3 and
Haven 4 studies. Emicizumab
prophylaxis led to statistically
significant and clinically
meaningful reductions in
treated bleeds compared to
no prophylaxis and across all
other bleed-related endpoints
in the Haven 3 study, and
showed control of bleeding in
the Haven 4 study.
Haven 3 is a randomised,
multicentre, open-label, phase
III study evaluating the efficacy,
safety andpharmacokinetics of
emicizumabprophylaxis versus
no prophylaxis in people
with haemophilia A without
factor VIII inhibitors. The
study included 152 patients
with haemophiliaA who were
previously treated with factor
VIII therapy.
Dacomitinib to
treat metastatic
NSCLC
P
fizer Inc said the USFDA
has approved dacomitinib
(Vizimpro) to treat non-small
cell lung cancer (NSCLC) that
has spread to other parts of
the body.
Dacomitinib is a kinase
inhibitor indicated for firstline
treatment of patients
with metastatic NSCLC with
epidermal growth factor
receptor (EGFR) exon 19
deletion or exon 21 L858R
substitution mutations as
detected by an FDA-approved
test.
The safety and efficacy of
dacomitinib wasdemonstrated
in Archer 1050, a randomized,
multicenter, multinational,
open-label study. A total of
452 patients were randomized
36 / FUTURE MEDICINE / NOVEMBER 2018

1:1 to dacomitinib or gefitinib.
A statistically significant
improvement in PFS, as
determined by the IRC, was
demonstrated for patients
randomized to dacomitinib
compared with gefitinib (HR
= 0.59 [95% CI: 0.47, 0.74],
p months (95% CI: 11.1, 16.6)
compared with 9.2 months
(95% CI: 9.1, 11.0) in the
gefitinib arm.
Vonicog to
treat bleeding
disorder in EU
T
he European Commission
(EC) has granted Marketing
Authorization for vonicogalfa
(Veyvondi) for the treatment
of bleeding events and
treatment of surgical bleeding
in adults with von Willebrand
disease (VWD).
Vonicog alfa is the first
and only recombinant von
Willebrand Factor (rVWF)
treatment in the EU for VWD
that specifically addresses the
primary deficiency, Shire Plc
said.
EC has reviewed the
outcomes from three clinical
trials of a total80 patients with
VWD exposed to vonicogalfa.
These include a Phase 1
multicentre, controlled,
randomized, single-blind,
dose-escalation study of
the safety, tolerability, and
pharmacokinectics(PK) of
rVWF:rFVIII in subjects 18 to
60 years of age with severe
VWD.
VWD is caused by a
deficiency or dysfunction of
VWF, one of several types of
proteins in the blood that
are needed to facilitate
proper blood clotting.
Only a minor proportion of
Fremanezumab to
prevent migraine
The USFDA has approved
fremanezumabvfrm(Ajovy)
injection
for the preventive
treatment of migraine in
adults,announced Teva
Pharmaceuticals.
Fremanezumabis a
humanized monoclonal
antibody that binds to
calcitonin gene-related
peptide (CGRP) ligand and
blocks its binding to the
receptor. It is the first and
only anti-CGRP treatment
for the prevention of
migrainewith quarterly
affected individuals have the
severe form of the disease
and are in need of VWF
replacement.
Vonicog alfa is indicated
in adults with VWD, when
(675 mg) and monthly (225
mg) dosing options, Teva
said.
Fremanezumab was
evaluated in two Phase
III, placebo-controlled
clinical trials that enrolled
patients with disabling
migraine and was studied
as both a stand-alone
preventive treatment and
in combination with oral
preventive treatments.
In these trials, patients
experienced a reduction
in monthly migraine days
during a 12-week period.
desmopressin (DDAVP)
treatment alone is ineffective.
Axicabtagene
gets orphan drug
status in Japan
Axicabtagene ciloleucel
has been granted Orphan
Drug designation by the Japan
Ministry of Health, Labour
and Welfare (MHLW) for the
treatment of diffuse large
B-cell lymphoma (DLBCL),
primary mediastinal large
B-cell lymphoma (PMBCL),
high-grade B-cell lymphoma
(HGBL) and transformed
follicular lymphoma (TFL),
which are aggressive forms
of non-Hodgkin lymphoma
(NHL).
Axicabtagene ciloleucel is
a chimeric antigen receptor T
cell (CAR T) therapy directed
against CD19, which harnesses
a patient’s own immune
system to fight certain types
of B-cell lymphoma.
Based on the results of
a phase 1/2 study (ZUMA-1),
axicabtagene ciloleucelhas
been approved in the US
and Europe. A phase 2 study
similar to the ZUMA-1 study
is currently being planned in
Japan.
The Japan MHLW Orphan
Drug designation system is
designed to promote research
activities and support the
development of orphan drugs
for serious, difficult-to-treat
diseases that affect fewer than
50,000 patients in Japan, and
for which significant unmet
medical need exists.
Baloxavir to
treat acute flu
The US FDA has granted
approval to baloxavir
marboxil for the treatment of
acute uncomplicated influenza.
The oral antiviral drug has
been approved for all patients
12 years of age and older who
have been symptomatic for no
more than 48 hours.
The safety and efficacy of
baloxavir were demonstrated
in two randomized controlled
clinical trials of 1,832 patients
where participants were
assigned to receive either
baloxavir, a placebo, or another
antiviral flu treatment within
48 hours of experiencing
flu symptoms. In both
trials, patients treated with
baloxavir had a shorter time
to alleviation of symptoms
compared with patients who
took the placebo.
NOVEMBER 2018 / FUTURE MEDICINE / 37

case reports
GENE THERAPY
FOR BLINDNESS
LCA - a congenital eye defect that
continues to defy remedy
A
four-month old male child was brought to Lilawati
Hospital in Mumbai with complaints of blindness and
frequent rubbing of eyes. The child had an uneventful
birth history and was active, with no other clinical symptoms
other than roving, or searching, movements of the eyes.
His family history indicated that four out of his father’s
six first cousins had congenital blindness. Brain MRI was
normal, as was the fundoscopy done by an ophthalmologist.
Electroretinogram (ERG), which measures the activity in the
retina, showed a reduction in photoreception function in
the entire retina including both rods and cones. There was
also a poor response to cone stimulation as seen by visual
evoked potential (VEP). Keeping the family history and clinical
observations in mind, the working diagnosis was that of
Leber’s congenital amaurosis (LCA).
LCA is a rare autosomal recessive genetic eye disease that
appears at birth or during the first few months thereafter, and
can affect males and females with an equal probability. While
it affects 1-3 newborns in 1,000,000, it is one of the most
common causes of blindness in children. This eye disease
affects the retina that detects both light and colour, resulting
in severe visual impairment early in the infancy. A common
sign associated with LCA is the Franceschetti’s oculo-digital
sign, characterized by the poking, rubbing, and/or pressing of
the eyes.
LCA can be caused due to
mutations in the genes necessary
for normal vision. There are
over 26 known genes that
are implicated in LCA, and the
list is still growing. LCA genes
encode proteins important in a
wide variety of retinal functions;
for example, CRB1 and CRX are
important for photoreceptor
morphogenesis, GUCY2D and
AIPL1 for phototransduction,
LRAT, RDH12 and RPE65 for
vitamin A cycling, etc. The
mutations in some of the genes such
as CEP290, CRB1, GUCY2D, or RPE65
are the most commonly associated with
LCA, though 20-30% of the children
with LCA have no identifiable cause.
Treatment for LCA is still primarily at
the clinical trials stage, with only one FDA
approved treatment for the RPE65 mutation
THE AAV2 VECTOR DOES NOT
CAUSE ANY DISEASE AND IS
AN ATTRACTIVE VIRAL VECTOR
FOR GENE THERAPY.
so far. The current gene therapy involves
delivering the RPE65 gene via sub-retinal
injection, which allows for normal RPE65
protein to be expressed and the consequent
restoration of the visual cycle. Voretigene
neparvovec (Luxturna) is a novel gene
therapy developed by Spark Therapeutics
and Children’s Hospital of Philadelphia, USA,
and is the first in vivo gene therapy approved
by the FDA. Voretigene consists of the
Adeno-associated virus serotype 2 (AAV2)
vector containing the RPE65 cDNA. The AAV2
vector does not cause any disease and is
an attractive viral vector for gene therapy.
Vortigene treatment comes with its own
hurdles; the cost of treatment for one eye
is estimated to be a whopping $425,000!
However, this is a one-time therapy, where
the treatment is expected to have long-term
benfits.
38 / FUTURE MEDICINE / NOVEMBER 2018

While Voretigene has
passed clinical trials and
is now an FDA-approved THE CHILD’S BLOOD
therapy, several other genetic SAMPLE WAS SENT
therapy options for other FOR GENETIC TESTING.
gene mutations for LCA are THE PANEL INCLUDED
currently being researched in
20 POTENTIAL GENES
mouse models and cell lines.
GUC2YD cDNA constructs IN WHICH A MUTATION
in AAV vector, when subretinally
injected in the BLINDNESS. THE RESULTS
IS KNOWN TO CAUSE
eyes of Gucy2e-/-Gucy2f-/- INDICATED A MUTATION
knockout (GCdKO) mice, IN THE GUCY2D GENE.
have been shown to evoke
scoptopic and photopic
ERG responses. In a slightly
different approach, researchers are also attempting to use
Antisense Oligonucleotide-Based Splicing Correction to allow
normal protein expression in case of CEP290 gene mutations.
Results have been promising so far for human cell lines and
in CEP290 mutant mouse models. However, these studies
still need to undergo clinical trials and obtain
human use approvals, and are currently far
from reaching the patient’s bedside.
To confirm the diagnosis of LCA and to
identify the genetic mutation in the fourmonth
old baby, paediatric neurologist Dr.
K. N. Shah sent the child’s blood sample for
genetic testing using the LCA panel. This
panel included 20 potential genes in which
a mutation is known to cause blindness. The
results indicated a mutation in the GUCY2D
gene. Since, currently there is no therapy
for the GUCT2D mutations, no treatment
is possible for this baby. However, there
is a large potential for the evolution of a
treatment for the condition in the future, and
it is likely that therapeutic options will start
becoming available going forward.
DR SHIVANEE SHAH
NOVEMBER 2018 / FUTURE MEDICINE / 39

case reports
A RARE SYNDROMIC
ASSOCIATION
A case of jaw tumour with hyper-parathyroidism, which posed several
challenges in resection and reconstruction
DR KRISHNAKUMAR THANKAPPAN &
DR SUBRAMANIA IYER
A
19-year old male from Jharkhand presented with a
10-year history of left sided swelling on the face. It
was insidious in its onset, with a rapid increase in
size during last three years. He had difficulties in breathing
as well as taking his diet orally. The swelling had pushed
his eyes outwards and upwards causing visual problems.
He could only perceive light with his left eye. Clinical
examination showed 15x15 cm swelling on the left side of
face, (Figure 1) extending from the supraorbital ridge to
the angle of the mandible. The swelling was distorting the
external osseocartilaginous framework of the nose. Ala of
the right nostril was preserved. There was also a separate
swelling on the right nasolabial region. Intraoral examination
showed a bulge on the right side, distorting the maxillary
alveolar ridge. Imaging with a CT scan showed a fibroosseous
lesion with a ‘soap-bubble’ appearance. A threedimensional
reconstruction was also done to aid in planning.
Biopsy was suggestive of a fibro-osseous
pathology.
Challenges in resection: The challenges
were to remove the tumour completely
with the preservation of normal structures.
The preservation of the distorted eye
anatomically and functionally was a major
issue. Preserving the oral aperture with
the intact musculature was also important.
The skin was expanded by the tumour and
hence could be preserved if not involved by
the tumour.
Challenges in reconstruction: The principle
was to mirror the normal side and to follow
the anatomical landmarks for fixation. All the
bones were grossly expanded, preventing
fixation. Hence there was no anatomical
reference point. A computer-based planning
was done on the three-dimensional images.
40 / FUTURE MEDICINE / NOVEMBER 2018

1 2
3 4
The tumour was subtracted
digitally and the remnant
bones on right were mirrored
to the left. Plates were
prebent as a frame to which
free fibula bone flap was to
be contoured and placed
(Figure 2).
THE CASE DEMONSTRATED
THE IMPORTANCE
OF METICULOUS
MULTIDISCIPLINARY
PLANNING AND
SUCCESSFUL EXECUTION.
Surgical procedure: The
tumour was resected
completely through an
incision placed on the swelling. Much of the skin, the left oral
commissure and the left eye could be preserved structurally. A
left total maxillectomy and right partial maxillectomy was done.
The defect was mainly left maxillary and total hard palate.
There was also a loss of dorsal nasal support. A free fibula
osteocutaneous flap was taken from the left leg of the patient.
Three osteotomies were done to make four bone segments.
Contouring was done on the prebent plate. Three segments
were used to reconstruct the upper jaw; the last segment
was placed vertically for malar eminence and orbital support.
Fixation was done with plate and screws. The nasal deformity
was corrected with dorsal augmentation from the remaining
free fibula graft. Another piece was also used as a columellar
strut. The flap was anastomosed to the facial artery and vein.
The surgery lasted for about 14 hours.
A week later, the pathology was reported as juvenile
ossifying fibroma, psammomatoid type. Juvenile ossifying
fibroma can be rarely associated with
hyperparathyroidism. The patient was
seen by an endocrinologist. Investigations
for hyperparathyroid related syndromes
were done. Serum Calcium (14.6 mg/
dl) and parathyroid hormone (426 ng/L)
were elevated. A Technitium Sestamibi scan
showed increased uptake in the left inferior
parathyroid. Ultrasonogram of the abdomen
showed hamartoma of both kidneys. Left
inferior parathyroidectomy was done as a
second surgery. The PTH level dropped
to 92 ng/L intraoperatively. The post-operative
serum calcium was 8.5 mg//dl). The patient
recovered well from the surgeries and was
discharged. The visual acuity in the left eye
remained the same. He may also require some
additional corrective cosmetic procedures for
the left eye later (Figure 3, 4).
Hyperparathyroidism jaw tumour
syndrome is a rare entity. It is inherited as an
autosomal dominant pattern with incomplete
penetrance. The syndromic associations are
parathyroid adenomas, ossifying fibroma
of the jaw, renal lesions, polycystic kidney
disease, hamartomas and Wilm’s tumour.
Absolute treatment is the removal of the
jaw tumour and the offending parathyroid
adenoma.
It is important to look for the association
of hyperparathyroidism in juvenile ossifying
fibroma of the jaw. Treatment is complete only
if parathyroidectomy is done. There is a 24%
chance of the adenoma to turn malignant.
The case demonstrated the importance of
meticulous multidisciplinary planning and
successful execution. Head and neck surgeons,
plastic surgeons, craniomaxillofacial surgeons,
radiologists, nuclear medicine specialists,
ophthalmologists and pathologists were
involved. The nursing and technical staff also
helped immensely.
Dr Krishnakumar Thankappan is Professor,
Department of Head & Neck Surgery and Oncology
and Dr Subramania Iyer is Professor and Head,
Department of Head and Neck and Plastic Surgery,
Amrita Institute of Medical Sciences, Kochi.
drkrishnakumart@gmail.com
NOVEMBER 2018 / FUTURE MEDICINE / 41

case reports
ABERNETHY -
AN UNUSUAL
SUSPECT
When the cause of breathlessness in a child
turned out to be a very rare congenital
venous system anomaly
An eight-year-old boy was presented to his
paediatrician with breathlessness. Upon regular
examination, the pediatrician identified a murmur and
referred the child to Dr. Shine Kumar, Paediatric Cardiologist
at Amrita Institute of Medical Sciences, Kochi, for further
evaluation. The child underwent ECG, X-ray, and echo. ECG
and X-ray were nonconclusive. However, echo identified
high pressure in the lung arteries, indicative of pulmonary
hypertension.
Pulmonary hypertension is a type of elevated blood
pressure, but one that involves the arteries of the lung and
the right side of the heart. Symptoms include breathlessness,
fatigue, dizziness, as well as fast heart beats. There are
several causes of pulmonary hypertension like congenital
heart conditions, left-sided heart disease, lung disease, blood
clots in the lungs, other conditions such as blood disorders or
tumours pressing against pulmonary arteries etc. Treatment
is dependent on the cause of pulmonary hypertension and
majority of the time, it is not curable, and only supportive
treatment is available. Doctors can at best help manage
the condition; often having to change and improvise on the
medication or treatment options.
For an effective treatment, it was important to
accurately diagnose the cause of pulmonary hypertension
in this patient. Dr. Kumar’s team therefore carried out
further investigative testing that included an abdominal
ultrasound. The abdominal ultrasound identified an
Abernethy malformation in the liver. Abernethy malformation
is a congenital condition in which there is abnormal
communication between the portal vein and the inferior
vena cava, which causes elevated lung pressures. These
are very rare vascular anomalies of the venous system of
the abdominal region. Normally, de-oxygenated blood from
the abdominal organs is drained by the portal vein into the
liver and then circulated to the heart via the inferior vena
cava. However, in case of Abernathy malformation, the
liver is bypassed due to an extrahepatic
portosystemic shunt and the blood is
diverted directly to the systemic circulation
via the inferior vena cava to reach the
heart. These malformations are remnants
of embryonic vessels and are typically
congenital. There are two types of Abernathy
malformations. Type I is predominantly found
in females in whom there is a congenital
absence of blood flow from the portal vein
to the liver. Type II patients have an end-toend
shunt or an extrahepatic communication
that allows for a complete diversion of the
portal blood into the systemic veins. Type II
on the other hand is predominant in males
where the portal vein is hypoplastic and the
blood gets partially diverted from the portal
vein to the inferior vena cava via a side-toside
shunt or extrahepatic communication.
Abernathy malformations are rare,
42 / FUTURE MEDICINE / NOVEMBER 2018

occurring in less than 1%
of the general population.
They are generally detected
incidentally in the paediatric
population, during an
investigation of associated
liver or cardiac anomalies.
It is much more challenging
to identify in older patients
especially in those with other
chronic liver diseases and
with no early diagnosis of
congenital portosystemic
shunts. Once identified,
treatment is dependent on
TYPE I MALFORMATIONS
TYPICALLY REQUIRE A
LIVER TRANSPLANTATION,
WHEREAS TYPE II
MALFORMATIONS ARE
COMPLETELY CURABLE
WITH EITHER
SURGICAL LIGATION OR
ENDOVASCULAR OCCLUSION.
the type of malformation. Type I malformations typically
require a liver transplantation, whereas type II malformations
are completely curable in a simpler manner with either
surgical ligation or endovascular occlusion.
Within 2 weeks of diagnosing a type II Abernathy
malformation, the 8-year-old boy underwent
a keyhole surgery through a vein in the leg,
and the abnormal extrahepatic channel
was occluded using a metallic plug. Regular
follow ups showed that the treatment
was successful, and the child did not have
pulmonary hypertension. It has been 2 years
since the procedure and the patient is doing
well.
“Pulmonary hypertension can be caused
due to many conditions, most of them are
not curable. The ultrasound identified a type
II Abernathy malformation in our patient,
which was a very fortunate diagnosis as it
is one of the few treatable conditions that
causes pulmonary hypertension,” says Dr.
Kumar.
DR SHIVANEE SHAH
NOVEMBER 2018 / FUTURE MEDICINE / 43

case reports
PROBE ON CULTURE-NEGATIVE
LESIONS
Why it is important to pin down non-tuberculous mycobacteria species rapidly
A
72-year-old woman presented with multiple painful
lesions on the abdomen to the dermatology
department at Amrita Institute of Medical Science,
Kochi. The consulting dermatologist, Dr. Soumya Jagadeesan,
noted that the lesions were purulent and the patient had
previously undergone surgical drainage multiple times
without any benefit. Gram staining of smears and routine
cultures were negative and the patient had been treated
with multiple courses of broad spectrum antibiotics, with
no response even after several weeks. A skin biopsy had
revealed a granulomatous inflammation and the patient was
started on anti-tuberculosis treatment on the presumption
that it might be an extra-pulmonary
tuberculosis infection, as the chest X-ray was
normal. At the time of her presentation to
the centre, the patient had not responded
to even anti-tuberculosis treatment. An
atypical (non-tuberculous) mycobacterial
infection was then suspected. While there
was no history of trauma or surgery, the
patient was taking insulin injections at the
same site and admitted that she was not
taking efforts to take these injections in an
aseptic manner. Further testing including
44 / FUTURE MEDICINE / NOVEMBER 2018

