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FUTUREMEDICINEINDIA.COM 

THE mAb 

ARMOURY 

AS AN ADD-ON THERAPY, BIOLOGICS HAVE OPENED UP 

AN EXCITING FRONT IN SEVERE ASTHMA MEDICINE 

CASE REPORT MEDICAL PRACTICE PULMONOLOGY GENETICS 

AVOIDING AN AORTIC 

CATASTROPHE 

VIOLENCE 

GOES VIRAL 

BRONCHIAL 

THERMOPLASTY 

MANAGING 

THALASSEMIA

editor’s note 

editor’s note 

Dear Doctor, 

May 2019 / Vol. 6 / Issue 1 

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

CH Unnikrishnan 

Executive Editor 

S Harachand 

Science Editor 

Dr Rajanikant Vangala 

Consulting Editors 

Dr Founder Shivanee & Editor Shah 

Jeetha CH Unnikrishnan D’Silva 

Dr 

Executive 

Sumit 

Editor 

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Copy S Harachand Editor 

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Science Editor 

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© 2018 NextGen Science Media Pvt. Ltd, RNI Number KERENG/2012/44529 

This time, let me also invite your attention to a deserving cause in the context 

of a recently held conference of Undiagnosed Diseases Network International 

in Delhi. Dear Doctor The conference re-emphasised the need for more collaborative 

efforts from the clinical as well as the scientific community to investigate 

the We cause know of rare you are diseases. busy. There It is always has been reassuring an increased that the interest trust and among faith the of 

clinician hundreds community, of patients mainly your some healing research touch enthusiastic keeps you geneticists busy in this since noble most 

of these profession. conditions In the are hectic linked practice, to some it’s or quite other natural genetic that disorders, you might collecting miss 

valuable out on data some from of the real-world latest developments experience as well in emerging as dedicated medicine. researches. In this era 

But, of millions innovation, of patients medical suffering science from is getting such diseases redefined are almost still left by untreated the day. Old 

as technologies research hasn’t are yet being culminated replaced in to by development the new in the of blink effective of an treatment eye. Robots 

for and many artificial disorders intelligence or they are are not taking really over accessible a good to part a large of the section procedures, of the 

patient while population. genomics and This molecular should change. science unveil the mysteries of life further. 

Today’s We are need fortunate is for to the have young such and breakthroughs enthusiastic clinicians as they help from specialists across the like 

globe, 

you 

especially 

rise above 

India 

the expectations 

where the disease 

of today’s 

burden 

informed 

is huge, 

patient. 

to dedicate a 

fraction of their time to observe the patients who come with rare symptoms, 

and try to analyse the cause and take it forward with communities like UDNI. 

Similarly, it is also a time when India is witnessing revolutionary growth in 

Perhaps, you yourself can help provide a solution. As Dr I C Verma, the father 

healthcare industry, especially in the private sector, wherein an increasing 

of Indian medical genetics, advises in this edition’s Holy Grail, this is the age 

number of doctors are taking up multiple roles of clinician, researcher and 

of genomic medicine and do spend some time to learn this technology and 

entrepreneur. This requires expansion of your focus to a wider canvas. In 

try to interpret your findings in its light. 

this context, it becomes important how a busy professional like you can 

In many ways, this is applicable to even the age-old and established 

diseases 

keep pace 

as well, 

with 

as 

these 

highlighted 

latest 

in 

developments 

the cover story 

in a 

on 

quick 

asthma 

and 

— 

easy 

a 

way. 

well-recognised medical condition. The story extensively talks about the 

changing At Future concepts Medicine, of asthma which is since conceived recent studies and crafted observed by a that team there of senior is 

no journalists, one universal scientists definition and for doctors, this disease. our aim The is heterogeneity to help you do of just asthma that. We 

prompts are equipped us to look to at bring it more you as the an latest umbrella from term. the science of care from across 

In the Straight world Talk, in an Dr interesting Vijay Chandru, convenient founder of Strand way, supplemented Life Sciences, by calls the for best a 

renewed of views effort and to analyses from India’s the actual masters disease in each burden field. as We the present country you hasn’t this 

understood specialised its knowledge actual patient vehicle population, that plugs not only you into under the rare emerging diseases world but of 

also care widely seamlessly. prevalent Come, cancer-like let’s join afflictions. hands in this information journey. 

Happy CH Unnikrishnan 

reading 

editor@futuremedicineindia.com 

C H Unnikrishnan 

editor@futuremedicineindia.com 

www.futuremedicineindia.com futuremedicineindia FutureMedIndia 

AUGUST 2018/ FUTURE MEDICINE / 3

CASE REPORT MEDICAL PRACTICE PULMONOLOGY GENETICS 

Vol 6 Issue 1 

May 2019 

₹ 250.00 


PAGES 100 

MAY 2019 


THE mAb 

ATTACK 

40 

AS AN ADD-ON THERAPY, BIOLOGICS HAVE OPENED UP 

AN EXCITING FRONT IN SEVERE ASTHMA MEDICINE 

AVOIDING AN AORTIC 

CATASTROPHE 

VIOLENCE 

GOES VIRAL 

BRONCHIAL 

THERMOPLASTY 

MANAGING 

THALASSEMIA 

CASE REPORT 

ROBOTIC 

BYPASS 

REGULAR FEATURES 

06 Letters 

08 News updates 

30 Pulmonology 

32 Drug approvals 

52 Research snippets 

56 Hospital news 

62 Devices&gadgets 

72 Guidelines 

90 Events 

96 Calendar 

98 Holy grail 

Columns 

14 THE CATALYST 

Muralidharan Nair 

48 THE CELLVIEW 

Dr Rajani Kanth Vangala 

60 TRIALOMICS 

Dr Arun Bhatt 

50 

MEDICAL PRACTICE 

VIOLENCE 

GOES VIRAL 

Doctors are the most 

vulnerable when it comes 

to workplace violence 

36 

STRAIGHT TALK 

“WE STILL DON’T 

HAVE A CLEAR 

UNDERSTANDING 

OF THE ACTUAL 

DISEASE BURDEN 

IN INDIA” 

Vijay Chandru

58 

FROM THE INDUSTRY 

“OUR AIM IS TO HELP 

OPHTHALMOLOGISTS TO 

REMAIN STRAIN-FREE” 

12 

GENETICS 

ADVANCES IN 

MANAGING 

THALASSEMIA 

Several promising therapy 

regimens are underway to 

deal with the hereditary 

haemolytic disease 

68 

AMRITA CENTRE 

FOR ROBOTIC 

SURGERY TRAINING 

It’s important that 

we recognize that 

asthma treatment 

is not “one size 

fits all”, 

Andy Nish MD 

Fellow of American 

Academy of Allergy, 

Asthma & 

Immunology, USA 

16 

COVER STORY 

18 

COVER STORY 

UNLOCKING 

ASTHMA: 

MALARIA 

THE mAb WAY 

The emergence of biologics as 

RISEN an add-on therapy AGAIN? 

has opened 

up an exciting front in the new 

Global 

era of 

efforts 

severe 

to 

asthma 

contain 

medicine 

the 

curable disease suffers a 

backlash as cases shoot up in 

several regions

EDUCATION CASE REPORT GENETICS OPHTHALMOLOGY 

letters to the editor 

DIPLOMA TO 

DEGREE 

A DELICATE 

TRANSLOCATION 

GENETIC PATHWAYS 

TO TACKLE 

PLASMODIUM 

Better medium for 

getting updates 

₹ 250.00 


PAGES 100 

APRIL 2019 


MALARIA 

STRIKES BACK 

A STEADY SPURT IN NEW CASES WARNS OF A RESURGENCE 

OF A CURABLE DISEASE FROM NEAR ELIMINATION 

TIP OF AN 

‘EYES’BERG? 

Hello sir, 

I found this magazine from 

our medical college library 

3 months ago. As a medical 

student I am interested 

in knowing new updates 

in medical field and this 

magazine really helps to fulfill 

it. Special thanks to the editor 

for the same. Is there any 

special subscription offer for 

medical students? 

Lakshmi 

Medical Student 

Calicut 

Rich in content 

Dear editor, 

I have gone through the cover 

story regarding the topic 

Malaria published in April 19 

issue. It was very informative 

story and it covered all latest 

updates of the topic. Honestly 

great work by the editorial 

team. 

Dr. Vineeth 

UAE 

To be noticed more 

Hi, 

The article “Starting to forget” 

based on Alzheimer’s in 

February issue was really an 

important topic and it is to be 

delivered to all doctors as well 

as public. Lot of people in our 

society are suffering from this 

disease and not recognizing 

by their beloved people since 

they are considering it as 

geriatric problem. 

Dr. Jacob Mathews 

Hyderabad 

Hats off 

Dear sir, 

Great work by team Future 

Medicine. I just completed 

my reading at a stretch while 

traveling from Mumbai to 

Pune. The articles were fresh, 

catching and interesting. This is 

the a magazine we are looking 

for and hats off guys for the 

same. 

Dr. Hafiz Hamza 

Pune 

Guidance from medical 

experts 

Hi, 

I have been a subscriber of 

Future Medicine for the last 4 

months. The interviews with 

experienced doctors have 

helped me to understand the 

approach they following in 

various medical situations. I 

believe that experience makes 

a doctor an expert in it. Great 

work and keep it up. 

Dr. Praveen 

Kochi 

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news updates 

J&J donates 

10,000 more doses 

of bedaquiline 

to India 

Johnson & Johnson (J&J) 

will be providing an 

additional 10,000 courses of 

bedaquiline free of charge 

to Indian patients through 

US Agency for International 

Development (USAID), for 

a total of 20,000 donated 

courses. 

Earlier, 10, 000 courses 

of the drug to treat multidrug 

resistant TB have been 

supplied through Janssen 

Pharmaceutical Companies, 

J&J in 2016 as part of a 

global donation programme, 

operated in partnership with 

USAID under conditional 

access programme (CAP). 

“Ensuring access to 

bedaquiline in India is a top 

priority for J&J, given the 

country’s high burden of 

MDR-TB,” said Paul Stoffels, 

vice chair of the Executive 

Committee and chief scientific 

officer, Johnson & Johnson, in 

a statement. 

Following this, India 

will be able to procure 

bedaquiline via the Stop TB 

Partnership’s Global Drug 

Facility at J&J’s special-effort 

price of $400, announced in 

July 2018. This price enables 

More drug combos 

under scanner 

India may ban more fixed dose 

combinations (FDCs), currently available 

in the market, which are suspected to be 

`irrational’. 

The Drugs Technical Advisory Board 

(DTAB), which advises the drug regulator on 

safety issues of pharmaceutical products, 

has constituted a sub-committee to 

examine some 150-odd FDCs, reports said. 

The government slapped a ban on 344 

FDCs in 2016 following a report submitted 

by a panel led by Kokate, vice-chancellor of 

KLE University in Karnataka. 

Deliberating on a petition filed by drug 

companies challenging the government’s 

ban, the Supreme Court referred the matter 

to DTAB for a fresh review in December 

2017. The SC asked the board to check 

whether these drugs should continue to be 

sold. 

As per order, an expert panel under 

the chairmanship of Dr Kshirsagar 

reviewed the safety and efficacy of these 

drugs and recommended to continue the 

ban as the FDCs in question had no 

rational basis. 

the company to support 

manufacturing, distribution 

and surveillance programmes 

to safeguard the antibiotic’s 

effectiveness, he added. 

There are an estimated 

135,000 new cases of drugresistant 

TB in India every 

year, and currently less 

than 30% of these patients 

are diagnosed and put on 

an appropriate treatment 

regimen. 

The government of India 

has set the ambitious goal 

of ending TB by 2025, five 

years ahead of the global 

Sustainable Development Goal 

(SDG) target of 2030. 

India to regulate 

OPS as drugs 

India will regulate organ 

preservative solutions (OPS) 

as drugs, according to a new 

official notification. 

The government has 

included Organ Preservative 

Solutions (OPS) to the list of 

notified medical devices placing 

it under the purview of Section 

3 (b) (iv) of the Drugs and 

Cosmetics (D&C) Act 1940 with 

immediate effect. 

Section 3(b) of the Drugs 

and Cosmetics (D&C) Act 1940 

talks about “drugs” as inclusive 

of such devices intended for 

internal or external use in the 

diagnosis, treatment, mitigation 

or prevention of disease or 

disorder in human beings or 

animals. 

8 / FUTURE MEDICINE / May 2019

According to a Gazette 

notification, issued to this 

effect, the government 

specified OPS intended for 

external or internal use in 

human beings as drugs. OPS is 

a crucial medical device that is 

used to supply oxygen and vital 

nutrients to harvested organs, 

thereby increasing their life and 

maintaining their vitality. 

Drug regulator 

slaps safety 

alerts on 

antibiotics 

Drugs Standard Control 

Organisation (CDSCO) 

has ordered drug companies 

manufacturing certain 

commonly used antibiotics to 

carry safety warning on the 

labels of these medicines. 

The drug regulator wanted 

to ensure that this information 

is made available to the 

general public. 

The decision comes 

after the National Coordination 

Centre of 

the Pharmacovigilance 

Programme of India 

(PvPI) sounded caution on 

commonly used antibiotics 

including cefotaxime, ofloxacin 

and cefixime. 

PvPI reported the risk of 

developing Stevens-Johnson 

Syndrome and toxic epidermal 

necrolysis among people 

WARNING 

using the antibiotic ofloxacin. 

Injectable cefotaxime has 

been implicated for causing 

angioedema. 

The PvPI recommended 

that CDSCO take necessary 

steps to incorporate the 

adverse drug reactions in 

the prescribing leaflet of 

these drugs marketed in the 

country, reports said. 

The subject expert 

committee under the 

Drug Controller General 

India (DCGI) examined 

PvPI’s suggestions and 

recommended to incorporate 

safety cautions in its packages 

of all such antibiotics. 

Feeder 

qualification for 

super specialty 

courses revised 

The Medical Council 

of India has revised 

the feeder qualifications 

of six super specialty 

courses. Feeder 

qualification for 2 DM 

(Doctor of Medicine) and 

4 MCh courses (Master of 

Chirurgie) has been revised 

through an amendment 

to the older regulations 

Postgraduate Medical 

Education Regulations, 2000 

and are effective from April 1, 

2019. 

The council has removed 

many other redundant 

qualifications which act as 

prior requirements to various 

DM and MCh courses through 

a gazette notification. 

Following the amendment, 

candidates with MD in 

General Medicine or Radiation 

Oncology can now pursue 

DM (Medical Oncology). The 

prior requirements were MD 

(Medicine), MS (Radiotherapy), 

MD (Paediatrics). For DM 

(Interventional Radiology), 

earlier the feeder qualification 

was stated as MD (Radiology) 

and now the name has 

been changed to MD 

(Radiodiagnosis). 

Similarly, the candidate 

qualified with MS (General 

Foetus over 20 weeks can be aborted to 

save a life: Bombay HC 

Aregistered clinician 

can perform medical 

termination of pregnancy 

(MTP) on a foetus that has 

crossed the legal abortion 

limit of 20 weeks without 

the court’s permission if it is 

deemed necessary to save 

the life of the woman, the 

Bombay high court said in a 

recent ruling. 

The permission for MTP, 

however, still has to be 

sought when a pregnancy 

has exceeded 20 weeks 

and the woman “fears its 

continuation would involve 

grave injury to her physical or 

mental health or where there 

is a substantial risk that if 

the child were born, it would 

suffer from such physical or 

mental abnormalities as to be 

seriously handicapped”. 

In such cases, the 

pregnant woman will have 

to seek permission from the 

high court and unless such 

permission is granted, no 

registered medical practitioner 

can terminate such pregnancy, 

the HC ruled. 

The court directed the 

state government to establish 

medical boards in every 

district to examine pregnant 

women and to furnish reports 

in cases where women 

have approached courts for 

permission after 20 weeks 

of gestation, within three 

months, reports said. 

May 2019 / FUTURE MEDICINE / 9

Surgery) can now go for MCh 

Surgical Oncology. Earlier 

the prior requirements were 

MS (Surgery), MS (ENT), MS 

(Orthopaedics), MD (Obst. 

& Gyn). Surgeons with MS 

(General Surgery) can apply 

for MCh (Head & Neck 

Surgery). Earlier they were 

MS (ENT) or MS (General 

Surgery) or MCh (Plastic & 

Reconstructive Surgery) or 

MCh (Surgical Oncology) or 

MCh (Neuro Surgery). 

Generic eribulin 

launched in India 

Ageneric version of the anticancer 

drug eribulin, which 

is currently marketed under 

the brand name Halaven by 

Eisai Pharmaceuticals, is now 

available in India. 

The generic eribulin will be 

40% cheaper than Halavan, 

said Emcure Pharmaceuticals, 

which launched the cancer 

treatment. 

Eribulin, originally isolated 

halichondrin B from the 

natural Japanese marine 

sponge Halichondria okadai, 

was approved by the US FDA 

on November 15, 2010 for the 

treatment of metastatic breast 

cancer. 

Considered less toxic, 

eribulin is currently used as 

second-line treatment for 

relapsing triple-negative breast 

cancer. Triple-negative breast 

cancer is tough to treat as the 

patients with this sub-type 

are tested negative for all 

the three receptor proteins — 

oestrogen, progesterone as 

well as HER2. 

Eisai won the second 

approval from the US FDA for 

eribulin in January 2016 or the 

treatment of liposarcoma in 

patients who had undergone 

anthracycline-based 

chemotherapy. 

Presently, eribulin is being 

investigated for use in various 

cancers such as non-small cell 

lung cancer, prostate cancer 

and sarcoma. 

Measles cases 

shoot up 

globally: WHO 

Reported cases of measles 

rose by 300 per cent 

Stop Thal to prevent thalassemia 

Kanakia Health Care, 

Mumbai, has created a 

program called STOP THAL 

under the guidance of Dr 

Swati Kanakia, a paediatric 

haemato-oncologist with 

a PhD in Thalassemia from 

Mumbai University. STOP 

THAL, Screening 

for Thalassemia and Opting 

for PREVENTION, is aimed 

at preventing thalassemia 

major cases in an effort 

to reduce the disease 

burden. Dr Kanakia firmly 

believes that the only way 

to reduce thalassemia 

major cases is by 

prevention. 

However, how does 

one suspect thalassemia? 

The “Magic Mantra” for 

considering thalassemia 

minor is low or normal 

hemoglobin, high RBC 

count, microcytosis and 

a normal RDW. This is 

followed up by hemoglobin 

electrophoresis, which 

detects only beta 

thalassemia. If there is 

a strong suspicion of 

thalassemia despite a 

normal Hb electrophoresis, 

mutations for the alpha 

thalassemia gene may be 

carried out to clinch the 

diagnosis. 

Each and every doctor 

can play a pivotal role by 

considering thalassemia 

on a regular CBC report 

done for any reason. 

Dr Kanakia hopes that 

STOP THAL will prove 

to be useful in reducing 

thalassemia major cases. 

The program, available at 

http://kanakiahealthcare. 

com/stopthal/, helps one 

to estimate the chances 

of having a completely 

normal, thalassemia minor, 

or thalassemia major child. 

It will be an important 

asset to increase awareness 

amongst thalassemia 

patients, and doctors may 

use it as an aid for patient 

education. 

in the first three months 

of 2019 compared to the 

same period in 2018, shows 

preliminary global data by 

WHO. 

This follows consecutive 

increases over the past two 

years. 

Measles, a highly 

contagious airborne viral 

infection, can be entirely 

prevented through a twodose 

vaccine. But vaccination 

rates have been slipping in 

recent months. 

Global coverage with 

the first dose of measles 

vaccine has stalled at 85 

percent for several years. 

This is still short of the 95 

percent needed to prevent 

outbreaks, and leaves 

many people in many 

communities at risk. Second 

dose coverage, while 

increasing, stands at 67 

percent. 

“While this data is 

provisional and not yet 

complete, it indicates a 

clear trend. Many countries 

are in the midst of sizeable 

measles outbreaks, with 

all regions of the world 

experiencing sustained rises 

in cases,” WHO said in a 

statement. 

Current outbreaks 

include the Democratic 

Republic of the Congo, 

Ethiopia, Georgia, Kazakhstan, 

Kyrgyzstan, Madagascar, 

Myanmar, Philippines, 

Sudan, Thailand and Ukraine, 

causing many deaths – 

mostly among young 

children. 

Over recent months, 

spikes in case numbers 

have also occurred in 

countries with high overall 

vaccination coverage, 

including the United States 

of America as well as Israel, 

Thailand, and Tunisia. The 

agency noted that only 

about one in 10 actual 

measles cases are reported, 

meaning the early 

trends for 2019 likely 

underestimate the severity 

of the outbreaks. 

10 May 2019

Transvaginal mesh banned in US 

amid safety concerns 

The US Food and Drug 

Administration ordered the 

manufacturers of all remaining 

surgical mesh products 

indicated for the transvaginal 

repair of pelvic organ prolapse 

(POP) to stop selling and 

distributing their products 

immediately. The order is the 

latest in a series of escalating 

safety actions related to 

protecting the health of the 

thousands of women each 

year who undergo surgery 

transvaginally to repair POP. 

The FDA has determined 

that the manufacturers, Boston 

Scientific and Coloplast, have 

not demonstrated a reasonable 

assurance of safety and 

effectiveness for these devices, 

which is the premarket review 

standard that now applies 

to them since the agency 

reclassified them in class III 

(high risk) in 2016. 

As part of the 2016 

reclassification, manufacturers 

were required to submit and 

obtain approval of 

premarket approval (PMA) 

applications, the agency’s 

most stringent device review 

pathway, in order to continue 

marketing their devices in the 

US. 

“In order for these mesh 

devices to stay on the market, 

we determined that we 

needed evidence that they 

worked better than surgery 

without the use of mesh to 

repair POP. That evidence was 

lacking in these premarket 

applications, and we couldn’t 

assure women that these 

devices were safe and effective 

long term,” said Jeffrey Shuren, 

MD, director of the FDA’s Center 

for Devices and Radiological 

Health. 

In 2002, the first mesh 

device for transvaginal repair 

of POP was cleared for use 

as a class II moderate-risk 

device. About 1 in 8 women 

has surgery to repair POP over 

her lifetime, and a subset of 

these surgeries are completed 

transvaginally with the use of 

surgical mesh. 

Two manufacturers 

have been marketing three 

surgical mesh products for 

transvaginal repair of POP. In 

reviewing the PMAs submitted 

by the two manufacturers, 

the agency determined they 

failed to provide an adequate 

assessment of the long-term 

safety of these devices and 

failed to demonstrate an 

acceptable long-term benefit 

of these devices compared 

to transvaginal surgical tissue 

repair without the use of mesh, 

the agency said in a press 

statement. 

InARI signs MoU with NTTE Med 

University on translational research 

The present translational 

research in India will 

not be able to achieve its 

objectives unless important 

changes in education 

and training modules 

are addressed. The T1 

(bench to bedside) and T2 

(bedside to bench) phases 

of translational research 

are complementary and 

need important resources 

— mostly financial — that 

require quality collaborations 

between clinical and 

molecular scientists. It is 

important to note that in 

India, a lot of emphasis was 

given to develop physicianscientists 

(T2) and despite 

all the euphoria, innovations 

in the biomedical field have 

been negligible. The T1 cycle 

that exploits the expertise of 

research scientists outside 

medical institutes like 

universities and academic 

institutions has not been well 

integrated. It is extremely 

important to link molecular 

networks with clinical 

observations to complete 

the T1-T2 cycle. Especially 

in a country as big as ours 

with our low investment in 

research, more emphasis 

must be given to biomedical 

related problems where the 

scientific community works 

in tandem with clinicians. In 

this direction, the Institute 

for Applied Research and 

Innovation (InARI) and NITTE 

Medical University have 

joined hands by signing 

an MoU to create training, 

education and research 

programmes suitable for 

Indian healthcare needs. 

InARI focuses on applied 

research with direct benefits 

to the society and healthcare 

is its top priority. By signing 

this MoU with NITTE Medical 

University, a premier medical 

institute, a new chapter 

has begun in translational 

research for India 

Prof Dr Satheesh Kumar Bhandary (Vice Chancellor of NITTE Medical 

University), Dr Rajani Kanth Vangala (Founder and Managing Trustee 

of InARI), Dr Poornima V (co-founder and trustee – InARI), Dr Suchetha 

Kumari (Head of Research, NITTE Medical University) 


genetics 

ADVANCES IN MANAGING 

THALASSEMIA 

Several promising therapy regimens are underway to deal with the 

hereditary haemolytic disease 

DR RAJANI KANTH VANGALA 

Thalassemia comes from two Greek 

words “Thalassa” and “emia” 

meaning “sea” and “blood”. This 

naming has a unique meaning as the 

disease affects the hemoglobin and 

was described almost 90 years ago 

by Cooley and Lee. Two gene clusters 

controlling haemoglobin synthesis are 

located on chromosome 16 (α-like 

globins) and chromosome 11 (β-like 

globins) in such a manner that they 

are differentially expressed at different 

stages of development like embryonic, 

foetal and adult. This is seen in 

β-globin gene cluster where, ε-gene is 

only expressed in early embryos and 

two γ-genes, which are expressed 

during gestation, are found in foetal 

haemoglobin (Hb F, α2γ2). The δ-gene 

used in diagnosing thalassemias is a 

component of Hb A2 (α2δ2), whereas 

α and β-globins combine to form 

major haemoglobin component Hb 

A (α2β2) carried by adult red blood 

cells. The heritable mutations in α and 

β gene clusters in thalassemias results 

in defective haemoglobin which binds 

to less oxygen and also reduces the 

transport of oxygen. 

There are three types of 

β-thalassemia, based on the β-globin 

chain imbalance and severity of 

anaemia; namely minor, intermedia and 

major. Several mutations have been 

identified and were classified into silent 

— which have no effect, mild — leading 

to a reduction in β-globin production 

levels, and severe — causing a complete 

absence of the β-globin gene product. 

The minor trait or carrier patients have 

heterozygous inheritance of mutations 

and are often clinically asymptomatic. 

Patients with the major trait have severe 

anaemia from infancy and become 

life-long dependents on transfusion. 

However, β –thalassemia intermedia has 

variable anaemia of mild to moderate 

requiring variable transfusions. 

β-thalassemia major and intermedia 

THE CLASSIFICATION 

OF α-THALASSEMIA IS 

DEPENDENT ON HOW THE 

TWO α-GLOBIN GENES ARE 

DELETED OR REDUCED IN 

ACTIVITY DUE TO MUTATIONS 

can be due to several homozygous or 

compound heterozygous inheritances 

of mutations in β-globin gene. Different 

modifications like the extent of 

α-globin to β-globin chain imbalance, 

ineffective erythropoiesis and the 

severity of anaemia cause β-thalessemia 

intermedia, rather than β-thalessemia 

major in most patients. Most frequent 

are mutations in the β-globin 

gene, second are co-inheritance of 

α-thalassemia, higher levels of γ-chains 

of globin and sustained production of 

foetal haemoglobin after infancy. The 

last factor — hereditary persistence of 

foetal haemoglobin — can be due to 

several rare mutations like deletions of 

upstream promoter or regulatory region 

but the presence of an intact gene, 

and the complete deletion of δ-globin 

and β-globin genes. These patients 

have one intact γ-globin gene which 

is called δβ-thalassemia. Some of the 

other complications, such as dominant 

inclusion body β-thalassemia, have a 

triplicated or quadruplicated α-genotype 

along with β-heterozygosity or E/ 

β-thalassemia where β-thalassemia is 

co-inherited with a structural variant of 

hemoglobin E. 

Clinical categories 

The classification of α-thalassemia 

is dependent on how both the α-globin 

genes are deleted or reduced in activity 

due to mutations. The first group of 

α+-thalassemias are of several types, 

but are dominated by –α3.7 and –α4.2 

that correspond to the lengths of 

deletion in the α-globin gene. The other 

α+-thalassemias have several point 

mutations, the most common being 

chain-termination mutant haemoglobin 

Constant Spring called αCSα. The second 

group α0-thalassemias are due to 

deletion of both the α-globin genes (-/- 

), which might occur in heterozygous 

condition with α+-thalassemias (-α/- or 

αCSα/-). The ATR-16 syndrome, which 

involves α-globin gene on chromosome 

16, was shown to be associated 

with mental retardation, also called 

α-thalassemia x-linked intellectual 

disability (ATRX). 

The clinical categorization of 

thalassemias is being simplified based 

on clinical-management criteria. As 

transfusion remains the major form of 


therapy, the patients are divided into 

transfusion-dependent thalassemia 

(TDT) and non-transfusion-dependent 

thalassemia (NTDT). The NTDT may 

still need a transfusion but not at the 

same rate as TDT, primarily for the 

prevention or management of certain 

diseases. Patients with β-thalassemia 

intermedia, haemoglobin H and 

moderate forms of haemoglobin E/βthalassemia 

usually constitute NTDT. The 

TDT patients have β-thalassemia major 

and severe forms of haemoglobin E/βthalassemia. 

Suppressing the abnormal 

erythropoiesis by transfusion can control 

downstream pathological mechanisms 

in thalassemia. Some of the long-term 

follow-up studies which evaluated birth 

cohorts of patients with β-thalassemia 

major found that transfusion along 

with iron-chelation improves survival. 

Transfusion therapy, however, does 

have the risk of secondary-iron overload 

as the human body does not have a 

means to excrete iron. Patients receiving 

2-4 units of blood per month will have 

5,000-10,000 mg of iron per year. This 

leads to more iron than the capacity 

of transferrin, thus causing hepatic 

and extrahepatic tissue damage. The 

extra non transferrin-bound iron also 

can transport into cardiomyocytes, 

hepatocytes, pancreatic β cells and 

anterior pituitary cells, generating 

reactive-oxygen species damaging 

subcellular organelles. 

Controlling iron overload 

The iron overload warrants prompt 

diagnosis in NTDT as it can cause 

substantial morbidity and mortality and 

in patients with TDT, excess iron can 

be seen as early as 2-6 years of age. 

Cardiomyopathy has been observed 

as a leading cause of mortality in 

TDT patients, whereas osteoporosis, 

thrombosis, pulmonary hypertension, 

silent strokes, hypogonadism, 

hypothyroidism and renal diseases 

are strongly associated with NTDT 

iron overload. Of the several methods, 

serum ferritin assessment is commonly 

used to indicate the need for initiation 

of iron-chelation therapy, for example 

in TD. Maintaining concentrations 

lower than 1000µg/L of ferritin leads 

to better-sustained therapy. Serum 

ferritin concentrations above 2500 

µg/L are strongly associated with an 

increased risk of cardiac and other 

diseases. Superconducting Quantum 

Interference Device (SQUID) is one of 

the important technologies to assess 

liver iron concentration, but is not widely 

used. Magnetic Resonance Imaging 

(MRI) has become the best alternative 

for non-invasive liver iron concentration 

evaluation. There are three iron chelators 

currently available for iron overload 

namely deferoxamine, deferasirox and 

deferiprone. 

Traditionally, splenectomy is 

performed as an alternative or as 

an adjunct to transfusion therapy. 

However, it has become obsolete in 

patients with TDT due to potential 

infections, but is used in NTDT. In 

patients with β-thalessemia intermedia, 

there is an increased risk of long-term 

thrombosis along with end-organ 

damage as the spleen also acts as 

a reservoir of toxic iron. Presently, 

splenectomy is recommended only 

for patients who are unable to receive 

transfusion and iron-chelating therapy 

and also have clinical symptoms of 

splenomegaly or hypersplenism. 

One of the best cures available for 

thalassemia with more than 80% 

disease-free survival is the replacement 

of mutant haematopoietic cells with 

haematopoietic stem cells when 

matched sibling donors are available. 

Further improvements in the graftversus-host 

disease and inducing 

graft tolerance have resulted in more 

unrelated donors with overall survival of 

65%. These improvements are showing 

that more novel therapies are in good 

progress and might result in better 

treatment regimes for thalassemia. 

The author is medical scientist and former 

director of SGRF, Bangalore 


column 

the catalyst 

Bridging the trust deficit 

Time for private players to think in tandem with 

policy directions 

MURALIDHARAN NAIR 

The private sector healthcare delivery 

in India has been the bedrock of 

healthcare capability and capacity, 

particularly in the area of high-end 

secondary, tertiary and quaternary care. 

Multi-specialty, corporate hospital chains 

have been the flag bearers of capacity and 

capability growth in high-end care over the 

last decade or more, but they are currently 

struggling with the changing dynamics of 

healthcare business, which is rendering 

traditional business models suboptimal. 

While private sector promoters and investors 

see the changing dynamics characterised 

by increasing focus on affordability as an 

overbearing development, in my view, this 

was imminent, if not long overdue. The 

reason why this was possibly missed by the 

leaders and managers could be traced to the 

key tenets of their belief system. In essence, I 

have observed three, distinct tenets: 

Relative affordability compared to 

international prices: This has been an 

overwhelming influence in the minds of 

leaders of the private healthcare industry 

in India and has been a real deterrent in 

facilitating the requisite focus on affordable 

care in India. I could never understand the 

rationale behind this belief, as it has very 

little practical relevance for the consumer or 

payor for whom the affordability is defined 

by the size of their own pocket not by what 

would have been the relative burden in a 

hypothetical situation of being in a foreign 

land. This has singularly contributed in 

catalysing a self-righteous attitude among 

healthcare managers and leaders, which 

manifested in the use of price increases 

as the key tool for realising commercial 

objectives, instead of focusing on efficiency 

and the evolution of an operating 

model that responds effectively to the 

consumer context. 

Inordinate focus on experience: The quest 

to offer a differentiated experience from 

public healthcare facility is understandable, 

but in the course of time, this has stretched 

beyond a limit, which has not only resulted 

in higher capital and operations cost, but 

has given a perception of insensitivity to the 

large masses of population who were neither 

used to that kind of experience nor were 

seeking it, but had little or no option but to 

avail them in the absence of affordable and 

credible alternatives. In some ways, what is 

perhaps a welcome offering for a minuscule 

percentage of the population with the means 

is being perceived as vulgar compulsion by 

the masses. Barring some extreme exceptions, 

most of the time, the experience factors do 

not contribute as significantly to the overall 

cost of delivery when compared to the 

perception it creates of expenditure that the 

poor consumer perceives as an avoidable 

burden. 

Making healthcare affordable is 

government’s responsibility, not ours: 

This tenet has a rational basis, without doubt, 

and it is also true that the government has 

failed miserably to offer a credible alternative 

through public health delivery systems or 

to facilitate a robust ecosystem for health 

education to ensure adequate supply of 

clinical talent, particularly at the specialist 

level. This has significantly contributed to 

the excessive use of private care as well as 

the high cost of private care. But the irony is 

that the private sector was happy until the 

government started taking responsibility for 

affordable care and is now unhappy when 

it is pursuing the same with great intensity. 

That’s where the private sector erred, in 

assuming that government ownership of 


affordable healthcare will come on its terms, 

with the government playing the role of 

the payor, and will help them expand their 

market without changing their character. In 

reality, government ownership will expand 

the market significantly, but can find its 

sustainability only by changing the economics 

significantly to match its fiscal capacity, given 

the large percentage of needy population 

(approximately 70 percent). 

In conclusion, it is a fact that the vision of 

corporate healthcare chains (and even many 

of the trust hospitals whose commercial 

agenda seem no weaker than those of 

“for profit” healthcare enterprises) for their 

enterprise was not really in tandem with 

the needs of the vast majority of India’s 

population, even though they have played 

a stellar role in providing quality healthcare 

to multitudes of needy customers both rich 

and poor. However, it is equally true that 

government policies should target 

the good of the greatest population 

THE PRIVATE SECTOR WAS HAPPY 

UNTIL THE GOVERNMENT STARTED 

TAKING RESPONSIBILITY FOR 

AFFORDABLE CARE AND IS NOW 

UNHAPPY WHEN IT IS PURSUING 

THE SAME WITH GREAT INTENSITY 

and hence it is imperative that private 

healthcare providers must not waste time 

in defending status quo, but put in all their 

managerial, financial and entrepreneurial 

might to redefine their vision for the future in 

a way that is in harmony with the needs of 

the larger chunks of the population as well 

as the policy direction. This will, in fact, go 

a long way in bridging the significant trust 

deficit that exists between private players 

and policymakers, leading to better mutual 

empathy, and consequently, more effective 

policies, principles and practices for the 

benefit of all. 

The author has long-standing association with 

EY India but the views are strictly personal. 


cover story 

UNLOCKING 


ASTHMA 

THE 

mAb WAY 

The emergence of biologics as an 

add-on therapy has opened up an 

exciting front in the new era of 

severe asthma treatment 

S HARACHAND 

Asthma is a heterogeneous disease, characterised by 

inflammation of the air passages of the lungs. 

World over, an estimated 235 million people suffer 

from asthma, a chronic condition characterised by symptoms 

such as difficulty in breathing, tightness in the chest and 

wheezing. 

Caused by a combination of complex environmental 

and genetic interactions, the underlying mechanisms of this 

airway disorder is yet to be fully figured out. 

Since there is no known cure for the disease, symptoms 

are controlled through therapeutic interventions. 

Corticosteroids, mostly in the inhaled form, is the centerpiece 

of the current treatment to check the inflammatory process. 

Inhaled bronchodilators and/or leukotriene pathway inhibiting 

agents are also added if symptoms remain uncontrolled. 

The drug regimen, comprising inhaled corticosteroids 

(ICS) and long-acting beta agonists (LABA), has been used 

to manage asthma symptoms successfully in most of the 

patients. 

However, 10%–20% of patients do not achieve control 

with the current gold standard of care. This population of 


slug 

Rapidly-expanding suite 

of biologics to reduce 

asthma exacerbations 

Monoclonal antibodies 

(mAbs) are antibodies 

produced artificially through 

genetic engineering and 

related techniques. 

mAbs target various 

proteins that influence cell 

activity, such as receptors or 

other proteins present on 

the surface of normal and 

cancer cells. These biologic 

therapeutics are currently 

used extensively 

to treat cancer, 

cardiovascular 

diseases, 

inflammatory conditions etc. 

Several mAbs have been developed 

to target asthma phenotypes. 

Omalizumab 

Omalizumab is directed against 

immunoglobulin E (IgE). It binds 

circulating IgE, causing decreased IgE 

levels, inhibition of IgE binding with its 

receptors, and downregulation of IgE 

receptors on mast cells, basophils and 

dendritic cells. This results in decreased 

release of inflammatory mediators 

related to the allergic response. 

Omalizumab is the only biologic 

therapy approved for paediatric use in 

children 6 years and older. 

A recent Cochrane review of 

omalizumab use in adults and children 

with asthma found that omalizumab use 

compared with placebo reduced asthma 

exacerbations. 

In the adolescent/adult studies, high 

levels of type 2 inflammatory markers 

such as fractional exhaled nitric 

oxide (FeNO) levels, eosinophilia, 

periostin levels, and IgE 

levels23 have predicted 

severe refractory asthmatics is at increased risk of morbidity 

and mortality, and make up the majority of the economic 

costs of asthma, studies indicate. 

Also, the long-term use of some asthma treatments, 

especially oral steroids, come with noticeable risks. 

Phenotypic pathways 

Search for newer, safer and better treatments for severe 

asthma has opened the door to exploring and identifying 

different types of this disease. 

Over the last decade, specific phenotypes and 

endotypes of asthma have been evaluated, leading to more 

personalised, targeted approaches to fit patient-specific 

disease, abandoning the one-size-fits-all treatments. 

A better understanding of the role of the inflammatory 

modulators involved in asthma paved the way for the 

development of therapies using biologics as a treatment 

option. 

Today, biologic therapies, which are made from 

living organisms using recombinant DNA technology, are 

increasingly being considered in patients with severe asthma. 

People with a severe form of the disease constantly struggle 

with persistent symptoms. This makes it tough for them to 

maintain a good quality of life. 

Traditionally, asthma is classified based on severity. 

Experts today hold that asthma is no longer single disease. 

Rather, it is increasingly recognised as an umbrella term — just 

like cancer or arthritis — for various phenotypes. Finding ways 

to identify subgroups that respond well to different types of 

treatments is a current, critical goal of asthma research. 


improved response to omalizumab. 

A 2003 analysis of pooled clinical 

trial data reported a malignancy risk of 

0.5% in omalizumab-treated patients. 

Ligelizumab 

Currently in development, ligelizumab 

is a humanized anti-IgE monoclonal 

antibody that binds circulating IgE. In 

a phase 1 study, ligelizumab has been 

shown to be more potent at suppressing 

free IgE and IgE bound to mast cells and 

basophils than omalizumab. 

In a phase 2 double-blind parallelgroup 

trial in 37 adults with mild allergic 

asthma, ligelizumab elicited a 3-fold 

greater provocative concentration of 

allergen, causing a 15% decrease in 

FEV1 compared with omalizumab and 

16-fold greater than placebo at 12 

weeks. Ligelizumab was administered 

subcutaneously every 2 weeks. So far, 

no studies have been done in children 

or adolescents, and there is no data on 

phenotypic response. 

Mepolizumab 

Mepolizumab targets IL5, a cytokine 

that promotes both the activation 

and longevity of eosinophils. The 

Mepolizumab as Adjunctive Therapy in 

Patients with Severe Asthma (MENSA) 

study randomised 576 adolescents and 

adults with severe eosinophilic asthma 

found that asthma exacerbations 

requiring oral corticosteroids (OCS) were 

reduced 47% and 53% with IV and SC 

mepolizumab compared with placebo, 

respectively. Asthma exacerbations 

requiring an ED visit were reduced 32% 

and 61% with intravenous (IV) and 

subcutaneous (SC) mepolizumab. 

The 3 randomized controlled trials 

included only patients with eosinophilic 

asthma on the basis that an antibody 

that reduces eosinophil levels would be 

most effective in eosinophilic asthma. 

Mepolizumab has been shown to 

decrease eosinophil counts in both 

serum and sputum. 

There are no studies on children 

above 12 years old, as of now, although 

many studies included adolescents. 

Mepolizumab is approved by USFDA 

as add-on maintenance therapy in 

patients who are 12 years and older 

with eosinophilic asthma. 

Reslizumab 

Two randomised, double-blind, placebocontrolled 

trials (RDBPCT) have been 

conducted on reslizumab in adolescents 

and adults with eosinophilic asthma. 

A phase 3 trial of 374 adolescents 

and adults aged 12–75 years with 

inadequately controlled eosinophilic 

asthma. This study noted improved 

asthma control compared with placebo. 

However, the quality of life measure 

trended to improve in the 0.3mg/ 

kg dose of reslizumab but was only 

significant for the higher dose. 

Two duplicate RDBPCTs (phase 

3) in adolescents and adults with 

uncontrolled eosinophilic asthma with 

serum eosinophils =400 cells/µL on 

medium-to-high dose ICS therapy 

noted a significant reduction in asthma 

exacerbation frequency as well as 

improvements in time to exacerbation, 

asthma control, and quality of life 

As with mepolizumab, the presence 

of eosinophilia as a biomarker for 

reslizumab efficacy was demonstrated 

in an RDBPCT of reslizumab in adult 

asthmatics, which demonstrated no 

clinically significant effect on either lung 

function or symptom control in patients 

unselected for baseline eosinophil levels. 

Reslizumab has been shown to 

decrease blood eosinophil counts, 

but studies are not available to show 

differentiation between responders and 

One of these phenotypic pathways is thought to be type 2 

pathway — T helper 2 (Th2). About half of the individuals with 

severe asthma exhibit the type 2 phenotype, with increase in 

Th2 cells. There is an increase in the number of CD4+ T cells, 

predominantly TH2 cells, in the airways of asthmatic patients, 

whereas in normal airways, TH1 cells predominate. TH2 cells 

have a central role in asthmatic inflammation. Also called the 

“atopic” pathway, it refers to a hypersensitive reaction to an 

allergen. Patients with typ2 phenotype release cytokines such 

as interleukin [IL]-4, IL-5, IL-13, which drive immunoglobulin E 

(IgE) production. 

Targeting the cause 

The majority of asthma patients are also allergic. IgE, the 

antibody intimately involved in allergic responses, is the target 

of omalizumab, the first approved monoclonal antibody 

treatment for asthma. 

“Since omalizumab was first introduced to the United 

States market in 2003, it, and other more recent biologics 

for asthma, have made a tremendous difference in the lives 

of many asthmatics. Their impact can be likened to the 

introduction of the combination of inhaled steroids and longacting 

beta agonists in the 1990s, which allowed a number 

of asthmatics to attain greater control of their asthma and a 

number of severe asthmatics to get off of systemic steroids,” 

says Dr Andy Nish, MD Fellow of American Academy of 

Allergy, Asthma & Immunology (FAAAAI), USA. 

The asthma biologic drug research pipeline today contains 

12% monoclonal and 17% non-monoclonal antibodies. 

Some groups of white blood cells, such as eosinophils, 


slug 

nonresponders in the magnitude of 

reduction in blood eosinophils. 

Reslizumab is USFDA approved for 

add-on therapy in adults aged 18 and 

older with eosinophilic asthma. 

Benralizumab 

An RDBPCT of 369 adults with severe 

asthma requiring oral steroid therapy 

use noted that benralizumab use of 30 

mg SC either every 4 weeks or every 

8 weeks reduced median final oral 

glucocorticoid dose from baseline by 

75%, compared with a 25% reduction 

in the placebo group. Benralizumab 

use reduced the annual exacerbation 

rate by 55% versus placebo when 

administered every 4 weeks and by 70% 

when administered every 8 weeks. No 

significant effect on forced respiratory 

volume 1 (FEV1) was noted. 

Increased blood eosinophil levels 

of more than 300 cells/µL have 

been identified in some studies as a 

biomarker of benralizumab efficacy. 

However, a pooled analysis of SIROCCO 

and CALIMA study data supported the 

use of benralizumab in patients with 

blood eosinophil counts =150 cells/ 

µL73 and a newly released subsequent 

pooled analyses extended the efficacy 

irrespective of eosinophil count, 

although noting that the higher the 

eosinophil count the greater the benefit. 

Benralizumab is FDA approved 

for patients with severe asthma aged 

12 years and above, who have an 

eosinophilic phenotype. 

Dupilumab 

Dupilumab is a human monoclonal 

antibody to the alpha subunit of the IL4 

receptor, thereby blocking the activity of 

IL4 and IL13. Dupilumab is the only drug 

approved for self-administration. 

The IL4 cytokine is an essential 

cytokine to T helper 2 (Th2) cell 

polarization, whereas the IL13 cytokine 

is associated with periostin production 

in the bronchial epithelial cells, 

ultimately resulting in smooth muscle 

contraction, mucous production, airway 

remodeling and hyper-responsiveness. 

IL13 also works with IL4 to result in IgE 

production. 

An RDBPCT of dupilumab use in 

104 adults aged between 18 and 65 

years with moderate-to-severe 

asthma and high blood or sputum 

eosinophil counts above 300 cells/ 

µL and 3% respectively on mediumto-high 

dose ICS plus LABAs resulted 

in an 87% reduction in asthma 

exacerbations and increased time to 

asthma exacerbation despite stopping 

LABA and ICS therapy while on 

dupilumab compared with placebo. 

There was noted improvement in 

FEV1 as early as the second week 

of treatment, which was maintained 

for the 12 weeks of the study. An 

RDBPCT of dupilumab using 300mg 

SC every 2 weeks for 24 weeks in 210 

adults with OCS-dependent asthma 

noted a 59% decrease in severe 

exacerbations in the dupilumab group 

despite a -70.1% reduction in OCS. 

An RDBPCT of 1902 adolescents 

and adults with uncontrolled asthma 

noted that dupilumab reduced severe 

exacerbations by 47.7% compared 

with placebo while increasing FEV1. 

Dupilumab has been shown to 

reduce FeNO levels and other levels 

of Th2 inflammation including TARC, 

eotaxin-3, and IgE. 

Dupilumab has been approved by 

US FDA for adolescents and adults aged 

12 years and older with moderate-to- 

are found to be critically involved in the inflammatory process 

in the airways that results in the loss of lung function in 

asthma. Several products have been developed to inhibit 

the production, the function, and the survival of eosinophils. 

These antibodies seem to work particularly well in individuals 

with high eosinophil counts prior to treatment and who 

have not responded to current treatment with inhaled 

corticosteroids. Collectively, these products are well tolerated 

and are effective in reducing eosinophil numbers and 

preventing asthma exacerbations. 

Multiple antibodies seek to tackle cytokines, which are 

key in fuelling allergic-type responses and inflammation. But 

the therapeutic agents that single out individual cytokines 

for targeting proved to be largely ineffective due to the 

overlapping effects of cellular signalling proteins. However, 

antibodies blocking the effect of more than one cytokine have 

shown promise. 

Mepolizumab, reslizumab, and benralizumab are targeted 

towards IL5, a cytokine that promotes both the activation and 

longevity of eosinophils. Dupilumab is an anti-IL4 cytokine 

antibody which is essential for Th2 cell polarization. Whereas, 

biologic tralokinumab, that targets IL13 cytokine, is currently 

under phase 2 development. IL13 is associated with periostin 

production in the bronchial epithelial cells, ultimately resulting 

in smooth muscle contraction, mucous production, airway 

remodelling and hyper-responsiveness. 

Today, clinicians have more than 10 years of clinical 

experience with IgE targeting omalizumab and extensive trial 

data with anti-eosinophil antibody mepolizumab. Unlike for 

most drugs, outcomes in clinics with omalizumab have often 


severe asthma as add-on maintenance 

therapy. 

Lebrikizumab 

Lebrikizumab is a humanized 

monoclonal antibody against IL13. IL13 

also works with IL4 to result in IgE 

production. The IL4 receptor (alpha 

subunit) is critical for both IL4 and IL13 

signal transduction. 

A phase 2 RDBPCT of lebrikizumab 

using 250 mg dosage strength SC once 

a month in 219 adults with asthma 

uncontrolled on medium-to-high 

dose ICS therapy noted a significant 

improvement in FEV1 after 12 weeks of 

lebrikizumab (5.5% points higher than 

placebo) although no significant change 

was noted in several other secondary 

efficacy outcomes including asthma 

control. 

Another phase 2 RDBPCT of 212 

adults aged 18–65 years not receiving 

ICS therapy noted no significant 

improvement in FEV1 with multiple 

different doses of lebrikizumab 

compared with placebo even with 

stratification based on periostin levels, 

although there was a reduced risk of 

treatment failure in all lebrikizumab dose 

groups. 

Periostin levels have emerged from 

the mentioned studies as a biomarker 

strongly correlated with lebrikizumab 

efficacy. Lebrikizumab has been 

associated with a decrease in FeNO, 

with greater reductions in FeNO in the 

high periostin groups. 

There are a small number of studies 

thus far that are limited to the adult 

population 

Tralokinumab 

Tralokinumab targets IL13. A phase 

2 RDBPCT of multiple doses of 

tralokinumab in 194 adults aged 18–65 

years with moderate-to-severe asthma 

noted no significant improvement in 

control with tralokinumab although 

there was a significant decrease in betaagonist 

use. 

A phase 2 RDBPCT of tralokinumab 

in 452 adults with severe uncontrolled 

asthma noted that tralokinumab use of 

300 mg SC every 2 or 4 weeks did not 

result in significant percentage change 

in annual asthma exacerbation rates. 

Prebronchodilator FEV1 was significantly 

increased in the tralokinumab every 2 

weeks group compared with placebo 

but not in the tralokinumab every 

4 weeks group. Subgroup analysis 

identified adults with a high baseline 

serum dipeptidyl peptidase-4, or high 

serum periostin levels had improved 

FEV1, asthma control and exacerbation 

rates. 

Tezepelumab 

Tezepelumab is a human anti-TSLP 

monoclonal immunoglobulin that 

prevents binding of TSLP with its 

receptor, preventing TSLP-initiated 

inflammatory responses through the 

activation of dendritic cells and mast 

cells. There has only been one proofof-concept 

RDBPCT of tezepelumab 

in 31 adults with allergic asthma that 

noted attenuation of both the early and 

late asthmatic responses, with a 45.9% 

smaller decrease in FEV1 during the 

late phase response after 12 weeks of 

treatment. 

A phase 2 RDBPCT of tezepelumab 

in adults with uncontrolled asthma 

despite medium-to-high ICS and 

LABA therapy noted significant 

reductions in exacerbation rates with 

tezepelumab, independent of baseline 

serum eosinophil levels, as well as an 

improvement in FEV1. No studies have 

been done in the paediatric population, 

the biomarker profile of those most likely 

to respond remains unknown. 

Many small molecule drugs are also 

showing great promise. 

been better than those seen in clinical 

trials. It is considered a surprising feature of 

omalizumab in clinical practice. 

Rising incidence; dearth of biomarkers 

Estimates show that the incidence of 

asthma may have increased as much as 

12% over the past decade. Several theories 

postulate as to why the incidence of asthma 

is on the rise. 

First, asthma is more recognized and 

coded as such, as opposed to in the past, 

when it may have been diagnosed using 

terms such as bronchitis, explains Dr Nish. 

According to him, allergic diseases, in 

ESTIMATES SHOW 

THAT THE INCIDENCE 

OF ASTHMA MAY HAVE 

INCREASED AS MUCH 

AS 12% OVER THE PAST 

DECADE 

general, have been increasing; not only 

asthma, but also allergic rhinitis, food 

allergy and atopic dermatitis. “One theory 

is called the hygiene hypothesis, that 

our lymphocytes no longer have to fight 

infection as much as in the past, so they are 

becoming more Th2 cells and producing 

allergic disease,” he remarks. 

Air pollution has been linked to 

increased incidence of asthma in children, 

as has exposure to cigarette smoke, 

particularly if the mother smokes while 

pregnant. In addition, if a child’s diet is 

leading to obesity, it can be associated with 

an increased risk of asthma. Caesarean 


irths change gut flora and increase the risk of asthma too. 

So, the rise in asthma is likely multifactorial. 

Even though biologic therapies allow the selection of 

patients suitable for intervention with antibody infusions, 

defining a set of predictive and monitoring biomarkers 

to assess the likelihood of a patient who will respond to 

a biologic continues to be a challenge. It is also difficult 

to determine whether there is a favourable response to 

continuing the biologic. Biomarkers, which will provide a 

profile of those patients most likely to respond favourably and 

also to discontinue medication if there is a low likelihood of a 

response, are yet to be a reality. It took several years to define 

the subgroup of patients with severe asthma who respond to 

anti-IL-5 treatment. 

The concept of subtypes of asthma is new and clinically 

still evolving. Much has been made of endotypes, with many 

different pathways described as potentially contributing to 

the asthma phenotype. There has been much debate about 

type 2 (IgE and eosinophilia driven by IL-4, IL-5 and IL-13) and 

non-type 2 asthma. The RASP-UK study, adjusting therapy 

according to type 2 biomarkers, exhaled nitric oxide, blood 

eosinophils and serum periostin (an IL-13 induced epithelial 

“We recognize 

that asthma 

treatment is not 

‘one size fits all’” 

Andy Nish, MD is Fellow of American 

Academy of Allergy, Asthma & 

Immunology (FAAAAI) and the President 

of Northeast Georgia Physicians Group 

(NGPG) — Allergy and Asthma, GA. Dr Nish 

talks about the impact of biologics therapy 

in asthma, as well as the other advances 

in better defining and managing the 

chronic airway inflammatory disease. Edited 

excerpts: 

Nearly half a dozen biologics are now 

approved to treat asthma. And many more 

are under development. Can biologics 

eventually replace the current line of 

steroid-centred management of the 

symptoms and offer a lasting solution, if 

not a permanent cure, for the disease? 

Biologics have made a tremendous 

difference in the lives of many asthmatics. 

However, it is unlikely that the biologics 

will be able to completely replace current 

asthma therapies. For one, the biologics 

target a specific pathway which provides a 

narrower therapeutic efficacy than current 

standard therapies. And asthmatics in the 

intermittent, mild persistent and moderate 

persistent categories can typically be 

controlled with currently available therapies 

with a very acceptable risk to benefit 

ratio. In addition, the current costs of 

manufacturing the biologics make them 

cost-prohibitive to be used broadly. 

Unfortunately, the currently available 

biologics have not been shown to have 

disease-modifying properties for asthma. 

Studies have shown that asthma returns 

to its previous state of inflammation and 

pathology over time once the biologics are 

stopped. 

So, it’s unlikely that biologics, as we 

currently know them, can function as 


monotherapy for asthma or produce a 

cure, but then twenty years ago who 

could have known of the advances we 

have available today. 

Apart from monoclonals, what are 

the other approaches using biologics, 

currently being explored to address 

asthma? 