Ziehl–Neelsen staining of smears and mycobacterial cultures
were done. Staining showed acid-fast bacilli. Nonpigmented
colonies were observed on the 6th day in the cultures.
Multiplex PCR was done and confirmed the presence of M.
chelonae. The patient was then started on doxycycline and
clarithromycin. Clarithromycin
had to be substituted with
linezolid as the patient had
severe diarrhea due to the
medication. The lesions
healed within 4 weeks of
starting this treatment and
the treatment was continued
for an additional 6 weeks. No
recurrence was observed at
the sixth-month follow up.
Incidence of nontuberculous
mycobacteria is
on the rise. Non-tuberculous
mycobacteria include
mycobacterial species other
INCIDENCE OF
NON-TUBERCULOUS
MYCOBACTERIA IS ON THE
RISE. NON-TUBERCULOUS
MYCOBACTERIA INCLUDE
MYCOBACTERIAL
SPECIES OTHER THAN
MYCOBACTERIUM
TUBERCULOSIS.
than Mycobacterium tuberculosis, and contribute to causing
infections in the lungs, lymph nodes, bone, brain, kidneys,
genital tract as well as skin tissue. Different mycobacterial
species respond to different treatment regimens and
therefore rapid identification of the correct species is
extremely important for appropriate treatment. Further,
many non-tuberculous mycobacteria are resistant to typical
M. tuberculosis treatments, making it essential to accurately
determine the causative species. In India, the most prevalent
non-tuberculous mycobacterial species include M. abscessus,
M. fortuitum and M. chelonae in extrapulmonary tissue
samples.
While rapid and accurate identification of these species
is extremely important, diagnosis is challenging as they may
not be identified via routine culture techniques. Recently,
high performance liquid chromatography (HPLC) analysis of
mycolic acids, probe-based tests and DNA sequencing have
been used. However, they come with their own limitations.
HPLC requires special expertise in interpreting the data
generated and needs expensive equipment. Kit-based
probe assays are costly and may not be readily available,
while DNA sequencing is time consuming. Multiplex PCR
options are also now available for accurate identification of
rapid grower mycobacterium. It can differentially diagnose
between M. abscessus, M. fortuitum,and M. chelonae, and is
a useful diagnostic test in case rapid grower mycobacterium
is suspected. Rapid identification is critical, since the
treatment will depend on the species. For instance, M.
chelonae responds well to medical management, however,
M. abscessus may not and may require surgical management
such as drainage of pus and removal of necrotic tissue to
augment the treatment.
This case was one of four M.chelonae infected cases
that came to Dr. Jagadeesan’s attention in the past one
and a half years, and she advises that
“a high index of suspicion is necessary if
a patient presents with lesions that are
culture negative and has a history of injury
or surgical treatment.” She advocates that
since these infections often occur at surgical
sites, especially following laparoscopic
procedures, inadequate sterilization
practices at the hospitals maybe a source of
the infection and doctors may need to be
ready to inform the source sites to prevent
further cases.
Dr. Jagadeesan is now quick to consider
M. chelonaein case of culture-negative
cases and is prompt in carrying out the
multiplex PCR to confirm her working
diagnosis. Recently, a 42-year old lady
presented with lesions on the abdomen.
These lesions were at the site of a recent
laparoscopic sterilization procedure.
Multiplex PCR was done and M. chelonae
was identified fairly quickly. The patient
was started on clarithromycin and ofloxacin
tablets and recovered within 4 weeks. The
treatment was however continued up to
12 weeks to prevent any recurrence. Thus,
accurate early identification can substantially
reduce the lag time in correct diagnosis
and avoid inappropriate antibiotic use and
anti-tuberculosis therapy that can result in
adverse side effects and undue toxicity.
DR SHIVANEE SHAH
46 / FUTURE MEDICINE / NOVEMBER 2018

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case reports
BRACHYTHERAPY FOR
BRAIN CANCER
An instance where localised internal radiation therapy has been successfully
used to control tumour growth
Brachytherapy is an age-old method that is effective for
irradiating cancer cells, especially in cervical, prostate,
breast and skin cancers. This radiotherapy technique
involves the introduction of a sealed source of radiation close
to the area requiring treatment. Because of the proximity to
the cancer cells, there is reduced probability of unnecessary
damage to the neighbouring healthy cells. It is therefore
relatively less harmful, even though high doses of localized
radiation are delivered.
Brachytherapy is a minimally invasive technique that
reduces the treatment duration for certain
types of cancer and is often considered to
be an alternative treatment for challenging
cases. Due to the simplicity of the technique,
it offers the ease of an outpatient treatment
regimen with a quicker recovery time. It
has also been proposed that the short
treatment duration of brachytherapy may
also be of potential benefit in preventing
cancer recurrence. With all these benefits, it
48 / FUTURE MEDICINE / NOVEMBER 2018

could well have been the treatment of choice in such cases.
However, it is effective only in cases when the tumour is
accessible. Moreover, the survival rates are not consistently
superior to other radiation oncology techniques.
In India, brachytherapy is widely used for treating
gynecological cancers. Some of the other types of cancer
where it is used are those affecting the skin, prostate,
head and neck, breast and even eyes. Despite its overall
acceptability, this form of irradiation has not been reported
for the treatment of brain tumours in India. In perhaps one of
the first brachytherapy treatment cases for brain cancer, Dr.
Manish Chandra, a Radiation Oncologist at Jupiter Hospital,
Thane, successfully used this method on a patient recently.
A 40-year old man, who had high grade glioblastoma
(WHO Grade IV), had previously undergone tumour resection
surgery, followed by radiation therapy. By the end of 18
months post treatment, the cancer recurred and the patient
had to undergo a second surgical procedure, followed by
chemotherapy. Unfortunately, within a span of 2 months
after the second surgery, the tumour was found to have
recurred again. Since the tumour was recurring and repeated
brain surgery has adverse effects, the patient was referred
to Dr. Chandra for further treatment and follow-up. After
carefully considering the patient’s previous history, age, the
accessibility of the tumour, and most importantly, the fact
that the patient was otherwise healthy, Dr. Chandra proposed
brachytherapy as the best choice to go forward. The patient
was also explained the reasons behind the proposed choice,
and was willing to undergo
the procedure. One of the
challenges of this technique
is the need to anticipate
possible brain damage as
the needles go through
the brain tissue to reach
the tumour. This procedure
was performed in local
anaesthesia and patient
was conscious during the
procedure.
Pre-procedure planning
was quite elaborate as the
exact location of the tumour
needed to be mapped. A
team of doctors, including
Dr. Chandra, Neurosurgeon
Dr. Harshad Purandare and
technical person Mr Devarsh
(3D – Rendering), first set
about preparing a grid-based
model using 3D images from
MRI scans to determine the
location at which the holes
would need to be drilled in
the skull for needle insertion
ONE OF THE CHALLENGES
OF THIS TECHNIQUE IS
THE NEED TO ANTICIPATE
POSSIBLE BRAIN DAMAGE
AS THE NEEDLES GO
THROUGH THE BRAIN
TISSUE TO REACH THE
TUMOUR.
and the length of the individual needles. At
the time of the procedure, the pre-designed
grid was marked on the skull of the patient
such that the specific points within the grid
were identified with a label and each label
corresponded to the depth of the hole that
was to be drilled. The process of pre-fixing
the depth of the needle insertion to deliver
the radiation is a very delicate and complex
process and must be done keeping in mind
not just the location of the tumour, but also
the positioning of underlying blood vessels
and the surrounding healthy tissue. Dr.
Purandare then drilled 17 holes in the skull
for needle insertion. The entire procedure
was carried out under local anaesthesia
and the patient was able to communicate
with the operating surgeons throughout
the surgery. Once the needles were fixed,
confirmatory MRI and CT scans were done.
After computerized treatment planning,
the radiation therapy was delivered.
Approximately 36 Gy was delivered in six
fractions over three days.
The needles were then removed in the
operation theatre on the 3rd day, as some
blood/fluid leakage was expected. However,
anaesthesia was not required for the needle
removal process. The patient was kept in
the ICU, where he was closely monitored
over the next two days. A CT scan was done
immediately after the removal of the needles
and was found to be normal. By 24 hours,
the CT showed minor bleeding, which was
expected, and by 48 hours, the condition
was stable. The patient was discharged and
advised to come for regular follow-ups every
three months. In his latest follow-up at six
months, the MRI showed that the tumour
size was stable. The patient had been
relieved of his pre-brachytherapy symptoms
of nausea, vomiting, and headache.
Many patients and their families have
approached Dr. Chandra since the success
of this treatment procedure. However, Dr.
Chandra is very careful in selecting only
those cases that are likely to benefit from
this treatment. He further cautions that this
therapy only prolongs life by 6-9 months on
average and is not a cure for brain tumour,
but just another way of managing the
condition.
DR SHIVANEE SHAH
NOVEMBER 2018 / FUTURE MEDICINE / 49

education
NEUBERG-ANAND TO OFFER
POST-MD FELLOWSHIP COURSE
NAALM aims to create awarenness on nextgen diagnostics by education and research
PHOTO: DEEPAK PAWAR
As advances in genomics and
bioinformatics revolutionize the
field of diagnostics, the medical
fraternity in India is forced to play
catch up. This is the idea behind the
creation of Neuberg Anand Academy
of Laboratory Medicine (NAALM), a
new school for pathologists and other
specialists. The aim behind this firstof-its
kind project is to create a unique
platform for academics and encourage
research in this field.
Neuberg founder and managing
director GSK Velu is unambiguous
about his objective. “Low awareness
about next generation diagnostics is
a key challenge in Indian healthcare
today. This is true across healthcare
providers as well as seekers. So, we
want to first create awareness among
the decision makers, which is the
medical fraternity, by giving them a
live exposure to the new tests and
processes.”
The potential for the clinical
application of genomic technologies,
despite their relative novelty, is
vast. They offer a wide range of
opportunities across medical specialities
to ensure a more accurate diagnosis
and treatment. But these benefits
will not reach the needy unless
the clinician is familiar with these
possibilities.
While many new-generation
clinicians are already exposed to such
technologies and are quick to adopt the
new methods, especially in the metros
and urban areas, awareness is still very
low among old-school practitioners,
particularly in semi urban and rural
areas. Similarly, there is also a severe
shortage of technicians who can handle
these new technologies.
The diagnostics education and
research initiative under NAALM is
expected to not only help fill the gap
to a certain extent, but also trigger
more such initiatives in the industry
to address the need. Large-scale
awareness will automatically lead to
50 / FUTURE MEDICINE / NOVEMBER 2018

etter availability and affordability,
which are the other big challenges
in the adoption of these new
technologies in India.
NAALM is a not-for-profit
foundation set up by Neuberg
Diagnostics, an international diagnostic
alliance, to provide fellowship
programmes in the fields of laboratory
medicine and laboratory management
to MD/DNBs in the specialties of
pathology, microbiology, biochemistry
and transfusion medicine. DCPs with
one year experience can also apply for
this programme, which will start from
this year.
Neuberg, an alliance of established
diagnostic chains from India, Sri Lanka,
South Africa and UAE, has a proven
NAALM IS A NOT-FOR-
PROFIT FOUNDATION SET UP
BY NEUBERG DIAGNOSTICS,
TO PROVIDE FELLOWSHIP
PROGRAMMES IN THE
FIELDS OF LABORATORY
MEDICINE AND
LABORATORY MANAGEMENT
TO MD/DNBS.
skill-set and experienced resources in
different areas of diagnostics. It claims
to have at least three world class
global reference laboratories located
in Bangalore, Ahmedabad
and Durban (South Africa), carrying
out an advanced range of testing
using new generation in vitro
diagnostic techniques, total lab
automation and big data analytics
supported by a robust laboratory
information system.
The NAALM Foundation has
already tied up with Sri Devraj Urs
Academy of Higher Education &
Research, Karnataka, and is also
talking to other universities and
research and education institutions
in different regions to get its
programmes affiliated with them.
“We will reinvest revenue
from NAALM back to
education and research”
What was the inspiration
behind NAALM?
Neuberg Diagnostics was formed
with a strategic vision that it will
be in the top league of diagnostic
industry in terms of technology,
experience and volume, as it is an
alliance of five leading and most
reputed diagnostic chains from India
and other countries. We wanted
to pursue the same vision by
developing the overall sector as well
as the market by creating awareness
about the benefits of these modern
technologies. We also want to
encouraging research in this field for
future growth in technology.
Why did you start this
programme under a non-profit
entity?
With this, we wanted to create
a platform that will contribute
immensely to the growth of the
sector; by building awareness
through education. So, it cannot
be mixed with business. Since we
won’t have any external investors, at
least for the next 3-4 years, we are
free to invest in such activities that
GSK Velu
won’t result in revenue and profit
immediately. In the future too, we
would like to continue to invest in it
by putting back the income from this
venture into education and research.
How do you want to take
Neuberg forward in the emerging
healthcare trend?
Neuberg Diagnostics, which has
a combined diagnostic expertise of
over 250 years, brings advanced
diagnostics that is affordable to
people across the globe. It is an
alliance of top laboratories like
Anand Diagnostic Laboratory,
Supratech Micropath, Ehrlich Lab,
Global Labs and Minerva Labs, which
have already made their presence
felt in their respective markets such
as Karnataka, Gujarat, Tamil Nadu,
South Africa and UAE. It will have
three global reference laboratories
located in Bangalore, Ahmedabad
and Durban (South Africa), carrying
out an advanced range of testing
using new-generation in vitro
diagnostic techniques along with
total lab automation and big data
analytics tools. Currently, there are
10 labs and 40 satellite centres for
all the five companies put together
in southern and western India.
The plan is to increase it to 100 in
the next two years. About ₹450
crore has been already invested
in acquiring major sharesand
upgrading the labs. The plan is
to invest another ₹300 crore for
expansion in coming years to bring
in, and develop, new technologies,
which include acquisitions in the US
and Europe.
PHOTO: PRASHANTH KADAM
NOVEMBER 2018 / FUTURE MEDICINE / 51