Despite the advances and benefits 

of currently available biologics, which 

are genetically engineered proteins, 

continued improvement is welcomed 

and there are definitely holes in our 

treatment choices. For the Th17 (non 

T2) type asthmatic, there are currently 

no highly effective biologics. Whereas 

currently 98% of all asthma treatment 

is small particle, the research pipeline 

contains 12% monoclonal and 17% 

non-monoclonal antibodies. 

The incidence of asthma is on 

the rise the world over despite 

wider availability of effective and 

comparatively less costly medicines 

to control the attacks. Why? 

It is estimated that asthma may 

have increased as much as 12% over 

the past decade. There are a number 

of theories as to why the incidence 

of asthma is on the rise. In reality, it is 

probable that a number of these are 

contributing. 

First, it is suggested that asthma is 

more recognized and coded as such. 

Allergic disease, in general, has 

been increasing, not only asthma 

but also allergic rhinitis, food allergy, 

and atopic dermatitis. One theory is 

called the hygiene hypothesis, that our 

lymphocytes no longer have to fight 

infection as much as in the past, so 

they are becoming more Th2 cells and 

producing allergic disease. 

Air pollution has been linked to 

increased incidence of asthma in 

children, as has exposure to cigarette 

smoke, particularly if the mother 

smokes while pregnant. In addition, if 

a child’s diet is leading to obesity and 

overweight, it can be associated with 

an increased risk of asthma. Birth by 

It’s unlikely that biologics, 

as we currently know 

them, can function as 

monotherapy for asthma or 

produce a cure. 

Andy Nish MD 

Fellow of American Academy of 

Allergy, Asthma & Immunology, USA 

c-section changes the gut flora and 

increases the risk of asthma also. 

So, the rise in asthma is likely 

multifactorial, but the good news is 

that we do have more and better 

asthma medicines to use over time. 

Some of the experts in the field 

argue that the term “asthma” 

needs to be redefined, giving more 

emphasis on the heterogeneity of 

the disease. What is your comment? 

I definitely agree with this concept. 

As we have learned particularly 

in recent years, there is so much 

heterogeneity in the pathology of 

asthma and the inflammation thereof 

and response to treatment. 

The more medicines that have been 

developed, the more we learn about 

which patients do or don’t respond to 

particular of those medicines, and 

then research helps to delineate why 

that is. 

Some patients are primarily T2 

driven and some primarily Th17 driven. 

Some are primarily eosinophil driven 

and some primarily neutrophils. Some 

asthmatics respond dramatically to very 

small doses of inhaled corticosteroids 

and some respond minimally to 

very high doses of inhaled or even 

systemic steroids. It’s important that we 

recognize that asthma treatment is not 

“one size fits all”. 

Are corticosteroids being 

overprescribed for managing 

asthma? 

If the question is in regard to 

inhaled steroids, I would suggest 

that the answer is no. It may even be 

that inhaled steroids are not being 

prescribed often enough, partly 

because of steroid phobia, particularly 

on the part of parents. Other studies 

have suggested that asthma is 

underdiagnosed in general and the 

severity is underappreciated. 

It is recommended by experts 

that the drug of choice for the firstline 

treatment of mild, moderate 

and severe persistent asthma is 

inhaled steroids, of course with other 

medicines as needed as severity 

increases. 

We have good evidence from 

longitudinal studies that, if inhaled 

steroids affect children’s final adult 

height, it is a minimal effect and that 

other potential side effects, in general, 

present a favourable risk to benefit 

ratio. It is worth pointing out that 

inhaled steroids are in microgram 

doses and systemic steroids, if needed 

for an asthma flare, are in milligram 

doses, or 1000 times stronger. 

It is important to note that 

objective measures, such as 

pulmonary function tests, should be 

used to make sure that treatment is 

effective, and at the lowest possible 

dose for the fewest side effects. 


protein), should help define which patients have controlled 

type 2 disease, and which have a non-type 2 mechanism 

driving their symptoms. 

The outlook for severe non-allergic asthma, however, is 

less rosy at present. This is because a lot of efforts have been 

devoted to finding effective drugs for severe allergic asthma, 

but severe non-allergic asthma has not been the focus of 

as much research. This is an area where more research is 

urgently needed, believes leading organisations like Asthma 

UK. 

But many researchers are still uncertain about the 

existence of non-type 2 asthma in the severe asthma 

population. 

“For the Th17 (non T2) type asthmatic, there are currently 

no highly effective biologics,” points out Dr Nish. 

Clinical trials should inform on the role of biomarkers 

in determining treatment response. Benefits of anti- 

IL-5 approaches with mepolizumab, reslizumab and 

benralizumab, and dupilumab (anti-IL4/IL-13) have been 

documented by large clinical trials. Phase III studies of 

lebrikizumab (anti-IL-13) did not show significant clinical 

benefit compared to placebo. The lebrikizumab phase 3 

studies did not enrich for exacerbations. 

Efficacy in children — Expanding evidence 

Asthma in childhood is quite different from asthma in 

adulthood. Phenotypically, paediatric asthma is more 

commonly allergic in nature. Likewise, the prevalence of 

asthma is higher in male children, whereas adult females 

have more severe and persistent disease. Hence, results 

from adult studies may not be extrapolated to the paediatric 

population. Evidence is expanding for biologic therapies 

such as omalizumab in children, despite the fact that 

evidence is limited for most of these drugs in the case of 

adult-onset asthma. 

Omalizumab is now approved up to 6 years of age in 

some countries. This makes it the first choice for children 

with severe asthma if the serum IgE is within limits. 

Mepolizumab and benralizumab, the anti-IL5 therapies, are 

available for use in some countries for adolescents of 12 

years of age. The treatment is likely to reduce exacerbations 

in cases where the blood eosinophil count is more than 300 

cells/µL and perhaps 150 cells/µL. Dupilimab, which has 

been found not having significant adverse effects in adult 

studies, is being considered for home administration. 

Adjunctives for uncontrolled asthma 

Omalizumab and anti-IL5 medications are currently 

included for use in patients with severe asthma, including 

children and adolescents, by several international asthma 

guidelines. The National Heart, Lung and Blood Institute’s 

Expert Panel 3 (NHLBI EPR3) guideline recommends the 

use of omalizumab as adjunctive therapy in patients above 

12 years who have atopic, severe and persistent asthma 

NOVEL BIOLOGIC AND SMALL MOLECULAR THERAPIES 

IN ASTHMA 

MEDICATION 

Omalizumab 

Ligelizumab 

Mepolizumab 

Reslizumab 

Benralizumab 

Dupilumab 

Lebrikizumab 

Tralokinumab 

Tezepelumab 

Fevipiprant 

MECHANISM OF 

ACTION 

Binds circulating 

IgE—↓IgE levels, 

downregulation of IgE 

receptors on mast cells, 

basophils, and dendritic 

cells. 

Binds circulating 

IgE—↓IgE levels, 

downregulation of IgE 

receptors on mast cells, 

basophils, dendritic cells. 

Binds IL5, which recruits 

eosinophils from the 

bone marrow and 

promotes activation and 

longevity of eosinophils 

Binds IL5, which recruits 

eosinophils from the 

bone marrow and 

promotes activation and 

longevity of eosinophils 

Binds IL5 receptor, 

preventing binding of 

IL5 

Blocks activity of IL4 

and IL13 

Binds IL13, thereby 

blocking its activity 

Binds IL13, thereby 

blocking its activity 

Prevents binding of 

TSLP with its receptor, 

preventing TSLPinitiated 

inflammatory 

response through 

activation of dendritic 

cells and mast cells 

Antagonist to CRTh2, 

which is a PGD2 

receptor that mediates 

inflammatory effects 

through production of 

mast cells and other 

allergic cells 

MODE OF 

ADMINISTRATION 

SC every 2–4 

weeks based on 

body weight and 

serum IgE level 

SC every 2 weeks 


IV every 4 weeks 

SC every 4 or 8 

weeks 

SC every 2 week 


SC every 2–4 

weeks 

IV every 2–4 weeks 

Orally once a day 

inadequately controlled with high-dose ICS and LABA 

therapy. 

The Global Initiative for Asthma (GINA) 2017 update 

recommends phenotype-guided add-on treatment with 

omalizumab in patients above 6 years with severe allergic 

asthma with elevated IgE, and mepolizumab or reslizumab 

in patients above 12 years with eosinophilic asthma as step 


CALCILYTICS OFFER A 

NEW LINE OF ASTHMA 

THERAPY 

Researchers at the MRC-Asthma UK 

Centre in Allergic Mechanisms of 

Asthma and Cardiff University found 

that people with asthma have more of a 

special type of calcium receptor in their 

lungs than people without asthma. 

Called calcium-sensing receptors or 

CaSR, they sit on the surface of a cell, 

respond to chemicals in the environment 

such as pollutants or allergens that trigger 

asthma. 

The scientists later found that a class 

of drugs called calcilytics can inhibit 

CaSRs. 

‘Calcilytic’ drugs can reverse or abolish 

twitchiness of the airways which are 

responsible for the symptoms of asthma, 

say researchers. 

Existing drugs, such as preventer 

inhalers, address this problem only 

indirectly, by reducing the inflammation 

of the airways which is thought to be one 

of the triggers for this twitchiness, while 

reliever inhalers make the muscle cells 

relax, temporarily alleviating the blockage. 

By using calcilytic drugs, the cause of 

the twitchiness can be directly targeted, 

instead of working on the reaction, 

regardless of what has caused it. It can 

thus treat all asthma. 

The challenge now is to develop a 

form of these drugs which can be inhaled 

safely to the airways and then explore 

their effects in people with asthma. 

The next logical step will be clinical 

trials to see if the drugs work. 

4 (medium dose ICS +LABA) therapy. 

The Canadian Thoracic Society (CTS) recommends 

omalizumab in patients above 6 years with severe asthma 

that is inadequately controlled on high dose ICS and at least 

1 other controller, sensitization to more than 1 perennial 

aeroallergen, and serum IgE levels between 30 and 1,300 

IU/mL (6–11 years) or 30–700 IU/mL in patients above 12 


years. The CTS also recommends anti-IL5 therapies in adults 

with severe eosinophilic corticosteroid-dependent asthma 

in an attempt to decrease or withdraw oral corticosteroids 

(OCS). 

Benefits ‘at best Incremental’ 

Omalizumab, mepolizumab, reslizumab, benralizumab, 

and dupilumab are currently the five US FDA-approved 

monoclonal antibodies that affect the pathways involved 

in either allergic or type 2 inflammatory phenotypes of 

asthma. Presently, there are no head to head randomized 

or observational trials to study the comparative clinical 

effectiveness of these mAbs. Estimates from Cochrane 

meta-analyses showed that all five drugs reduced the 

annual exacerbation rate by about 50% with overlapping 

confidence intervals. The average improvement for four of 

the drugs, compared with a placebo, is modest and none 

of them reach the minimally important difference, although 

all were statistically significant. Dupilumab had the largest 

reduction in exacerbations and benralizumab the smallest, 

according to a meta-analysis by the Institute for Clinical 

and Economic Review (ICER), an independent nonprofit 

research organisation. The risk for serious 

adverse events was low for all five drugs. The only 

consistent and common adverse event was 

injection-site reactions. The dosing schedule 

varies between the drugs. Dupilumab is 

given every two weeks, omalizumab is given 

every two to four weeks, mepolizumab and 

reslizumab are given every four weeks, and after the first 

three doses, benralizumab is given every eight weeks. 

Notably, none of the drugs prevented most 

exacerbations requiring systemic corticosteroids or improved 

average daily quality of life to a degree considered clinically 

significant. Thus, the overall health benefit for all five drugs 

is at best incremental, notes ICER report. 

“Unfortunately, the currently available biologics have 

not been shown to have disease-modifying properties for 

asthma,” comments Dr Nish, who is also the President of 

Northeast Georgia Physicians Group (NGPG) — Allergy and 

Asthma, GA. Studies have shown that asthma returns to 

its previous state of inflammation and pathology over time 

once the biologics are stopped, he adds. 

The long-term safety and effectiveness of these 

drugs, however, is yet to be established particularly in 

older patients. For omalizumab and mepolizumab, longterm 

extension trials and real-world experience provide 

supportive but uncontrolled evidence. Response to therapy 

is yet to be well-defined to help guide patients and 

clinicians in deciding when to stop one therapy and consider 

switching to another. 

At what cost? 

Biologics comes with high treatment costs. Analysis indicate 

that biologic agents provide gains in quality-adjusted 

survival over the standard of care alone. Exacerbation 

reductions and chronic oral steroid reductions are 

potentially the most influential benefit associated with 

biologic therapy. 

A survey by the Asthma and Allergy Foundation of 

America involving 805 Americans living with asthma, 

including 185 with severe, uncontrolled asthma, found that 

an average of 82% chose effectiveness as a key criterion 

while an average of 52% cited cost as a key criterion for 

selecting a therapy. 

Patients report that their asthma prevents them from 

living the life that they want to live, besides impacting their 

loved ones. They also fear the side effects of corticosteroids 

and want to minimize the use of both systemic and inhaled 

corticosteroids as much as possible. 


Looking for loci 

Asthma is a multifactorial 

disease with a complex genetic 

inheritance. Collective evidence 

suggests that genetic factors account 

for approximately 60–80% of its 

susceptibility. More than a hundred 

genetic variations positioned 

throughout the genome have been 

implicated in asthma susceptibility. 

However, studies could replicate only 

a subset of these genes. Besides, the 

exact mechanism of the interaction of 

these genotypes with the environment 

is not clearly understood. 

The incidence of asthma, which 

is the highest in childhood, tends to 

show a bias towards boys. While boys 

are at a higher risk of asthma in early 

childhood, girls are more frequently 

affected after puberty. Hypersensitivity 

to aeroallergens is the key feature 

of childhood-onset asthma. Atopic 

dermatitis and hay fever are closely 

associated with asthma, constituting 

what is known as the atopic triad. 

Genetic factors determining the 

age of onset of asthma has been 

traced to diverse chromosomal loci. 

Two regions — 5q13 and 1p31 — with a 

suggestive linkage to time of onset of 

asthma, have been specifically identified 

in French families. Also, a region on 

7q was found linked to asthma in the 

same population, but with different 

risks. The -28G allele of the RANTES 

promoter region at chromosome 17q 

increased the risk of late-onset asthma 

in Japanese individuals 

A genome-wide association (GWA) 

study revealed that the 17q12-21 region 

(IKZF3-ZPBP2-GSDMB-ORMDL3 region) 

IN SPITE OF THE HIGH 

HERITABILITY OF ASTHMA 

SUSCEPTIBILITY, GENETIC 

FACTORS ACCOUNT FOR 

ONLY AROUND 35% 

OF THE VARIATION IN 

THE AGE AT ONSET 

is predominantly a locus of childhoodonset 

asthma. Despite these findings, 

it is not clear whether sex differences 

in asthma risk at different ages can be 

explained by genetic factors. 

Molecular genetic studies suggest 

an association of a variant on 

chromosome 5, situated within the 

TSLP gene, among patients with severe 

asthma. Similarly, polymorphisms within 

the beta2-adrenergic receptor gene, 

the IL-4 gene and the TGF-ß1 and CD14 

genes have been shown to play a role 

in asthma severity. 

Positional cloning identified five 

asthma genes or gene complexes, 

including ADAM33, PHF11, DPP10, GRPA 

and SPlNK5. Though the functions of 

these genes are largely obscure, the 

expression of DPP10, GRPA and SPlNK5 

in terminally differentiating epithelium 

suggests that they respond to the 

external environment. 

Many of the genes identified by 

candidate gene studies, including lL13 

that modifies mucous production, FccRl- 

/J which modifies an allergic trigger 

on mast cells, and microbial pattern 

recognition receptors of the innate 

immune system, may also exert their 

effects within the cells that make up the 

mucosa. 

There is also evidence of genetic 

heterogeneity within the clinical 

expression of asthma. In spite of the 

high heritability of asthma susceptibility, 

genetic factors account for only around 

35% of the variation in the age at onset 

and for around 25% of the variation 

in the overall symptomatic severity of 

the disease and for even less of the 

variation in the severity of individual 

asthma symptoms such as wheezing, 

shortness of breath, chest tightness and 

cough, according to studies. 

Given the high cost of these therapies, GINA 

recommends the use of biologics in patients whose 

asthma is refractory or relatively refractory to 

conventional inhaled therapies. 

Biologics are also indicated for eosinophilic 

asthma. Eosinophils are part of the immune 

response to parasitic infections. It is unknown if the 

therapies that decrease eosinophil counts will affect 

patients’ ability to fight such infections. Current 

guidelines recommend that physicians treat patients for 

existing parasitic infections prior to initiating anti IL-5 

therapy. 

Researchers call for designing a large, pragmatic trial 

comparing all available drugs in order to clarify whether 

or not there are clinically important differences between 

the drugs. 


ASTHMA ALERT 

Asthma is increasing in many parts of the world, 

notably in developing nations. 

339 

million 

people suffer from asthma. It is 

estimated that asthma has increased as 

much as 12% over the past decade 

383,000 

people die of asthma every year 

INFOGRAPHICS: GOPAKUMAR K 

SOURCE: WHO/ GLOBALASTHMAREPORT.ORG 

80% 

deaths occur in 

low and 

lower-middle 

income 

countries 


WORLD vs INDIA 

A CHANGING CONCEPT? 

14% 

Children 

6% 

22.6% 

8% 

INHALER MARKET 

Americans use more inhalers 

than any other population 

8% 

15% 

45% 

Asia Pacific 

Europe 

of population 

suffer from 

asthma 

globally 

of Indian 

population are 

asthmatics 

32% 

8.6% 

Adult 

2% 

Middle East & Africa 

America 

Asthma is a well-recognized medical condition. 

However, there is not one universal, agreed-upon 

definition for the disease 

The Global Initiative for Asthma (GINA) 

defines the condition as “a chronic 

inflammatory disorder of the airways in 

which many cells and cellular elements 

play a role. The chronic inflammation 

is associated with airway hyperresponsiveness 

that leads to recurrent 

episodes of wheezing, breathlessness, 

chest tightness and coughing, particularly 

at night or in the early morning. These 

episodes are usually associated with 

widespread but variable airflow obstruction 

within the lung that is often reversible 

either spontaneously or with treatment”. 

Concepts of asthma have changed 

substantially over the past 50 years. 

GINA now explicitly emphasises the 

heterogeneity of asthma and uses the 

term asthma as an umbrella term like 

anaemia, arthritis and breast cancer. 

Unlike with anaemia, arthritis or cancer, 

evidence about underlying mechanisms of 

asthma is incompletely understood. 

Years ago, when we had fewer 

medicines with which to treat asthma, 

and a much more basic concept of the 

disease as primarily bronchoconstriction, 

it was easier to think of it as one 

disease, says Dr Andy Nish, MD, Fellow of 

American Academy of Allergy, Asthma & 

Immunology (FAAAAI), USA. 

“Now, it’s probably much more 

appropriate to think of it as a syndrome 

whose patients have in common 

reversible airflow disease, bronchial 

hyperresponsiveness, airway inflammation 

and typically symptoms of wheezing, 

coughing, shortness of breath and chest 

tightness brought on by some common 

factors such as viruses, weather changes, 

exercise, smoke,etc, “ he adds. 

Many studies exploring the 

inflammatory pathways are restricted to 

patients with severe asthma. 

For the diagnosis and management 

of asthma, clinicians rely on evidencebased 

recommendations, including those 

developed as formal clinical practice 

guidelines. Different bodies make different 

recommendations from the same 

evidence, as is the case with the UK in 

asthma guidelines published by the British 

Thoracic Society/Scottish Intercollegiate 

Guideline Network (BTS/SIGN) and the 

National Institute for Health and Care 

Excellence (NICE). 

Therefore, it is essential to have 

national or regional guidelines in order to 

provide locally-specific recommendations. 

Spirometry and breathomics 

Presently, there is no precise test for 

asthma diagnosis. Diagnosis is typically 

based on the pattern of symptoms 

and the response to therapy over time. 

Clinicians suspect asthma if there is a 

history of recurrent wheezing, coughing 

or difficulty in breathing, and these 

symptoms occur or worsen due to 

exercise, viral infections, allergens or air 

pollution. Spirometry is then used to 

confirm the diagnosis. 

Spirometry is the single best test 

for asthma. If the FEV1 measured by 

this technique improves more than 

12% and increases by at least 200 

milliliters following the administration of 

a bronchodilator such as salbutamol, it is 

supportive of the diagnosis. It, however, 

may be normal in those with a history of 

mild asthma. 

COPD overlap 

Asthma is a chronic obstructive condition. 

But it is not considered as a part of 

chronic obstructive pulmonary disease 

(COPD). One of the most characteristic 

features of efficacy studies in asthma and 

COPD is their restriction to “pure” asthma 

and “pure” COPD, point out asthma 

researchers. 

COPD refers specifically to 

combinations of disease that are 

irreversible, such as bronchiectasis, chronic 

bronchitis and emphysema. Unlike these 

diseases, the airway obstruction in asthma 

is usually reversible; however, if left 

untreated, the chronic inflammation from 

asthma can lead the lungs to become 

irreversibly obstructed due to airway 

remodelling. Unlike emphysema, asthma 

affects the bronchi, not the alveoli. 


pulmonology 

BRONCHIAL THERMOPLASTY 

DEVICE THERAPY FOR 

ASTHMA 

A novel modality, BT aims to prevent the structural changes in 

airway smooth muscle 

DR GEORGE MOTHI JUSTIN 

Asthma is a complex inflammatory 

disorder of the airways 

characterized by airway hyperresponsiveness 

(AHR) and variable 

airflow obstruction. Although advances 

in clinical and basic research over 

the past few decades have led to the 

development of effective treatments 

and dissemination of detailed disease 

management guidelines, difficult-totreat 

asthma continues to affect 5-10% 

of adults with this disorder. 

Bronchial thermoplasty (BT) is 

a modality for treating asthma and 

is thought to prevent the chronic 

structural changes that occur in airway 

smooth muscle (ASM) in individuals 

with asthma. BT targets ASM via the 

delivery of a controlled specific amount 

of radiofrequency (RF) energy (RF 

ablation [RFA]) to the airway wall 

through a dedicated catheter. 

It is an innovative treatment 

whose clinical efficacy and safety are 

beginning to be better understood. 

Since this is a device-based therapy, 

the overall evaluation of risk-benefit 

is unlike that of pharmaceutical 

products; safety aspects, regulatory 

requirements, study design and effect 


size assessment may be unfamiliar. 

The mechanisms of action and optimal 

patient selection need to be addressed 

in further rigorous clinical and scientific 

studies. 

Indications 

Candidates for bronchial thermoplasty 

include adults with severe persistent 

asthma who require regular 

maintenance medications of inhaled 

corticosteroids (>1000 µg/day of 

beclomethasone or the equivalent) and 

a long-acting beta agonist (≥100 µg/ 

day of salmeterol or the equivalent). 

These patients would have received 

add-on therapies such as leukotriene 

modifiers, omalizumab, or oral 

corticosteroids (≤10 mg/day). 

These patients should be on stable 

maintenance asthma medications 

according to accepted guidelines, 

should have a pre-bronchodilator 

forced expiratory volume in 1 second 

(FEV1) of 60% or more of predicted, 

and should have a stable asthma 

status (FEV1 within 10% of the best 

value, no current respiratory tract 

infection, and no severe asthma 

exacerbation within the preceding 4 

weeks). 

Patients are usually selected 

on the basis of the AIR 2 trial. The 

patient should be stable in terms 

of asthma status, defined as a post 

bronchodilator FEV1 within 15% of 

baseline values with no respiratory 

tract infection or asthma exacerbations 

within the preceding 14 days. 

Contraindications 

Contraindications for BT include the 

following: 

• Presence of an implantable 

electronic device 

• Known hypersensitivity to drugs 

used during bronchoscopy 

• Severe comorbid conditions that 

would increase the risk of adverse 

events 

Patients are not considered 

candidates for BT if they had three or 

more hospitalisations for asthma, three 

or lower respiratory tract infections and 

four or more oral corticosteroids used 

for asthma in the previous year. 

Although the benefits of BT may 

be large, the potential harm may be 

large as well, and the long-term side 

effects are unknown. Studies are still 

needed to assess exacerbation rates 

and long-term effects on lung function. 

It remains to be determined which 

phenotypes will respond best to BT, 

what the effects may be on obstructed 

patients with an FEV1 higher than 

60%, and what the applicability of the 

procedure may be in patients receiving 

systemic steroid therapy 

Procedure considerations 

BT is performed via fibreoptic 

bronchoscopy in three separate 

procedures, separated by 

approximately 3 weeks, as 

PATIENTS ARE NOT 

CONSIDERED CANDIDATES 

FOR BT IF THEY HAD THREE 

OR MORE HOSPITALISATIONS 

FOR ASTHMA 

demonstrated by previous studies.] 

Dividing the treatments into three 

bronchoscopy sessions minimizes 

the risk of inducing an asthma 

exacerbation or diffuse airway oedema. 

It also avoids excessive procedural 

length. BT takes longer (30-60 

minutes) than a standard fiber-optic 

bronchoscopy (5-20 minutes) does, 

and the longer duration implies the 

use of larger doses of medication for 

sedation. 

All accessible airways are treated, 

with the exception of the right middle 

lobe, because of the theoretical 

concern about the risk of inducing 

right-middle-lobe syndrome.] 

Oxygen delivery should be started 

via a nasal or oral cannula during 

the procedure, with appropriate 

monitoring of vital signs. Heart rate, 

pulse oximetry, and noninvasive blood 

pressure should be continuously 

monitored. 

Outcomes 

Patients may experience respiratoryrelated 

adverse events such as cough, 

wheezing, and chest tightness during 

the treatment period. Most of these 

symptoms occur within 1 day of the 

procedure and resolve in an average of 

7 days with standard therapy. 

It is unclear why an intervention 

aiming at a reduction of smoothmuscle 

mass would not affect 

FEV1. Given that the number of 

exacerbations is reduced with no 

change in FEV1, it may be that altered 

response to the inflammatory triggers 

plays a role in addition to the reduction 

in smooth-muscle mass. 

Complications 

Recurrent lung atelectasis secondary 

to fibrin plugs has been reported 

as an early complication of BT. 

In the susceptible patient, high 

thermal stimulation may lead to 

an inflammatory reaction with 

microvascular alteration, induced 

either by heat or by the release of 

inflammatory mediators. Lung abscess 

has also been described as a direct 

complication; thus, collecting and 

publishing safety data continue to 

be important. A prospective cohort 

study performed as part of the 

TASMA trial reported a high incidence 

of acute radiologic abnormalities 

after BT. Postprocedural CT of 

the chest identified four different 

radiologic patterns: (1) peribronchial 

consolidations with surrounding 

ground-glass opacities (94%), (2) 

atelectasis (38%), (3) partial bronchial 

occlusions (63%), and (4) bronchial 

dilatations (19%). These complications 

resolved without clinical impact in 

virtually all cases. 

The author is Head, Department of 

Respiratory Medicine, Medical Trust 

Hospitals, Cochin 


drug approvals 

Hydrogel 

capsule for 

weight loss 

Plenity manufactured by the 

Gelesis has been granted 

approval by USFDA as an aid 

in weight management in 

adults with a body mass index 

(BMI) of 25–40 kg/m2, when 

used in conjunction with diet 

and exercise. 

It is an oral, non-systemic, 

superabsorbent hydrogel 

capsule which when taken 

together with diet and 

exercises aids in weight 

loss by inducing satiety and 

reducing hunger. 

The drug can be 

administered in the form 

of capsules that could be 

taken with water before 

dinner and lunch. It is made 

of two naturally derived 

compounds called cellulose 

and citric acid which are cross 

linked together in a manner 

that they create a threedimensional 

matrix. 

The hydrogel-based 

capsule release thousands 

of non-aggregating gel-like 

particles that rapidly 

absorbs water in the stomach. 

These small gellike particles 

have an elasticity of plantbased 

foods but they do 

not have any caloric value. 

These gel particles increase 

the elasticity of the contents 

stored in the stomach and 

intestine giving out a feeling 

of fullness that aids in weight 

loss. 

The clinical studies 

of Plenity have shown 

positive effects on weight 

management. 

Breakthrough 

therapy 

designation to 

elafibranor 

Genfit announced that its 

lead product candidate 

elafibranor was granted 

Breakthrough Therapy 

Designation by the US FDA 

for the treatment of primary 

biliary cholangitis (PBC) 

in adults with inadequate 

response to ursodeoxycholic 

acid (UDCA). 

Elafibranor is a first-inclass 

double peroxisome 

proliferator-activated receptor 

alpha and delta (PPAR alpha/ 

delta) agonist which has 

produced positive results 

in a phase 2 clinical trial 

evaluating its safety and 

efficacy in adults with PBC 

and inadequate response to 

UDCA. 

Elafibranor is also 

currently evaluated in a phase 

3 clinical trial in non-alcoholic 

steatohepatitis (NASH). 

Genfit presented detailed 

results from its positive phase 

2 clinical trial evaluating 

elafibranor in PBC during 

the European Association for 

Hormone therapy 

for menopausal 

symptoms 

The US FDA has approved 

first of its kind capsule 

Bijuva which contains 

progesterone and 

estradiol, announced 

TherapeuticMD. 

It is the first bioidentical 

hormone therapy 

combination that has been 

approved by the FDA. 

The approval is based 

on the Bijuva clinical 

development programme 

that included the pivotal 

phase III Replenish Trial. 

This trial evaluated the 

safety and efficacy of 

Bijuva in generally healthy, 

postmenopausal women 

with a uterus for the 

the Study of the Liver (EASL) 

annual International Liver 

Congress (ILC). 

In a 12-week doubleblind 

randomized placebocontrolled 

phase 2 trial of 

non-cirrhotic patients with 

PBC and with inadequate 

response to UDCA, elafibranor 

showed a significant decrease 

of alkaline phosphatase (ALP) 

levels, resulting in significant 

treatment of moderate to 

severe hot flashes. 

The co-primary efficacy 

endpoints in the Replenish 

Trial were the change from 

baseline in the number 

and severity of hot flashes 

at weeks 4 and 12 as 

compared to placebo. 

Bijuva demonstrated 

a statistically significant 

reduction from baseline 

in both the frequency and 

severity of hot flashes 

compared to placebo while 

reducing the risks to the 

endometrium. The results 

of the trial were published 

in the journal Obstetrics & 

Gynecology. 

treatment effects versus 

placebo on the primary 

endpoint. 

Gene-edited 

stem cell 

therapy for 

thalassemia 

T 

he US FDA has granted 

Fast Track Designation for 

CTX001 for the treatment of 

transfusion-dependent beta 

thalassemia (TDT). 

CTX001 is an 

investigational, autologous, 

gene-edited haematopoietic 

stem cell therapy for patients 

suffering from severe 

haemoglobinopathies. 


form of haemoglobin. 

The elevation of HbF by 

CTX001 has the potential 

to alleviate transfusion 

requirements for TDT patients 

and painful and debilitating 

sickle crises for SCD patients. 

Speedy approval 

for erdafitinib 

to treat bladder 

cancer 

had previously not responded 

to anti-PD-L1/PD-1 therapy. 

Erdafitinib is the first 

approved drug in a class 

known as FGFR inhibitors 

that targets growth factor 

receptors involved in cell 

growth and division. 

In February 2019, CRISPR 

Therapeutics and Vertex 

announced that the first 

patient had been treated with 

CTX001 in a phase 1/2 clinical 

study of patients with TDT, 

marking the first companysponsored 

use of a CRISPR/ 

Cas9 therapy in a clinical trial. 

The Phase 1/2 open-label 

trial is designed to assess 

the safety and efficacy of 

a single dose of CTX001 in 

patients ages 18 to 35 with 

TDT, non-beta zero/beta zero 

subtypes. The companies are 

also evaluating CTX001 for the 

treatment of sickle cell disease 

(SCD) and received Fast Track 

Designation for CTX001 from 

the FDA in January 2019 for 

SCD. 

In CTX001 therapy, a 

patient’s haematopoietic 

stem cells are engineered 

to produce high levels of 

foetal haemoglobin (HbF) 

in red blood cells. HbF is a 

form of the oxygen-carrying 

haemoglobin that is naturally 

present at birth and is 

then replaced by the adult 

Erdafitinib (Balversa) has 

been granted accelerated 

approval by US FDA to treat 

adult patients with locally 

advanced or metastatic 

bladder cancer that has a 

type of susceptible genetic 

alteration known as FGFR3 or 

FGFR2. 

Patients should be 

selected for therapy with 

erdafitinib using an FDAapproved 

companion 

diagnostic device. 

The efficacy of erdafitinib 

was studied in a clinical trial 

that included 87 patients with 

locally advanced or metastatic 

bladder cancer, with FGFR3 

or FGFR2 genetic alterations, 

that had progressed following 

treatment with chemotherapy. 

The overall response rate 

in these patients was 32.2%, 

with 2.3% having a complete 

response and almost 30% 

having a partial response. 

The response lasted for an 

average of approximately fiveand-a-half 

months. 

Responses to erdafitinib 

were seen in patients who 

Sakigake desig 

for valemetostat 

in Japan 

D 

aiichi Sankyo announced 

that valemetostat, an 

investigational and potential 

first-in-class EZH1/2 dual 

inhibitor, has received 

Sakigake Designation for the 

treatment of adult patients 

with relapsed/refractory 

peripheral T-cell lymphoma 

(PTCL) by the Japan Ministry 

of Health, Labour and Welfare 

(MHLW). 

Valemetostat targets 

epigenetic regulation by 

inhibiting both the EZH1 

(enhancer of zeste homolog 

1) and EZH2 enzymes that act 

through histone methylation 

to regulate gene expression. 

Reactivation of the silenced 

genes results in decreased 

proliferation of EZH2- 

expressing cancer cells. 

Preclinical research has 

shown that valemetostat 

suppressed trimethylation of 

H3K27 in cells more strongly 

than EZH2 selective inhibitors. 

Valemetostat also displayed 

antitumour activity in various 

haematological malignancies 

in preclinical models. 

Sakigake Designation 

was granted based on the 


Olaparib to treat advanced 

breast cancer in EU 

The European Commission has 

approved olaparib (Lynparza) as 

monotherapy for the treatment of adult 

patients with germline 

BRCA1/2-mutations (gBRCAm), and 

who have human epidermal growth 

factor receptor 2 (HER2)-negative 

locally-advanced or metastatic breast 

cancer. 

Patients receiving the therapy 

should have previously been treated 

with an anthracycline and a taxane in 

the (neo)adjuvant or metastatic setting 

unless they were unsuitable for these 

treatments. Patients with hormone 

receptor (HR)-positive breast cancer 

should also have progressed on or 

after prior endocrine therapy or be 

considered unsuitable for endocrine 

therapy. 

The approval was based on data 

from the randomised, open-label, phase 

III OlympiAD trial which tested olaparib 

vs. physician’s choice of chemotherapy 

(capecitabine, eribulin, or vinorelbine). 

In the trial, olaparib provided patients 

with a statistically-significant median 

progression-free survival improvement 

of 2.8 months. 

This is the third indication for 

olaparib in the EU, said AstraZeneca 

and MSD. 

preliminary results of an 

ongoing phase 1 study 

assessing the safety and 

efficacy of valemetostat in 

patients with non-Hodgkin 

lymphomas (NHL) including 

PTCLs, which were presented 

at the 2017 annual meeting 

of the American Society of 

Hematology (ASH). 

The Sakigake Designation 

System promotes R&D in 

Japan, driving early practical 

application for innovative 

pharmaceutical products, 

medical devices, and 

regenerative medicines. 

Dolutegravir 

+ lamivudine 

combo for HIV1 

The US FDA approved 

dolutegravir and 

lamivudine (Dovato) as a 

complete regimen for the 

treatment of HIV-1 infection 

in adults with no antiretroviral 

treatment history. 

This is the first FDAapproved 

two-drug, fixed- 

dose, complete regimen for 

HIV-infected adults who 

have never received 

treatment for HIV, ViiV 

Healthcare said. 

The efficacy and safety 

of Dovato, one tablet taken 

daily, were demonstrated in 

two identical, randomized, 

double-blind, controlled 

clinical trials in 1,433 HIVinfected 

adults with no prior 

antiretroviral treatment 

history. 

The trials showed that 

a drug regimen containing 

dolutegravir and lamivudine 

had a similar effect of 

reducing the amount of 

HIV in the blood compared 

to another drug regimen, 

which included dolutegravir, 

emtricitabine, and tenofovir. 

Fast track for 

oral tebipenem 

to treat UTI 

The US FDA has granted 

Fast Track designation to 

SPR994, an oral carbapenem 

for complicated UTI and 

acute pyelonephritis. 

SPR994 is tebipenem 

pivoxil hydrobromide — 

an oral formulation of 

tebipenem, an antibiotic in 

the carbapenem class. 

The preclinical models of 

SPR994 have already shown 

its efficacy against gram 

negative bacteria including 

E. coli, producing extendedspectrum 

beta-lactamase 

(ESBLs) and ESBLs producing 

Klebsiella pneumoniae, 

similar to IV ertapenem. 

The drug has been 

already given Qualified 

Infectious Disease Product 

(QIDP) designation. 

Completion of phase 

1, double-blind, placebocontrolled, 

ascending dose, 

a multi-cohort study has 

enabled dose selection for 

the company’s upcoming 

phase 3 trial, ADAPT-PO. 

This will be a randomized, 

double-blind, double-dummy, 

multicentre, prospective 

study designed to assess 

the efficacy, safety, and 

pharmacokinetics of 

tebipenem vs intravenous (IV) 

ertapenem in patients with 

complicated UTI or AP. 

Dacomitinib to 

treat patients 

with NSCLC 

in EU 

Pfizer Inc. announced that 

the EC has approved 


under the Priority Review 

programme. 

Romosozumab 

to treat 

osteoporosis 

Amgen and UCB 

announced that the 

US FDA has approved 

romosozumab-aqqg 

(Evenity) for the treatment 

of osteoporosis in 

postmenopausal women at 

high risk for fracture. 

Romosozumab-aqqg 

has a dual effect that both 

increases bone formation and 

to a lesser extent reduces 

bone resorption. A full course 

of the therapy is 12 monthly 

doses. 

The FDA based its 

approval of romosozumabaqqg 

on the results of two 

phase 3 studies. In the 

placebo-controlled FRAME 

study, treatment with 

dacomitinib (Vizimpro), a 

tyrosine kinase inhibitor 

(TKI), as monotherapy for 

the first-line treatment 

of adult patients with 

locally advanced or 

metastatic non-small cell 

lung cancer (NSCLC) with 

epidermal growth factor 

receptor (EGFR)-activating 

mutations. 

The EC approval of 

dacomitinib was supported 

by data from ARCHER 1050, 

a randomized, multicentre, 

multinational, open-label, 

phase 3 study conducted in 

patients with unresectable, 

metastatic or recurrent 

NSCLC, harbouring EGFR 

exon 19 deletion or exon 21 

L858R substitution 

mutations. 

Dacomitinib is also 

approved in the US for the 

first-line treatment of patients 

with metastatic NSCLC with 

EGFR exon 19 deletion or 

exon 21 L858R substitution 

mutations as detected 

by an FDA-approved test. 

Additionally, it is approved 

in Japan for EGFR gene 

mutation-positive, inoperable 

or recurrent NSCLC, and 

in Canada for the first-line 

treatment of adult patients 

with unresectable locally 

advanced or metastatic 

NSCLC with confirmed 

EGFR exon 19 deletion or 

exon 21 L858R substitution 

mutations. The applications 

in the US and Japan were 

reviewed and approved 

Cladribine as oral treatment for 

multiple sclerosis 

Cladribine (Mavenclad) has been granted approval 

to treat relapsing forms of multiple sclerosis (MS) in 

adults by the USFDA. 

Cladribine is not recommended for MS patients 

with clinically isolated syndrome. Because of its safety 

profile, the use of the drug is generally recommended 

for patients who have had an inadequate response to, or 

are unable to tolerate, an alternate drug indicated for the 

treatment of MS. 

The efficacy of cladribine was shown in a clinical 

trial in 1,326 patients with relapsing forms of MS who 

had at least one relapse in the previous 12 months. The 

drug significantly decreased the number of relapses 

experienced by these patients compared to placebo. 

Cladribine also reduced the progression of disability 



resulted in a significant 

reduction of new vertebral 

fracture at 12 months 


This significant reduction 

in fracture risk persisted 

through the second year in 

women who received the 

drug during the first year and 

transitioned to denosumab 

compared to those who 

transitioned from placebo to 

denosumab. 

In addition, 


significantly increased bone 

mineral density at the 

lumbar spine, total hip and 

femoral neck compared 

to placebo at 12 months. 

Following the transition 

from romosozumab-aqqg 

to denosumab at month 12, 

BMD continued to increase 

through month 24. 

In the active-controlled 

ARCH study, treatment 

with romosozumab-aqqg 

for 12 months followed by 

12 months of alendronate 

significantly reduced the 

incidence of new vertebral 

fracture at 24 months. 


straight talk 

“WE STILL DON’T HAVE A 

CLEAR UNDERSTANDING 

OF THE ACTUAL DISEASE 

BURDEN IN INDIA” 

VIJAY CHANDRU, Co-Founder and 

Director, Strand Life Sciences, and INAE 

Distinguished Technologist at Indian 

Institute of Science, is an academic 

turned entrepreneur. He got his PhD 

in mathematics of decision sciences at 

MIT in 1982. He taught and conducted 

research in computational mathematics of 

optimization, geometry, logic and biology 

at Purdue University (1982-1993) and 

the Indian Institute of Science (1992- 

2005). The vision that drove him to 

entrepreneurship was to create successful, 

world-class, technology innovation 

companies out of India. In 1998, he joined 

hands with kindred spirits to create the 

Simputer (a handheld computer). He also 

co-founded PicoPeta Simputers, which 

commercialized the Simputer to create 

the Amida Simputer. Strand Life Sciences 

started out as an exciting life science 

informatics company based in Bangalore, 

India. Strand, which has captured around 

30% of the global market for analytics 

software in research biology for the 

various “omics” - genomics, proteomics, 

metabolomics, etc., is a global, personalized 

medicine company that uses clinical 

genomics for oncology and inherited 

disorders. He also helped create non-profit 

agencies that work for neglected disease 

communities. In an exclusive interview 

with Editor CH UNNIKRISHNAN, Chandru, 

who is pursuing the vision of affordable 

precision medicine, says that India needs 

to do a lot more to have clarity on its 

actual disease burden, especially rare and 

undiagnosed diseases. Edited excerpts: 

India is one of the large geographies where the burden 

of rare and undiagnosed diseases, mainly linked to genetic 

disorders, is high with a prevalence of around 70 million. 

But the country still doesn’t have accurate data or a 

registry to formulate appropriate policies or a budget to 

take care of the patients. Why? 

We still don’t have a clear understanding of the actual 

disease burden in the country, especially in case of the rare 

and undiagnosed diseases linked to genetic causes. I think 

the challenge here is that there has been no systematic 

surveying. As per information from government agencies, 

at least all the diseases that have been given the disability 

status will show up in census data by the 2020-21 survey, 

which will start giving us some clue. With this, at least major 

disabilities like hemophilia, thalassemia, sickle cell anaemia, 

muscular dystrophy, multiple sclerosis and perhaps a few 

more will be captured and those numbers will be known 

with better accuracy. Secondly, there is also a hope that 

because there are a lot of patient communities, awareness 

activities, camps, etc. happening now, that will help slowly 

build the data, as these platforms will be able to provide 

useful information and numbers. 

ICMR has announced that it will build a registry of 

rare diseases in India. We will have to wait and see how 

successful that effort will be. Though the apex medical 

research body was claimingly successful in building India’s 

cancer registry, the numbers still do not seem very 

accurate. While the cancer registry shows about 1.3 million 

new cases per year, there seems to be something wrong 

with this number. For instance, China, which has almost the 

same level of disease burden as India, had recently declared 

its data of new cancer patients as 4.1 million per year. So, 

apparently, the data claimed by the Indian 

registry has probably underestimated the prevalence. 

ICMR is using some kind of sampling technique and then 

extrapolating it. But for some reason, this number seems 

conservative, I feel. 

On rare diseases, it’s true that some pharma companies 


Vijay Chandru 

PHOTO: UMESH GOSWAMI 

have somewhat better-estimated data since 

they have information that is collected 

from doctors or directly from the market. 

But when you ask these companies 

about lysosomal storage disorders, they 

estimate it as a few hundreds. Similarly, 

many haematologists estimate thalassemia 

cases at 1 to 1.5 lakh patients. So, where is 

this number of 70 million patients of rare 

diseases that are projected at every forum 

coming from, I often wonder. China has 

published that their population with rare 

diseases as 20 million. I agree that India 

has more consanguineous marriage within 

the same community, among other factors, 

that cause genetic disorders. But still, such 

a huge difference! So, we don’t know what 

the numbers are. But I feel there is plenty 

Where is this 

number of 

70 million 

patients of rare 

diseases that 

are projected 

at every forum 

coming from, I 

often wonder. 

of work to be done to have a clarity on the 

actual disease burden. These numbers are 

important to formulate our priorities, 

where funds should be given and what 

sort of facilities have to be created, among 

others. 

There are government bodies like IGIB 

and ICMR, private companies and charity 

organisations working to address patient 

needs. At what stage are these works at 

present, any idea? 

As far as rare diseases are concerned, 

some areas have seen better progress. 

For example, patient tracking and 

diagnosis in haematological disorders are 

comparatively better organised and there 

is a lot of work currently going on. While 


that the allocation of the budget is not possible unless the 

government knows the burden. 

But I think it is just a matter of time; It will happen and 

the good thing is that the country is looking at healthcare 

much more seriously now and it is also an era when medical 

records are largely being digitized. Even for rare diseases, 

the country is looking much more carefully at the data and 

digital records from various sources. 

What about the therapy side? 

The therapy side is always a challenge. There are many 

therapies that are used for the maintenance of patients. 

Those therapies, I think, patient communities and hospitals 

are tracking and providing. But even then, we don’t have 

a comprehensive list of medicines. Rather, none has put 

together a good collection of information about medicines 

that the patients would need for rare diseases. By this, 

what I am referring to is the kind of a comprehensive 

list that India prepared on essential medicines, that the 

country’s physicians would require along with all other 

related information about availability, pricing of generics and 

patented products and so on, when the country was about 

to sign the Dunkel Draft. Such a list needs to be prepared 

for rare diseases as well, detailing the use, cost, availability 

and accessibility. Such an effort will help in ensuring the 

availability and accessibility of treatment for Indian patients 

in case of rare diseases. Otherwise, a large section of the 

population will still be left untreated as most of the targeted 

treatments currently available in the market is beyond the 

reach of the mass. 

activities for muscular disorders is slowly 

picking up, other segments like primary 

immuno-deficiency and others are still 

poorly covered and there is very little 

help for patients at present. Overall, I think 

we have a fundamental issue of really 

starting to think about evidence-based 

planning for the care of rare diseases, 

moving away from the eminence-based 

planning. 

I remember, the health Secretary of 

Karnataka once asked us (the industry), 

while the state was proposing a draft on its 

health policy, if we can provide data about 

the actual burden and he made it a point 

The genetic study of the Indian population, which is 

essential to address rare diseases, is still minuscule. What 

needs to be done to expand it? 

There are some broad-based genetic studies that are 

being planned as part of projects like Genome India and so 

on. But there are also more focused cohort studies such as 

the neurological disorder study that is done by NIMHANS 

etc., going on in parallel. So, it has slowly started to build up, 

but the volume of work is yet to pick up. However, the good 

thing is that the country has the capacity now. 

Large sequencers have been set up at least in five to six 

locations in the country. So, the ability to run the sequences 

to do the bioinformatics has been built and we are in a 

position to do it. But if you ask me if we have done it, I would 

say it is not very visible. Though a few companies, including 

Strand Life Sciences and MedGenome, have probably 

generated a fair amount of data, I don’t think academic 

groups have done as much. However, since capacities have 

been built, they seem to be getting adequately funded 

shortly. Going forward, we will see better, and more data 

being generated as things are moving in the right direction. 

Rare diseases are definitely on the agenda and it is time to 

think positive. 


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case reports 

ROBOTIC BYPASS 

A unique case where the least invasive option of minimally invasive 

cardiac surgery is employed 

Mrs Malliga, a 63-year old lady from Ambattur in 

Chennai, had been suffering from chest pain for the 

past six months. As her condition worsened and 

the chest pains increased, she was brought to 

Apollo Hospital Chennai, where she consulted with Dr. 

Mohammed M Yusuf, a cardiothoracic surgeon specializing 

in Minimally Invasive Cardiac Surgery and Dr Damodharan, 

Senior Consultant Cardiologist. Mrs Malliga complained of 

chest pain on minimal exertion. Her case history 

showed that she was diabetic and had slightly higher 

cholesterol levels than normal, two high-risk factors for 

heart disease. 

An angiography revealed blocks in three major arteries 

that supply blood to the heart. Typically in such cases, an 

open-heart bypass surgery or stents would be indicated. 

Keeping the history of diabetes and cholesterol in mind, an 

open-heart bypass surgery was deemed the best treatment 

option. This procedure involves using a healthy blood vessel 

from another part of the body to allow blood to bypass the 

block in the vessel. For blocks in the left anterior descending 

artery, a healthy artery from the chest wall itself is preferred. 

However, for other less important arteries, surgeons may use 

veins from the leg as well. 

“A bypass surgery is more effective for blocks in the 

major arteries, compared with stents. The majority of stents 

are beneficial for up to 5-10 years, after which blocks may 

reappear”, says Dr Yusuf. While the treatment outcome is 

excellent and mortality rates are extremely low in bypass 

surgeries, the procedure involves making a 6-8 inch long 

incision in the chest and cutting through the breastbone to 

access the heart, resulting in a considerably long recovery 

period that can last up to 4 months. 

Recent advances in open-heart surgery techniques 

include minimally invasive approaches that require smaller 

incisions and offer faster recovery periods. Instead of the 

large 6-8 inch incision for the conventional bypass surgery, a 

smaller cut in the chest is sufficient for a minimally invasive 

procedure. This reduces morbidity and brings the recovery 

time to 2 weeks. Dr Yusuf and his medical team have been 

performing minimally invasive bypass surgeries for over a 

year with excellent results. 

More recently, robotic assistance to perform the 

procedure has gained interest. Dr Yusuf and his team opted 

to conduct this minimally invasive operation using robotic 

assistance rather than the conventional 

approach. Two of the three major blood 

vessels of the patient were severely blocked 

and required bypass surgery. The blocks 

in other vessels could be treated with 

angiography stent insertion. Dr Yusuf’s 

team, therefore, decided on a 2-step 

approach. Under the guidance of Dr Frank 

Vanpraet, Director of Robotic and Minimally 

Invasive Cardiac Surgery, OLV Hospital, Aalst, 

Belgium, Dr Yusuf performed the minimally 

invasive coronary artery bypass grafting 

surgery using robotic assistance. In the 

ROBOT-ASSISTED MINIMALLY 

INVASIVE CORONARY ARTERY 

BYPASS TECHNIQUE LOWERS 

THE RISK OF COMPLICATIONS 

SUCH AS STROKE, EXCESSIVE 

BLOOD LOSS, AND INFECTION 

second step, two days after the first 

surgery, Dr Damodharan performed 

angiography and drug-eluting stent insertion 

for the remaining blocks in Mrs Malliga’s 

coronary arteries. This was done with the 

assistance of a specialized intravascular 

ultrasound. 

Robot-assisted minimally invasive 

coronary artery bypass grafting has several 

advantages, as it is the least invasive 

option among minimally invasive cardiac 

surgeries. This technique lowers the risk 

of complications such as stroke, excessive 

blood loss, and infection. Patients also 

have reduced pain, smaller scars and 

faster recovery periods and it is ideal 

for multivessel blocks. “Even though it is 

more expensive than conventional bypass 


surgeries, it should be recommended for young patients 

who would like to get back to work immediately and in 

high-risk patients with other comorbidities”, says Dr Yusuf. 

With our lifestyle changes, more and more young people 

are suffering from heart conditions and such quick recovery 

treatment approaches are likely to be more economical in 

the long run. 

Robotic Minimally Invasive Hybrid Revascularization is 

already being performed in countries such as Japan, United 

Kingdom and the United States. However, this was the first 

instance of the minimally invasive approach with robotic 

assistance in India. 

The multiple step approach used for 

Mrs Malliga showed excellent results as 

she was discharged in 48 hours after the 

procedure and has since returned to full 

normal activity. She will, of course, be 

regularly followed up to ensure that no new 

complications arise. 

DR SHIVANEE SHAH 


case reports 

ECMO RESCUE 

Extracorporeal membrane oxygenation must be initiated for ARDS 

as soon as standard therapy starts failing 

Nagesh, a middle-class executive 

at a local shopping mall in Bengaluru, was 

34-year-old 

suffering from fever and severe shortness of 

breath and was admitted to St. John’s Hospital, 

Bengaluru. His clinical history indicated no comorbidities or 

other illnesses; however, he had recently travelled to 

another city. 

As his condition was worsening, he was diagnosed with 

severe community-acquired pneumonia and admitted to 

the intensive care unit where he was started on anti-flu 

medicines and placed on a mechanical 

ventilator to help with breathing. However, 

his oxygen parameters did not improve 

even after artificial ventilation in the prone 

position after sixteen hours. Doctors at 

St. John’s recommended extracorporeal 

membrane oxygenation (ECMO) support as 

a last, life-saving resort. ECMO is a medical 

device used to supply oxygen to circulating 

blood through an oxygenator in an effort 


to bypass the requirement of an injured or non-functional 

lung. 

Unfortunately, most hospitals do not have ECMO facilities 

in India and St John’s hospital is no exception. The medical 

team at St. John’s therefore reached out to Narayana Health 

City, Bengaluru, for assistance. Ideally, Nagesh would be 

transferred to Narayana Health City before ECMO treatment. 

However, his condition was critical, and he was not able to 

be transported. In a life-saving move, the 12-member ECMO 

team led by Dr Harish M M, consultant and in-charge of the 

multi-disciplinary intensive care unit, Narayana Health City, 

came to St John’s with a portable ECMO unit, initiated venovenous 

ECMO at St John’s, and then transferred Nagesh to 

Narayana Health City while on ECMO support. 

At Narayana Health City, Nagesh underwent a repeat 

X-ray, while his previous treatment regime of Tamiflu and 

antibiotics was continued along with the ECMO. Because of 

his deteriorating condition in terms of clinical presentation 

with bilateral infiltration and a low response to ventilation 

support, he was considered to be a case of severe acute 

respiratory distress syndrome (ARDS). A tracheal aspirate 

was used for molecular testing using polymerase chain 

reaction to identify the causative agent for the respiratory 

illness. Molecular testing has the benefit of being rapid as 

well as having high sensitivity, and within 24 hours, he was 

confirmed with H1N1 infection. 

ARDS is a severe form of lung injury and is defined based 

on the development of acute dyspnea and hypoxemia within 

7 days after the insult, along with radiographic changes 

showing bilateral infiltrates. ARDS can be classified as mild 

to severe, depending on the ratio of the partial pressure of 

oxygen in the patient’s arterial blood (PaO2) to the fraction 

of oxygen in the inspired air (FiO2). If this is ratio is less than 

100, the patient is classified as suffering from severe ARDS. 

Nagesh’s PaO2/FiO2 ratio was less than 100, classifying him 

as having severe ARDS. 

While there is no specific therapy for ARDS, treatment 

should depend on the underlying condition, along with 

appropriate supportive care and artificial ventilation. Nagesh 

was continued on Tamiflu and ECMO and a broad-spectrum 

antibiotic to prevent bacterial infections during ventilation 

support. 

The decision to remove ECMO support is dependent on 

the oxygen levels as well as the general condition of the 

patient. Absence of high-grade fever and infections, normal 

electrolytes, a normal heart rate and brain function are 

all factors indicating whether the patient can be weaned 

of the ECMO support. Though blood culture is a definitive 

indicator of infection, its yield is very poor especially when 

patients are already on antibiotics. Other indirect indicators 

of infection, including WBC count, body temperature, 

and infiltration in the lungs are monitored daily, whereas 

biomarkers like procalcitonin, C reactive protein etc. 

are monitored every 2-4 days. Once these biochemical 

parameters return to normal, the patient 

can be weaned off ECMO. Even after 

discharge, sequelae of ARDS, such as 

weight loss, fatigue, functional compromised 

life, myopathy etc. can often linger for 

months. 