education
BRIDGE COURSE AT
CROSSROADS
IMA questions Gujarat govt’s move to implement six-month `bridge course’ for
Ayush practitioners in court
BANO SARKAR
Even though a Union Cabinet
meeting chaired by Prime
Minister Narendra Modi removed
a provision from the National Medical
Commission (NMC) Bill for a bridge
course for AYUSH practitioners to
practice modern medicine in March,
allopathic medical practitioners under
the Indian Medical Association (IMA)
have approached the Gujarat High
Court questioning a similar move by
the state government.
Gujarat government issued an
advertisement calling for applications
for a six-month-long bridge course to
permit those who completed Bachelor
of Science (Nursing), Bachelor of
Ayurvedic Medicine and Surgery (BAMS)
and General Nursing and Midwifery
(GNM) courses to practice modern
medicine.
The court, observing that the same
plea is pending before the State Health
Department, asked the department to
consider the IMA’s arguments on the
matter.
IMA has been opposing the idea
of replacing the Medical Council of
India (MCI) from the time when the
suggestion was made in the NMC
Bill. It has also been raising an alarm
on the potential dangers of allowing
bridge courses for alternative medicine
practitioners.
IMA’s stand against the practitioners
of other systems of medicine
practising allopathic medicine has
been there for many years. “It is
estimated that about 10 lakh
quacks are practising allopathic
medicine, out of which 4 lakh belong
to practitioners of Indian Medicine
(Ayurvedic, Siddha, Tibb and Unani),”
states its anti-quackery wing on its
website.
With doctors under the leadership
of IMA announcing a strike against
these decisions, the Union Cabinet had
IMA HAS BEEN RAISING AN
ALARM ON THE POTENTIAL
DANGERS OF ALLOWING
BRIDGE COURSES FOR
ALTERNATIVE MEDICINE
PRACTITIONERS.
removed the provision dealing with
bridge courses for AYUSH practitioners.
However, it had also said that it was
“leaving it to state governments to take
necessary measures for addressing and
promoting primary health care in rural
areas.”
The idea behind the decision go
offer bridge courses was, in a way,
to address the acute shortage of
qualified allopathic doctors to attend
to the underserved population,
especially in rural areas.
Infrastructure and
availability of
medical practitioners are crucial to the
success of government’s prestigious
national health scheme Ayushman
Bharat Yojana.
According to a recent report by
IndiaSpend, a public interest data
journalism initiative, public health
centres need 25,650 doctors to attend
to a minimum of 40 patients per doctor
per day for outpatient care across the
country. But there is a shortage of 3,027
doctors, leaving 1,974 PHCs without
doctors, which means almost 1,21,080
patients cannot meet a doctor for their
health requirement every day.
While a section of allopathic
medicine practitioners oppose bridge
courses tooth and nail, another section
from the same fraternity are of the
view that making qualified healthcare
professionals in the rural areas would
help to address the healthcare need
of the country and can also relieve
doctors from undergoing compulsory
rural practice. It could also address the
issue of quacks and practitioners of
other systems of medicines practising
allopathic medicine and putting
the lives of people in rural
areas at risk.
52 / FUTURE MEDICINE / NOVEMBER 2018

straight talk
“I AM IN FAVOUR OF OPEN
ACCESS, IT’S A GOOD MODEL”
MYLES AXTON, chief editor,
Nature Genetics, believes that open
access is a good model for online
publications, though it doesn’t have
the same reader responsiveness
as the subscription model. But the
bigger challenge for the publishers
of the world’s most read
peer-reviewed journals is still
the large overhead costs,
especially for the ones which
do not charge article processing
charges, says Axton in Straight Talk
with CH UNNIKRISHNAN.
Edited excerpts:
One of the key concerns of scientists and medical
researchers, who dream of getting their research papers
published in reputed peer-reviewed journals like yours, is
the fear of rejection. How would you react to this?
It is important to make sure that scientists have access to
the best advice so that they can get their research published
quickly and in a robust form that can be used as a research
tool by other people. Any research, which meets the basic
and the strong elements of novelty and conceptual advance
shouldn’t ideally face any such issue.
I don’t have much respect for the concept of symbolic
publication. The idea is that if there is a breakthrough or
something big that needs to be known by everyone, it is
more important that scientists should know this first as a tool
to move the field forward. And at the end, when you look
at one’s career, you should be able to say that you made a
lot of good scientific decisions and some clever experiments
with dedication to solve a particular set of problems. This is
what makes you a great scientist.
Often a great scientist is somebody on the ground close
to the problem and who realises that this is a problem and
therefore it has a technical solution. Often, this solution is
not very difficult. But it requires new resources, knowledge
and years of dedication. Finally you may find that it was
essentially a simple solution.
How do you prioritise the papers for publishing from the
large number of submissions by authors?
It is the same, like novelty and conceptual advance,
like any other journal. And of course, a voice in your head
saying how many labs would do their projects differently
after reading this paper is another key consideration.
The interesting insights that we get on the research from
the authors and the paper about how significant was the
knowledge gap that they tried to fill in while bringing up the
point for conclusion, whether it led to positive or negative
result, also contributes to the decision. Ideally, the best paper
to publish is the one that helps in moving the field forward.
In terms of interviewing authors, it is quite satisfying for
my team of managers as they ask questions to know the
story behind the story. And they will tell you what happened
in the lab and so on and so forth, which helps the editor to
really take a much better view of the paper, which is often
appreciated by the authors as well as readers. That way, as
an editor of a peer-reviewed science journal, it is nice to get
54 / FUTURE MEDICINE / NOVEMBER 2018

to start the communication with a question
to which they wanted answers and reward
them with an answer to know more on
what they are looking for. For example,
in your case, the doctors would be more
interested in science if that has a direct
clinical application.
Similarly, it will be difficult to
communicate to a clinical researcher unless
you are close to clinical research. In clinical
research, the doctor is always curious to
know why the condition of one group of
patients improves while it worsens for the
other. He also wants to know if he can
have a marker or the patients need to be
put on a different course of treatment.
As an editor of a peer-reviewed science
magazine, I have to always think in the
perspective of a peer reviewer asking a
question to the author in the language of a
scientist. But for science editors who cater
to the information needs of a public or
professional audience, they need to think
in users’ perspective.
paid as a professional appreciator.
As far as communicating the science is
concerned, how is it different in a magazine
like Nature Genetics, which is read by a
scientific audience, compared to journals
that are aimed at a translational audience?
The mistake in communicating science
to translational or non-scientific audience is
often that the scientists or the communicator
approach them thinking that they
understand science. It will never work unless
the audience finds it connected to their
area of work or interest. The translational
audience will get interested or try to
understand the subject only if it answers
their questions or they find some direct
applications of the same in their field. It
is true across professions whether it is an
agriculturist or a doctor. So it is always better
PHOTO: UMESH GOSWAMI
Translational
audience will
get interested
or try to
understand the
subject only
if it answers
their questions
or they find
some direct
applications
of the same in
their field.
What about an open access policy for
journals like Nature?
I am in favour of open access, I
think it’s a good model. But it doesn’t
have the same reader responsiveness
as subscription model, except the fact
that it can be read by everybody. In the
subscription model, the readers take it
as valuable and place it in the library
of research, but on the contrary, in the
open access model, one can say that it
is valuable as even the students who are
not affiliated with wealthy institutions can
be inspired by the research. So, the draw
aspect of the open access is very attractive
indeed. Certainly, we can get 50% more
readership for Nature Genetics if we make
every article open access and that would
be appealing.
Nature is a big open access publisher.
We have got Nature Communications with
nearly 70 editors and making a big effort
with open access. We publish Reference
Genomes under open access because the
community demands it. But we don’t take
any article processing charge as we don’t
have any business model to accept that.
So there is no prospect of making all of the
journals open access as that’s not the way
the journal was set up.
NOVEMBER 2018 / FUTURE MEDICINE / 55

esearch snippets
eLiquid biopsy detects
early lung cancer
Wei et al demonstrate electric fieldinduced
release and measurement
(EFIRM) as a novel platform for liquid
biopsy (LB) which enables the diagnosis
of early-stage non-small-cell lung
cancer (NSCLC) when surgical cure is
still possible. The EFIRM-liquid biopsy
(eLB) accurately detects two actionable
epidermal growth factor receptor
(EGFR) mutations seen in the blood of
patients with early-stage NSCLC. The
study showed specific detection of two
specific EGFR mutations- p.L858R and
Exon 19del. The scientists collected
plasma samples from 248 patients with
suspected lung cancer, of which 44
were diagnosed with Stage I or Stage
II NSCLC. EFIRM was able to detect the
p.L858R mutation in 11 of 12 samples
and the Exon 19del mutation in seven of
nine samples, resulting in greater than
90 percent sensitivity and 80 percent
specificity. The clinical sensitivity of
EFIRM to detect patients with early-stage
NSCLC is limited by the percentage of
tumours containing either or both of the
two variants, which is estimated at 27
percent of NSCLC tumours. The research
suggests more studies to be performed
to optimize the technical and clinical
performance of the assay which once
validated can be useful in screening
and for many other high-throughput
applications.
The Journal of Molecular Diagnostics, November
2018, Volume 20, Issue 6, Pages 738–742 /
https://doi.org/10.1016/j.jmoldx.2018.06.008/
ctDNA shows promise
for monitoring
paediatric glioma
Panditharatna E. et al shows early
evidence in proper monitoring of
EGF receptors drive hair cell
formation in mice cochlea
paediatric diffuse midline gliomas (DMGs)
using liquid biopsy. The researchers
indicate the study to be the first to
focus on the clinical utility of circulating
tumour DNA (ctDNA) for longitudinal
surveillance of DMGs in children. The
assay quantified the levels of a mutation,
H3K27M, which is known to be present
in over 70 percent of patients with DMG
correlating with a poorer clinical outcome.
The study reported the identification of
H3K27M in pre-treatment samples from
42 of the 48 patients, a frequency that
is comparable to what is seen in tissue
samples showing cerebral spinal fluid to
exhibit the presence of more mutated
DNA, overall, than blood. Researchers
observed a significant decrease in ctDNA
in a subset of children with Diffuse
Intrinsic Pontine Glioma (DIPG) who had
liquid biopsy testing before and after
radiation treatment in a clinical trial.
Researchers also reported an agreement
Zhang et al outlined a new approach
in restoring hearing loss by activating
ERBB2 pathway, which could enable the
regeneration of sensory hair cells found
in the cochlea of the inner ear. Their
research was based on the hypothesis
that signaling from epidermal growth
factor receptor (EGF) family of receptors
could play a role in cochlear regeneration
in mammals. Thus, the study focused on
activating a specific receptor ERBB2 of
the EGF family by constitutively activating
the receptor in neonatal mouse cochlear
supporting cells using viruses, transgenic
expression and also by using certain
drugs which are known to activate
ERBB2 signalling. The researchers
found that activating the ERBB2
pathway triggered a cascading
series of cellular events by which
cochlear support cells began to
proliferate and activate the neighbouring
stem cells to become new sensory
hair cells. The study thus suggests a
new model where the interplay of cell
signalling regulates regeneration by
endogenous stem-like cells.
European Journal of Neuroscience 30
September 2018 doi: 10.1111ejn.14183/
of 75 percent between ctDNA response
(a 50 percent decrease or more) and MRI
tumour volume measurements (at least
10 percent decrease). The liquid biopsy
approach thus provides a molecularly
based tool for tumour characterization
helping doctors to monitor how well
treatments are working in children with
DMGs.
Source: American Association for Cancer Research,
October 15, 2018/ DOI: 10.1158/1078-0432.CCR-
18-1345 /
Editing of mtDNA
may correct genetic
disorder
Payam A. Gammage et al reported the
first in vivo successes in using zinc
finger nucleases (ZFN) for selectively
editing away pathogenic mitochondrial
56 / FUTURE MEDICINE / NOVEMBER 2018

DNA (mtDNAs) in a heteroplasmic
mammalian mitochondrial population.
They demonstrated the correction of a
cardiac-specific mitochondrial disorder
with the concomitant therapeutic
restoration of molecular and biochemical
hallmarks to an undiseased state by
exploiting a recently developed mouse
model that recapitulates common
molecular features of heteroplasmic
mtDNA disease in cardiac tissue.
Each of the two ZFN proteins used
was systemically delivered to the
mouse via a cardiotropic version of
the adenovirus. The research offers a
potential therapeutic route for treatment
of heteroplasmic mitochondrial disease
using programmable nucleases, where
amelioration or halting of disease
progression could be expected. Though
the development has the potential
to transform the prospects of many
patients with mitochondrial disease, the
researchers suggest for further work to
be executed to enable the translation of
these tools into effective medicines.
Nature Medicine (2018)/ https://www.nature.com/
articles/s41591-018-0165-9 /24 September 2018
CRISPR-mediated
prenatal metabolic
gene editing
C. Rossidis et al performed the first
A. prenatal gene editing to prevent a
lethal metabolic disorder in mice models,
offering the potential to treat human
congenital diseases before birth. The
scientists used CRISPR-Cas9 and base
editor 3 (BE3) gene editing tools in utero
to reduce cholesterol levels in a wildtype
mice. They also used prenatal gene
editing to improve liver function and
prevent neonatal death in a subgroup
of mice that had been engineered
with a mutation causing the lethal liver
disease hereditary tyrosinemia type 1
(HT1). Adenovirus vectors were used
for the delivery of CRISPR-Cas9 and
BE3. Scientists observed a long-term
postnatal persistence of edited cells in
both models with reduced cholesterol
levels and rescue of the lethal phenotype
of HT1 following in utero gene targeting
in respective mice models. Thus the
research offers proof-of-concept for the
prenatal use of a sophisticated, lowtoxicity
tool in efficient gene editing
that helps point to a potential new
therapeutic approach in treating selected
congenital genetic disorders.
Nature Medicine, Volume 24, pages1513–1518
(2018) https://www.nature.com/articles/s41591-
018-0184-6/ 8th October 2018
Protein marker
indicates breast
cancer recurrence
Borgen et al identified a protein
E. marker that can indicate the
chances of reoccurrence and lethality
of metastatic cancer in breast cancer
patients. The researchers found a
correlation between the low amounts
of a protein NR2F1 (COUP-TF1) in bone
marrow (BM) aspirations of patients
whose breast cancer tumour had
metastasized to BM and had led to
sudden demise. Patients who had high
concentrations of NR2F1 in the cancer
cells in their bone marrow, however,
did not frequently develop this type of
metastatic cancer and survived longer.
The presence of high concentration of
NR2F1 was found related to dormancy
of the disseminated tumour cells (DTC).
Thus NR2F1 detection in BM DTCs may
be a promising tool to determine the
phenotype of DTCs and the prognosis of
breast cancer patients. The study
paves the way for testing new
treatments that prevent metastasis
by inducing dormancy or eradicating
the dormant disseminated cancer cells
that have not yet initiated metastatic
growth. The researchers suggest that
markers such as NR2F1 coupled with
DTC genetics and other host-derived
indicators may provide a breakthrough
in the management of minimal
residual disease (MRD) and metastasis
prevention.
Breast Cancer Research2018 https://doi.
org/10.1186/s13058-018-1049 /16 October 2018
Metarrestin slows
spread of ovarian
cancer
novel anti-cancer drug, ML246
A (metarrestin), reveals its ability to
attenuate the growth and progression
of ovarian cancer. The study conducted
by Kanis et al reports for the first time
on the effects of ML246, an inhibitor of
the perinucleolar compartment (PNC),
in ovarian cancer cells. PNCs were
detected in the human ovarian cancer
cell lines, SKOV3 and OVCAR3, which
were treated with ML246 for its invasive
activity in vitro and was tested for its
efficacy on tumour growth and spread
in xenograft mice models in vivo. The
results showed a remarkable decrease
in the invasive ability of ovarian cancer
cell lines and attenuated the growth of
tumour in human xenografts of ovarian
cancer which reduced the abdominal
spread of the xenografts. The study
data demonstrate ML246 is as effective
as cisplatin in inhibiting ovarian cancer
growth and thus suggests its utility in
platinum-resistant disease. These data
warrant additional investigation into
the therapeutic potential of ML246 for
ovarian cancer as well as its mode of
action while showing PNC structure as
a potential reliable target in treating
ovarian cancer.
Source: Gynecologic Oncology Research and
Practice20185:7 2nd October 2018 https://doi.
org/10.1186/s40661-018-0064-2 /
—Compiled by Divya Choyikutty
NOVEMBER 2018 / FUTURE MEDICINE / 57

column
trialomics
Medical devices as
healthcare tools
Diagnostic devices are required to generate robust clinical
evidence to stand scientific scrutiny
DR ARUN BHATT
Writer is a consultant
on clinical research &
development from
Mumbai.
arun_dbhatt@hotmail.com
Today, medicine has become highly
specialised and technology-driven,
leading to the widespread use of
medical devices as diagnostic and therapeutic
healthcare tools. This has led to the rapid
growth of the medical device industry. A
medical device is different from a drug,
as it acts by physical interaction with body/
body part and the outcome depends on
the skill or experience of the clinician or
the technician. Hence, there are separate
international and Indian regulations for
medical devices.
A medical device is any instrument,
apparatus, appliance, software, material or
any other article used in human beings for a)
diagnosis, prevention, monitoring, treatment
or alleviation of disease or alleviation of or
compensation for an injury or handicap, b)
investigation, replacement or modification of
the anatomy or of a physiological process, or
c) control of conception.
For regulatory approval purpose, medical
devices are classified by risk assessment
based on:
• Intended purpose
• Duration of continuous use
• Transient - less than 60 minutes
• Short term - not more than 30 days
• Long-term - more than 30 days
• Invasiveness
• Critical anatomical locations - central
circulatory system, central nervous system
• Active medical devices
As such, medical devices could be
1) non-invasive - stethoscopes, syringes,
wound dressings, hemodialyser; 2) invasive
- lancets, tracheal tubes, cardiac catheters,
coronary stents, contraceptive devices, joint
replacement prosthesis; 3) active - hearing
aids, MRI, nebulizers dental implants; 4)
special category - drug-eluting stents,
contraceptive intrauterine devices, biological
heart valves, blood bags; 5) In vitro diagnostic
medical devices for detecting transmissible
agents - HIV , blood grouping or tissue typing,
and self-testing – glucometer.
A device which is invasive or for long-term
continuous use or used in critical anatomic
location or is active carries a higher risk.
The risk categories are:
• Class A Low Risk: e.g. surgical gauze, sterile
plasters
• Class B Low-Moderate: e.g. hearing aids,
ultrasonic diagnostic equipment
• Class C Moderate-High: e.g. infusion
pumps, ventilators, surgical lasers, dental
implant
• Class D High: e.g. many implants,
replacement heart valves, pacemakers
Classification of the device provides a
practical, economic, and feasible approach
to decide which category requires rigorous
regulatory evaluation. Indian medical devices
rule 2017 mandate regulatory approval
requirements for all device categories.
These requirements describe submission
requirements for technical information, quality
documentation and clinical evidence. Clinical
evidence studies include those that look at 1)
Pilot Preliminary Safety and Performance in
a few patients; 2) Pivotal Efficacy and Safety/
Adverse Effects in a larger number, and 3)
Postmarketing long-term safety. The higher
the risk category, the greater the regulatory
requirement for data and clinical evidence.
The development and marketing of a
medical device or a diagnostic medical device
require critical attention to technology, quality
and the scientific challenges of generating
robust clinical evidence.
58 / FUTURE MEDICINE / NOVEMBER 2018