Nagesh had to be supported on ECMO 

for 12 days before his PaO2/FiO2 ratio 

started to stabilise and his lung function 

returned to normal. After discharge, he was 

continued on multivitamins, and followed 

up after 1 week. Luckily, he did not have to 

witness prolonged effects of ARDS and he 

returned to normalcy at the 1-week follow 

up. 

According to Dr Harish, ECMO comes 

with a high cost, running into a few lakhs. 

However, the most important criteria for 

THE MOST IMPORTANT 

CRITERIA FOR STARTING 

ECMO THERAPY IS THAT THE 

PATHOLOGY SHOULD BE 

REVERSIBLE 

starting ECMO therapy is that the pathology 

should be reversible. It is not recommended 

for severe stroke or advanced cancer 

patients with ARDS, who may already be 

bedridden. Side effects of ECMO include 

bleeding, air embolism, low platelet counts 

(platelets may be destroyed in the external 

tubes), and hemolysis. Platelet or blood 

transfusions may often be required to 

address platelet/blood loss. 

Despite the costs and side effects, 

ECMO must be initiated early once standard 

therapy (including prone ventilation) for 

ARDS fails, as ARDS will not respond to 

ECMO once the lung moves to a fibrotic 

phase. While few hospitals have ECMO 

facilities, Dr Harish advocates that patients 

should be referred to a suitable health care 

centre as early as possible and definitely 

no later than 2 sessions of ineffective 

ventilation in prone position. 



case reports 

A 

AVOIDING 

AN AORTIC 

CATASTROPHE 

Should an ECG rule out a heart attack, consider performing an echo 

to check for aortic dissection 

Satish (name changed) suddenly 

started having chest pains and was rushed to a 

55-year-old 

local hospital in Pallakad, Kerala. As an ex-army 

man, he had never experienced such pain and his family 

assumed he was having a heart attack. However, all initial 

tests that were run were negative and an echo cardiography 

was performed. The echo showed an aortic dissection and 

Satish was transferred to Amrita Hospital, Kochi, which has a 

dedicated Centre for Aortic Diseases and Marfan Syndrome. 

Here he was immediately rushed to the operation theatre 

without further ado by the medical team led by Dr Praveen 

Varma, Head of Cardiovascular and Thoracic Surgery. 

An aortic dissection is a tear in the inner lining of 

the aorta, just above the aortic valve, and results due to 

increased stress within the walls of the aorta. Type A aortic 

dissection such as this one is a life-threatening medical 

emergency requiring immediate surgery, without which 

mortality can be almost 100%. Once the aorta dilates from 

the normal range of 2.5-3 cm to 4.5-5 cm, it is likely to 

dissect. Right before the team started operating on Satish, 

his aortic wall ruptured outside However, the procedure was 

already underway, and the medical team remained unfazed 

as they proceeded with the aortic root 

replacement surgery, which is a complex 

surgery often taking 8-10 hours. 

This procedure involves multiple steps. 

The first step involves a surgical technique 

called total circulatory arrest in which the 

body is cooled to less than 18°C before 

cutting off blood circulation to the whole 

body. The cool temperatures allow the brain 

to survive the circulatory arrest, however, 

brain activity must be closely monitored 

to ensure that the cool temperatures keep 

the brain quiescent throughout the surgery. 

This is critical while performing delicate 

procedures on large blood vessels such as in 

this case. The patient is typically connected 

to a cardiopulmonary bypass, an external 

heart-lung machine, which drains the blood 

out of the body and cools it to less than 18 

°C. Brain activity is monitored by monitoring 

blood flow to the brain by Near Infrared 

Spectroscopy. Once the brain function has 


stopped, the actual aortic root replacement surgery can 

commence. This was done following the Bentall procedure, 

in which the aortic valve, the aortic root and the ascending 

aorta are replaced with a composite graft, and the coronary 

arteries are then re-implanted into the new graft. Once the 

replacement surgery is completed, the blood is warmed 

again, and the patient is then returned to normal blood flow 

and brain activity. 

Satish’s surgery went well, and he was kept in the ICU 

for 2 days and discharged 8 days post-surgery. Now he is 

on strong anti-hypertensive drugs, which will be his lifelong 

companions. He is also given a blood thinner to ensure the 

proper functioning of the new artificial mechanical valve. 

While aortic dissection and rupture are relatively 

uncommon, major risk factors are uncontrolled high blood 

pressure, atherosclerosis, cocaine abuse, bicuspid aortic 

valve, or genetic diseases such as Turner’s syndrome or 

Marfan syndrome. Patients with Turner’s syndrome have 

a missing or structurally altered X-chromosome resulting 

in many abnormalities including aortic valve defects. 

Marfan syndrome is caused due to an autosomal dominant 

mutation in the FBN1 gene which encodes a protein called 

fibrillin 1. This protein is an extracellular matrix glycoprotein 

that provides structural support to connective tissue 

throughout the body. Patients with Marfan syndrome have 

typical visual clinical features of elongated limbs, fingers 

and toes, and scoliosis. Marfan syndrome may also affect 

other organs including eyes, bones, lungs, and heart. Marfan 

syndrome patients are at a high risk of aortic dilation, aortic 

aneurysm and mitral valve prolapse, and aortic dissection 

which may well be the most serious of all 

the complications associated with Marfan 

syndrome. 

In 2016, a special Centre for Aortic 

Diseases and Marfan Syndrome was 

started at Amrita Hospital, Kochi. This 

is the only such center in India that is 

dedicated to patients with Marfan syndrome 

and other aortic diseases. It comprises 

of a multidisciplinary team including 

cardiologists, surgeons, ophthalmologists, 

geneticists, obstetricians as well as 

radiologists. These doctors together offer 

comprehensive care including genetic 

counselling and associated medical support 

as required. The cardiovascular surgeons 

are skilled to deal with the most serious 

complications like aortic ruptures. Today 

WHILE AORTIC DISSECTION 

AND RUPTURE ARE RELATIVELY 

UNCOMMON, MAJOR RISK 

FACTORS ARE UNCONTROLLED 

HIGH BP, ATHEROSCLEROSIS, 

COCAINE ABUSE, BICUSPID 

AORTIC VALVE, OR GENETIC 

DISEASES SUCH AS TURNER’S 

SYNDROME 

over 50 patients are registered with this 

clinic and undergo regular screenings every 

6 months. In case clinical observations 

indicate that the aorta is dilating, elective 

aortic root replacement may also be offered. 

According to Dr Varma, even though 

aortic diseases and acute aortic syndromes 

are more catastrophic and complicated, 

they are not given much importance in India 

and are often overlooked and misdiagnosed 

as heart attacks. Should an ECG rule out a 

heart attack, consider performing an echo 

to check for aortic dissection. Patients with 

aortic dissection should immediately be 

transferred to the nearest hospital with 

surgical expertise. 



case reports 

SILENT THALASSEMIA 

Alpha thalassemia is under-reported in India because of the need for genetic 

testing to confirm the blood disorder 

Two-and-a-half-year-old Pratik (name changed), a 

normal, seemingly healthy child, was visiting his 

paediatrician for a regular check-up. The paediatrician 

thought that Pratik was pale looking and requested a 

complete blood count investigation to be done. The results 

indicated low haemoglobin levels, high RBC counts, and 

high red cell distribution width. In addition, cells were small, 

indicative of microcytic hypochromic anaemia. Pratik was 

therefore suspected to have iron deficiency anaemia and 

serum iron studies were done. These also showed evidence of 

iron deficiency and Pratik was started on iron supplements. At 

the one month follow up, his repeat complete blood counts 

showed improved haemoglobin levels. However, the RBC 

count was still high and the microcytosis was severe. He was 

referred to Dr Swati Kanakia, Paediatric Hemato-Oncologist, 

Lilavati Hospital and Research Center, Mumbai. Based on 

complete blood count results, Dr Kanakia suspected Pratik 

may have thalassemia minor. 

Thalassemia is a genetic disorder in which 

the body produces low levels of functional 

haemoglobin. Haemoglobin is made up of 

alpha and beta chains. Depending on which 

protein levels are affected, a patient can have 

either alpha thalassemia or beta thalassemia. 

BASED ON THE SEVERITY 

OF CLINICAL FEATURES, 

ALPHA THALASSEMIA 

CAN BE CLASSIFIED AS A 

SILENT CARRIER 

Based on the severity of clinical features, 

alpha thalassemia can be classified as a silent 

carrier, thalassemia trait, haemoglobin H 

disease, or hydrops fetalis. Beta thalassemia 

can be classified as thalassemia minor, 

thalassemia intermediate or thalassemia 

major. Alpha thalassemia is caused due to 

mutations in the HBA1 or HBA2 gene on 

chromosome 

16, while beta thalassemia is caused due 

to mutations in the HBB gene on 

chromosome 11. 


Haemoglobin electrophoresis is a low cost, easily available 

test which takes only 24 hours and can rapidly confirm the 

diagnosis of beta thalassemia. It is therefore typically done 

first. However, alpha thalassemia cannot be detected by this 

method and requires genetic testing. Results on Pratik’s blood 

sample ruled out beta thalassemia. However, because of the 

persistent high RBC count and severe microcytosis, Dr Kanakia 

suggested genetic testing to look for mutations in the alpha 

haemoglobin chain. Genetic test results revealed a mutation 

in the HBA1 gene, confirming that Pratik was a silent carrier 

for alpha thalassemia. Similar genetic tests done on Pratik’s 

mother showed that she was also a silent carrier. However, her 

complete blood count results were absolutely normal, and she 

showed no signs of haemoglobin deficiency 

or microcytic anaemia. The reason for Pratik’s 

iron deficiency turned out to be because of 

his diet as he was predominantly on milk. Had 

the doctors not pursued the reason for his 

microcytic anaemia, Pratik and his mother’s 

alpha thalassemia silent carrier status might 

have gone undetected. 

With genetic testing conveniently 

available, screening for thalassemia should be 

considered in patients who seem to have iron 

deficiency anaemia with microcytic anaemia 

and high RBC counts. Correct diagnosis can 

prevent incorrect supplementation with 

iron and avoid excessive investigation in an 

attempt to treat ‘suspected’ refractory iron 

deficiency. Further, patients like Pratik, who 

are silent carriers, can be counselled so as to 

prevent thalassemia cases later. 

In India, beta thalassemia is much more 

prevalent than alpha thalassemia and is a 

major public health concern. Because of the 

need for genetic testing to confirm alpha 

thalassemia, it is likely that alpha thalassemia 

is under-reported as well. “The main goal is to 

prevent the birth of children with thalassemia 

major”, says Dr Kanakia. If Pratik’s father was 

also a carrier for alpha thalassemia, Pratik’s 

siblings could have a much more severe 

version of thalassemia that may require 

regular blood transfusions and even bone 

marrow transplantation. Treatment can be 

very expensive and heavily dependent on 

the availability of suitable donors for bone 

marrow transplantation. It is therefore 

important to screen for carriers of alpha and 

beta thalassemia. This will help in identifying 

future pregnancies that need to undergo 

prenatal testing to rule out severe forms of 

thalassemia. 

In an effort to aid patient education and 

prevent thalassemia major cases, Dr Kanakia 

and Kanakia Health Care have created a 

programme called Stop Thal, Screening for 

Thalassemia and Opting for Prevention. The 

programme helps one estimate the chances 

of having a completely normal, thalassemia 

minor, or thalassemia major child and would 

increase awareness amongst thalassemia 

patients and prove to be useful in reducing 

thalassemia major incidents. 



column 

the cellview 

Future of thalassemia care: 

An Indian perspective 

Screening, along with proper genetic counseling, can help 

eradicate the disease 

DR RAJANI KANTH 

VANGALA 

The author is medical 

scientist and former 

director of SGRF, 

Bangalore 

In the past few decades, there have 

been profound developments in the 

management of thalassemia around 

the world, as well as in India. Regular 

transfusion and iron chelation have 

drastically improved the quality of life for 

patients and transformed thalassemia from 

a fatal disease to a clinically manageable 

one. Regular transfusions to maintain pretransfusion 

haemoglobin levels to around 

9-10g/dl has reduced complications such 

as anaemia and compensatory bone 

marrow expansion. Repetitive transfusions 

lead to iron overload as each transfusion 

has 200mg of iron, leading to significant 

morbidity and mortality due to damage to 

the heart, liver and other organs. Patients in 

India develop iron overload complications 

like hypogonadism, hypothyroidism, 

hypoparathyroidism, diabetes mellitus and 

cardiac disorders in the second decade of 

life. Iron overload related hepatic diseases 

like cirrhosis and fibrosis are very poorly 

addressed in India. Some of the major 

obstacles leading to high mortality are poor 

availability of medical care, lack of safe 

and adequate red blood cell transfusions 

with high cost, and poor compliance with 

chelation therapy. Splenectomy, which is 

rare in western countries, is needed for 

many patients in India due to insufficient 

transfusions. Understanding these 

requirements, the major diagnostic and 

therapeutic approaches have changed. 

Use of MRI scanning to assess iron 

overload helps in understanding the 

patient condition better to tailor treatments 

with reduced co-morbidities. For cardiac 

iron overload, non-invasive MRO based 

relaxation parameters T2 and T2* are 

used frequently. Low T2* indicates high 

myocardial iron and is often associated 

with poor ventricular function, arrhythmias 

and a need for clinical intervention. With 

respect to therapies, there are increased 

instances of haematopoietic stem cell 

transplantation (HSCT) since 1982, as this 

gives a better chance of a cure. Even though 

the majority of HSCT have been done from 

HLA identical related donor, an unrelated 

but properly selected match can give good 

results too. Recently, more data is being 

generated about using cord-blood-based 

transplantation. In India, HSCT was not 

considered as a life-saving procedure but an 

elective option. However, with better quality 

of molecular tissue tying, conditioning 

regimens and support therapies, it is now 

accepted as the better option. As patients 

do not need life-long transfusions, it 

becomes cost-effective and sustainable. It 

is estimated that almost 12,000 children 

are born with thalassemia to parents who 

are asymptomatic carriers. The carrier 

population in India, at about 3.3%, is 

significant enough to give importance to 

various aspects like prevention too. There 

is a need to translate clinical and scientific 

data to the population at large to bring 

awareness, which in turn can enable 

preventive screening. Screening results, 

along with proper genetic counseling, 

can help eradicate the disease. In small 

countries like Cyprus, a near complete 

elimination was possible due to mandatory 

antenatal testing. We, in our country, have 

to evolve with possible mechanisms to 

enable people to overcome this disease. 


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medical practice 

VIOLENCE GOES 

VIRAL 

Doctors are the most vulnerable 

when it comes to workplace violence 

A 

research article 

published in the 

Indian Journal of 

Psychiatry claims that 

while violence against 

doctors is prevalent world 

over, Indian doctors face 

more violence as compared to those 

in western countries. Almost every day, 

we hear of patients getting violent 

against doctors for one reason or the 

other. 

This has been attributed to various 

factors like poor healthcare budget 

allocation by the government, scarcity 

of healthcare professionals and 

even a lack of training on empathy 

and communication in the medical 

curriculum. 

“It is the junior doctors that bear 

the brunt of physical violence by 

patients as per research,” 

says Dr Jateen Ukrani, 

consultant psychiatrist at PsyCare 

Neuropsychiatry Centre, Delhi and 

one of the authors of the research 

paper: Violence against doctors: A viral 

epidemic. 

He adds that “in emergency rooms, 

100% of doctors face some kind of 

verbal violence”. 

Often, government hospitals are 

poorly equipped to deal with the 

amount of patient load than what 

they actually receive, which makes the 

overall experience for the patient and 


the doctors stressful. This becomes a 

fertile soil for breeding violence. 

Another factor that contributes 

to this growing violence is the lack of 

training on effective communication in 

the medical curriculum. According to 

Dr Indla Ramasubba Reddy, a senior 

psychiatrist from VIMHANS Vijayawada, 

“Communication and empathy are 

not part of the medical curriculum. 

These are important for being a good 

medical professional. Psychiatrists can 

help improve communication skills for 

doctors and also help in identifying 

early indicators of violence”. 

Communication crucial 

Experts also point out that with the 

advancement of medical science, it has 

become more investigation-oriented 

which means there is less opportunity 

to talk and interact with the patient. 

Thus communication suffers, and 

patients often don’t understand the 

risks. This, combined with all other 

factors, has led to a higher rate of 

violence against doctors in India. This 

leads to many doctors becoming 

depressed or quitting the profession 

prematurely or not taking risky cases. 

“Women doctors are also not 

spared from violence and are often 

soft targets”, says Dr Varsha Ukrani, 

senior psychiatrist from Pandit Madan 

Mohan Malviya Hospital, Delhi. It is 

pointed out that those working in Obs 

& Gyn department are more prone to 

violence than any other department. 

Dr Vishal Indla, chief psychiatrist 

at VIMHANS, Vijayawada says doctors 

are the most vulnerable among 

all professionals when it comes to 

workplace violence due to various 

factors ranging from poor budget 

allocation for health and weak laws. 

The study suggests that though 

WOMEN DOCTORS ARE 

ALSO NOT SPARED FROM 

VIOLENCE AND ARE OFTEN 

SOFT TARGETS 

acts are in place in 19 states for 

protecting doctors against violence, 

these are not applied strictly, 

and till date, no convictions have been 

made. The government should work 

on improving the infrastructure and 

also on the proper implementation 

of these acts, which will reduce the 

burden of violence against doctors to 

a great extent. Further, doctors are 

advised to undergo workshops on the 

enhancement of communication 

skills and stress management to 

deal with such situations. It is also 

advised that institutions have a zero 

tolerance policy towards violence 

against their doctors, and that it 

must be reported to the authorities 

immediately. Such a thing is being 

done abroad and needs to be 

implemented in our country so that 

healthcare delivery is done in a safe 

and stress-free environment. 


esearch snippets 

Removal of damaged mitochondria 

may stop inflammatory diseases 

Elsa Sanchez-Lopez et al have 

discovered that eliminating damaged 

mitochondria before they trigger 

excessive inflammation may help 

alleviate chronic inflammatory diseases. 

NLRP3 inflammasome- a multiprotein 

oligomer is responsible for the activation 

of inflammatory responses in the body. 

However, during mitochondrial damage 

due to stress or bacterial toxins NLRP3 

can remain ‘switched on’ leading to 

excess inflammation. Researchers 

have found that NLRP3 is deactivated 

when damaged mitochondria are 

eliminated during cellular cycling 

called mitophagy. Scientists showed 

that mitophagy can be induced by 

inhibiting the uptake of the nutrient 

choline by mitochondria. Choline is 

taken up through specific transporters 

and metabolized by enzyme choline 

kinase (ChoK). Decreasing the uptake of 

choline altered the mitochondrial lipid 

profile, decreasing the ATP synthesis in 

mitochondria. This activates the energy 

sensor AMP-activated protein kinase 

(AMPK) which stimulates mitophagy. 

Choline uptake by cells was prevented 

by inhibiting choline transporter CTL1 or 

choline phosphorylation by using ChoK 

inhibitors. This attenuated the NLRP3 

inflammasome activation and IL-1β and 

IL-18 cytokine production in stimulated 

macrophages. Researchers also showed 

that on treating a mouse model of 

Muckle-Wells syndrome with ChoK 

inhibitors reversed the inflammation. 

The in vivo study 

in mice showed that treatment with 

ChoK inhibitors prevented acute 

inflammation caused by uric acid 

accumulation (seen in gout) 

and a bacterial toxin. ChoK 

inhibitor treatment also 

reversed chronic 

inflammation 

associated with a 

genetic disease 

called Muckle- 

Well Syndrome 

in mice which 

is caused by 

mutations in 

NLRP3 genes. 

Source: Cell Metabolism 

April 11, 2019 DOI: https://doi. 

org/10.1016/j.cmet.2019.03.011 

https://www.cell.com/cell- 

metabolism/fulltext/S1550-4131(19)30139- 

1#%20 

Faecal microbiota transfer could 

improve autism symptoms 

Dae-Wook Kang et al have 

demonstrated longterm 

beneficial effects of 

microbiota transfer therapy 

(MTT) in children with autism 

spectrum disorders (ASD). The 

researchers had previously 

conducted an open-label trial 

of microbiota transfer 

therapy in a cohort of 

18 children in 2017. 

The study involved 10 

weeks of treatment, 

including pre-treatment 

with vancomycin, a 

bowel cleanses, a 

stomach acid suppressant, and fecal 

microbiota transfer daily for seven to 

eight weeks. Two years since the study, 

a follow up conducted by researchers 

revealed significant improvements in 

gastrointestinal and autism-related 

symptoms in accordance with an 

increase in gut microbiota. Scientists 

reported a 45% decrease in ASD 

symptoms compared to baseline. At the 

start of the study, 83% of participants 

were rated to have severe autism. At the 

end of the study, only 17% were severe, 

39% were found to have moderate, 

and 44% were below the cut-off for 

moderate ASD. The findings showed 


Oxytocin could help treat alcohol dependence 

Brendan J. Tunstall et al demonstrated 

that administration of neuropeptide 

oxytocin may help normalize the alcohol 

use disorder and thereby help reduce 

alcohol addiction. The research was 

performed using alcohol-dependent 

rat models. The study demonstrated 

that oxytocin administered systemically, 

intranasally or into the brain blocked 

excess drinking in alcohol-dependent 

rats. Researchers found that the effect 

was specific to enhanced alcohol 

drinking problem in alcohol-dependent 

models as the procedure did not affect 

other normal behaviours or alcohol 

drinking in the alcohol-independent 

cohort. The researchers also found that 

the oxytocin blocked neurotransmitter 

gamma-aminobutyric acid (GABA) 

signalling in the central nucleus of the 

amygdala (CeA). CeA is a key brain 

region in the network affected by 

alcohol dependence. The study provides 

evidence suggesting that oxytocin likely 

blocks enhanced drinking by altering CeA 

GABA transmission. The findings provide 

evidence showing that aberrations in the 

oxytocin signalling may underlie alcohol 

use disorder which on targeting might 

prove a promising therapy in people who 

misuse alcohol. 

Source: PLOS Biology April 16, 2019 https://doi. 

org/10.1371/journal.pbio.2006421 

persistence of change in gut microbiota 

involving an increase in overall diversity 

and abundance of beneficial microbes 

including Bifidobacteria and Prevotella. 

The results encourage intensive MTT 

intervention as a promising therapy for 

treating children with ASD who have GI 

problems. The researchers recommend 

in conducting future research involving 

larger cohort trials. 

Source: Scientific Reports April 9, 2019 volume 9, 

Article number: 5821 (2019) https://www.nature. 

com/articles/s41598-019-42183-0 

Adiponectin plays key 

in male bias of liver 

cancer 

Elisa Manieri et al discovered that a 

decrease in a hormone secreted by 

fat cells is responsible for an increased 

risk of liver cancer in males. The 

levels of hormone adiponectin 

decrease in males during 

puberty which make them 

prone to a higher incidence 

of hepatocellular carcinoma 

(HCC) than women. HCC 

risk is also higher among 

obese individuals during 

which the body secretes 

low adiponectin levels. 

Researchers found that 

adiponectin protects against 

liver cancer development 

through the activation of AMPactivated 

protein kinase (AMPK) 

and p38α. The study showed that 

testosterone in males activates JNK 

protein (c-Jun N-terminal kinases) in 

human and mice adipocytes. JNK protein 

mediates inhibition of adiponectin 

which results in their lower secretion. 

The research also showed that genetic 

deletion of JNK1 in mouse adipose 

tissue resulted in higher adiponectin 

levels and protection against HCC. 

Quantification of circulating adiponectin 

in mice models detected more than 

twice the level in females than in males. 

This correlated with the vigorous growth 

of subcutaneously implanted mouse 

HCC-derived tumour cells in males than 

in females. Gender disparity in HCC was 

confirmed by subcutaneously injecting 

colon adenocarcinoma-derived tumour 

cells or melanoma-derived tumour in 

male and female mice models which 

showed no difference in growth patterns. 

The study unravels the relation between 

sex hormones and adipocytes signalling 

clarifying the disparity in liver cancer 

development. 

Source: Journal of Experimental Medicine April 

3, 2019 DOI: 10.1084/jem.20181288 http:// 

jem.rupress.org/content/early/2019/04/02/ 

jem.20181288 

Alcohol-induced brain 

damage continues 

after cessation 

Silvia De Santis et al show evidence 

in the progression of damage within 

the white matter of the brain during 

the initial period of alcohol cessation. 

The researchers used Diffusion 

Tensor Imaging (DTI), a magnetic 

resonance imaging-based 

technique capable of detecting 

the anisotropy of the brain’s 

white matter tracts. The study 

revealed that the damage 

in the brain could continue 

up to two to six weeks of 

abstinence from alcohol. The 

study involved 91 volunteers 

of average 46 years of age 

who had alcohol use disorder 

(AUD) and were interned for 

rehabilitation. A control group 

involving 36 men without alcohol 

problems with an average age 


of 41 years was also involved in the 

study. The findings showed comparable 

alterations in the white matter with 

intense preferential involvement of 

corpus callosum and fimbria which are 

connected with memory and decision 

making. The results were compared 

in parallel with rat models showing 

preference to alcohol consumption. 27 

male rats showing AUD were compared 

against 9 male control rats. The research 

reveals that the damage progression 

can still continue in the brain during 

initial abstinence from severe alcohol 

consumption. 

Source: JAMA Psychiatry April 3, 2019 

doi:10.1001/jamapsychiatry.2019.0318 https:// 

jamanetwork.com/journals/jamapsychiatry/articleabstract/2729425 

Electrostimulation 

can improve working 

memory in elderly 

Robert M. G. Reinhart et al 

demonstrated that electrostimulation 

can improve the working memory of 

older adults by temporarily reversing 

the age-related cognitive decline. The 

study involved 42 people aged 20–29 

years and 42 people aged 60–76 years 

and was assessed in a working memory 

task. The study showed that the core 

feature of cognitive decline was caused 

due to a disconnection between the two 

brain networks of the frontotemporal 

cortex. The researchers subjected the 

older participants to 25 minutes of noninvasive 

electrical stimulation across the 

brain using electrodes with frequency 

personalized to their individual brain 

circuits. After the stimulation the cohort 

showed a preferential increase in neural 

synchronization patterns between the 

frontotemporal regions of the brain. All 

participants were subjected to test their 

working memory. The results before 

and after stimulation were compared 

between the two cohorts. The findings 

revealed that the older participants 

showed a rapid improvement in working 

memory that lasted for 50 minutes post 

stimulation. The findings unveil a new 

approach towards non-pharmacological 

intervention in improving cognitive 

decline by targeting aspects of agerelated 

cognitive impairment. 

Source: Nature Neuroscience April 8,2019 https:// 

www.nature.com/articles/s41593-019-0371-x 

—Compiled by Divya Choyikutty 

Scientists `print’ 3D heart using patient’s own cells 

Nadav Noor et al have successfully 

printed the first 3D vascularised 

engineered heart using a patient’s 

own cells and biological materials. 

The researchers utilized biopsy of 

fatty tissue from the patient 

for the study. The cells were 

then reprogrammed to 

become pluripotent stem 

cells that differentiated 

into cardiomyocytes and 

endothelial cells. The 

extracellular matrix (ECM) 

which is a three-dimensional 

network of extracellular 

macromolecules such as collagen 

and glycoproteins were processed into 

personalized hydrogel that served as 

the printing ink. The two cell types were 

separately combined with the hydrogels 

to form the bio ink for parenchymal 

cardiac tissue and blood vessels. Blood 

vessel architecture was developed by 

mathematical modelling of oxygen 

transfer. The researchers demonstrated 

the ability to print functional, patient 

specific, immune-compatible cardiac 

patches with blood vessels forming the 

entire heart. The study thus revealed 

the first successful approach to 3D-print 

personalized, thick, vascularised and 

perfusable cardiac tissues which may 

be developed for drug screening and 

patient specific requirements in the 

future. 

Source: Advanced Science 15 April 2019 https:// 

doi.org/10.1002/advs.201900344 


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hospital news 

Everstone to buy controlling 

stake in Sahyadri Hospitals 

Everstone, an investment group, has 

agreed to buy a 51% stake in Sahyadri 

Hospitals Ltd (SHL). 

Pune-based Sahyadri Hospitals is the 

largest hospital chain in Maharashtra, 

founded in 1994. Currently, it operates 

five tertiary care and three secondary 

care hospitals with 750 beds across 

Pune, Nashik and Karad. Sahyadri has 

more than 1,000 clinicians and 2,300 

supporting staff, reports said. 

The transaction is expected to 

help Sahyadri further strengthen its 

position as the leading healthcare 

chain in Maharashtra and increase its 

bed-count significantly in the next five 

years. 

For Everstone, the deal will increase 

its exposure to India’s healthcare sector 

where it is already present in numerous 

segments such as pharmaceuticals and 

diagnostics. 

LVPEI completes 

100 transplants 

in rural India 

V Prasad Eye Institute (LVPEI) 

L performed its 100th corneal 

transplant in a rural eye care centre at 

Mudhole secondary eye centre. 

Started in March 2016 with a 

corneal transplant at the Institute’s 

Dhulipalla secondary eye centre in 

Guntur District, experts from LVPEI 

have collectively performed a hundred 

corneal transplants in a span of just 

three years across the secondary 

centre networks in Mudhole (Nirmal 

District), Dhulipalla (Guntur District), 

Venkatachalam (Nellore District) and 

Paloncha (Bhadradri Kothagudem 

District). 

“This achievement is an example 

of a road never travelled,” stated Dr 

Gullapalli N Rao, founder and chair, L V 

Prasad Eye Institute in a statement. 

India is home to half of the world’s 

blind population. Out of the 15 million 

blind people in the country, 6.8 million 

are victims of corneal blindness. This 

number is expected to rise to 10.6 

million by 2020. 

Healthcare sector outlook stable: ICRA 

India’s healthcare sector outlook remains 

stable despite regulatory headwinds, says 

ICRA, an Indian credit rating agency. 

The hospital sector’s performance has 

been falling in the last two years due to 

several regulatory restrictions, including 

demonetisation, the cap on prices of 

stents and knee implants by the National 

Pharmaceutical Pricing Authority (NPPA), 

stiff regulatory action by certain states 

and the implementation of the Goods and 

Services Tax (GST). 

In the latest order, issued on March 8, 

2019, the NPPA put a cap of 30 per cent 

on the trade margin earned on 390 drugs 

that are primarily used for treatment of 

cancer. The price cap led to a reduction of 

up to 87 per cent in the prices of the anticancer 

drugs. The current order by NPPA 

adds on to the list of products already 

placed under price restrictions. Most of 

the cancer-related drugs are high-value 

medicines and are sold directly through 

the hospital chains, oncology being one 

of the highest-value-added specialty for 

hospitals due to the increasing incidence 

of cancer-related ailments. Nonetheless, 

several oncology drugs are still out of the 

purview of the price cap. 

“The regulatory environment continues 

to be the overarching challenge for the 

hospital sector and the recent NPPA order 

reinforces this view. The wide-ranging 

regulatory restrictions from multiple 

authorities have suppressed the margins 

of the players,’’ said Shubham Jain, group 

head and vice president – corporate sector 

ratings, ICRA, in a statement. 

However, hospitals’ decision on 

repricing of service/product component of 

packages and usage of different drugs is 

expected to correct the lopsided pharma 

component margins and partly negate 

the impact of the current NPPA order, he 

noted. 


from the industry 

“OPHTHALMOLOGISTS ARE 

MOST OVERSTRETCHED IN 

INDIA, SO OUR AIM IS TO HELP 

THEM REMAIN STRAIN-FREE” 

With 15 million blinds, India is home for 50% of 

the world’s total blind population, according to 

a 2016 study by the World Health Organisation. 

While the status hasn’t changed much in the last two years, 

another most worrying fact is that the country is also one 

of the geographies in the world where the number of 

ophthalmologists in proportion to its total population is the 

lowest. And thus, it wasn’t a surprise that why the country was 

also infamous for the highest number of medical negligence 

in the area of eye care until recently. While the cases of 

negligence have significantly come down in the last few years, 

the credit to a great extent should go to the technology players 

who changed the scenario by bringing the much-needed 

sophistication into this field of care. Sandeep Bothra, Country 

Business Head- Surgical, Alcon Laboratories India, says that 

most of the recent technologies, those were introduced in 

the area of eye care in India, have visibly improved the way 

the diagnosis and procedures are done in the eye care setups 

and the emerging technologies will make the visualisation and 

diagnosis more easier and accurate, in an interview with editor 

CH Unnikrishnan. Edited excerpts: 

Eye care scenario in India has been quite challenging 

because of several factors including a shortage of 

ophthalmologists, lack of better training and infrastructure 

and accessibility issues with best technologies. Alcon has 

been in India for some time now and could you tell us what 

has been your experience so far and do you think the 

market has improved in terms of quality of care? 

Alcon as a global leader in eye care, we always try to 

discover new ways to enhance sight and improve patient lives. 

As we have been doing this successfully in this market through 

innovative products, partnerships with eye care professionals 

and programs that create greater access to quality eye care. 

We identify and develop technologies that deliver better visual 

outcomes and address unmet patient needs, continuously 

improving the options that exist today. Since our research 

team observes surgeries and visits clinics to gain real-world 

insights, we also regularly meet with 

eye care professionals to get their 

feedback on our products and their 

future needs. So, I can confidently say 

that the technology and training have 

significantly improved the situation in 

the Indian eye care. Also, the customers, 

as well as patients, have become quite 

demanding as they are already aware 

of the latest products and procedures. 

It is also evident from the change that 

the cases of medical negligence have 

come down drastically in recent time. 

And I am proud to say that our products 

touch the lives of millions of people 

each year living with conditions like 

cataracts, glaucoma, retinal diseases, 

and refractive errors. Since we are the 

only company that offers the complete 

line of ophthalmic surgical devices, as 

well as a differentiated contact lens and 

lens care portfolio, this also gives us a 

premium and most trusted position in 

the market. 

Alcon, through its social 

responsibility and advocacy efforts, 

also help to create sustainable access 

to eye care for patients around the 

world, thereby reducing the incidence 

of preventable blindness and visual 

impairment. By investing in professional 

education, the group help to advance 

the eye care industry and ultimately 

create better outcomes for patients and 

consumers. 

How do you see the pricing scenario 

here as the government is slowly 


vast country with varied needs and priorities depending 

on the profiles of different regions, optimising the 

market opportunities will depend on the adaptability 

of the players. Still, I feel the country offers ample 

opportunities for both national and international 

companies. 

As you know, India is also a very competitive as 

well as value conscious market with so many players, 

including foreign and local brands in the ophthalmic 

segment. So, what made you the largest and how do 

you maintain the leadership? 

The key factor that made us the market leader is 

the unparalleled reach that we have in this market. We 

are present in every corner of the market, spanning 

from one end to the other in the length and breadth 

of the country. In addition, we have the entire portfolio 

of products catering to every disease and age groups. 

The other important factor is the quality and innovation 

that we maintain in every class of product knowing our 

partners’ needs and helping them consistently with the 

latest technologies, enhancing their choice of practice. 

That’s why the surgeons love to work with us. 

bringing cost regulation on most 

medical devices, implants and 

health equipment? 

A couple of thoughts on this. 

No doubt, the intention of the 

government is noble as it wants to 

expand the access of healthcare 

to every stratum of society. But I 

would say, the opportunity in India 

for every segment is big enough 

for everybody. In general, I think 

the changes in market dynamics 

will ultimately depend on how 

these are rolled out and how agile 

are the companies to adapt to the 

changing requirements. India as a 

The key factor 

that made us the 

market leader is 

the unparalleled 

reach that we have 

in this market. We 

are present in every 

corner of the market, 

spanning from one 

end to the other in the 

length and breadth of 

the country. 

What are the key challenges in this market? 

In the current context, one of the challenges is how 

do you ensure that our products and services are 

available in the same quality across the country. For 

example, if we want to sell or service our products in 

Imphal or Mandya, Srinagar or Lakshadweep, I want 

to ensure the same quality of service that I provide in 

Mumbai or Delhi. But, managing the logistics of that is 

a big challenge in such a vast country. Just to explain 

the technical aspect of it, I would take the example 

of a cataract surgery, where there are two important 

equipment required—the main equipment and the 

library of implants. In this case, we have to reach the 

entire library even if the surgeon uses just one particular 

implant, which is decided at the surgery table. So, we 

need to make the stock available so that the doctor can 

do the surgery without compromising the quality. And 

this is about every geography and climatic conditions. 

Similarly, the doctors, though fundamentally they are 

the same everywhere, in India often need to balance 

the quality of work as well as the value proposition 

as the majority of the patients here still pay out of 

pocket. While the lack of patient awareness is a 

problem, the work pressure that is often faced by the 

overstretched surgeons in this branch of medicine is 

another big challenge. In India, there are only 12 to 13 

ophthalmologists for a million patients, which is much 

below the global average. So, we aim to overcome 

these challenges, both at the patient side as well as the 

clinical side using more innovative technologies. 


column 

trialomics 

Speedy approval vs 

safety? 

Unless Indian regulators develop in-house expertise, the 

fast-track approval for investigational drugs could put 

clinical trial participants at high risk 

DR ARUN BHATT 

Writer is a consultant 

on clinical research & 

development from 

Mumbai. 

arun_dbhatt@hotmail.com 

Recently released new Indian drug 

rules have been hailed as allowing 

fast and time-bound approval within 

30 calendar days for clinical trials of “Indian 

new drugs”. This step can improve “ease of 

business”, support “Make in India”, and will 

encourage innovation in drug discovery. But 

this is a major shift from the uncertain and 

long regulatory approval process of the last 

few years. Hence, the concern is how Indian 

health authorities (HA) plan to implement 

this. Will the expedited approval be at the 

cost of ensuring protection for Indian clinical 

trial participants? 

The rules define an “Indian new drug” 

as 1) a drug discovered in India, or (2) 

its research and development (R&D), 

manufacture, and marketing are done 

in India. Current Indian cost of R&D, 

extrapolated from Dr Mashelkar 

committee’s 1999 estimate of Rs 150 crores, 

would be Rs 500 crores. In contrast, the 

US R&D cost estimate of $ 2.6 billion (Tufts 

Center 2016) or Rs 19,500 crores is 39 

times higher! Considering the tremendous 

cost advantage, quicker approval and 

faster completion of clinical trials, western 

companies would find it commercially 

attractive to develop a new drug in India 

in collaboration with an Indian partner. 

Such collaborations will boost Indian drug 

research capabilities. 

New drug development begins with 

phase I trials. In this first-in-human (FIH) trial, 

serious adverse events (SAE) can jeopardize 

the safety of clinical trial participants. In 

2006, TGN1412 resulted in life-threatening 

multiorgan failure in all 6 healthy volunteers 

who received the first dose of the drug. In 

2016, BIA 10-2474 caused the death of a 

healthy volunteer and SAEs in 4 participants 

who received the drug. Hence, thorough riskbenefit 

assessment of an investigational new 

drug (IND) is essential before approving FIH 

clinical trial. 

US Food and Drug Administration (FDA) 

allows a pharma company to initiate 

phase I trial 30-days after receiving IND 

application. But FDA can place the trial 

on-hold if it finds that human subjects 

would be exposed to unreasonable and 

significant risk. FDA has an in-house team 

of pharmacologists, toxicologists and clinical 

pharmacologists to review IND application. 

Indian HA depends on IND committee for 

review and approval of the phase I trial. 

This committee, consisting of ICMR experts 

and other consultants, meets at intervals 

of 2-3 months to review pre-clinical data - 

animal pharmacology, pharmacokinetic, 

and toxicity - and decide whether the phase 

I trial should be approved. The committee 

may ask for additional pre-clinical data or 

modifications in the clinical trial protocol. 

For Indian R&D based pharma companies, 

which have complained about long and 

unpredictable IND review process, the new 

30-day clinical trial approval is a dream 

come true. However, unless Indian HA 

develop in-house expertise or establish a 

fast track IND committee process before the 

30-day approval rule and have well-defined 

post-approval oversight process and clinical 

hold rules, Indian clinical trial participants 

will be at high risk from investigational new 

drugs. 


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devices&gadgets 

Breakthrough status to 

preeclampsia device 

Targeted Apheresis 

Column for Preeclampsia 

(TAC-PE) has been 

granted a Breakthrough 

Device Designation by the 

USFDA, Advanced Prenatal 

Therapeutics announced. 

The device specifically 

removes disease-causing 

factors such as sFlt-1 from the 

mother’s blood. It is intended 

to treat preeclampsia, a 

leading cause of prematurity 

and maternal/foetal death, 

and holds the potential to 

substantially reduce 

mortality, incidence or 

severity of preterm birth, and 

the use of neonatal intensive 

care. 

The company is now 

preparing for initial clinical 

studies using the device. 

The FDA grants 

Breakthrough Device 

Designation to devices 

that provide more effective 

treatment of life-threatening 

or irreversibly debilitating 

diseases. Devices must also 

represent a breakthrough 

technology, treat a disease 

where no approved 

alternatives exist, offer 

significant advantages 

over existing approved 

alternatives, or otherwise 

be in the best interest of 

patients. 

501k clearance for pain drug delivery device 

Avanos Medical has 

received US FDA 501(k) 

clearance for its ON-Q with 

bolus pump. 

The new ON-Q with 

bolus design incorporates 

improvements that make it 

simpler for providers and 

patients to use while reducing 

postoperative opioid use to 

achieve pain management. 

The new ON-Q bolus 

provides customised control 

for patients recovering 

from post-surgical pain by 

delivering continuous, nonopioid 

medication to the 

surgical site or peripheral 

nerves for up to five days. 

The bolus pump is 

ergonomically designed to fit 

comfortably in the patient’s 

hand with an easy to remove 

the priming tab and large 

level indicator markings. The 

device can also be used for 

incisional applications. 

Studies have shown that 

using bolus rates as low 

as 3 ml in addition to the 

basal rate can reduce the 

total amount of anaesthetic 

needed for pain relief. ON-Q 

is indicated to significantly 

reduce opioid use for surgical 

patients and provide better 

pain relief than opioids alone, 

helping patients to get back 

to normal faster after surgery. 


located on the top face and 

both sides of the monitor for 

easy access and comfort. 

Omron developed 

Complete in partnership with 

AliveCor, the market leader 

in FDA-cleared personal EKG 

technology. Complete uses 

the advanced new algorithm 

designed by AliveCor for 

improved detection of the 

possibility of Afib along with 

trusted medical-grade blood 

pressure measurement from 

Omron. 

Complete is the recipient 

of the iF Design Award 2019, 

presented by iF International 

Forum Design GmbH. 

US FDA approves 

novel portable 

gas exchange 

monitor 

T 

he US FDA has approved 

the Gas Exchange Monitor, 

a portable respiratory 

monitoring device. 

The device provides realtime, 

clinically actionable 

data measuring pulmonary 

gas exchange in a wide 

Contec 

Americas 

launches medical 

monitors 

Contec Americas Inc has 

developed a new line 

of medical-grade monitors 

to meet the stringent 

image quality and safety 

requirements of clinical 

applications. The initial release 

of seven displays features 

DICOM Part 14 image quality 

and IEC 60601 compliance 

with medical safety and 

performance standards. 

The monitors are designed 

for original equipment 

manufacturers (OEMs) looking 

for versatile, long life solutions 

suited for a wide variety 

of hospital and laboratory 

applications. 

Contec’s new clinical 

displays range in size from 

15” to 27” and include 5-wire 

resistive touch and projected 

capacitive touch (PCAP) 

options. 

The Legacy group features 

a 4:3 aspect ratio. 

Contec’s Modern 

line boasts a sleek, 

contemporary 

look, 16:9 

widescreen 

aspect ratio, high 

brightness up to 350 

nits, wide viewing angles 

up to 178 degrees and trueflat 

front, IP65 rating for easy 

cleaning and sanitation. 

Contec’s new clinical 

display line is part of a series 

of new products which will be 

introduced in 2019. 

Omron 

introduces home 

BP monitor with 

EKG capability 

Omron Healthcare has 

secured USFDA clearance 

on its new Complete, the 

first blood pressure monitor 

with EKG capability in a single 

device. 

Complete is an upper 

arm blood pressure monitor 

that allows users to 

simultaneously monitor EKG 

and blood pressure readings 

at home. EKG readings can 

be measured by touching 

electrodes conveniently 

Tack endovascular system for 

PAD gets US FDA approval 

Intact Vascular, Inc has received 

the US FDA approval for the 

Tack Endovascular System (6F), a 

dissection repair device implanted 

post-angioplasty in patients with 

the peripheral arterial disease 

(PAD). 

The approval was based on 

data from Intact Vascular’s Tack 

Optimized Balloon Angioplasty 

II (TOBA II) pivotal trial, which 

demonstrated the safety and 

effectiveness of the Tack implant 

to resolve dissections following 

angioplasty. 

The inflation of an angioplasty 

balloon and resulting mechanical 

stress inherently injures vessels 

and creates dissections. If left 

untreated, dissections can 

compromise clinical outcomes, 

resulting in acute thrombosis and 

arterial occlusions, leading to lower 

long-term patency rates and repeat 

procedures. 

The TOBA II pivotal trial, 

notably the first peripheral 

vascular study to enroll 

patients with 100% 

dissected vessels, met all 

primary endpoints with 

92% of dissections completely 

resolved following treatment, the 

company reported. 


variety of respiratory disease, 

manufactured and marketed 

by MediPines. 

The Novel physiologic 

results on world elite 

freedivers’ using the noninvasive 

gas exchange 

monitor were presented at 

the Experimental Biology 

2019 conference. The 

new device makes it now 

possible for a non-invasive 

portable measurement that 

can support evaluation and 

trending of pulmonary gas 

exchange status of a patient 

in a point of care setting. 

Freedivers place 

themselves in extreme 

conditions, which push the 

outer limits of human lung 

physiology and can lead 

to a high oxygen deficit. 

The device provided rapid 

feedback to the research 

team tasked with assessing 

the freedivers’ gas exchange 

status. 

Baxter launches 

haemostatic 

product 

Floseal Hemostatic Matrix 

has been granted approval 

by the USFDA, Baxter 

International announced. 

Floseal has 20 per cent 

fewer components and steps 

to prepare, making it easier 

and faster for operating room 

(OR) nurses to get Floseal 

in the hands of surgeons to 

help stop bleeding during 

procedures. 

The device has been 

proven to perform quickly and 

consistently across a range of 

bleeds in surgical procedures. 

A 13cm Malleable Applicator 

is included with every kit that 

allows surgeons to maneuver 

the product into the proper 

position. 

In this latest design, the 

diluent ampoule has been 

replaced by pre-filling the 

existing mixing syringe so 

that Floseal can be prepared 

more quickly than the current 

configuration. 

Both active and passive 

adjunctive haemostatic 

Cryotherapy device to treat 

heavy menstrual bleeding 

Cerene cryotherapy device 

has been granted approval 

by US FDA as a new approach 

to treating heavy menstrual 

bleeding. 

The device uses cryotherapy 

to freeze the endometrial 

lining of the uterus to reduce 

future menstrual bleeding in 

premenopausal women who 

are not planning to become 

pregnant. 

This procedure does not 

require general anaesthesia. It 

can, therefore, be performed 

in the gynaecologist’s office 

in contrast, heat-based 

endometrial ablation devices 

which are more often 

performed with general 

anaesthesia in hospitals. 

CLARITY, the pivotal study 

supporting the safety and 

effectiveness of the Cerene 

device and its FDA approval 

included treatment of 242 

subjects. 

At 12 months, the observed 

reduction in menstrual bleeding 

exceeded treatment goals. 


agents are available to help 

control bleeding in surgical 

procedures when ligature or 

conventional methods are 

ineffective or impractical. 

US FDA approves 

Duaklir inhaler 

for COPD 

The US FDA has approved 

Duaklir Pressair for the 

maintenance treatment of 

chronic obstructive pulmonary 

disease (COPD). 

Duaklir Pressair combines 

aclidinium bromide, a longacting 

muscarinic antagonist 

(LAMA), and 

formoterol fumarate, a 

long-acting beta2 -adrenergic 

agonist (LABA). It is intended 

for twice-daily use with the 

breath-actuated Pressair 

inhaler. 

The approval was 

supported by data from the 

phase 3 ACLIFORM, AUGMENT, 

and AMPLIFY studies which 

included patients with 

moderate to very severe 

COPD. 

Results showed that 

treatment with Duaklir 

Pressair led to a statistically 

significant increase in mean 

change from baseline in 

trough FEV1 and change from 

baseline in 1-hour post-dose 

FEV1 at week 24 relative to 

formoterol fumarate 12mcg 

and aclidinium 400mcg, 

respectively. 

Circassia who is planning 

to launch Duaklir in the US in 

the second half of 2019 via its 

dedicated COPD sales force. 

Medtronic 

launches spinal 

device for pain 

management 

Medtronic has launched 

Intellis platform for the 

management of certain types 

of chronic intractable pain. 

EU nod for endoscopic ablation system 

HeartLight X3 Endoscopic 

Ablation System has 

received European CE 

Mark approval for ablation 

treatment for atrial 

fibrillation. 

HeartLight X3 

Endoscopic Ablation System 

is a third-generation 

technology building upon 

the advanced features of 

the HeartLight Endoscopic 

Ablation System, which 

performs pulmonary vein 

isolation (PVI) using laser 

The platform was designed 

to overcome limitations with 

current spinal cord stimulation 

(SCS) systems, such as battery 

performance, and can power 

the Evolve workflow, which 

standardises guidance and 

balances high-dose (HD) 

and low-dose (LD) therapy 

settings. 

It can record and track 

patient activity 24/7 and is 

managed on the Samsung 

Galaxy Tab S2 tablet interface, 

enabling physicians to address 

the subjective and personal 

nature of chronic pain by 

monitoring progress and 

making modifications to better 

suit their patients’ therapy 

needs. 

Intellis platform can help 

optimize treatment and 

improve patient-physician 

energy to create lines 

of scar tissue to block 

the abnormal electrical 

pathways that cause AFib. 

Using direct tissue 

visualization, titratable 

laser energy, and compliant 

balloon technology, the 

HeartLight X3 System’s 

unique RAPID mode 

leverages a precise motor 

control system that enables 

uninterrupted, high-speed, 

circumferential lesion 

creation under the direct 

communication by tracking 

and sharing daily activities, 

body positions and therapy 

usage and by giving physicians 

an objective look at mobility 

and progress. 

The device also addresses 

a common patient complaint: 

battery recharge issues. 

control of the physician 

resulting in consistently 

reduced procedure times. 

In the pivotal 

confirmatory evaluation of 

60 patients, the HeartLight 

X3 System consistently 

achieved very rapid PVI, in 

as few as three minutes for 

a single vein. The trial also 

found that the System has 

the potential to complete 

all required ablations in less 

than 20 minutes. 

With Medtronic’s proprietary 

Overdrive battery technology, 

the Intellis battery can be fully 

recharged from empty to full 

in approximately one hour and 

physicians can now estimate 

recharge intervals based on 

therapy settings. 

Additional advances in 

the device include secure 

wireless Samsung Galaxy Tab 

S2 programmers for physicians 

that enable faster delivery 

of evolving workflows and 

software upgrades. 

Medtronic neurostimulation 

therapy for chronic intractable 

pain uses a medical device 

placed under a patient’s 

skin to deliver mild electrical 

impulses through a lead 

implanted in the epidural 

space to block pain signals 

from going to the brain. 


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AMRITA CENTRE 

FOR ROBOTIC 

SURGERY 

TRAINING 

Started in 2016, the centre has trained 

over 250 surgeons from all over India in 

robotic assisted surgery 

NARRATION: DR SHIVANEE SHAH 

Technology in surgery has seen 

several leaps of advances in 

the past few decades;. from 

conventional open surgeries to minimally 

invasive procedures such as laparoscopic 

techniques, video-assisted thoracoscopic 

surgeries and more recently, robotic 

assisted minimally invasive surgeries. 

These innovations and technological 

advances are primarily focused on 

improving surgical procedures so that 

the final outcome in terms of hospital 

stay, procedural time, blood-loss, and 

post-operative complications such as 

infections and pain, are considerably 

reduced. 

Robot-assisted minimally invasive 

procedures are a fairly recent 

development in the field of surgical 

science. These types of procedures 

mainly involve the use of computer 

assistance for performing an array of 

surgical manipulations through the 

smallest of incisional openings. The 

use of robotic assistance has several 

known benefits, including improved 

procedural dexterity, ergonomics, 

safety and ease of surgery, all of which 

translate to improved patient outcomes. 

Some of the major surgical specialties 

that have embraced robotic assisted 

procedures include gynecology, urology, 

gastroenterology, and thoracic surgery. 

In terms of the actual procedure, 

one of the primary advantages of using 

robotic assistance is the magnification 

of the surgical field that is available 

to the surgeon. To put this in context, 

surgical procedures performed under 

conventional techniques do not allow 

any magnification of the surgical site, 

while moderate magnification (2.5 times) 

is obtained in laparoscopic techniques. 

However, robotic assisted methods allow 

up to 10 times magnification, which 

by far is a significant improvement 

compared to its predecessors, and also 

makes a huge difference in how the 


I was trained at McGill 

University, Montreal, 

Canada, and now 

it’s my turn to train 

others. 

Dr Anupama R 

Robotic Surgeon and 

Professor in Gynecologic 

Oncology, Amrita Institute 

of Medical Sciences, Kochi 

surgeon makes operative decisions 

during the procedure. The second and 

perhaps the most important advantage 

that robotic assistance provides is the 

way surgical instruments are negotiated 

within the surgical site. In open 

surgeries, the surgeon directly holds 

the instruments, while in laparoscopic 

techniques, the surgeon uses the 

instruments by viewing them through a 

screen that is connected to a peripheral 

camera. However, in robotic assisted 

procedures, the surgeon maneuvers the 

instruments via a console. This consolebased 

control of surgical instruments, in 

addition to the enhanced magnification 

of the surgical site, provides the surgeon 

with an increased ability to be dexterous 

and perform difficult surgical maneuvers 

with ease. 

Simple to learn 

Considering the advantages offered 

by the newer, minimally invasive 


techniques, it would appear that their 

acceptance would be widespread. 

However, adapting to viewing through 

a camera in laparoscopic techniques 

and maneuvering instruments through 

an indirect console in robotic assisted 

techniques is something that needs 

skill-based adaptation for the surgeons. 

Even leading surgeons may be unwilling 

to perform procedures involving 

newer techniques without training. 

A well-known example is that of Dr. 

Robert Cerfolio, previously at University 

of Alabama and presently Chief of 

Clinical Thoracic Surgery, NYU Langone 

Center, New York, who is a leader in 

the field of thoracic surgery and has 

performed thousands of thoracic 

surgical procedures. According to Dr 

Balasubramoniam K. R., Cardiothoracic 

Surgeon at Amrita Institute of Medical 

Sciences, Kochi, “Even though Dr 

Cerfolio had performed countless 

open surgeries, he was initially 

unable to adapt to the video-assisted 

thoracoscopic surgeries. Nonetheless, 

Dr. Cerfolio went on to do thousands 

of robotic assisted surgeries and is 

currently one of the leading surgeons 

utilizing robotic assisted techniques 

in his field.” Dr Balasubramoniam 

underwent robotic surgery training 

at the University of Alabama and has 

since then performed over 150 robotic 

assisted surgeries in the past few 

years at Amrita Hospital. He recognizes 

the true benefits of this technology 

and highly recommends the need 

for training and procuring the skills 

required for performing robotic assisted 

surgeries. 

Such advances in technology 

undoubtedly come with unique 

challenges in terms of bringing 

surgeons up to speed and can require 

significant training to develop the 

special skill sets required to use 

the new technology. While all new 

techniques require training, some 

techniques are easier to master. 

Robotic-assisted techniques are simple 

to learn, and due to the significant 

improvements and benefits of using 

robotic assistance, surgeons worldwide 

are embracing this technology. 

However, formal training and 

competency assessment are required. 

Many of our renowned, experienced 

Indian surgeons have had to go 

abroad to complete training for robotic 

assisted surgeries, spending money 

and valuable time out of the country. A 

training centre in India was a growing 

need, and this was accomplished in 

2016. 

Dr A K K Unni, Professor and Head, 

Central Animal Facility, Amrita Institute 

of Medical Sciences, Kochi, explained to 

me how it all came about over a cup 

of tea and cookies. “Intuitive Surgical 

Inc. reached out to our Medical Director 

to set up a training center at Amrita 

hospital. Why Amrita you may ask? One 

of the major requirements of a training 

DUE TO THE BENEFITS OF 

USING ROBOTIC ASSISTANCE, 

SURGEONS WORLDWIDE 

ARE EMBRACING THIS 

TECHNOLOGY 

centre is an animal facility where 

training can be undertaken in large 

animals. Amrita hospital already had 

a large animal facility and was able to 

provide the necessary support required. 