policy
MENTAL HEALTH CARE ACT 2017
TAKING OUT
THE STIGMA
Notwithstanding the
new law, experts feel
protecting the rights of
the mentally ill will be
an uphill task
The Mental Health Care Act
2017, which came into force in
May this year, is set to make
drastic changes in the treatment of
psychological disorders. The Act, hailed
as one of the most progressive pieces
of legislation on mental health care in
the world, entitles mentally ill patients
to humane treatment and assures
them the right to access mental health
care. As per the Act, every person
shall have the right to access mental
health care and treatment from mental
health services run or funded by the
government. It entitles patients to
access affordable and quality mental
60 / FUTURE MEDICINE / NOVEMBER 2018

health services without any kind
of discrimination. The Act has also
decriminalised suicide attempts by
mentally ill people.
“The Act is a phenomenal, rightsbased
approach, a game-changer in
mental health care and one of the
best health legislations in the world. It
is an ideal and aspirational legislation,”
observed Dr. Suresh Bada Math,
Professor of Psychiatry at the National
Institute of Mental Health and Neuro
Sciences (NIMHANS)
Upholding the legislation,
Dr. Mala Kapur Shankardass,
Sociologist, Gerontologist, Health and
Development Social Scientist and
Associate Professor, Dept. of Sociology
at Delhi’s Maitreyi College, said: “The
Mental Healthcare Act is a good
legislation which is very much required
in the country for better outreach to
affected people”.
Upholding rights
The Act directs the government
to make sufficient provision for
providing a range of services required
by persons with mental illness. It
directs the government to ensure
the availability of minimum mental
health services run or funded by the
government in each district. Patients
should not be made to travel long
distances to access mental health. If
it is not available in the district where
a person with mental illness resides,
the person is entitled to access any
other mental health service in the
district and the cost of treatment will
be borne by the government. It directs
the government to make necessary
budgetary provision for the effective
implementation of the Act.
“It is a rights-based legislation.
Hence it is the responsibility of the
state to provide mental health care.
But do all the states have the political
will and the financial commitment
to implement the Act? Considering
various constraints like poor human
resources, it may take time to set
up and receive the funds that are
warranted to ensure its effectiveness
– which is why the impAct of the law
INDIA’S MENTAL DISEASE BURDEN
Despite increasing incidence of mental disorders the
economic impact of it is yet to be quantified
38
million
have anxiety
disorders
IT IS A RIGHTS-BASED
LEGISLATION. HENCE IT IS
THE RESPONSIBILITY OF
THE STATE TO PROVIDE
MENTAL HEALTH CARE.
BUT DO ALL THE STATES
HAVE THE POLITICAL
WILL AND THE FINANCIAL
COMMITMENT TO
IMPLEMENT THE ACT?
may not be immediate and may not be
seen in the near future,” said Dr. Math.
The Act also stipulates the criteria
for the admission, treatment and
discharge of mentally ill people. An
adult patient can be admitted only
if the patient has mental illness of a
severity requiring admission, is likely
to benefit from the admission and
has the capacity to make decisions
regarding admission and treatment.
All admissions in the mental health
establishment shall, as far as possible,
56
million
Indians suffer
from depression
7.5%
Indians suffer from
major or minor
mental disorders
that require expert
intervention
}
A mental health
survey found that
the incidence of
depression is roughly
1 20 in
Indians
SOURCE: WHO AND NIMHANS
be independent admissions except
when such conditions exist as to make
supported admission unavoidable.
An independent patient shall not be
given treatment without his informed
consent. The independent patient
can discharge themselves without
the consent of the medical officer.
However, the patient can be made to
stay in the hospital for 24 hours if the
mental health professional feels that
the patient has impaired decisionmaking
capacity, poses a risk to self or
others and is incapable of self-care.
Disorder criteria: A drawback?
Though the Act focuses on the rights
of patients, it is comes with lots
of regulations and related control.
“The rights of the mentally ill should
be protected, but the numerous
mechanisms involved may create
more stigma to the patients. The
main drawback of the Act is that the
patients who do not meet the criteria
of ‘substantial disorder with gross
impairments’ for mental illness cannot
be admitted even if they are keen to
do so and their doctor is willing to
provide treatment. It poses a violation
NOVEMBER 2018 / FUTURE MEDICINE / 61

of the right of individual to seek
treatment in the most appropriate
setting. Even though the criteria
for admission are described, the
mental health review board does
not have the power to review such
admissions,” said Dr. John C. J., Senior
Consultant, Psychiatrist, Medical Trust
Hospital.
In case of the admission of minors,
the nominated representative of a
minor, usually the legal guardian,
needs to apply for admission. Two
professionals — two psychiatrists or
one psychiatrist and one mental health
professional — need to independently
assess and conclude that the minor
has a mental illness of the severity
requiring admission, that it is in the
best interest of the minor and that
all community-based interventions
are unsuitable or have failed. The
admission of a minor should be
reported to the mental health review
FOR SUPPORTED
ADMISSION UNDER THE
ACT, TWO PROFESSIONALS
SHOULD INDEPENDENTLY
EXAMINE THE PATIENT IN
THE PRECEDING SEVEN
DAYS.
board within seven days and if the
minor remains in the hospital for
more than 30 days, the mental health
review board should be informed
immediately. When the board is
informed about the hospital stay of
a minor exceeding 30 days, it must
review the concerned minor within
seven days.
For supported admission under
the Act, two professionals — one
psychiatrist and one mental health
professional — should independently
examine the patient in the preceding
seven days and independently
conclude that the mental illness is
severe. Both professionals must certify
that admission is the least restrictive
option available and the patient’s
capacity to make mental health care
treatment decisions is impaired. If
the patient requires hospital stay in
excess of 30 days, the patient must
be independently examined by two
psychiatrists at any time during the
preceding seven days. They should
independently conclude that the
patient meets severity criteria, and
that admission is the least restrictive
option and that the patient’s capacity
to make decisions about mental health
treatment is impaired.
Dearth of resources
Even as the Act gives utmost
62 / FUTURE MEDICINE / NOVEMBER 2018

importance to the right of patients,
the implementation of the Act poses
a challenge for the authorities. “The
challenges exist in trying to reach
out to rural and illiterate populations
and and those residing in areas
where mental health care services are
limited. The problem is about raising
awareness regarding the Act and how
it is an empowering tool. It has to be
implemented properly and people
must understand its uses,” said Dr.
Mala Kapur Shankardass.
Dr. Suresh Bada Math observed
that the main challenge is the abysmal
number of trained mental health
human resources when compared with
the prevalence of mental disorders,
which are mind-boggling in numbers.
“Though approximately 10 crore
people require mental health, only
7,000 (approximately) psychiatrists are
available. The mental health human
resources numbers in the public health
sector are very meager, considering
the rights-based mental health care
[approach] and the number of people
requiring attention. To fill this human
resources gap, we may require 20
years or more,” he said
Dr Math said the current mental
health budget is very minimal, while
the required budget is at least Rs
3,000 crore per month just for
treatment. “At present, there are only
a few rehabilitation centers in the
public sector. The non-availability of
halfway homes, long-stay homes,
supported accommodation, sheltered
accommodation, vocational rehab
centers and the lack of daycare
centers are the uphill tasks faced by
governments in implementing the
Act,” he said . He added that the
government has been proactive and
has taken a number of initiatives, such
as digital academies at NIMHANS, CIP
Ranchi and at LGB institute, Tezpur.
The aim of these academies is to
exponentially increase human resources
for mental health care. Dr. Math
emphasized that, considering the large
treatment gap, all stakeholders need to
work for a long time before the dream
of the Act can be fully realized.
MHA 2017 pledges right
to live with dignity
The long-awaited legislation
empowers a person with
mental illness and his nominated
representative to access information
on the provisions of the Act, the
nature of mental illness, the proposed
treatment plan and the known side
effects of the proposed treatment
plan in a language he can understand.
The Act also extends the right
to confidentiality, access to medical
records, legal aid and the right to
make complaints about deficiencies in
the provision of services.
The Act pledges the right to
community living for the patients and
to not put them in a mental health
establishment merely because the
patient does not have a family, is not
accepted by his family or is homeless,
or due to the absence of communitybased
facilities.
It promises the right to live with
dignity and protection from cruel,
inhuman and degrading treatment
in any mental health establishment
and the right to equality and nondiscrimination.
As per the provisions
of the Act, every person with mental
illness shall be treated as equal to
persons with physical illness.
It directs every insurer to make
provision for medical insurance for
treatment of mental illness on the
same basis as is available for
treatment of physical illness.
The Act directs the
government to plan, design
and implement programmes
for the promotion of mental
health and the prevention
of mental illness in the
country. The Act puts the
onus on the government to
take appropriate steps to
address the human resource
requirements of mental health
services in the country.
The Act proposes setting up a
Central Mental Health Authority and
State Mental Health Authorities in
each state. The central authority shall
be responsible for the registration of
all mental health establishments under
the control of the central government
and shall maintain a register of all
the mental health establishments in
the country. It will also be responsible
for training all persons, including
law enforcement officials, mental
health professionals and other health
professionals, on the provisions and
the implementation of the Act. The
state authority will perform similar
duties at the state level. The Act also
proposes the constitution of a Central
Mental Health Authority Fund and
State Mental Health Authority Funds.
According to the Act, no person
or organization shall establish or run a
mental health establishment unless it
has been registered with the authority
under the provisions of the Act.
Another major highlight of
the Act is the provision for the
constitution of Mental Health Review
Boards. Each board shall consist
of a district judge or retired district
judge, a representative of the district
collector, persons with mental illness
or caregivers or persons representing
organisations of persons with
mental illness or caregivers or nongovernmental
organisations working in
the field of mental health.
NOVEMBER 2018 / FUTURE MEDICINE / 63

COPD
technology
EBV INTERVENTION
IN EMPHYSEMA
Endoscopic lung volume reduction using endobronchial valves is an emerging
option for COPD patients
DR GEORGE MOTHI JUSTIN
Chronic obstructive pulmonary
disease (COPD) is characterised
by the presence of bronchitis
and emphysema. The latter process,
due to breakdown of elastic alveolar
tissue, leads to increased lung
compliance and gas trapping. Lung
hyperinflation worsens with exercise,
leading to breathlessness and is
associated with reduced physical
activity and reduced survival. Inhaled
bronchodilator medications have only
modest impact on the symptoms and
do not alter the natural history of the
disease. In selected patients with a
heterogeneous pattern of emphysema,
surgical resection can be targeted at
the worst affected areas of lung tissue
which contribute disproportionately
to gas trapping and hyperinflation,
and improve respiratory mechanics.
Lung volume reduction surgery (LVRS)
improves symptoms and prolongs
survival, but can be associated with
significant morbidity and a risk of
death, with a cost per quality adjusted
life year (QALY).
A more recent approach has
been to instead use endobronchial
valves to occlude the airways
supplying the worst affected part of
the lung. This is intended to cause
a collapse in the target lobe, with
a similar impact on the function of
the rest of the lung as seen in LVRS.
However, atelectasis will only occur in
the absence of significant collateral
ventilation between the
target lobe and the adjacent one.
Because of this, the success rate
of valve placement in early studies
was low, impacting the value of
endobronchial valves as a therapeutic
intervention.
Case series and single-centre
trials have demonstrated that
endobronchial valve treatment in
patients with emphysema can lead
to improvements in symptoms,
lung function and exercise capacity,
reduction in dynamic hyperinflation
and improvements in oxygen
kinetics and chest-wall synchrony.
Moreover, where target lobe
volume loss is seen on CT, a
substantial survival benefit has
been observed, compared with cases
where valve treatment has been
ineffective.
During a bronchoscopic procedure,
endobronchial valves are placed in the
airways to occlude a diseased part of
SINGLE-CENTRE TRIALS
HAVE DEMONSTRATED THAT
ENDOBRONCHIAL VALVE
TREATMENT IN PATIENTS
WITH EMPHYSEMA CAN
LEAD TO IMPROVEMENTS
IN SYMPTOMS.
64 / FUTURE MEDICINE / NOVEMBER 2018

ENDOBRONCHIAL
VALVES FOR
LUNG VOLUME
REDUCTION
Endobronchial valves (EBV)
are small implantable
devices. These one-way
valves are implanted in an
airway in the pulmonary
system using a flexible
delivery catheter through a
bronchoscope. This minimally
invasive procedure is used
to treat emphysema and
several other lung conditions.
ZEPHYR
Developed by Pulmonx, the Zephyr device
is an implantable bronchial valve intended
to decrease the volume of targeted regions
of the lung. It is indicated for the treatment
of patients with severe emphysema. The
EBV are placed in the diseased region of the
lung using bronchoscopy. Once implanted,
the one-way valve prevents airflow into the
diseased region, while allowing trapped air
and fluids to escape. Reducing the volume
of the diseased region may allow healthier
regions to expand and function more
efficiently. The Zephyr valve is removable if
found to be not working properly.
The Chartis System and the StratX Lung
Analysis Platform are diagnostic companion
products developed by Pulmonx. They are
designed to identify likely responders and
non-responders to Zephyr valve therapy.
The US FDA granted approval for Zephyr
endobronchial valve in June 2018 based
on positive clinical data from the pivotal
LIBERATE Study and two other multicenter
randomized control trials. The LIBERATE
study found Zephyr EBV provides clinically
meaningful benefits for lung function, exercise
tolerance, dyspnea and quality of life out to
at least 12-months, with an acceptable safety
profile in patients with little or no collateral
ventilation in the target lobe.
According to Pulmonx data, since 2007, more
than 14,000 patients have been treated
with the Zephyr Valve worldwide. Zephyr
Valve treatment is included in emphysema
treatment guidance issued by leading health
organizations, including the Global Initiative
for Chronic Obstructive Lung Disease (GOLD)
and the UK’s National Institute for Health and
Care Excellence (NICE).
SPIRATION
The Spiration Valve blocks incoming breath
from entering damaged portions of the lung,
while it permits trapped air and mucous to
escape the damaged and potentially hyperinflated
lung. That air is redirected to healthier
portions of the lung through the valve without
a pressure fit, allowing secretions to escape
naturally along the bronchial wall. The valve
has an anchoring system and an umbrellashaped
design with 0% migration and
expectoration even in complex airways.
Marketed by Olympus, Spiration valves have
also received the CE mark.
EPIDEMIOLOGY
OF ASTHMA
The disease in adults pose an
enormous health care burden
Estimated the
prevalence of
asthma in India
to be
2.05%
adults aged ≥15 years
National
burden of
asthmatics
18,000,000
SOURCE: Lung India
the lungs and reduce hyperinflation,
allowing the healthier parts of the
lungs to take in more air and work
more effectively. The valves are
designed to be permanent, but can be
removed if necessary.
The most common side effect
associated Zephyr valve treatment
was pneumothorax, which occurred
in roughly one third of the patients.
No intervention was required in about
20% of the incidents; the majority of
the rest of such cases were addressed
with standard medical management.
Other side effects, which occurred
less frequently, included COPD
exacerbation, pneumonia, respiratory
failure and death.
The Zephyr valve is contraindicated
in patients with active lung infections;
those who are allergic to nitinol,
nickel, titanium or silicone; active
smokers; and those who are not
able to tolerate the bronchoscopic
procedure.
The author is Head,
Department of Respiratory
Medicine, Medical Trust
Hospitals, Cochin
NOVEMBER 2018 / FUTURE MEDICINE / 65

hospital news
Continental Hospital
starts heart failure
clinic in Hyderabad
Hyderabad-based Continental Hospital
has launched a Heart Failure Clinic at
its premises in the city.
The clinic aims to provide advanced
cardiac services to the people suffering
from severe heart-related diseases. The
number of heart failure cases are rising
at an alarming rate in Hyderabad, with
an estimated 15,000 new cases being
registered every year.
The Heart Failure Clinic offers
comprehensive cardiac care services
under one roof. Treatment decisions are
made in a team approach, based on the
medical details of each patient.
The Hospital is equipped with
state-of-the-art technology, including
the implantation of artificial pumps to
support the heart’s functions. Continental
Hospitals is planning to extend the
services with a dedicated outpatient
department and a 24x7 helpline.
Facility for children with
multiple disabilities at Wadia
Boehringer Ingelheim, one of the
world’s leading pharmaceutical
companies, inaugurated a facility for
children with multiple disabilities at Bai
Jerbai Wadia Hospital, Mumbai.
Started in association with Muskan
Foundation, the facility is designed with
the aim of training visually impaired
children who have additional disabilities.
At the Facility, children are trained
to manage their disabilities under a
multi-disciplinary approach. The facility
also focuses on educating parents, who
will receive comprehensive training for
effective management of these children
at home.
A part of the social entrepreneurial
initiative at Boehringer Ingelheim (BI),
the programme in Mumbai intends
to help such children communicate
effectively and develop modification to
their behaviour essential for their daily
routine.
In India, there are 20.42 lakh
disabled children who are aged
between 0 and 6 years. Out of this,
14.52 lakh and 5.9 lakh children live in
rural and urban areas respectively. Of
them, 11.04 lakh are male and 9.38 lakh
female. Among them, 1.49 lakh
children have multiple disabilities,
according to BI.
Jaslok Hospital launches clinic for elderly
Jaslok Hospital and Research Centre
has launched a geriatric clinic at
Peddar Road in Mumbai.
Planned as a one-stop elderly
care centre, the dedicated geriatric
care department will have outpatient
care, in-patient care, emergency care
and home health care. It will offer
physical, cognitive and psychosocial
assessment, a personal care plan,
recommendations to improve health
and functional ability, rehabilitation,
the safe use of medicines and will
address home and emergency care
for the elderly.
According to the Indian
Ageing Report 2017, based on the
2011 Census, the overall old-age
dependency ratio shows that there
are over 14 elderly per 100 working
age persons, out of which 7 are
termed as a dependent.
The proportion of the elderly
is expected to increase from 10.5
percent to 22.4 percent during 2012–
2050, according to estimates.
66 / FUTURE MEDICINE / NOVEMBER 2018