Being a leading center for postgraduate 

education and research, we also felt 

that there was a dire necessity for 

training potential surgeons in robotic 

surgical techniques.’ 

The first and until very recently, the 

only robotic surgery training center 

in India, Amrita Centre for Robotic 

Surgery Training and Animal Cath Lab 

is a productive collaboration between 

Intuitive Surgical Inc., and Amrita Institute 

of Medical Sciences. This is a symbiotic 

relationship where Intuitive Surgical Inc, 

which is the only company that makes 

the da Vinci system for robotic assisted 

surgeries, provides trainers for the 

robotic assistance equipment and Amrita 

Hospital provides the infrastructure, 

manpower, facilities and the animals 

required for training. 

Eligibility criteria 

Dr Unni has laid out some basic 

requirements for the training programme 

to ensure that the programme is not 

misused. He has put in place a minimum 

academic qualification of MS or MCh for 

a surgeon to be eligible for this training 

programme. The surgeon’s affiliation 

hospital must have their own robotic unit 

or the surgeon should have prior robotic 

surgery exposure. Further, the surgeon’s 

institute must give an assurance that 

the surgeon would be allowed to pursue 

and utilize his training skills after the 

training is completed. Once the surgeon 

is found to be eligible to undergo the 

training programme, he/she must first go 

through an online course before visiting 

Amrita for a 1-day training session. The 

session starts with dry training on the 

state of the art da Vinci surgical system 

to familiarize the trainee with the system 

and the instruments, followed by wet 


training where surgeons get handson 

training on anesthetized pigs. They 

undergo training that covers a series of 

exercises, including dissection, ligation of 

vessels, suturing and energy applications. 

At the end of the day, the trainees are 

evaluated and then provided a certificate 

for this basic training. So far, about 250 

surgeons from all over India have been 

trained and qualified from the Amrita 

Center for Robotic Surgery Training. 

The surgeons are also requested to 

provide feedback on the training facility 

and the programme, and the feedback 

has been extremely positive so far. 

The training does not end there. All 

surgeons who undergo basic training are 

recommended to observe real surgeries 

before performing their first robotic 

procedure on a patient. Then, to finally 

complete the training, they are required 

to perform 3-4 cases in the presence of 

a proctor. There is however no sign off or 

certificate provided at this stage. 

Cadaver training 

As of 2017, In addition to the basic 

training in collaboration with Intuitive 

Surgical, Amrita also offers an advanced 

training programme for specialist 

surgeons that involves training on 

cadavers. Trained and experienced 

robotic surgeons with expertise in 

various specialties provide training 

for this advanced programme. I was 

fortunate to catch Dr Anupama R, 

Robotic Surgeon and Professor in 

Gynecologic Oncology at Amrita Institute 

of Medical Sciences, Kochi, between 

surgeries. She was instrumental in setting 

up the Minimally Invasive and Robotic 

Surgery Programme at Department of 

Gynecologic Oncology in February 2015 

and since then has performed over 500 

robotic surgeries. She has also been 

instrumental in the training programme 

at Amrita and proctors for other trainees 

across the country as well. When 

asked how she manages training and 

proctoring with her busy schedule, Dr 

Anupama says, ‘‘I was trained at McGill 

University, Montreal, Canada, and now it’s 

my turn to train others.’’ 

While Amrita Centre for Robotic 

Surgery Training remains the only animal 

training facility in India, very recently, a 

basic training center has been started in 

Ramaiah Medical College, Bengaluru. This 

new facility is currently equipped only 

for training on cadaver models. Animal 

training, however, will remain critical for 

getting real, hands-on experience as a 

first step towards patient surgeries. 

Based on trainee conversions and 

surgical outcomes in patients, Amrita 

Centre for Robotic Surgery Training 

has been ranked as the best training 

center outside USA by Intuitive Surgicals, 

which is a great achievement for all the 

management and staff involved. Dr Unni 

has set still higher goals and is in talks 

with IRCAD, a renowned training center 

in France, in an effort to make Amrita 

Centre for Robotic Surgery Training one 

of the best International training centers 

in the world. 

This is part of a series that features India’s 

First & Most Unique institutions, facilities, 

technologies, products etc in the medical and 

healthcare space. 


guidelines 

URINARY 

INCONTINENCE 


PELVIC ORGAN 

PROLAPSE IN WOMEN 

Urinary incontinence can be a result of functional 

abnormalities in the lower urinary tract or of illnesses. 

Stress urinary incontinence is involuntary urine leakage 

on effort, exertion, sneezing or coughing. Urgency urinary 

incontinence is involuntary urine leakage accompanied or 

immediately preceded by urgency (a sudden compelling 

desire to urinate that is difficult to delay). Mixed urinary 

incontinence is involuntary urine leakage associated with 

both urgency and exertion, effort, sneezing or coughing. 

Overactive bladder (OAB) is defined as urgency that occurs 

with or without urgency urinary incontinence and usually with 

frequency and nocturia. 

Pelvic organ prolapse is defined as symptomatic descent 

of 1 or more of the anterior vaginal wall, the posterior vaginal 

wall, the cervix or uterus, or the apex of the vagina (vault 

or cuff). Symptoms include a vaginal bulge or sensation 

of something coming down, urinary, bowel and sexual 

symptoms, and pelvic and back pain. These symptoms affect 

women's quality of life. 

The prevalence of pelvic organ prolapse is high; in primary 

care in the UK, 8.4% of women reported vaginal bulge or 

lump, and on examination, prolapse is present in up to 50% 

of women. One in 10 women will need at least 1 surgical 

procedure, and the rate of re‐operation is as high as 19%. 

There is likely to be an increasing need for surgery for urinary 

incontinence and pelvic organ prolapse because of the ageing 

population, according to National Institute for Health and Care 

Excellence (NICE),UK. 

1.1 Organisation of specialist 

services 

Local multidisciplinary teams 

1.1.1 Local multidisciplinary teams (MDTs) 

for women with primary stress urinary 

incontinence, overactive bladder or 

primary prolapse should: 

• review the proposed treatment for 

all women offered invasive procedures 

for primary stress urinary incontinence, 

overactive bladder or primary prolapse 

• review the proposed management 

for women with primary stress urinary 

incontinence, overactive bladder or 

primary prolapse if input from a wider 

range of healthcare professionals is 

needed 

• work within an established clinical 

network that has access to a regional 

MDT. 

1.1.2 Local MDTs for women with primary 

stress urinary incontinence, overactive 

bladder or primary prolapse should 

include: 

• 2 consultants with expertise in 

managing urinary incontinence in 

women and/or pelvic organ prolapse 

• a urogynaecology, urology or 

continence specialist nurse 

• a pelvic floor specialist 

physiotherapist 

• and may also include: 

• a member of the care of the elderly 

team 

• an occupational therapist 

• a colorectal surgeon. 

1.1.3 Members of the local MDT (listed in 

recommendation 1.1.2) should attend all 

local MDT meetings. 

Regional multidisciplinary teams 

1.1.4 Regional MDTs that deal with 

complex pelvic floor dysfunction and 

mesh-related problems should review 

the proposed treatment for women if: 

• they are having repeat continence 

surgery 

• they are having repeat, same-site 

prolapse surgery 

• their preferred treatment option is 

not available in the referring hospital 

• they have coexisting bowel problems 

that may need additional colorectal 

intervention 

• vaginal mesh for prolapse is a 

treatment option for them 

• they have mesh complications or 

unexplained symptoms after mesh 

surgery for urinary incontinence or 

prolapse 

• they are considering surgery and 

may wish to have children in the 

future. 



mesh-related problems should include: 

• a subspecialist in urogynaecology 

• a urologist with expertise in female 

urology 

• a urogynaecology, urology or 

continence specialist nurse 

• a pelvic floor specialist 

physiotherapist 

• a radiologist with expertise in pelvic 

floor imaging 

• a colorectal surgeon with expertise 

in pelvic floor problems 

• a pain specialist with expertise in 

managing pelvic pain 

• and may also include: 

• a healthcare professional trained 


in bowel biofeedback and trans-anal 

irrigation 

• a clinical psychologist 

• a member of the care of the elderly 

team 

• an occupational therapist 

• a surgeon skilled at operating in the 

obturator region 

• a plastic surgeon. 



mesh-related problems should have 

ready access to the following services: 

• psychology 

• psychosexual counselling 

• chronic pain management 

• bowel symptom management 

• neurology. 

1.1.7 Members of the regional MDT (listed 

in recommendation 1.1.5) should attend 

regional MDT meetings when their 

specific expertise is needed. 

1.2 Collecting data on surgery and 

surgical complications 

1.2.1 Ask women having surgery 

for stress urinary incontinence or 

pelvic organ prolapse, or who have 

experienced complications related 

to these types of surgery, for their 

consent to enter the data listed in 

recommendation 1.2.2 in a national 

registry. Give each woman a copy of her 

data. 

1.2.2 Providers must ensure that 

the following data are recorded in a 

national registry of surgery for urinary 

incontinence and pelvic organ prolapse 

in women: 

• the woman's NHS number 

• hospital and consultant identifiers 

• date and details of the procedure 

• for procedures involving mesh, the 

mesh material, manufacturer, product 

unique identification code and type of 

sutures used 

• for procedures involving 

colposuspension, the type of sutures 

used 

• for procedures involving bulking 

agent, the bulking material, 

manufacturer and product unique 

identification code 

• date and details of any investigation 

for complications 

• date and details of any surgical 

or non-surgical intervention for 

complications. 

1.2.3 The national registry of surgery for 

urinary incontinence and pelvic organ 

prolapse in women must ensure that 

follow‐up data are collected on key 

short- and long-term (at least 5 years) 

outcomes, including: 

• validated relevant outcome 

measures 

• adverse events including pain 

• suspected and confirmed meshrelated 


1.2.4 The national registry of surgery 

for urinary incontinence and pelvic 

organ prolapse in women should report 

annually and be quality assured. 

1.3 Assessing urinary incontinence 

History taking and physical 

examination 

1.3.1 At the initial clinical assessment, 

categorise the woman's urinary 

incontinence as stress urinary 

incontinence, mixed urinary incontinence 

or urgency urinary incontinence/ 

overactive bladder. Start initial 

treatment on this basis. In mixed urinary 

incontinence, direct treatment towards 

the predominant symptom. 

1.3.2 If stress incontinence is the 

predominant symptom in mixed urinary 

incontinence, discuss with the woman 

the benefit of non-surgical management 

and medicines for overactive bladder 

before offering surgery. 

1.3.3 During the clinical assessment seek 

to identify relevant predisposing and 

precipitating factors and other diagnoses 

that may require referral for additional 

investigation and treatment. 

Assessing pelvic floor muscles 

1.3.4 Undertake routine digital 

assessment to confirm pelvic floor 

muscle contraction before the use of 

supervised pelvic floor muscle training 

for the treatment of urinary incontinence. 

Urine testing 

1.3.5 Undertake a urine dipstick test 

in all women presenting with urinary 

incontinence to detect the presence of 

blood, glucose, protein, leucocytes and 

nitrites in the urine. 

1.3.6 If women have symptoms of 

urinary tract infection (UTI) and their 

urine tests positive for both leucocytes 

and nitrites, send a midstream urine 

specimen for culture and analysis 

of antibiotic sensitivities. Prescribe 

an appropriate course of antibiotic 

treatment pending culture results. 

See the NICE guideline on urinary 

tract infection (lower): antimicrobial 

prescribing for more information. 

1.3.7 If women have symptoms of UTI 

and their urine tests negative for either 

leucocytes or nitrites, send a midstream 

urine specimen for culture and analysis 

of antibiotic sensitivities. Consider the 

prescription of antibiotics pending 

culture results. 

1.3.8 If women do not have symptoms 

of UTI, but their urine tests positive for 

both leucocytes and nitrites, do not 

offer antibiotics without the results of 

midstream urine culture. 

1.3.9 If a woman does not have 

symptoms of UTI and her urine tests 

negative for either leucocytes or nitrites, 

do not send a urine sample for culture 

because she is unlikely to have UTI. 

Assessing residual urine 

1.3.10 Measure post-void residual volume 

by bladder scan or catheterisation in 

women with symptoms suggestive of 

voiding dysfunction or recurrent UTI. 

1.3.11 Use a bladder scan in preference 

to catheterisation on the grounds of 

acceptability and lower incidence of 

adverse events. 

Symptom scoring and quality-of-life 

assessment 

1.3.12 Use a validated urinary 

incontinence-specific symptom and 

quality-of-life questionnaire when 

therapies are being evaluated. 

Bladder diaries 

1.3.13 Use bladder diaries in the initial 

assessment of women with urinary 

incontinence or overactive bladder. 

Encourage women to complete a 


minimum of 3 days of the diary covering 

variations in their usual activities, such as 

both working and leisure days. 

Pad testing 

1.3.14 Do not use pad tests in the routine 


incontinence. 

Urodynamic testing 

1.3.15 Do not perform multichannel 

filling and voiding cystometry before 

primary surgery if stress urinary 

incontinence or stress-predominant 

mixed urinary incontinence is diagnosed 

based on a detailed clinical history and 

demonstrated stress urinary incontinence 

at examination. 

1.3.16 After undertaking a detailed 

clinical history and examination, 

perform multichannel filling and voiding 

cystometry before surgery for stress 

urinary incontinence in women who have 

any of the following: 

• urge-predominant mixed urinary 

incontinence or urinary incontinence in 

which the type is unclear 

• symptoms suggestive of voiding 

dysfunction 

• anterior or apical prolapse 

• a history of previous surgery for 

stress urinary incontinence. 

Other tests of urethral competence 

1.3.17 Do not use the Q‐tip, Bonney, 

Marshall and Fluid-Bridge tests in the 


incontinence. 

Cystoscopy 

1.3.18 Do not use cystoscopy in the 

initial assessment of women with urinary 

incontinence alone. 

Imaging 

1.3.19 Do not use imaging (MRI, CT, 

X‐ray) for the routine assessment of 

women with urinary incontinence. Do 

not use ultrasound other than for the 

assessment of residual urine volume. 

Indications for referral to a specialist 

service 

1.3.20 In women with urinary 

incontinence, indications for 

consideration for referral to a specialist 

service include: 

• persisting bladder or urethral pain 

• palpable bladder on bimanual or 

abdominal examination after voiding 

• clinically benign pelvic masses 

• associated faecal incontinence 

• suspected neurological disease 

• symptoms of voiding difficulty 

• suspected urogenital fistulae 

• previous continence surgery 

• previous pelvic cancer surgery 

• previous pelvic radiation therapy. 

1.3.21 Follow the recommendations on 

referral for urinary tract cancer in the 

NICE guideline on suspected cancer, for 

women with haematuria or recurrent or 

persistent unexplained UTI. 

1.4 Non-surgical management of 

ADVISE WOMEN WITH 

URINARY INCONTINENCE OR 

OVERACTIVE BLADDER WHO 

HAVE A BMI GREATER THAN 

30 TO LOSE WEIGHT 

urinary incontinence 

Lifestyle interventions 

1.4.1 Recommend a trial of caffeine 

reduction to women with overactive 

bladder. 

1.4.2 Consider advising women with 

urinary incontinence or overactive 

bladder and a high or low fluid intake to 

modify their fluid intake. 

1.4.3 Advise women with urinary 

incontinence or overactive bladder who 

have a BMI greater than 30 to lose 

weight. 

Physical therapies 

Pelvic floor muscle training 

1.4.4 Offer a trial of supervised pelvic 

floor muscle training of at least 3 

months' duration as first-line treatment 

to women with stress or mixed urinary 

incontinence. 

1.4.5 Pelvic floor muscle training 

programmes should comprise at least 8 

contractions performed 3 times per day. 

1.4.6 Do not use perineometry or pelvic 

floor electromyography as biofeedback 

as a routine part of pelvic floor muscle 

training. 

1.4.7 Continue an exercise programme if 

pelvic floor muscle training is beneficial. 

Electrical stimulation 

1.4.8 Do not routinely use electrical 

stimulation in the treatment of women 

with overactive bladder. 

1.4.9 Do not routinely use electrical 

stimulation in combination with pelvic 

floor muscle training. 

1.4.10 Electrical stimulation and/or 

biofeedback should be considered for 

women who cannot actively contract 

pelvic floor muscles to aid motivation 

and adherence to therapy. 

Behavioural therapies 

1.4.11 Offer bladder training lasting 

for a minimum of 6 weeks as first-line 

treatment to women with urgency or 

mixed urinary incontinence. 

1.4.12 If women do not achieve 

satisfactory benefit from bladder 

training programmes, the combination 

of an overactive bladder medicine with 

bladder training should be considered if 

frequency is a troublesome symptom. 

Neurostimulation 

1.4.13 Do not offer transcutaneous sacral 

nerve stimulation (surface electrodes 

placed above the sacrum, often known 

as transcutaneous electrical nerve 

stimulation [TENS]) to treat overactive 

bladder in women. 

1.4.14 Do not offer transcutaneous 

posterior tibial nerve stimulation for 

overactive bladder. 

1.4.15 Do not offer percutaneous 

posterior tibial nerve stimulation (needles 

inserted close to the posterior tibial 

nerve) for overactive bladder unless: 

• there has been a local MDT review 

and 

• non-surgical management including 

overactive bladder medicine treatment 

has not worked adequately and 


slug 

• the woman does not want 

botulinum toxin type A or 

percutaneous sacral nerve stimulation. 

Absorbent containment products, 

urinals and toileting aids 

1.4.16 Do not offer absorbent 

containment products, hand-held 

urinals or toileting aids to treat urinary 

incontinence. Offer them only: 

• as a coping strategy pending 

definitive treatment 

• as an adjunct to ongoing therapy 

• for long-term management of 

urinary incontinence only after 

treatment options have been explored. 

1.4.17 Offer a review at least once a year 

to women who are using absorbent 

containment products for long-term 

management of urinary incontinence. 

The review should cover: 

• routine assessment of continence 

• assessment of skin integrity 

• changes to symptoms, comorbidities, 

lifestyle, mobility, medication, BMI, and 

social and environmental factors 

• the suitability of alternative 

treatment options 

• the efficacy of the absorbent 

containment product the woman is 

currently using and the quantities 

used. 

1.4.18 Reviews for women who are 

using absorbent containment products 

for long-term management of urinary 

incontinence should be carried out by 

either: 

• a registered healthcare professional 

who is trained in assessing continence 

and making referrals to specialist 

services or 

• a non-registered healthcare worker, 

under the supervision of a registered 

healthcare professional who is trained 

in assessing continence and making 

referrals to specialist services. 

Catheters 

1.4.19 Bladder catheterisation 

(intermittent or indwelling urethral or 

suprapubic) should be considered for 

women in whom persistent urinary 

retention is causing incontinence, 

symptomatic infections or renal 

dysfunction, and in whom this cannot 

otherwise be corrected. Healthcare 

professionals should be aware, and 

explain to women, that the use 

of indwelling catheters in urgency 

urinary incontinence may not result in 

continence. 

1.4.20 Offer intermittent urethral 

catheterisation to women with urinary 

retention who can be taught to selfcatheterise 

or who have a carer who can 

perform the technique. 

1.4.21 Give careful consideration to the 

impact of long-term indwelling urethral 

catheterisation. Discuss the practicalities, 

benefits and risks with the woman or, 

if appropriate, her carer. Indications for 

the use of long-term indwelling urethral 

catheters for women with urinary 

incontinence include: 

• chronic urinary retention in 

OFFER INTERMITTENT 

URETHRAL CATHETERISATION 

TO WOMEN WITH URINARY 

RETENTION WHO CAN 

BE TAUGHT TO SELF- 

CATHETERISE OR WHO HAVE 

A CARER WHO CAN PERFORM 

THE TECHNIQUE 

women who are unable to manage 

intermittent self-catheterisation 

• skin wounds, pressure ulcers or 

irritations that are being contaminated 

by urine 

• distress or disruption caused by bed 

and clothing changes 

• where a woman expresses 

a preference for this form of 

management. 

1.4.22 Indwelling suprapubic catheters 

should be considered as an alternative 

to long-term urethral catheters. Be 

aware, and explain to women, that they 

may be associated with lower rates 

of symptomatic UTI, 'bypassing', and 

urethral complications than indwelling 


urethral catheters. 

Products to prevent leakage 

1.4.23 Do not use intravaginal and 

intraurethral devices for the routine 

management of urinary incontinence 

in women. Do not advise women to 

consider such devices other than for 

occasional use when necessary to 

prevent leakage, for example during 

physical exercise. 

Complementary therapies 

1.4.24 Do not recommend 

complementary therapies for the 

treatment of urinary incontinence or 


Medicines for overactive bladder 

1.4.25 Before starting treatment with a 

medicine for overactive bladder, explain 

to the woman: 

• the likelihood of the medicine being 

successful 

• the common adverse effects 

associated with the medicine 

• that some adverse effects of 

anticholinergic medicines, such as dry 

mouth and constipation, may indicate 

that the medicine is starting to have 

an effect 

• that she may not see substantial 

benefits until she has been taking the 

medicine for at least 4 weeks and 

that her symptoms may continue to 

improve over time 

• that the long-term effects of 

anticholinergic medicines for 

overactive bladder on cognitive 

function are uncertain. 

1.4.26 When offering anticholinergic 

medicines to treat overactive bladder, 

take account of the woman's: 

• coexisting conditions (such as 

poor bladder emptying, cognitive 

impairment or dementia) 

• current use of other medicines that 

affect total anticholinergic load 

• risk of adverse effects, including 

cognitive impairment. 

1.4.27 For women who have a 

diagnosis of dementia and for whom 

anticholinergic medicines are an 

option, follow the recommendations 


on medicines that may cause cognitive 

impairment in the NICE guideline on 

dementia. 

Choosing medicine 

1.4.28 Do not offer women flavoxate, 

propantheline or imipramine to treat 

urinary incontinence or overactive 

bladder. 

1.4.29 Do not offer oxybutynin 

(immediate release) to older women 

who may be at higher risk of a sudden 

deterioration in their physical or mental 

health. 

1.4.30 Offer the anticholinergic medicine 

with the lowest acquisition cost to treat 

overactive bladder or mixed urinary 

incontinence in women. 

1.4.31 If the first medicine for overactive 

bladder or mixed urinary incontinence 

is not effective or well-tolerated, offer 

another medicine with a low acquisition 

cost. 

1.4.32 Offer a transdermal overactive 

bladder treatment to women unable to 

tolerate oral medicines. 

1.4.33 For guidance on mirabegron, see 

the NICE technology appraisal guidance 

on mirabegron for treating symptoms of 


1.4.34 The use of desmopressin may be 

considered specifically to reduce nocturia 

in women with urinary incontinence 

or overactive bladder who find it a 

troublesome symptom. Use particular 

caution in women with cystic fibrosis 

and avoid in those over 65 years with 

cardiovascular disease or hypertension. 

1.4.35 Do not use duloxetine as a 

first-line treatment for women with 

predominant stress urinary incontinence. 

Do not routinely offer duloxetine as a 

second-line treatment for women with 

stress urinary incontinence, although it 

may be offered as second-line therapy 

if women prefer pharmacological to 

surgical treatment or are not suitable 

for surgical treatment. If duloxetine is 

prescribed, counsel women about its 

adverse effects. 

1.4.36 Do not offer systemic hormone 

replacement therapy to treat urinary 

incontinence. 

1.4.37 Offer intravaginal oestrogens to 

treat overactive bladder symptoms in 

postmenopausal women with vaginal 

atrophy. 

Reviewing medicine 

1.4.38 Offer a face-to-face or telephone 

review 4 weeks after starting a new 

medicine for overactive bladder. Ask 

the woman if she is satisfied with the 

treatment and: 

• if improvement is optimal, continue 

treatment 

• if there is no or suboptimal 

improvement, or intolerable adverse 

effects, change the dose or try an 

alternative medicine for overactive 

THE USE OF DESMOPRESSIN 

MAY BE CONSIDERED 

SPECIFICALLY TO REDUCE 

NOCTURIA IN WOMEN WITH 

URINARY INCONTINENCE WHO 

FIND IT A TROUBLESOME 

SYMPTOM 

bladder (see recommendations 1.4.31 

and 1.4.32), and review again 4 weeks 

later. 

1.4.39 Offer a review before 4 weeks 

if the adverse events of a medicine for 

overactive bladder are intolerable. 

1.4.40 Refer women who have tried 

taking medicine for overactive bladder, 

but for whom it has not been successful 

or tolerated, to secondary care to 

consider further treatment. 

1.4.41 Offer a further face-to-face 

or telephone review if a medicine 

for overactive bladder or urinary 

incontinence stops working after an 

initial successful 4‐week review. 

1.4.42 Offer a review in primary care 

to women who remain on long-term 

medicine for overactive bladder or 

urinary incontinence every 12 months, or 

every 6 months if they are aged over 75. 

Invasive procedures for overactive 

bladder 

1.4.43 For women with overactive 

bladder that has not responded to 

non-surgical management or treatment 

with medicine and who wish to discuss 

further treatment options: 


• offer urodynamic investigation 

to determine whether detrusor 

overactivity is causing her overactive 

bladder symptoms and 

• if detrusor overactivity is causing 

her overactive bladder symptoms, 

offer an invasive procedure in line with 

recommendations 1.4.44 to 1.4.56 or 

• if there is no detrusor overactivity, 

seek advice on further management 

from the local MDT in line with 

recommendation 1.4.45. 

Botulinum toxin type A injection 

1.4.44 After a local MDT review, offer 

bladder wall injection with botulinum 

toxin type A to women with overactive 

bladder caused by detrusor overactivity 

that has not responded to non-surgical 

management, including pharmacological 

treatments. 

1.4.45 Consider treatment with 

botulinum toxin type A after a local MDT 

review for women with symptoms of 

overactive bladder in whom urodynamic 

investigation has not demonstrated 

detrusor overactivity, if the symptoms 

have not responded to non-surgical 

management and the woman does not 

wish to have other invasive treatments. 

1.4.46 After a local MDT review, discuss 

the benefits and risks of treatment with 

botulinum toxin type A with the woman 

and explain: 

• the likelihood of complete or partial 

symptom relief 

• the process of clean intermittent 

catheterisation, the risks, and how 

long it might need to be continued 

• the risk of adverse effects, including 

an increased risk of urinary tract 

infection 

• that there is not much evidence 

about how long the injections work for, 

how well they work in the long term 

and their long-term risks. 

1.4.47 Start treatment with botulinum 

toxin type A only if the woman is willing, 

in the event of developing significant 

voiding dysfunction: 

• to perform clean intermittent 

catheterisation on a regular basis for 

as long as needed or 

• to accept a temporary indwelling 

catheter if she is unable to perform 

clean intermittent catheterisation. 

1.4.48 Use 100 units as the initial dose 

of botulinum toxin type A to treat 

CONSIDER TREATMENT 

WITH BOTULINUM TOXIN 

TYPE A AFTER A LOCAL 

MDT REVIEW FOR WOMEN 

WITH SYMPTOMS OF 

OVERACTIVE BLADDER 

overactive bladder in women. 

1.4.49 Offer a face-to-face or telephone 

review within 12 weeks of the first 

treatment with botulinum toxin type A 

to assess the response to treatment and 

adverse effects, and: 

• if there is good symptom relief, 

tell the woman how to self-refer for 

prompt specialist review if symptoms 

return, and offer repeat treatment as 

necessary 

• if there is inadequate symptom relief, 

consider increasing subsequent doses 

of botulinum toxin type A to 200 units 

and review within 12 weeks 

• if there was no effect, discuss with 

the local MDT. 

1.4.50 If symptom relief has been 

adequate after injection of 100 units of 

botulinum toxin type A but has lasted for 

less than 6 months, consider increasing 

subsequent doses of botulinum toxin 

type A to 200 units and review within 12 

weeks. 

1.4.51 Do not offer botulinum toxin type 

B to women with overactive bladder. 

Percutaneous sacral nerve stimulation 

1.4.52 Offer percutaneous sacral 

nerve stimulation to women after 

local or regional MDT review if their 

overactive bladder has not responded 

to non-surgical management including 

medicines and: 

• their symptoms have not responded 

to botulinum toxin type A or 

• they are not prepared to accept 

the risks of needing catheterisation 

associated with botulinum toxin type 

A. 

1.4.53 Discuss the long-term implications 

of percutaneous sacral nerve stimulation 

with women including: 

• the need for test stimulation and 

probability of the test's success 

• the risk of failure 

• the long-term commitment 

• the need for surgical revision 

• the adverse effects. 