insurance
MORE ILLNESSES TO COME
UNDER INSURANCE COVER
The process is on to limit the number of exclusions on
the current list of health policies
Health insurance policies will
soon cover more diseases, with
the Insurance and Regulatory
Authority of India (IRDAI) initiating
the process to minimise the number
of diseases that are not covered
under the health insurance policies at
present.
In order to examine the matter,
the regulator has constituted a tenmember
working committee headed
by Suresh Mathur, Executive Director,
Health, IRDAI. The committee will
examine the exclusions that are
prevalent in health insurance policies
and rationalize the exclusions by
minimizing the number, so as to
enhance the scope of health insurance
coverage
The terms of reference (ToR)
of the working committee include
rationalising the exclusions that
disallow coverage with respect to
new modalities of treatments and
technologically advanced medical
treatments and identifying the type of
THE MOVE WILL BENEFIT
POLICYHOLDERS IN A
GREAT WAY AS THE SCOPE
OF COVER AVAILABLE
UNDER HEALTH INSURANCE
POLICY WILL BE EXPANDED.
exclusions which shall not be allowed.
The committee has also been asked
to study the wordings/language of
the exclusions and standardize the
wordings of exclusions in simple and
easily understandable language, study
the scope for allowing individual
specific and/or ailment/disease specific
permanent exclusions at the time of
underwriting so that policyholders are
not denied health insurance claims
unrelated to the exclusions, and any
other matter relevant to the subject of
exclusions.
Welcoming the move,
Subramanyam Brahmajosyula,
Head of Underwriting and Reinsurance
at SBI General Insurance, said: “We are
broadly supportive of the regulator’s
move to expand the
ambit of health insurance coverage,
both in terms of increasing the
number of people covered, as well as
the various illnesses/diseases for
which coverage is granted under
health insurance policies. This needs to
be viewed as a national priority,
and not purely from the narrow
perspective of any challenges
it might pose to the insurance
industry.”
He added that the move will
benefit policyholders in a great
way as the scope of cover available
under health insurance policy will be
expanded.
Improve penetration;
increase rates
The insurers feel that an enhancement
68 / FUTURE MEDICINE / NOVEMBER 2018

in insurance coverage will lead to
greater penetration. “The order
will have implications for both
the consumer and the industry. It
will be beneficial to consumers,
because less exclusion will mean
more coverage for diseases. From
the industry perspective, it will lead
to a higher degree of insurance
penetration, thus more sales,”
said Vaidyanathan Ramani,
Head, Product andInnovation,
Policybazaar.com.
Brahmajosyula also
agreed that the move
will lead to greater awareness of
insurance and improve the penetration
of health insurance in the country.
However, insurance companies
hinted at the possibility of an increase
in policy rates. They said that some
of the conditions which are proposed
to be covered are either partially or
completely excluded under the current
health insurance policy coverage.
“With the enhancement of coverage,
it will be necessary for the insurance
companies to relook at their pricing
in order to cater to the expected
claims from allowing coverage of such
conditions,” said Brahmajosyula.
“The premium may go up
marginally in the long run, because
enhanced coverage will lead to more
claims and hence, the premium will
THE CHALLENGES WOULD
BE TO DEFINE, IN PRECISE
TERMS, WHAT CONSTITUTES
MENTAL ILLNESS TO AVOID
DISPUTES IN THE EVENT
OF CLAIMS, AS WELL AS
COMPILING SUFFICIENT
AND ACCURATE DATA TO
DECIDE THE APPROPRIATE
PREMIUM TO BE CHARGED.
also go up. In spite of this, the order
will impact positively for all those
involved in the insurance business –
the buyer and the seller,” according to
Ramani.
Cover for mental illness?
Meanwhile, in another significant
development, the IRDAI has asked
insurers to make provision for medical
insurance for the treatment of
mental illness on the same basis as is
available for the treatment of physical
illness. The move is set to benefit a
large number of people. The regulator
has issued a circular in this direction
after The Mental Healthcare Act 2017
came into force in May 2018. The act
has stipulated that every insurer shall
make provisions for the treatment
of mental illness. “The insurance
companies will have to re-price the
products to cater to the coverage
of mental illness. Other associated
challenges would be to define, in
precise terms, what constitutes mental
illness to avoid disputes in the event of
claims, as well as compiling sufficient
and accurate data to decide the
appropriate premium to be charged,”
said Brahmajosyula.
Ramani also welcomed the
decision to cover the treatment of
mental illness under health insurance
policies. “This is a great step for the
country as, with this move, we have
started to accept that mental illness is
a serious affair and needs treatment.
Therefore, medical insurance covering
the same is a great step. Mental
illness will probably be a much
higher risk than physical illness in
the future,” he said. However, he
added, there are a few issues which
are still in the grey, like what are
considered mental illnesses and what
are the degrees of those, with the
recommended treatments attributed to
them. He added that it will be easier
to define fair expenses and procedures
for such treatments if some light was
thrown over these issues, as mental
illness is a very vague and big topic
in itself.
DISEASES PRESENTLY
NOT COVERED*
HIV/AIDS
Infertility
Genetic disorders
Tobacco use and related
complications
Cosmetic surgery
Cataract
Hernia etc.
Mental health
*The list is incomplete. The rules and
regulations vary with different players.
NOVEMBER 2018 / FUTURE MEDICINE / 69

public healh
NOISE
HAZARDS
WHO guidelines for the EU region
provide strong evidence that noise
is one of the top environmental
hazards to both physical and
mental health
70 / FUTURE MEDICINE / NOVEMBER 2018

Environmental noise is an
important public health issue,
featuring among the top
environmental risks to health. It has
negative impacts on human health and
well-being and is a growing concern
among both the general public and
policy-makers in Europe.
The WHO Regional Office for
Europe has developed environmental
noise guidelines for the European
Region, proposing an updated set of
public health recommendations on
exposure to environmental noise.
Objectives
The main purpose of these guidelines
is to provide recommendations
for protecting human health from
exposure to environmental noise
originating from various sources:
transportation (road traffic, railway,
and aircraft) noise, wind turbine noise
and leisure noise. Leisure noise in this
context refers to all noise sources
that people are exposed to due to
leisure activities, such as attending
nightclubs, pubs, fitness classes, live
sporting events, concerts or live music
venues and listening to loud music
through personal listening devices.
The following two key questions
identify the issues addressed by the
guidelines.
• In the general population
exposed to environmental noise, what
is the exposure-response relationship
between exposure to environmental
noise (reported as various indicators)
and the proportion of people with a
validated measure of health outcome,
when adjusted for confounders?
• In the general population
exposed to environmental noise, are
interventions effective in reducing
exposure to and/or health outcomes
from environmental noise?
In light of these questions,
the guidelines set out to define
recommended exposure levels for
environmental noise in order to protect
population health.
Methods used
The process of developing the
WHO GUIDELINES
FOLLOWED A RIGOROUS
METHODOLOGY
INVOLVING SEVERAL
GROUPS WITH
SEPARATE ROLES AND
RESPONSIBILITIES.
WHO guidelines followed a rigorous
methodology involving several
groups with separate roles and
responsibilities. Throughout
the process, the Grading of
Recommendations Assessment,
Development and Evaluation (GRADE)
approach was followed. In particular,
the different steps in the development
of the guidelines include:
• formulation of the scope and key
questions of the guidelines;
• review of the pertinent literature;
•selection of priority health
outcome measures;
• a systematic review of the
evidence;
• assessment of certainty of the
bodies of evidence resulting from
systematic reviews;
• identification of guideline
exposure levels; and
• setting of the strength of
recommendations.
Based on the defined scope
and key questions, these guidelines
reviewed the pertinent literature
in order to incorporate significant
research undertaken in the area of
environmental noise and health since
the community noise guidelines and
night noise guidelines for Europe were
issued ..
In total, eight systematic reviews
of evidence were conducted to
assess the relationship between
environmental noise and the following
NOVEMBER 2018 / FUTURE MEDICINE / 71

health outcomes: cardiovascular and
metabolic effects; annoyance; effects
on sleep; cognitive impairment;
hearing impairment and tinnitus;
adverse birth outcomes; and
quality of life, mental health and
well-being.
A separate systematic review of the
evidence was conducted to assess the
effectiveness of environmental noise
interventions in reducing exposure
and associated impacts on health.
Once identified and synthesized,
EIGHT SYSTEMATIC
REVIEWS OF EVIDENCE
WERE CONDUCTED TO
ASSESS THE RELATIONSHIP
BETWEEN ENVIRONMENTAL
NOISE.
the quality of the evidence of the
systematic reviews was assessed
by the Systematic Review Team.
Subsequently, the Guideline
Development Group (GDG) formulated
recommendations, guided by the
Systematic Review
Team’s assessment and informed
by of a number of additional
contextual parameters. To facilitate
the formulation of recommendations,
WHO RECOMMENDATIONS ON ENVIRONMENTAL NOISE SOURCE
ROAD TRAFFIC NOISE
For average noise exposure, the
GDG strongly recommends reducing
noise levels produced by road traffic
below 53 decibels (dB) L den , as
road traffic noise above this level
is associated with adverse health
effects.
For night noise exposure, the GDG
strongly recommends reducing
noise levels produced by road
traffic during night time below 45
dB L night , as night-time road traffic
noise above this level is associated
with adverse effects on sleep.
To reduce health effects, the
GDG strongly recommends that
policy-makers implement suitable
measures to reduce noise exposure
from road traffic in the population
exposed to levels above the
guideline values for average and
night noise exposure. For specific
interventions, the GDG recommends
reducing noise both at the source
and on the route between the
source and the affected population
by changes in infrastructure.
Strong
RAILWAY NOISE
For average noise exposure, the
GDG strongly recommends reducing
noise levels produced by railway
traffic below 54 dB L den , as railway
noise above this level is associated
with adverse health effects.
For night noise exposure, the GDG
strongly recommends reducing
noise levels produced by railway
traffic during night time below 44
dB L night , as night-time railway noise
above this level is associated with
adverse effects on sleep.
To reduce health effects, the
GDG strongly recommends that
policy-makers implement suitable
measures to reduce noise exposure
from railways in the population
exposed to levels above the
guideline values for average and
night noise exposure. There is,
however, insufficient evidence
to recommend one type of
intervention over another.
Strong
AIRCRAFT NOISE
For average noise exposure, the
GDG strongly recommends reducing
noise levels produced by aircraft
below 45 dB L den ., as aircraft noise
above this level is associated with
adverse health effects.
For night noise exposure, the GDG
strongly recommends reducing
noise levels produced by aircraft
during night time below 40 dB
L night ., as night-time aircraft noise
above this level is associated with
adverse effects on sleep.
72 / FUTURE MEDICINE / NOVEMBER 2018

BY SOURCE
To reduce health effects, the
GDG strongly recommends that
policy-makers implement suitable
measures to reduce noise exposure
from aircraft in the population
exposed to levels above the
guideline values for average and
night noise exposure. For specific
interventions, the GDG recommends
implementing suitable changes in
infrastructure.
WIND TURBINE NOISE
For average noise exposure, the
GDG conditionally recommends
reducing noise levels produced by
wind turbines below 45 dB L den , as
wind turbine noise above this level
is associated with adverse health
effects.
No recommendation is made for
average night noise exposure
Lnight of wind turbines. The quality
of evidence of night-time exposure
to wind turbine noise is too low to
allow a recommendation.
To reduce health effects, the
GDG conditionally recommends
that policy-makers implement
suitable measures to reduce noise
exposure from wind turbines in the
population exposed to levels above
the guideline values for average
noise exposure. No evidence is
available, however, to facilitate the
recommendation of one particular
type of intervention over another.
LEISURE NOISE
For average noise exposure, the
GDG conditionally recommends
reducing the yearly average from
all leisure noise sources combined
to 70 dB L Aeq,24h as leisure noise
above this level is associated
with adverse health effects. The
equal energy principle can be
used to derive exposure limits for
other time averages, which might
be more practical in regulatory
processes.
For single-event and impulse noise
exposures, the GDG conditionally
recommends following existing
guidelines and legal regulations to
limit the risk of increases in hearing
impairment from leisure noise in
both children and adults.
Following a precautionary approach,
to reduce possible health effects,
the GDG strongly recommends that
policy-makers take action to prevent
exposure above the guideline
values for average noise and singleevent
and impulse noise exposures.
This is particularly relevant as a
large number of people may be
exposed to and at risk of hearing
impairment through the use of
personal listening devices. There
is insufficient evidence, however,
to recommend one type of
intervention over another.
strong
conditional
the GDG first defined priority health
outcomes and then selected the
most relevant health outcome
measures for the outcomes.
Consecutively, a process was
developed to identify the guideline
exposure levels with the help of
the exposure-response functions
provided by the systematic
reviews. To reflect the nature of the
research (observational studies)
underpinning the relationship between
environmental noise and health, the
GRADE procedures were adapted to
the requirements of environmental
exposure studies where needed.
Noise indicators
From a scientific point of view,
the best noise indicator is the one
that performs best in predicting
the effect of interest. There are,
however, a number of additional
criteria that may influence the
choice of indicator. For example,
various indicators might be suitable
for different health end-points. Some
considerations of a more political
nature can be found in the European
Commission’s Position paper on EU
NOVEMBER 2018 / FUTURE MEDICINE / 73

slug
NOISE POLLUTION:
RISK OF ADVERSE
HEALTH EFFECTS
The guideline document identifies four
priority health outcome measures
and
CARDIOVASCULAR
DISEASE: IHD AND
HYPERTENSION
High-quality epidemiological
evidence described in
the systematic review on
cardiovascular and metabolic
effects of environmental noise
indicates that exposure to road
traffic noise increases the risk
of IHD. The GDG was confident
that health risks resulting from
exposure at an RR increase
in the order of 5–10% in the
incidence of IHD. This is similar
to the reasoning in the WHO
air quality guidelines for fine
particulate matter (PM2.5).
To determine a relevant
risk increase for IHD, the GDG
took as a starting-point the
relative risk (RR) increase
of 5% measured in
epidemiological
studies of
environmental noise
or air pollution.
Taking into account the
incidence of IHD and the
seriousness of the disease,
it considered lowering the
RR increase for IHD to 1%,
as a 5% RR increase might
imply a comparatively high
absolute risk from a population
perspective. To decide on
the final benchmark value
for IHD, several aspects were
considered: the number of
people in a population affected
by IHD; whether health
risks caused by noise would
make up a large part of the
incidence of the disease; other
examples of health risks of
similar magnitude leading to
preventive action. For IHD, in
an average EU country with
20 million inhabitants, an RR
increase of 5% for IHD would
lead to several thousand extra
cases attributable to noise
yearly. This corresponds to
a proportion of cases of IHD
attributable to noise exposure
of less than 10%, which is still
relatively small. After extensive
discussion at the very end of
the guideline development
process, the GDG decided to
adhere to 5% as the relevant
risk increase.
noise indicators (EC, 2000).
The current guidelines are intended
to be suitable for policy-making in
the WHO European Region. They,
therefore, focus on the most used
noise indicators L den and/or L night .
They can be constructed using their
components (L day , L evening , L night
and the duration in hours of L night ),
and are provided for exposure
at the most exposed façade, outdoors.
The L den and L night indicators are
those generally reported by
authorities and are widely used for
exposure assessment in health effect
studies.
Recommendations
Specific recommendations have
been formulated for road traffic
noise, railway noise, aircraft noise,
SPECIFIC
RECOMMENDATIONS HAVE
BEEN FORMULATED FOR
ROAD TRAFFIC NOISE,
RAILWAY NOISE, AIRCRAFT
NOISE, WIND TURBINE
NOISE AND LEISURE NOISE.
wind turbine noise and leisure noise.
Recommendations are rated as either
strong or conditional.
Strength of recommendation
• A strong recommendation can be
adopted as a policy in most situations.
The guideline is based on the
74 / FUTURE MEDICINE / NOVEMBER 2018

Hypertension is a common
condition and is an important
risk indicator for IHD and other
cardiovascular diseases. Thus,
the hypertension risk increase
can be transformed into a risk
increase for cardiovascular
disease. To derive a relevant
risk increase, the GDG
focused on the incidence
of hypertension, owing to
the nature and quality of
epidemiological evidence. Since
hypertension is less serious
than IHD, and not all people
with hypertension will progress
to cardiovascular disease, the
relevant risk increase in the
incidence of hypertension
needed to be higher than that
for IHD. Therefore, the GDG
agreed on an RR increase of
10% for hypertension.
SLEEP DISTURBANCE
AND ANNOYANCE
The GDG initially considered
5%HSD and 10%HA due to
noise as relevant absolute
risks, not be exceeded at
the guideline level. After
discussion, however, members
agreed that these absolute
risks were too large since a
considerable proportion of
the population would still
be affected; they decided
to lower the relevant risk
from 5% being highly sleepdisturbed
to 3%. In doing so,
the GDG referred to the WHO
night noise guidelines (WHO,
2009), which concluded that
while there was insufficient
evidence that physiological
effects at noise levels below
40 dB Lnight are harmful to
health,
there were observed
adverse health effects at
levels starting from 40 dB
Lnight. At 40 dB, about 3–4%
(depending on the noise
source) of the population still
reported being highly sleepdisturbed
due to noise, which
was considered relevant to
health. The GDG considered
it important that this level is
consistent with the previous
health-based approach
adopted by the WHO
night noise guidelines, and
agreed that the absolute risk
associated with the guideline
value selected should not
exceed 3%HSD to be health
protective.
For annoyance, which
is considered a less serious
health effect than self-reported
sleep disturbance (as indicated
by the respective DWs),
the relevant risk remained
at 10%HA. This means the
absolute risk associated with
the guideline value selected
should be closest to, but not
above 10%HA, to be health
protective.
COGNITIVE
IMPAIRMENT
Acquiring skills in reading and
oral comprehension at a young
age is important for further
development: a delay in
acquiring these skills can have
an impact later in life. This
impact cannot be predicted
very accurately, but the GDG
considered a delay of one
month a relevant absolute risk.
PERMANENT HEARING
IMPAIRMENT
The literature on hearing
impairment as a result of
occupational noise exposure
is extensive. A noise exposure
level beyond 80 dB during
40 years of working a 40
hour work week can give
rise to permanent hearing
impairment. Given that
environmental exposure to
noise is much lower than these
levels and that noise-related
hearing impairments are not
reversible, the GDG considered
that there should be no risk
of hearing impairment due
to environmental noise and
considered any increased
risk of hearing impairment
relevant.
confidence that the desirable effects
of adherence to the recommendation
outweigh the undesirable
consequences. The quality of evidence
for a net benefit – combined with
information about the values,
preferences and resources – inform
this recommendation, which should be
implemented in most circumstances.
• A conditional recommendation
requires a policy-making process with
substantial debate and involvement
of various stakeholders. There is
less certainty of its efficacy owing
to the lower quality of evidence
of a net benefit, opposing values
and preferences of individuals
and populations affected or the
high resource implications of the
recommendation, meaning there may
be circumstances or settings in which
it will not apply.
Alongside specific
recommendations, several guiding
principles were developed to provide
generic advice and support for the
incorporation of recommendations into
a policy framework. They apply to the
implementation of all of the specific
recommendations.
Guiding principles: reduce,
promote, coordinate and involve
• Reduce exposure to noise, while
conserving quiet areas.
• Promote interventions to reduce
exposure to noise and improve health.
• Coordinate approaches to control
noise sources and other environmental
health risks.
• Inform and involve communities
potentially affected by a change in
noise exposure.
NOVEMBER 2018 / FUTURE MEDICINE / 75

esearch
SEPSIS: PATHOGEN AND
HOST BATTLE
Researchers found that in the onset and progression of sepsis, a protective
mechanism normally present in the host was disabled
SONIA FERNANDEZ
A
major cause of human disability
and death throughout the
world, sepsis is a condition that
begins with an infection, progresses
rapidly and can set off a chain of
effects that result in multiple organ
failure and irreparable damage to the
body.
Because of the condition’s rapid
onset, physicians must respond
immediately to the symptoms
with broad-spectrum antibiotics
for infection, drugs to combat
inflammation and, in the more critical
cases, vasopressors to manage shock.
Because sepsis is so difficult to
detect in its early stages, however,
little has been known about how it
develops. This may explain why no
new effective drugs to treat sepsis
have been developed in decades,
while it remains one of the leading
causes of hospital deaths. Sepsis also
can result in serious disabilities for
those who survive.
Now, researchers at UC Santa
Barbara, Sanford Prebys Medical
Discovery Institute (SBP) in La Jolla,
California, and UC San Diego have
developed a method for tracking, on
a molecular level, the development
of sepsis. Their resulting discoveries
could, in turn, lead to more advanced
76 / FUTURE MEDICINE / NOVEMBER 2018

therapies for sepsis that reduce its
mortality, minimise the lifelong effects
for survivors or even prevent the
cascade of life-threatening effects
before it begins, while reducing the
billions of dollars spent every year to
treat the condition.
Their paper, “Accelerated Aging and
Clearance of Host Anti-inflammatory
Enzymes by Discrete Pathogens Fuels
Sepsis” is published in the journal Cell
Host & Microbe.
“Sepsis is generally thought of as
one singular disease, especially as
it enters late stages,” said UC Santa
Barbara biology professor Jamey
Marth, who is the director of the
campus’s Center for Nanomedicine,
in addition to being a professor at
SBP. “At this point, inflammation,
and coagulopathy have caused the
vascular and organ damage common
to severe sepsis and septic shock. Our
comparative approach to monitor the
onset and progression of sepsis at the
molecular level supports the view that
there are different molecular pathways
in sepsis depending on host responses
to different pathogens.”
New sepsis model
In contrast to previous experimental
models of sepsis, which typically
release multiple and incompletely
identified pathogens into the
bloodstream, Marth and his team
developed a more quantitative
method that tracked the pathogen
and host over time, beginning with
infection. This method generated a
reproducible protocol that allowed
the scientists to map host responses,
in this case to five different human
pathogens representing common
strains and isolates from different
patients.
In the study, Marth’s team found
that in the onset and progression of
sepsis caused by Salmonella or E. coli,
a protective mechanism
normally present in the host was
disabled. The mechanism that the
bacteria used included a means to
accelerate the molecular aging and
clearance of two anti-inflammatory
alkaline phosphatase (AP) enzymes,
called TNAP and IAP, which are
normally present in the host
bloodstream.
This was achieved through
pathogen activation of the host’s own
Toll-like receptor-4 (TLR-4), and both
pathogens were thus able to induce
inflammatory compounds and reduce
the likelihood of host survival. The
scientists found that boosting the
level of protective anti-inflammatory
AP activity or using neuraminidase
inhibitors to block the downstream
IT’S POSSIBLE THAT SEPSIS
IS SIMILAR TO CANCER, IN
THAT WE NOW KNOW THAT
CANCER IS A NOT A SINGLE
DISEASE BUT REPRESENTS
HUNDREDS OF DISEASES AT
THE MOLECULAR LEVEL.
effect of TLR-4 activation on NEU1
and NEU3 induction were both
highly therapeutic approaches as
inflammatory markers were reduced
and host survival increased —
indicating a potential direction for drug
development.
“It has been known that AP
isozymes can reduce inflammation
in the context of some diseases and
pathogens — indeed AP is currently in
clinical trials focused on inflammatory
diseases, including colitis and sepsis,”
said Won Ho Yang, Ph.D., lead author
and a senior scientist in the Marth
laboratory at both UCSB and SBP.
“This study shows that the pathogen is
interacting with the host to disable a
protective response. The findings also
demonstrate how both pathogen and
host battle each other by altering the
rates of protein aging and clearance
— which itself is a newly discovered
regulatory mechanism we recently
reported that controls the half-lives of
proteins in the blood.”
In contrast, these responses
weren’t seen in infections caused
by other bacteria tested, including
methicillin-resistant Staphylococcus
aureus (MRSA) and Streptococcus
pneumoniae. The different host
responses, in this case, appeared
divided between Gram-positive
and Gram-negative bacteria, which
describes the existence or the absence
of an inflammatory compound found
on Gram-negative strains.
“We are continuing to map and
compare host responses to different
pathogens in sepsis, using state-ofthe-art
technical approaches, and
hope to ultimately stratify the
disease,” said Marth, who is the
Professor of Biochemistry and
Molecular Biology at UC Santa Barbara,
as well as the Mellichamp Chair of
Systems Biology.
“It’s possible that sepsis is similar
to cancer, in that we now know that
cancer is a not a single disease but
represents hundreds of diseases at the
molecular level.”
Research on this project was also
conducted by Douglas M. Heithoff,
Peter V. Aziz, Benjamin Haslund-
Gourley and Michael J. Mahan, SBP
and UC Santa Barbara; Julia S.
Westman, Sonoko Narisawa, Anthony
B. Pinkerton and José Luis Millán, SBP;
and Victor Nizet, M.D., UC San Diego.
The research was supported by
National Institutes of Health (NIH)
Heart, Lung, and Blood Institute (HLBI)
grants HL125352 and HL131474.
Additional support was provided
by the Swedish Research Council
2017-00192 and the Wille Family
Foundation.
—Reproduced with permission
NOVEMBER 2018 / FUTURE MEDICINE / 77

orthopaedics
REPAIRING
ROTATOR CUFF
Rotator cuff tear should be treated
aggressively to prevent its return
DR. ADITYA SAI KADAVKOLAN
The shoulder is a ball and socket
joint formed between the upper
end of the arm bone and the
shoulder blade. It is surrounded by
a group of muscles called the
rotator cuff; there are in all four
muscles that constitute the
rotator cuff group. The muscles
form fibrous structures called
tendons, which insert into the
bone. The muscle has a very
good blood supply whereas
the tendons have a poor
blood supply and that
has implications in injury healing.
The function of the rotator cuff
muscles is two fold:
Movement of the shoulder joint
Stabilization of the shoulder joint
The rotator cuff muscles glide
under a bone called the acromion,
which is an extension of your shoulder
blade. In any population, there are
broadly three variants of the acromion:
a) Flat b) Curved c) Congenitally
abnormal or hooked.
Abnormal acromion morphology or
conditions called scapular dyskinesia
can cause increased contact between
the acromion and the rotator cuff,
leading to tendinitis or tear.
Injuries like a fall on an
outstretched hand or a fall on the
shoulder can also lead to rotator cuff
tears.
Symptoms
• Pain
• Pain in the night
• Difficulty in reaching behind the back
or reaching for the top shelf
Stiffness
Many a time, shoulder pain due to
rotator cuff tears is misdiagnosed as a
frozen shoulder. A frozen shoulder, per
se, is an entity where there is a global
restriction in shoulder movement in
spite of the absence of any muscle
tear or any cartilage related issues.
A rotator cuff tear has a poor
tendency to heal as discussed
previously because of a poor blood
supply to the tendon.
Treatment
Surgical repair of acute / post-injury
78 / FUTURE MEDICINE / NOVEMBER 2018

otator cuff tears has been shown
to have excellent results and is the
preferred line of treatment. Due
to advances in technology, these
procedures can be done through
arthroscopic surgery, which restores
the normal biomechanical function
of the shoulder joint. With good
physiotherapy and rehabilitation,
individuals are able to get back to
normal levels of function at the end of
a certain period of time.
For rotator cuff tears that are a
result of impingement or abnormal
morphology of the acromion or caused
by an abnormal shoulder posture,
an initial trial of a non-operative
treatment can be given, with careful
observation of shoulder function over
a period of 3 months. If there is no
improvement in symptoms over a
period of time, then surgical treatment
is a better option.
Non-surgical treatment essentially
consists of physiotherapy and
rehabilitation; there is no role for
medicines in rotator cuff tears other
than to control the pain. Physiotherapy
and rehabilitation improve the
shoulder biomechanics and the intact
tendons compensate for the deficient
rotator cuff. However, it does not
lead to a healing of rotator cuff tears.
Physiotherapy and rehabilitation
can improve shoulder function to a
percentage of normal, but cannot
entirely restore normal function and
also need periodic follow up. Moreover,
there’s a risk of the disease worsening
in the future. Rotator cuff tears can
become bigger and tendon/muscle
quality can deteriorate, precluding a
surgical repair.
Neglected rotator cuff tears can
lead to an increase in the size of
the muscle tear and destabilize the
shoulder joint over a period of time
in what is called cuff tear arthropathy.
Individuals with these issues are not
able to lift the arm above the shoulder
level. Some individuals develop what
is termed a pseudoparalysis where,
although no paralysis is present, they
are not able to move the shoulder due
to deficient muscle function.
SUPERIOR RECONSTRUCTION
TORN
IRREPARABLE
CUFF
NEGLECTED ROTATOR CUFF
TEARS OVER A PERIOD
OF TIME CAN LEAD TO AN
INCREASE IN THE SIZE OF
THE MUSCLE TEAR AND
DESTABILIZE THE SHOULDER
JOINT, WHAT IS CALLED
CUFF TEAR ARTHROPATHY.
This is a very problematic issue
with regard to the shoulder joint and
hence some surgeons suggest a more
aggressive approach in the treatment
of rotator cuff tears to prevent
advanced disease.
In case of massive rotator cuff
tears, which are not repairable, we
have two options:
In younger individuals or patients
less than 60 years of age, two options
are generally employed to preserve
the shoulder joint:
a) Muscle transfers: Other
functioning muscles around the
shoulder girdle are substituted to aid
the rotator cuff function.
b) Superior reconstruction, in which
the patient’s tissue from thigh/allograft
tissue is introduced into the joint to
stabilize the shoulder and create a
new rotator cuff.
These procedures can be done on
SUPERIOR
CAPSULAR
RECONSTRUCTION
WITH GRAFT
selected individuals who are willing
to participate in the postoperative
rehabilitation programme.
In individuals above 60 years of
age who have massive rotator cuff
tears and presence of what is known
as cuff tear arthropathy, the only
surgical option that gives fair result
is inverse shoulder replacement. It is
called inverse because the relationship
between the ball and socket part of
the shoulder joint is reversed; this
negates the need for a functioning
rotator cuff to move the shoulder.
There are several treatment options
available for management of rotator
cuff tears, ranging from physiotherapy
to rotator cuff repair to a shoulder
replacement. The most important takehome
message for these problematic
issues is that neglecting a rotator cuff
tear may come back to haunt you
later; so it is better to be watchful
and to be more aggressive with the
treatment and participate
in the rehabilitation programme
actively. If treated surgically at an
early stage, these interventions yield
excellent results.
The author is Consultant,
Arthroscopy, Sports
Medicine & Shoulder
Surgery at Dr. LH
Hiranandani Hospital,
Powai, Maharashtra
80 / FUTURE MEDICINE / NOVEMBER 2018

devices&gadgets
Leica introduces
microsurgery microscope
Leica Microsystems has launched
Provido, a multidisciplinary microsurgery
microscope.
Provido features FusionOptics
technology that gives depth of field and
detail perception at the same
time. The illumination technology
brings light even to deep and narrow
cavities. Having the full surgical field
visible at once allows for better decision
making and limits interruptions from
readjusting the microscope. The surgeon
can focus on progressing smoothly
through the procedure, according to the
company.
Deep and narrow channels are a daily
challenge in many surgical disciplines,
particularly spine and otolaryngology. The
microscope integrates concentrated 300
W xenon light and specially-designed
Small Angle Illumination that helps limit
peripheral shadows. As a result, surgeons
are able to see more of the surgical field
without constantly refocusing or adjusting
the light. In addition, there is no longer any
limitation when longer surgical instruments
are required as Provido offers 600 mm of
free working space.
The electromagnetic brakes and
balancing system enables the Provido to be
positioned at the required angle with the
lightest touch. For even greater precision,
micro adjustments can be achieved with
the XY joystick control.
SpineEX lateral
lumbar device for
disc disease
S
pineEX, Inc, a medical
device company has
received 510(k) clearance
from the US Food and Drug
Administration (FDA) for
its Sagittae lateral lumbar
interbody fusion (LLIF) device.
The LLIF procedure
uses minimally invasive
techniques that approach
the spine from the side of
the patient, allowing for a
larger implant footprint, and
less disruption to lower back
muscles as compared to other
approaches.
This personalized,
expandable device is
designed to minimize
impaction, maximize indirect
decompression, and provide
a large graft space optimal
for lumbar fusion procedures.
It provides up to 8mm of
continuous in situ expansion,
with up to 30° of continuous
in situ lordotic adjustment.
Available in five
sizes,Sagittae provides
several options for surgeons
to address optimal sagittal
balance, while minimizing
burdensome implant inventory
traditionally required for each
procedure.
LLIF devices are indicated
for interbody fusion in
patients with degenerative
disc disease (DDD) at one or
two contiguous levels from
L2 to S1. DDD is defined as
back pain of discogenic origin
with degeneration of the disc
confirmed by history and
radiographic studies. These
DDD patients may also have
up to Grade I spondylolisthesis
or retrolisthesis at the involved
82 / FUTURE MEDICINE / NOVEMBER 2018

Zeiss laser tech to treat astigmatism
Carl Zeiss Meditec’s
expanding myopia
treatment for patients
with astigmatism received
premarket approval from the
USFDA.
ReLEx Smile utilises a highprecision
femtosecond laser
to create a lenticule inside the
cornea and access incision
in a single treatment step.
Incisions are made through
microscopic-photodisruptions
of tissue, created by ultrashort
pulses. VisuMax laser is the
first femtosecond laser to
receive FDA PMA approval for
the treatment of a refractive
indication in addition to 510k
clearances for LASIK flap,
keratoplasty, and ICR.
The technology behind
Smile was recently featured
in the scientific background
on the Nobel Prize in Physics
2018. Dr. Gérard Mourou and
Dr. Donna Strickland were
awarded the Nobel Prize
for his method to generate
high-intensity ultrashort
optical pulses. Their invention
of so-called chirped pulse
amplification is essential to
generate the ultrashort laser
pulses of the Zeiss VisuMax
femtosecond laser system,
according to the company.
Carl Zeiss Meditec AG
is the Medical Technology
Business Group of Zeiss.
level(s). These patients should
be skeletally mature and have
completed six months of
non-operative treatment, the
company said.
Fujifilm launches
endoscopes to
detect GI cancers
Fujifilm India Private Limited
launched a range of novel
image-enhanced endoscopy
products for the detection of
gastro cancers.
Eluxeo 7000 Series
endoscopes have Blue Light
Imaging (BLI)/Linked Colour
Imaging (LCI) technology to
aid early detection of all types
of stomach cancers.
Stomach cancer is the
second-most common cancer
among men and third-most
among females in Asia. The
symptoms and sign of the
stomach cancer are often
reported late when the
disease is already in advanced
stages, and the 5-year survival
rate is less than 30 percent
in developed countries
and around 20 percent in
developing countries.
The company said the
Eluxeo 7000 is targeted for
biopsy and early alarm by
helping obtain high-resolution
images to detect cancers at a
very early stage.
Drug-eluting
stent approved
for PAD
Boston Scientific
Corporation’s drugeluting
vascular stent system,
specifically developed for the
treatment of peripheral
artery disease (PAD), has
been approved by the
US FDA.
The Eluvia stent
utilizes a drug-polymer
combination to provide
sustained release of
the drug paclitaxel for a
one-year timeframe. It is
designed to prevent tissue
regrowth that might otherwise
block the stented artery.
The approval was based
on findings from the IMPERIAL
trial, the first superficial
femoral artery head-tohead
drug-eluting stent trial
evaluating the safety and
efficacy of Eluvia vs Zilver PTX
in 465 patients.
The results of the trial
showed that patients
treated with the Eluvia stent
experienced a significantly
greater 12-month primary
patency of 88.5 percent,
compared to 79.5 percent in
patients treated with Zilver
PTX.
The Eluvia stent system
is built on the Innova
Stent System platform,
a self-expanding nitinol
stent that has been designed
for use in the superficial
femoral and proximal popliteal
arteries, the main arteries that
supply blood to the legs.
Self-fitting OTC
hearing aid
gets nod
The USFDA has cleared
the Bose Hearing Aid,
a self-fitting hearing aid
for individuals 18 years or
older with perceived mild to
moderate hearing impairment.
This hearing aid enables
users to fit, programme and
control the hearing aid on
their own, without assistance
from a health care provider.
The Bose Hearing Aid
is a user-fitted wireless air
conduction hearing aid. Air
conduction hearing aids
work by capturing sound
vibrations through one or
more microphones. The
signal is processed, amplified,
and played back through an
earphone placed in the ear
canal.
Patients can adjust the
hearing aid through a mobile
application on their phone.
NOVEMBER 2018 / FUTURE MEDICINE / 83

This technology enables users
to fit the hearing aid settings
themselves, in real-time and
in real-world environments
without the assistance of a
healthcare professional.
In authorizing marketing
of the Bose device, the FDA
reviewed data from clinical
studies of 125 patients, which
demonstrated that outcomes
with self-fitting of the Bose
Hearing Aid are comparable
on average to those with
professional fitting of the
same device with respect to
the amount of amplification
selected, speech in noise
testing and overall benefit,
the regulatory agency said
announcing the approval.
Neuro imaging
system gets
clearance in US
The US Food and Drug
Administration has
okayed a new imaging
modality augmented reality
(AR) GLOW800 surgical
fluorescence for vascular
neurosurgery.
GLOW800 allows
surgeons to observe
cerebral anatomy in natural
colour, in combination with
ICG (Indocyanine Green),
augmented by real-time
vascular flow in a single image,
with full depth perception.
It provides the surgeon
with a complete view of
anatomy and physiology to
support crucial decisions
and actions during vascular
neurosurgery.
GLOW800 AR
fluorescence is the first of
many imaging modalities that
will be based on the GLOW
AR platform. GLOW AR
modalities can be fully
integrated into the ARveo
digital augmented reality
microscope, according to
Leica Microsystems, the
maker of the device.
Certara cloudbased
platform
to help HCPs
Certara has launched
BaseCase Portal cloudbased
platform that allows for
the rapid creation of fullycustomizable
mobile apps that
connect live to mathematical
models and algorithms, and
help HCPs optimize treatment
for individual patients.
BaseCase Portal
enables clinicians to use
Boston Scientific launches kidney stone
retrieval device
Boston Scientific Corporation has
launched LithoVue Empower Retrieval
Deployment Device, designed to be used
with the ureteroscope.
The device comes with a compatible
nitinol retrieval basket to enable urologists
to operate a ureteroscope and basket
simultaneously when retrieving kidney
stones via flexible ureteroscopy (URS).
According to Boston Scientific, until
now, urologists have traditionally relied
on another person to operate the basket
used to collect kidney stones during kidney
complex scientific models
and algorithms that were
previously only available in
research settings, to guide
therapeutic decision-making.
The platform keeps a strict
separation between the user
interface and the underlying
mathematical model. This
offers many benefits over
the old way of doing things
in which algorithms typically
were hardwired into a
website. On BaseCase Portal,
algorithms and models can be
validated and updated much
more easily.
BaseCase Portal also
features embedded version
control and release workflows,
and provides an audit trail,
allowing a new version of an
app to be uploaded as soon
as it receives the requisite
stone retrieval. Turning a two-person
stone basketing procedure into a singleperson
procedure provides greater control
for the surgeon, decreasing the risk of
miscommunication during stone basketing
without compromising time.
Retrieving kidney stones is one of
the most time-consuming steps during
ureteroscopy procedures, making this
an opportune area to improve physician
control, address communication/
coordination challenges and identify time
savings, says Boston Scientific.
84 / FUTURE MEDICINE / NOVEMBER 2018

AUGUST 2018/ FUTURE MEDICINE / 85

legal and regulatory approvals.
Besides precision dosing
apps, BaseCase Portal can also
be used for diverse purposes
such as providing education
and facilitating collaboration.
Examples include apps that
provide product information,
inform on guidelines and
treatment pathways, and track
the progress of global studies.
As BaseCase Portal is a
white label solution, it can be
tailored to reflect each clients’
brand identity, Certara informs.
BTG launches
cryoablation
system
BTG plc has announced the
global launch of the ICEfx
Cryoablation System. ICEfx,is
an updated version of the
existing Visual ICE system is
designed for interventional
radiologists who want to
offer their patients minimally
invasive treatment options.
It allows physicians to
provide safe and efficient
cryoablation procedures,
facilitating precise and
effective treatment without
the need for surgery or
repeated radiation treatments.
The advanced cryoablation
technology is currently
supporting a number of active
clinical research studies in
bone, kidney, lung, pain, and
prostate, the company said.
BTG Interventional
Oncology delivers IO ablation
solutions across multiple
physician specialties.
Stent to seal
coronary artery
tears cleared
The US FDA has cleared PK
Papyrus Covered Coronary
Stent System, a device to
treat acute coronary artery
perforations or tears in the
blood vessels of the heart.
A coronary artery
perforation can occur during
Percutaneous Coronary
Guide XT system for
visualization of DBS
Guide XT System for
visualization of deep
brain stimulation (DBS)
was launched in Europe,
said Boston Scientific
Corporation.
The Guide XT System
is built for directionality
that utilizes patientspecific
anatomy and
stimulation field modeling.
This technology provides
physicians with 3-D image
planning capability and
when used in conjunction
with the Vercise DBS
Systems, enables physicians
to personalise and optimise
DBS treatment.
DBS treats movement
disorder symptoms in
patients with Parkinson’s
disease, dystonia or essential
tremor. The procedure
stimulates a targeted
Intervention (PCI) procedures.
The PK Papyrus Stent
System is a balloonexpandable
covered coronary
stent and delivery system.
The device is advanced into
the perforated coronary
artery vessel using a balloon
catheter, similar to the
one used during the PCI
procedure. Once the PK
Papyrus stent is implanted,
it provides a physical barrier
to seal the tear in the artery
wall while still allowing
region of the brain through
implanted leads that are
powered by a device called
an implantable pulse
generator (IPG).
The Guide XT System
automatically detects
the location of the
leads, implanted by a
neurosurgeon, in the
imaging of the brain.
Following the implant, a
clinician programmes a
patient’s device and the
Guide XT System can be
used to help visualize
the stimulation field and
efficiently determine the
most appropriate settings for
each patient.
Guide XT was developed
in partnership with
Brainlab AG, a softwaredriven
medical technology
company.
blood to flow through the
device to the heart muscle.
Successful sealing of a
coronary perforation with the
PK Papyrus Covered Coronary
Stent System can be a lifesaving
procedure without the
need for open-heart surgery.
The FDA reviewed realworld
survey data from
80 patients who received
PK Papyrus stents to treat
coronary artery perforations.
PK Papyrus stents were
successfully delivered to the
perforation site in 76 of the
80 patients (95 percent), and
the device successfully sealed
the perforation in 73 patients
(91.3 percent), according to
US FDA.
Micro pump for
Parkinson’s gets
CE mark
Sensile Medical AG, a
Swiss medical technology
company, said its wearable
micro pump has received CE
certification from EU.
The micro pump is
designed to be used in
the treatment of advanced
Parkinson’s disease. The
handy-sized, discreet
pump has got easy to use
features such as automatic
filling with liquid medicine.
Technologies such as colour
display, charging unit and data
storage help enhance therapy
management.
A personally
programmable basal profile
enables treatment to be
optimized for Parkinson’s
patients and ensures that they
receive the precise dosage
they need. Likewise for the
bolus rate: A patient can
cause the device to deliver
a bolus at just one touch of
a button. Sensile’s patented
SenseCore micro rotary
piston pump in the device
ensures safe, precise drug
delivery, eliminating flow rate
calculations.
86 / FUTURE MEDICINE / NOVEMBER 2018

events
MVR CANCON2018 debates transition
in cancer diagnosis and treatment
Leading oncologists thrash out advances in GI, lung, breast and gynaec cancers
DIVYA CHOYIKUTTY
The first edition of International
Oncology Conference-MVR CANCON
2018 — organized by MVR Cancer
Care and Research Institute with the
theme “Consensus and Controversies
in Oncology” — highlighted the
latest therapeutic advances such as
immunotherapy.
The three-day CME, which concluded
at MVRCCRI Campus at Kozhikode on
30thSeptember 2018, was held with the
support of expert faculty from Cleveland
Clinic, USA. The conference involved
interactive sessions on current and
emerging treatment options and research
in oncology, with special emphasis on
gastrointestinal tract, breast, lung and
gynaec-oncological tumours.
“Our main aim behind organizing this
conference was to give clinical updates
on various cancers through specialists
and scientists from around the world and
to make them cognizant of and be able
to implement the knowledge through
their practice,” said Dr. Narayanankutty
Warrier, Medical Director and organizing
chairperson at MVR Cancer Research
Center.
PHOTO: SHIJITH
Our aim was to give clinical
updates on various cancers
to help clinicians implement
the knowledge through their
practice.
Dr. Narayanankutty Warrier,
Organising chairperson, CANCON
and Medical Director at MVR Cancer
Research Center.
Oncology experts from various
disciplines shared their views on how
the recent advances in genomics and
molecular genetics are transforming
cancer diagnosis and treatment
approaches .
“Until a decade or so ago, when a
patient got cancer at a particular location,
he got treated for that cancer, while
now we have moved on to treating
that cancer based on the mutation
in a particular receptor. So essentially,
we have moved from an anatomical
definition of the disease to a biological
definition,” said Dr. Kurt A Schalper,
Pathologist at Yale University, while
discussing the advancements that
precision medicine has brought about in
the landscape of cancer treatment.
Breast cancer is historically
considered to be immunologically silent.
However, several preclinical and clinical
studies suggest that immunotherapy
has the potential to improve clinical
outcomes for patients with breast cancer.
“We haven’t seen all the data yet,
but it appears that the first approval for
immunotherapy in breast cancer will
be in combination with chemotherapy.
Whether this is the best way to use
immunotherapy remains to be seen. It
may be active by itself or in combination
with other classes of drugs as well,” says
Dr. Thomas Budd, Professor of Medicine,
Cleveland Clinic.
Talking about the lack of mandatory
screening procedures that can lead to
advanced-stage lung cancer consultation
scenario, Dr. Rejiv Rajendranath,
Consultant Oncologist at Apollo Medical
Center, indicated the necessity of
incorporating low-dose CT scan as an
opportunistic screening technique among
the high-risk individuals to help diagnose
lung cancer at an early stage.
A proffered paper session, an annual
quiz test, a workshop coordinated by
radiation therapy technologists and a
palliative care programme were other
highlights of the symposium. Two young
doctors, who were adjudged to have
come up with the best oral and poster
presentation, were given the opportunity
for a one-month observership at
Cleveland Clinic, USA.
88 / FUTURE MEDICINE / NOVEMBER 2018

events
8th NGBT calls for greater awareness
on genomics amongst clinicians
Over 800 delegates from India and abroad attend the three-day meet at Jaipur
The 8th annual NGBT Conference
held at Jaipur emphasised the
urgent need for bringing greater
awareness on genomics among Indian
medical and healthcare fraternity.
Genetic science, which holds a critical
role in the emerging healthcare
scenario, is still nascent in the
country, and the key reason is a lack
of awareness among the healthcare
providers and seekers.
“Genomics is clearly the future in
the healthcare space, especially when
we need precision care to manage lifethreatening
disorders,” said Dr Sekar
Seshagiri, chair of NGBT Conference,
at the inaugural meet of the three-day
science event held from September
30 to October 2, 2018. “The science
directly impacts the cost of healthcare
positively by providing insights to
deliver personalized care to patients.”
NextGen Genomics, Biology,
Bioinformatics and Technologies
(NGBT), organised by SciGenom
Research Foundation, a not-for-profit
organization dedicated to promoting
PHOTOS: UMESH GOSWAMI
Snakebite
cure
-A revisit
One of the key highlights of 2018
Conference was the "Live and Let
Live: Snakebite Cure Symposia" that
brought together experts on snakes and
snake bite with a mission to find better
treatments for snake bites.
Dr. Manjunatha Kini, NUS, Singapore,
organised a special symposium with the
theme ‘Live and Let Live’.
“Snake venoms are complex mixtures
of lethal and pharmacologicallyactive
proteins and polypeptides that
contribute to both immobilization and
digestion of prey. The study of venom
proteins has expanded not just our
understanding of venom toxicity, but also
the knowledge of normal and disease
states in human physiology,” said Kini,
while presenting a paper “From Toxins
to Therapeutics: Contradictory Roles of
Snake Venom Toxins that Destroy Life on
One Hand and Gives Life on the Other”
In many cases, the study of snake
venom has led to the development
of powerful research tools, diagnostic
techniques and pharmaceutical
drugs. In the talk, he highlighted the
contribution of snake venom toxins in the
development of life-saving cardiovascular
drugs.
90 / FUTURE MEDICINE / NOVEMBER 2018

science in India through research and
education, was attended by over 800
delegates.
One of the marquee life sciences
conferences organised in India, NGBT
this time had 12 keynote lectures and
80 talks by speakers representing
various scientific organisations from
across the world. It showcased
applications of NextGen sequencing
and genomic technologies for basic
and translational science in various
areas of biology — including human
genetics, drug discovery, clinical
medicine, biomarkers, diagnostics and
animal, plant and agricultural sciences.
It also covered basic biology, cellular
signalling, cancer and plant biology.
“The genomics industry is still at a
nascent stage in India. While genomic
profiling is the way forward for
healthcare, we need to create ample
awareness in the medical community
to leverage its potential,” said Sam
Santhosh, Trustee, SGRF and Founder
& Chairman, MedGenome, a leading
US-India genomic research and
diagnostics organisation.
According to Sam Santhosh, NGBT
conference provides a platform that
brings together accomplished national
and international speakers, thinkers
and thought leaders who shape the
course of scientific discovery, research
and innovation. India, with its huge
biodiversity and genetic pool, can
contribute much more to the world’s
Genomics industry is still
at a nascent stage in India.
While genomic profiling
is the way forward for
healthcare, we need to
create ample awareness
amongst medical community
to leverage its potential.
Sam Santhosh
Trustee, SGRF
genomic database and to the growth
of future medicine.
“The Conference also provides an
environment of exchange of ideas
and provides opportunities for people
to form collaborations, and is an
ideal platform to share knowledge
and find out about the new and
emerging technologies in biology and
biology-enabling technology areas
like genomics. Such forums help in
understanding the real-life challenges
and the ways to address them by
engaging renowned experts from
across the globe,” he added.
NGBT Jaipur was hosted
in collaboration with Toronto
Recombinant Antibody Centre (TRAC),
Canada; Birla Institute of Scientific
Research (BISR), Jaipur; Rajasthan
University of Health Sciences (RUHS),
Jaipur; Eternal Heart Care Centre &
Research Institute (EHCC), Jaipur; SMS
Medical College Hospital (SMSMC),
Jaipur; and Institute of Bioinformatics
(IOB), Bengaluru.
It also featured technology
leaders from institutions like National
University of Singapore, University of
Toronto, University of Montreal, Pacific
Biosciences, MedGenome, Genentech,
Indian Institute of Science, BGI, Centre
for Cellular & Molecular Biology
(CCMB), Johns Hopkins University, 10X
Genomics, Nature Genetics, National
Institute of Biomedical Genomics,
REVOLUTION Medicines and others
from across the world.
Dr. Kuldeep Singh, Director ICAR-
National Bureau of Plant Genetic
Resources, New Delhi, has been
awarded the 2018 SGRF Excellence in
Science Award.
SGRF had also announced over
100 “meeting scholarships” for
students pursuing scientific research.
The recipients of the scholarship were
selected based on abstracts submitted
for the conference.
Using a combined toxicovenomics
and phage display approach, scientist
from the Technical University of
Denmark could develop an experimental
recombinant antivenom based
on a cocktail of fully human antiimmunoglobulin
G (IgG) monoclonal
antibodies that are capable of
neutralising the dendrotoxin mediated
neurotoxicity of Black Mamba whole
venom in a rodent model, said Dr
Andreas H Laustsen of Denmark.
This is the first report on the
development of a fully-human
monoclonal IgGs against animal toxins as
well as the first use of oligoclonal human
IgG mixture experimental snakebite
envenoming,” according to Laustesen of
Technical University of Denmark
Other participants at the symposium
included Kristen Wiley from Kentucky
Reptile Zoo, US; Priyanka Kadam,
Snakebite Healing and Education Society
Maharashtra, India; Ajay Kartik, Madras
Crocodile Bank Trust; Sadanand Raut,
Vighnahar Foundation, Narayangaon,
Maharashtra; Dr. Sekhar Seshagiri,
Genentech, San Fransisco, USA; Dr. Jay
Fox, University of Virginia, Charlottesville,
USA; Dr. Robin Doley, Tezpur University,
Assam; Dr. Viswanath BS, Mysore
University, Karnataka; Dr. Kemparaju K,
Mysore University, Karnataka; Dr. Dev
Sidhu, University of Toronto, Canada;
Dr. Gopi Kadiyala, Kyntox Biotech India
Pvt. Ltd, Banglore and Dr. Omesh Bharti,
Indira Gandhi Medical College, Shimla.
NOVEMBER 2018 / FUTURE MEDICINE / 91

essay
CRISPR/CAS 9- A
POWERFUL GENE
EDITING TOOL
Genome editing represents a potentially effective
means of eliminating the genetic cause of several
diseases
CONFERENCE
2018
competition
Binata is pursuing Ph.D
from All India Institute of
Medical Sciences (AIIMS),
New Delhi)
binata.marik@gmail.com
BINATA MARIK
CRISPR (Clustered regularly
interspaced short palindromic
repeats)/Cas9 (CRISPR associated
protein 9) mediated genome editing
has emerged as a promising tool for
the correction of genetic disorders.
CRISPR-Cas9 is a part of the adaptive
immune system in bacterial species,
which recognizes foreign DNA and
destroys it. There are various types of
CRISPR-Cas systems in prokaryotes but
only components of type II CRISPR are
employed in genome editing. A CRISPR
array is composed of a series of repeats
interspaced by spacer DNA sequences
derived from invading viral genomes.
The CRISPR immune system protects
bacteria from repeated viral attack via
three basic steps: (a) adaptation, (b)
production of CRISPR RNA (crRNA)
and (c) targeting viral genome. During
this immune response, following the
exposure to invading genetic material
from phages, short fragments of the
foreign DNA are integrated into the
CRISPR repeat-spacer array in the host
chromosome as new spacers, thereby
providing a genetic record of the
previous infection that allows the host
to prevent future invasion by the same
species. Subsequent transcription of the
CRISPR array and enzymatic processing
of precursor-CRISPR transcripts through
endonucleolytic cleavage produce
short mature CRISPR RNAs (crRNAs).
At the 5’ end, the crRNA contains the
spacer, a short segment of RNA that is
complementary to a sequence from the
foreign DNA, and the 3’ end contains a
piece of the CRISPR repeat sequence.
Endonucleolytic cleavage
Upon second or consecutive infections,
the hybridization of crRNA spacer and
complementary foreign DNA sequence
occurs, which triggers sequence-specific
destruction of the foreign DNA or RNA
by Cas nucleases. Cas9, which cleaves
the foreign genetic material, is a large
(1,368-amino-acid) DNA endonuclease. It
is composed of:
1. Two distinct nuclease domains:
HNH and RuvC,
2. Single guide RNA sequence
(sgRNA): A dual RNA sequence made up
of CRISPR-RNA (crRNA) and transcribed
crRNA (tracrRNA).
Cas9 cuts double-stranded DNA
(dsDNA) complementary to 20
nucleotides of guide RNA sequence after
recognizing Protospacer Adjacent Motif
(PAM) sequence. PAM is a component of
viral DNA and is usually composed of 3
base pair (bp) sequence (NAG or NGG).
The PAM sequence of the invading
bacteriophage that Streptococcus
pyogenes Cas9 recognizes as NAG or
NGG, also corresponds to the universal
splice acceptor sequence (AG) and
donor sequences (GG). Therefore,
directing Cas9 to the splice sites which
92 / FUTURE MEDICINE / NOVEMBER 2018

will make a double strand break of
DNA can allow deletion of an exon of a
gene containing mutations and thereby
restoring the function of the gene. Thus,
Genome editing with CRISPR/Cas9 has
become a popular genome-editing tool
for correcting or mitigating diseasecausing
mutations. It works by taking the
advantage of the introduction of doublestrand
breaks in DNA at a desired site
in the genome. The DNA break is useful
because it activates the cell’s natural
DNA repair machinery, which significantly
improves the efficiency of introducing
alterations into the genome. Thus,
genome editing makes it simpler to
develop animal models of disease and
possible clinical applications in patients
with genetic disorders. The cell has two
important ways of repairing DNA breaks.
The first method is nonhomologous end
joining (NHEJ), in which the free ends
from the DNA break are simply rejoined.
This method is the default repair
pathway operating in all cells at all the
time. But, NHEJ is an error-prone process
and it can result in the random addition
or deletion of DNA base pairs. Therefore,
NHEJ can introduce frameshift mutations
(deletions and insertions which disrupt
the open reading frame of a gene) into
a targeted gene, thereby disrupting (i.e
knocking out) the function of the gene.
Alternatively, the introduction of 2 DNA
breaks on the same chromosome will
often result in the deletion of entire DNA
base pairs between the DNA breaks. This
principle can be used to delete part of
a gene, a whole gene, or a portion of
a chromosome with many genes. The
second method by which the cell can
repair a DNA break is homology-directed
repair (HDR), which takes place only in
proliferating cells. Homology-directed
repair requires a repair template that
has sequences that is complementary
to the DNA sequence near the site
of the DNA break. If one introduces a
custom-made DNA repair template into
the cell that has matching sequences
but also has the desired alteration, HDR
can use the custom-made template to
stably introduce the alteration into the
genome. But, homology-directed repair
has 3 disadvantages in comparison to
NHEJ. First, HDR requires the delivery of
an extra custom- made template into
the target cells, whereas NHEJ does not.
Second, HDR generally occurs in less
frequently than NHEJ in proliferating
cells. Third, HDR does not occur in nonproliferating
cells, such as postnatal
cardiomyocytes and neurons.
DMD correction
CRISPR-Cas9 has created a revolution
in which researchers around the world
are using the technology for studying
genomic rearrangements and the
progression of cancers or other diseases
and potentially correcting genetic
mutations responsible for inherited
THE LARGE SIZE AND
COMPLICATED STRUCTURE OF
THE DMD GENE CONTRIBUTE
TO ITS HIGH RATE OF
SPONTANEOUS MUTATION.
disorders such as Duchenne Muscular
Dystrophy. This disorder is caused due
to mutations in dystrophin (DMD) gene
and people with this disorder rarely live
past their 20s because they die due to
heart failure. The DMD gene is the largest
known gene in the human genome,
encompassing approximately 2.6 million
base pairs and encoding 79 exons. The
large size and complicated structure
of the DMD gene contribute to its high
rate of spontaneous mutation. There
are ~3000 reported DMD mutations in
humans, which include large deletions
or duplications (~77%), small indels
(~12%), and point mutations (~9%).
Ousterout et al, 2015 deleted the entire
336-kb genomic region flanking exons
45 to 55 in human DMD myoblasts by
guide RNAs targeting introns 44 and 55
to correct multiple hotspot mutations in
the human genome. Young et al, 2016
deleted 725-kb from introns 44 to 55
to restore the dystrophin open reading
frame in multiple DMD patient-derived
induced pluripotent stem cells (iPSCs),
which contain mutations in this region.
To simplify the correction of diverse
DMD mutations by CRISPR/Cas9 gene
editing, Long et al, 2018 identified guide
RNAs capable of skipping the top 12
exons (hotspots), which account for
~60% of DMD patients. They have used
human iPSCs derived three dimensional
engineered heart muscles (3D-EHM) to
check whether the function of patientderived
induced cardiomyocytes (iCMs)
(i.e the contraction of the heart muscle)
has restored after genome editing.
They observed that correcting only a
proportion of cardiomyocytes (30%
to 50%) was sufficient to rescue the
mutant phenotype. Using CRISPR/Cas9
in beagle puppies, Amoasii et al, 2018
have fixed a genetic mutation that
causes Duchenne Muscular Dystrophy.
Researchers injected two 1-month-old
beagle puppies having a mutation with
different doses of a virus carrying the
gene-editing machinery. They measured
dystrophin levels in different muscles
after eight weeks. Levels of the protein
increased in every muscle group that the
team studied, but the effect was variable.
Dystrophin levels in the heart of the
dog receiving the higher dose were 92
percent of what was present in healthy
pups without the mutation, but levels in
the dog’s tongue were only 5 percent
in comparison to normal. Therefore,
these studies suggested that genome
editing represents a potentially effective
means of eliminating the genetic cause
and correcting the muscle and cardiac
abnormalities associated with DMD. One
key concern for the CRISPR/Cas9 system
is specificity because off-target effects
may cause unexpected mutations in
the genome that may lead to cancer.
Several approaches have been reported
to minimize potential off-target effects
and/or to improve the specificity of the
CRISPR/Cas9 system, including titration
of dosage of Cas9 and guide RNA, and
high-fidelity Cas9. Therefore, CRISPR/
Cas9 has proved to be a powerful
tool for genome editing research.
Further optimization and improvement
of this method are needed to meet
the requirements of gene therapy
application.
NOVEMBER 2018 / FUTURE MEDICINE / 93

calendar
Upcoming conferences
NOVEMBER
1-3 SKULL BASE SURGERY
Annual Conference of Skull
Base Surgery Society of India
(SKULLBASECON)
Ludhiana
UROLOGY
Annual Conference of Urological
Society of India East Zone
Chapter (ACUSIEZC)
Ahmedabadt
TELEMEDICINE
Telemedicon 2018 - 14th
International Conference of
Telemedicine Society of India
Amravati, Andhra Pradesh
10-11 SLEEP APNEA
AOCMF Seminar - Advances in
Sleep Apnea and Orthognathic
Chennai, Tamil Nadu
14-16 RESPIRATORYDRUG
DELIVERY
Respiratory Drug Delivery (RDD)
Asia Conference 2018
Kochi, Kerala
15-18
PAEDIATRIC NEUROLOGY
15th International Child
Neurology Congress
Mumbai, Maharashtra
15-18 IPS
46th IPS National Conference
Mangalore 2018
Mangalore, Karnataka
19-22 PATHOLOGY
International Conference on
Microbiome Research (ICMR)
Pune
22-25
NUCLEAR CARDIOLOGY
American Society of Nuclear
Cardiology (ASNC) Society of
Nuclear Medicine
Chandigarh, Chandigarh
NUCLEAR CARDIOLOGY
Annual Conference of
Cardiological Society of India
Mumbai
25-29 ANAESTHESIOLOGY
Conference of Indian Society of
Anaesthesiologists
Agra
28-29
28-
Dec 1
INFECTIOUS DISEASES
World Congress on Infectious
Diseases and Antibiotics
Bengaluru
GASTROENTEROLOGY
Annual Conference of Indian
Society of Gastroenterology
(CISG)
Ernakulam
29-30 GENOMICS
Next Generation Sequencing in
Clinical Genomics
Bengaluru
29-
Dec 2
30-
Dec 4
OPHTHALMOLOGY
Conference of Vitreo Retinal
Society
Jaipur
BURN INJURIES
19th Congress of the
International Society for Burn
Injuries (ISBI)
Gurugram, Delhi
DECEMBER
4-7 BIOETHICS
World Congress of Bioethics
(WCB)
New Delhi
5-7 BIOETHICS
World Congress Of Bioethics
(WCB)
Bengaluru
7-8 CLINICAL RESEARCH
SCDM India Conferenc
Hyderabad
6-9 RHEUMATOLOGY
IRACON
Guwahati
13-16 NEUROLOGY
Conference of Neurological
Society of India (NSICON)
Jaipur
NEONATOLOGY
Annual Convention of National
Neonatology Forum (NEOCON)
Varanasi
14-16 GYENAECOLOGY
Annual Congress of Indian
Fertility Society (Fertivision)
Kochi
RADIOLOGY
Annual State Conference of the
TN & PY Chapter of IRIA
Chennai
PEDIATRIC UROLOGY
Asia-Pacific Association Of
Pediatric Urologists Congress
(APAPU)
New Delhi
20-23 NEPHROLOGY
Indian Society of Nephrology
Conference (ISNCON)
Bhubaneswar
26-30 SURGERY
Conference of Association of
Surgeons of India
Chennai
JANUARY
4-6 CLINICAL RESEARCH
Joint International Conference
Ahmedabad
NEUROLOGY
Neuro Updates Conference
Chennai
9-11 MENTAL HEALTH
DYUTI International Symposium
on Evidences in Global Mental
Health
Kakkanad
17-19
VENOUS DISEASES
Vaicon
Hyderabad
17-20 DERMATOLOGY
National Conference of Indian
Association of Dermatologists,
Venereologists & Leprologists
Bengaluru
RADIOLOGY
Annual Conference of the
Indian Radiological and Imaging
Association (IRIA)
Chandigarh
23-26 UROLOGY
Annual National Conference of
The Urological Society of India
Bhubaneswar
24-26 GASTRO-ENTEROLOGY
National Conference on Obesity
and Metabolic Surgery Society
of India
Kolkata
24-27 SURGERY
Annual Conference of The
Asociation of Spine Surgeons of
India (ASSICON)
Ahmedabad
25-27 NEUROSURGERY
International Conference on
Complications in Neurosurgery
(ICCN)
Mumbai
30-31
31-
Feb2
ONCOLOGY
International Conference on
Cancer Rehabilitation (CAN-
REHAB)
Mumbai
CRITICAL CARE
Annual National Conference of
Indian Society of Critical Care
Medicine (CRITICARE)
Mumbai
PSYCHIATRY
Annual National Conference of
Indian Psychiatric Society
Lucknow
The announced dates of the conferences may change
94 / FUTURE MEDICINE / NOVEMBER 2018

ook review
A REBUTTAL TO
VACCINE NAYSAYERS
BETWEEN
HOPE AND FEAR:
A HISTORY OF
VACCINE AND HUMAN
IMMUNITY
By Michael Kinch
Pp 360 Pegasus Books
Gardasil, a vaccine against cervical
cancer, has been under attack for
some time. The concern is not against
its safety. But people think that the vaccine
encourages promiscuous behaviour among
adolescents: “Now that teenagers know they
are not going to get cervical cancer, they’re
going to be more sexually active.” Gardasil is
simply the latest target of vaccine fears.
The hostility to vaccines is as old as
the history of the vaccine itself. Every
introduction of a new vaccine met with some
sort of skepticism throughout the history.
But the most significant question today
is whether the anti-vaccine movement is
gaining ground. One look at social media
will strengthen this suspicion. Anti-vaccine
messages are certainly outperforming those
from pro-vaccinators with a hefty margin. In
a recent report, the CDC found that
the percentage of 2-year-olds who had
received no vaccinations grew to 1.3%
among those born in 2015, up from 0.9% for
those born in 2011. Supporters of vaccination
are starting to lose, despite overwhelming
evidence on the safety and efficacy of the
technique.
The biggest thing is to get access to the
facts. The real facts, not what you see on
Facebook or Twitter, according to Michael
Kinch, the author of the book - Between
Hope and Fear: A History of Vaccine and
Human Immunity.
Tracing the history of vaccines alongside
the history of deadly pathogens and the role
vaccines have played in human history, the
book shines light on the history of vaccine
hostility too.
In his book, Kinch notes that terrifying
ailments that have threatened humanity
since time immemorial are staging a
comeback, often infecting an unwitting
population that assumes they have already
been protected.
Unfortunately, most of the criticism
against the vaccine are centred around the
unfounded notions about the link between
vaccination and autism. Although all these
arguments have been scoffed at with the
backing of sound science and the safety of
vaccines have been repeatedly underscored,
negative sentiments have been winning the
day. Now, these present very real dangers to
ANTI-VACCINE PROPAGANDA
ORIGINATES OFTEN FROM A
RELATIVELY SMALL NUMBER
OF HIGHLY EDUCATED AND
POWERFUL ELITES, AND NOT
FROM THE INNER CITY OR
RURAL COUNTRYSIDE.
our societies and our families.
Most shockingly, anti-vaccine propaganda
originates often from a relatively small
number of highly educated and powerful
elites, and not from the inner city or rural
countryside. The waves of discoveries of
life-saving vaccines are contrasted with an
irrational rejection by fringe elements in the
public.
But Kinch is optimistic that it may not
be a daunting task to dispel the ignorance
of the vaccine naysayers with the objective
evidence showing that other than clean
water, nothing has saved more human lives
than vaccines.
NOVEMBER 2018 / FUTURE MEDICINE / 95

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96 / FUTURE MEDICINE / NOVEMBER 2018

DON’T RESTRICT YOURSELF
TO ‘DOTCOM’ ERA
PROF. BHASKAR D GOOLAB
Professor, Dept. of Obstetrics & Gynaecology, University of Witwatersrand, Johannesburg
One of the serious concerns about the new
generation in our profession is obviously the
increasing tendency to blindly follow modern
clinical procedures. And, when it occurs at the
cost of patient safety and comfort, it is all the more
worrying.
Completely ignoring time-tested conventional
methods, which are often much safer and better in
given circumstances, is not a good practice even in
the ‘dotcom’ era: A small peep into the past is always
rewarding.
It is a general trend of late that many clinical
procedures get over-mechanised in the name of
sophistication and technological “advancements”.
As we all know, many such trends do not often
contribute to a better clinical outcome, but merely
satisfy the of the promotion of the so-called
sophistication.
For instance, in gynaecological surgeries, the
latest trend is to do every procedure endoscopically;
rather, the young doctors learn it that way.
Endoscopy is certainly a big boon to clinicians as it
has made many surgical procedures easy and less
invasive. In certain cases, it is necessary too. But the
flip side is often an unnecessary cost escalation, and
sometimes, the risks associated with electric powered
scissors and other accessories.
Many conventional procedures, like vaginal
surgeries and bikini line incision etc., are proven to
be much safer and less expensive. These procedures
have been in practice for a very long time and often
proved more comfortable for patients too.
So, it is always good to put the patient at the
centre by giving them the choice. Be wise enough
to admit the good and bad of both the old and the
new, and try to adopt a complementary approach,
looking at what is ultimately good for the patient.
And, don’t just be a ‘dotcom’ doctor.
— As told to CH Unnikrishnan
98 / FUTURE MEDICINE / NOVEMBER 2018

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