1.4.54 Tell women how to self-refer for 

prompt specialist review if symptoms 

return following a percutaneous sacral 

nerve stimulation procedure. 

Augmentation cystoplasty 

1.4.55 Restrict augmentation cystoplasty 

for the management of idiopathic 

detrusor overactivity to women whose 

condition has not responded to nonsurgical 

management and who are 

willing and able to self-catheterise. 

Preoperative counselling for the 

woman or her carer should include 

common and serious complications: 

bowel disturbance, metabolic acidosis, 


mucus production and/or retention in 

the bladder, UTI and urinary retention. 

Discuss the small risk of malignancy 

occurring in the augmented bladder. 

Provide life-long follow‐up. 

Urinary diversion 

1.4.56 Urinary diversion should be 

considered for a woman with overactive 

bladder only when non-surgical 

management has failed, and if botulinum 

toxin type A, percutaneous sacral 

nerve stimulation and augmentation 

cystoplasty are not appropriate or are 

unacceptable to her. Provide life-long 

follow‐up. 

1.5 Surgical management of stress 

urinary incontinence 

There is public concern about the use 

of mesh procedures. For all of the 

procedures recommended in this section, 

including mesh procedures, there is 

evidence of benefit but limited evidence 

on the long-term adverse effects. In 

particular, the true prevalence of longterm 

complications is unknown. 

1.5.1 If a woman is thinking about a 

surgical procedure for stress urinary 

incontinence, use the NICE patient 

decision aid on surgery for stress urinary 

incontinence to promote informed 

preference and shared decision making. 

Discussion with the woman should 

include: 

• the benefits and risks of all surgical 

treatment options for stress urinary 

incontinence that NICE recommends, 

whether or not they are available 

locally 

• the uncertainties about the longterm 

adverse effects for all procedures, 

particularly those involving the 

implantation of mesh materials 

• differences between procedures 

in the type of anaesthesia, expected 

length of hospital stay, surgical 

incisions and expected recovery period 

• any social or psychological factors 

that may affect the woman's decision. 

1.5.2 If non-surgical management 

for stress urinary incontinence has 

failed, and the woman wishes to think 

about a surgical procedure, offer 

her the choice of: 

• colposuspension (open or 

laparoscopic) or 

• an autologous rectus fascial sling. 

Also include the option of a retropubic 

mid-urethral mesh sling in this 

choice but see recommendations 

1.5.7 to 1.5.11 for additional guidance 

on the use of mid-urethral mesh 

sling procedures for stress urinary 

incontinence. 

1.5.3 Consider intramural bulking agents 

to manage stress urinary incontinence if 

alternative surgical procedures are not 

suitable for or acceptable to the woman. 

Explain to the woman that: 

• these are permanent injectable 

materials 

• repeat injections may be needed to 

achieve effectiveness 

• limited evidence suggests that they 

DO NOT OFFER A 

TRANSOBTURATOR 

APPROACH UNLESS THERE 

ARE SPECIFIC CLINICAL 

CIRCUMSTANCES 

are less effective than the surgical 

procedures listed in recommendation 

1.5.2 and the effects wear off over 

time 

• there is limited evidence on longterm 

effectiveness and adverse events. 

1.5.4 If an intramural bulking agent 

is injected, give the woman written 

information about the bulking agent, 

including its name, manufacturer, date 

of injection, and the injecting surgeon's 

name and contact details. 

1.5.5 If the woman's chosen procedure 

for stress urinary incontinence is not 

available from the consulting surgeon, 

refer her to an alternative surgeon. 

1.5.6 Providers must ensure that data 

on surgical procedures for stress urinary 

incontinence are recorded in a national 

registry, as outlined in the section on 

collecting data on surgery and surgical 

complications in this guideline. 

Mid-urethral mesh sling procedures 

1.5.7 When offering a retropubic midurethral 

mesh sling, advise the woman 

that it is a permanent implant and 

complete removal might not be possible. 

1.5.8 If a retropubic mid-urethral mesh 

sling is inserted, give the woman written 

information about the implant, including 

its name, manufacturer, date of insertion, 

and the implanting surgeon's name and 

contact details. 

1.5.9 When planning a retropubic midurethral 

mesh sling procedure, surgeons 

should: 

• use a device manufactured from 

type 1 macroporous polypropylene 

mesh 

• consider using a retropubic midurethral 

mesh sling coloured for high 

visibility, for ease of insertion and 

revision. 

1.5.10 Do not offer a transobturator 

approach unless there are specific 

clinical circumstances (for example, 

previous pelvic procedures) in which the 

retropubic approach should be avoided. 

1.5.11 Do not use the 'top‐down' 

retropubic mid-urethral mesh sling 

approach or single-incision sub-urethral 

short mesh sling insertion except as part 

of a clinical trial. 

Artificial urinary sphincters 

1.5.12 Do not offer women an artificial 

urinary sphincter to manage stress 

urinary incontinence unless previous 

surgery has failed. 

1.5.13 For women who have had an 

artificial urinary sphincter inserted: 

• offer postoperative follow‐up and 

• ensure access to review if needed. 

Procedures that should not be offered 

1.5.14 Do not offer women the following 

procedures to treat stress urinary 

incontinence: 

• anterior colporrhaphy 

• needle suspension 

• paravaginal defect repair 

• porcine dermis sling 


• the Marshall–Marchetti–Krantz 

procedure. 

Follow-up after surgery 

1.5.15 Offer a follow‐up appointment 

within 6 months to all women who have 

had a surgical procedure to treat stress 

urinary incontinence. 

1.5.16 For women who have had 

retropubic mid-urethral mesh sling 

surgery, the follow‐up appointment 

should include a vaginal examination to 

check for exposure or extrusion of the 

mesh sling. 

1.5.17 Providers should ensure that 

women who have had surgery for stress 

urinary incontinence have access to 

further referral if they have recurrent 

symptoms or suspected complications. 

See also assessing complications 

associated with mesh surgery in this 

guideline. 

1.5.18 For women whose primary surgical 

procedure for stress urinary incontinence 

has failed (including women whose 

symptoms have returned): 

• seek advice on assessment and 

management from a regional MDT 

that deals with complex pelvic floor 

dysfunction or 

• offer the woman advice about 

managing urinary symptoms if she 

does not wish to have another surgical 

procedure, and explain that she can 

ask for a referral if she changes her 

mind. 

1.6 Assessing pelvic organ prolapse 

1.6.1 For women presenting in primary 

care with symptoms or an incidental 

finding of vaginal prolapse: 

• take a history to include symptoms 

of prolapse, urinary, bowel and sexual 

function 

• do an examination to rule out a 

pelvic mass or other pathology and to 

document the presence of prolapse 

(see the sections on ovarian cancer 

and bladder cancer in the NICE 

guideline on suspected cancer) 

• discuss the woman's treatment 

preferences with her, and refer if 

needed. 

1.6.2 For women referred to secondary 

care for an unrelated condition who have 

incidental symptoms or an incidental 

finding of vaginal prolapse, consider 

referral to a clinician with expertise in 

prolapse. 

1.6.3 For women who are referred for 

specialist evaluation of vaginal prolapse, 

perform an examination to: 

• assess and record the presence 

and degree of prolapse of the 

anterior, central and posterior vaginal 

compartments of the pelvic floor, using 

the POP‐Q (Pelvic Organ Prolapse 

Quantification) system 

• assess the activity of the pelvic floor 

muscles 

• assess for vaginal atrophy 

• rule out a pelvic mass or other 

pathology. 

1.6.4 For women with pelvic organ 

prolapse, consider using a validated 

pelvic floor symptom questionnaire to 

aid assessment and decision making. 

1.6.5 Do not routinely perform imaging 

to document the presence of vaginal 

prolapse if a prolapse is detected by 

physical examination. 

1.6.6 If the woman has symptoms of 

prolapse that are not explained by 

findings from a physical examination, 

consider repeating the examination with 

the woman standing or squatting, or at a 

different time. 

1.6.7 Consider investigating the following 

symptoms in women with pelvic organ 

prolapse: 

• urinary symptoms that are 

bothersome and for which surgical 

intervention is an option 

• symptoms of obstructed defaecation 

or faecal incontinence (the NICE 

guideline on faecal incontinence 

in adults has recommendations 

on baseline assessment of faecal 

incontinence) 


• pain 

• symptoms that are not explained by 

examination findings. 

1.7 Non-surgical management of 

pelvic organ prolapse 

1.7.1 Discuss management options with 

women who have pelvic organ prolapse, 

including no treatment, non-surgical 

treatment and surgical options, taking 

into account: 

• the woman's preferences 

• site of prolapse 

• lifestyle factors 

• comorbidities, including cognitive or 

physical impairments 

• age 

• desire for childbearing 

• previous abdominal or pelvic floor 

surgery 

• benefits and risks of individual 

procedures. 

Lifestyle modification 

1.7.2 Consider giving advice on lifestyle 

to women with pelvic organ prolapse, 

including information on: 

• losing weight, if the woman has a 

BMI greater than 30 kg/m2 

• minimising heavy lifting 

• preventing or treating constipation. 

Topical oestrogen 

1.7.3 Consider vaginal oestrogen for 

women with pelvic organ prolapse 

and signs of vaginal atrophy. For 

recommendations on managing 

urogenital atrophy, see managing shortterm 

menopausal symptoms in the NICE 

guideline on menopause. 

1.7.4 Consider an oestrogen-releasing 

ring for women with pelvic organ 

prolapse and signs of vaginal atrophy 

who have cognitive or physical 

impairments that might make vaginal 

oestrogen pessaries or creams difficult 

to use. 

Pelvic floor muscle training 

1.7.5 Consider a programme of 

supervised pelvic floor muscle training 

for at least 16 weeks as a first option for 

women with symptomatic POP‐Q (Pelvic 

Organ Prolapse Quantification) stage 1 

or stage 2 pelvic organ prolapse. If the 

programme is beneficial, advise women 

to continue pelvic floor muscle training 

afterwards. 

Pessaries 

1.7.6 Consider a vaginal pessary for 

women with symptomatic pelvic organ 

prolapse, alone or in conjunction with 

supervised pelvic floor muscle training. 

1.7.7 Refer women who have chosen a 

pessary to a urogynaecology service if 

pessary care is not available locally. 

1.7.8 Before starting pessary treatment: 

• consider treating vaginal atrophy 

with topical oestrogen 

• explain that more than 1 pessary 

fitting may be needed to find a 

suitable pessary 

• discuss the effect of different types 

of pessary on sexual intercourse 

• describe complications including 

vaginal discharge, bleeding, difficulty 

removing pessary and pessary 

expulsion 

• explain that the pessary should 

be removed at least once every 6 

months to prevent serious pessary 


1.7.9 Offer women using pessaries 

an appointment in a pessary clinic 

every 6 months if they are at risk of 

complications, for example because 

of a physical or cognitive impairment 

that might make it difficult for them to 

manage their ongoing pessary care. 

1.8 Surgical management of pelvic 

organ prolapse 

There is public concern about the use 

of mesh procedures. For all of the 

procedures recommended in this section, 

including mesh procedures, there is 

some evidence of benefit, but limited 

evidence on long-term effectiveness and 

adverse effects. In particular, the true 

prevalence of long-term complications is 

unknown. 

1.8.1 Offer surgery for pelvic organ 

prolapse to women whose symptoms 

have not improved with or who have 

declined non-surgical treatment. 

1.8.2 If a woman is thinking about a 

surgical procedure for pelvic organ 

prolapse, use a decision aid (use the 

NICE patient decision aids on surgery 

for uterine prolapse and surgery for 

vaginal vault prolapse where they apply) 

to promote informed preference and 

shared decision making. Discussion with 

the woman should include: 

• the different treatment options for 

pelvic organ prolapse, including no 

treatment or continued non-surgical 

management 

• the benefits and risks of each 

surgical procedure, including changes 

in urinary, bowel and sexual function 

• the risk of recurrent prolapse 

• the uncertainties about the longterm 

adverse effects for all procedures, 

particularly those involving the 

implantation of mesh materials 

• differences between procedures 

in the type of anaesthesia, expected 

length of hospital stay, surgical 

incisions and expected recovery period 

• the role of intraoperative prolapse 

assessment in deciding the most 

appropriate surgical procedure. 

1.8.3 Do not offer surgery to prevent 

incontinence in women having 

surgery for prolapse who do not have 

incontinence. 

1.8.4 Explain to women considering 

surgery for anterior or apical prolapse 

who do not have incontinence that there 

is a risk of developing postoperative 

urinary incontinence and further 

treatment may be needed. 

1.8.5 If the woman's chosen procedure 

for pelvic organ prolapse is not available 

from the consulting surgeon, refer her to 

an alternative surgeon. 

1.8.6 If mesh is to be used in prolapse 

surgery: 

• explain to the woman about the 

type of mesh that will be used and 

whether or not it is permanent 

• ensure that details of the procedure 

and its subsequent short- and longterm 

outcomes are recorded in a 

national registry (see collecting data 

on surgery and surgical complications 

in this guideline) 

• give the woman written information 

about the implant, including its name, 

manufacturer, date of insertion, and 


the implanting surgeon's name and 

contact details. 

1.8.7 Providers must ensure that data 

on surgical procedures for pelvic organ 

prolapse are recorded in a national 

registry, as outlined in the section on 


complications in this guideline. 

Surgery for uterine prolapse 

1.8.8 Discuss the options for treatment 

(see recommendation 1.8.2), including 

non-surgical options, hysterectomy and 

surgery that will preserve the uterus, 

with women who have uterine prolapse. 

1.8.9 For women considering surgery for 

uterine prolapse: 

• discuss the possible complications 

and the lack of long-term evidence on 

the effectiveness of the procedures 

• use the NICE patient decision aid on 

surgery for uterine prolapse to discuss 

the benefits and risks of treatment, 

including non-surgical options. 

1.8.10 For women with uterine prolapse 

who have no preference about 

preserving their uterus, offer a choice of: 

• vaginal hysterectomy, with or 

without vaginal sacrospinous fixation 

with sutures or 

• vaginal sacrospinous hysteropexy 


• Manchester repair. 

Also include the option of sacrohysteropexy 

with mesh (abdominal 

or laparoscopic) in this choice but see 

recommendation 1.8.6 for specific 

guidance on the use of mesh in prolapse 

surgery. 

1.8.11 For women with uterine prolapse 

who wish to preserve their uterus, offer 

a choice of: 

• vaginal sacrospinous hysteropexy 


• Manchester repair, unless the 

woman may wish to have children in 

the future. 

Also include the option of sacrohysteropexy 

with mesh (abdominal 

or laparoscopic) in this choice but see 

recommendation 1.8.6 for specific 

guidance on the use of mesh in prolapse 

surgery. 

1.8.12 If a synthetic polypropylene mesh 

is inserted, the details of the procedure 


outcomes must be collected in a 

national registry (see collecting data on 

surgery and surgical complications in this 

guideline). 

1.8.13 Ensure the proposed treatment 

is reviewed by a regional MDT (see 

recommendation 1.1.4) if the woman 

wishes to have children in the future. 

Surgery for vault prolapse 



non-surgical and surgical options, with 

women who have vault prolapse. 

1.8.15 For women considering surgery for 

vault prolapse: 

• discuss the possible complications 

A SYNTHETIC 

POLYPROPYLENE MESH IS 

INSERTED, THE DETAILS OF 

THE PROCEDURE AND ITS 

SUBSEQUENT SHORT- AND 

LONG-TERM OUTCOMES MUST 

BE COLLECTED 

and the lack of long-term evidence on 

the effectiveness of the procedures 

• use the NICE patient decision aid 

on surgery for vaginal vault prolapse 

to discuss the benefits and risks of 

treatment, including non-surgical 

options. 

1.8.16 Offer women with vault prolapse a 

choice of: 

• vaginal sacrospinous fixation with 

sutures or 

• sacrocolpopexy (abdominal or 

laparoscopic) with mesh. 

See recommendation 1.8.6 for 

specific guidance on the use of mesh in 

prolapse surgery. 

1.8.17 If a synthetic polypropylene mesh 

is inserted, the details of the procedure 


outcomes must be collected in a 

national registry (see collecting data on 

surgery and surgical complications in this 

guideline). 

Colpocleisis for vault or uterine 

prolapse 

1.8.18 Consider colpocleisis for women 

with vault or uterine prolapse who do 

not intend to have penetrative vaginal 

sex and who have a physical condition 

that may put them at increased 

risk of operative and postoperative 


Surgery for anterior prolapse 



non-surgical and surgical options, with 

women who have anterior prolapse. 

1.8.20 Offer anterior repair without mesh 

to women with anterior vaginal wall 

prolapse. 

1.8.21 Consider synthetic polypropylene 

or biological mesh insertion for women 

with recurrent anterior vaginal wall 

prolapse only after: 

• regional MDT review and 

• discussion with the woman about 

the risks of mesh insertion (see 

recommendation 1.8.2) 

and if: 

• apical support is adequate or 

• an abdominal approach is 

contraindicated. 

See recommendation 1.8.6 for 

specific guidance on the use of mesh in 

prolapse surgery. 

1.8.22 If a synthetic polypropylene or 

biological mesh is inserted, the details 

of the procedure and its subsequent 

short- and long-term outcomes must 

be collected in a national registry (see 


complications in this guideline). 

Surgery for posterior prolapse 

1.8.23 Offer posterior vaginal repair 

without mesh to women with a posterior 

vaginal wall prolapse. 

Follow-up after surgery 

1.8.24 Offer women a review 6 months 

after surgery for pelvic organ prolapse. 


Ensure that the review includes a vaginal 

examination and, if mesh was used, 

check for mesh exposure. 

1.8.25 Providers should ensure that 

women who have had surgery for pelvic 

organ prolapse have access to further 

referral if they have recurrent symptoms 

or suspected complications. See also 

assessing complications associated with 

mesh surgery in this guideline. 

1.9 Surgery for women with both 

stress urinary incontinence and 

pelvic organ prolapse 

1.9.1 Consider concurrent surgery for 

stress urinary incontinence and pelvic 

organ prolapse in women with anterior 

and/or apical prolapse and stress urinary 

incontinence. 

1.9.2 When considering concurrent 

surgery for stress urinary incontinence 

and pelvic organ prolapse, discuss 

the options for treatment (see 

recommendations 1.5.1 and 1.8.2) and 

explain to the woman: 

• that there is uncertainty about 

whether the combined procedure is 

effective for treating stress urinary 

incontinence beyond 1 year, and that 

stress urinary incontinence might 

persist despite surgery 

• the risk of complications related 

to having surgery for stress urinary 

incontinence at the same time as 

prolapse surgery compared with the 

risk of complications related to having 

sequential surgery. 

1.10 Assessing complications 

associated with mesh surgery 

1.10.1 For women who report newonset 

symptoms after having mesh 

surgery for urinary incontinence or pelvic 

organ prolapse, evaluate whether the 

symptoms might be caused by a meshrelated 

complication. These symptoms 

could include: 

• pain or sensory change in the back, 

abdomen, vagina, pelvis, leg, groin or 

perineum that is: 

• either unprovoked, or provoked 

by movement or sexual activity and 

• either generalised, or in the 

distribution of a specific nerve, such as 

the obturator nerve 

• vaginal problems including 

discharge, bleeding, painful sexual 

intercourse, or penile trauma or pain in 

sexual partners 

• urinary problems including recurrent 

infection, incontinence, retention, or 

difficulty or pain during voiding 

• bowel problems including difficulty 

or pain on defaecation, faecal 

incontinence, rectal bleeding or 

passage of mucus 

• symptoms of infection, either alone 

or in combination with any of the 

symptoms outlined above. 

1.10.2 Refer women with a suspected 

mesh-related complication to a 

SURGERY TO REMOVE 

MESH CAN HAVE 

SIGNIFICANT COMPLICATIONS 

INCLUDING ORGAN INJURY, 

WORSENING PAIN 

urogynaecologist, urologist or colorectal 

surgeon for specialist assessment. 

1.10.3 For women who are referred for 

specialist evaluation of a suspected 

mesh complication: 

• take a history of all past surgical 

procedures for prolapse or 

incontinence using mesh, including the 

dates, type of mesh and site of mesh 

placement and the relationship of the 

symptoms to the surgical procedure(s) 

• consider using a validated pelvic 

floor symptom questionnaire and a 

pain questionnaire to aid assessment 

and decision making 

• perform a vaginal examination to: 

• assess whether mesh is palpable, 

exposed or extruded 

• localise pain and its anatomical 

relationship to mesh 

• consider performing a rectal 

examination, if indicated, to assess for 

the presence of mesh perforation or 

fistula 

• consider performing a neurological 

assessment to assess the distribution 

of pain, if present, sensory alteration or 

muscle weakness. 

1.10.4 For women with a confirmed 

mesh-related complication or 

unexplained symptoms after a mesh 

procedure: 

• refer to a consultant at a regional 

centre specialising in the diagnosis 

and management of mesh-related 

complications or 

• if the woman has a vaginal exposure 

of mesh that is smaller than 1 cm 2 

and no other symptoms, follow 

recommendations 1.11.3 and 1.11.4 in 

this guideline. 

1.10.5 The responsible consultant should 

develop an individualised investigation 

plan for each woman with suspected or 

confirmed mesh-related complications, 

involving other members of the regional 

MDT if needed, and use table 1 in this 

guideline to inform decisions on possible 

investigations. 

1.10.6 The responsible consultant must 

ensure that details of any confirmed 

mesh-related complications are: 

• recorded in a national registry (see 

the section on collecting data on 

surgery and surgical complications in 

this guideline) and 

• reported to the Medicines and 

Healthcare products Regulatory 

Agency (MHRA). 

1.11 Managing complications 

associated with mesh surgery 

General considerations before 

removing mesh 

1.11.1 If a woman who has had a mesh 

procedure to treat urinary incontinence 

or pelvic organ prolapse is thinking 

about having the mesh removed, discuss 

the decision with her and with a regional 

MDT. 

1.11.2 When discussing surgery to 

remove mesh, explain to the woman 

that: 

• there is limited evidence on the 

benefits of partial or complete removal 

compared with no mesh removal 

• surgery to remove mesh can have 

significant complications including 

organ injury, worsening pain, and 


INDIVIDUALISED INVESTIGATION PLANS 

Investigation Type of mesh Indications Benefits and risks 

Examination under 

anaesthesia 

All types of mesh. 

Pain or suspected: 

• vaginal or rectal exposure or 

extrusion 

• sinus tract, urinary or bowel fistula. 

Cystourethroscopy All types of mesh. Suspected: 

• urethral perforation 

• bladder perforation 

• fistula 

• calculus on suture or mesh material. 

Sigmoidoscopy 

Laparoscopy 

MRI, protocolled and 

reported by a clinician 

with experience in 

interpreting mesh 

complications 

Ultrasound scan 

(transperineal, 

transvaginal or 

translabial, or 3D), 

performed and 

reported by a clinician 

with experience in 

interpreting mesh 

complications 

CT 

Fluoroscopic studies 

(cystography or contrast 

enema)* 

Urinary flow studies 

and post-void residual 

volume assessment or 

cystometry 

Neurophysiology, 

including nerve 

conduction studies 

Abdominally, 

laparoscopically or 

vaginally placed 

mesh for pelvic organ 

prolapse. 

Abdominally or 

laparoscopically placed 

mesh for pelvic organ 

prolapse. 


Vaginally placed mesh 

to treat incontinence. 

All types of mesh, 

although CT is not 

commonly used to 

show implanted 

material. 

Suspected bowel perforation by 

mesh. 

• Pain. 

• Suspected bowel entrapment 

around mesh. 

• Suspected adhesions secondary to 

mesh placement. 

Suspected mesh infection. 

Anatomical mapping of suspected 

fistula. 

Anatomical mapping and mesh 

localisation to guide further surgery. 

Back pain following abdominal mesh 

placement with mesh attachment to 

sacral promontory. 

Identification of discitis or 

osteomyelitis. 

Pain. 

Voiding dysfunction. 

Suspected infection. 

Suspected urethral mesh perforation. 

Anatomical mapping to guide excision 

surgery. 

Suspected: 

urinary tract injury 

bowel injury 

bowel obstruction. 

Benefits 

Allows diagnosis when not revealed by awake 

examination or when an awake, examination 

is not tolerated. 

Risks 

Anaesthetic risk. 

Benefits 

• Allows diagnosis by direct visualisation. 

• Aids management planning. 

Risks 

Anaesthetic risk and risk of urinary tract 

infection. 

Benefits 



Risks 

• Anaesthetic risk if carried out under 

anaesthesia. 

• Risk of bowel perforation. 

Benefits 



Risks 

• Anaesthetic risk. 

• Risks of laparoscopy, including bowel injury. 

Benefits 

Shows implanted material and complications 

nearby. 

Shows location of mesh in relation to the 

vaginal wall and sacrum. 

Risks 

Generally regarded as safe, with a low risk of 

short- and long-term harms. Risk of contrast 

media injection. 

Benefits 

Shows implanted material and local 


Identifies mid-urethral slings. 

Shows location of mesh in relation to the 

vaginal wall and urethra. 

Risks 

Discomfort. 

Benefits 

May be useful in assessing for urinary fistulae 

or bowel injury. 

Risks 

Potential radiation-related harms and risk of 

contrast media injection. 

All types of mesh. Suspected urinary or bowel fistula. Benefits 

Aids management planning. 

Risks 

Potential radiation-related harms. 


Voiding dysfunction. 

Urinary incontinence. 

Benefits 

Aids management planning. 

Risks 

Urinary tract infection and radiation risks if 

fluoroscopy is used. 

All types of mesh. Suspected nerve injury. Benefits 

Allows diagnosis of impaired nerve function. 

Risks 

Nerve conduction studies are difficult to 

perform and can induce more pain. 

* Perform with water-soluble contrast media. Fluoroscopic studies and CT may be used according to local preference and expertise. 


urinary, bowel and sexual dysfunction 

• it is not certain that removing the 

mesh will relieve symptoms 

• it might not be possible to remove 

all of the mesh 

• removing only part of the mesh 

might be just as effective at improving 

symptoms as removing all of it 

• urinary incontinence or prolapse 

can recur after the mesh has been 

removed. 

Managing vaginal complications 

1.11.3 Discuss non-surgical treatment 

with topical oestrogen cream with 

women who have a single area of 

vaginal mesh exposure that is smaller 

than 1 cm 2 . 

1.11.4 Offer a follow‐up appointment 

within 3 months to women with vaginal 

mesh exposure who choose treatment 

with topical oestrogen cream. 

1.11.5 Consider partial or complete 

surgical removal of the vaginal portion of 

mesh for women: 

• who do not wish to have treatment 

with topical oestrogen or 

• if the area of vaginal mesh sling 

exposure is 1 cm 2 or larger or 

• if there is vaginal mesh extrusion or 

• if there has been no response to 

non-surgical treatment after a period 

of 3 months. 

1.11.6 Offer imaging and further 

treatment to women who have signs 

of infection in addition to vaginal mesh 

exposure or extrusion. 

1.11.7 Discuss with women who have 

vaginal complications after mesh sling 

surgery for stress urinary incontinence 

that: 

• complete removal of the vaginal 

portion of mesh sling is associated 

with a greater risk of recurrence of 

stress urinary incontinence than partial 

removal 

• partial removal is associated with 

a higher rate of further mesh sling 

extrusion 

• complete removal might not be 

possible. 

1.11.8 Explain to women who have 

vaginal complications after vaginally 

placed mesh for pelvic organ 

prolapse that: 


possible 

• complete removal has a higher risk 

of urinary tract or bowel injury than 

partial removal 

• there may be a risk of recurrent 

prolapse. 

1.11.9 Explain to women who have 

vaginal complications after abdominally 

placed mesh for pelvic organ prolapse 

that: 

• removal is associated with a risk of 

urinary tract and bowel injury 

• there is a risk of recurrent prolapse 

• they might need abdominal surgery 

to remove the mesh 


possible. 

1.11.10 For women who have pain or 

painful sexual intercourse suspected to 

be related to previous mesh surgery: 

• if specialist assessment indicates 

a mesh-related complication, seek 

advice from a regional MDT 

• if assessment and investigation do 

not show a mesh abnormality such 

as vaginal extrusion or exposure, or 

an infection, consider non-surgical 

treatments such as pain management, 

vaginal oestrogen, dilators, counselling 

(including psychosexual counselling) 

and physiotherapy 

• if pain does not respond to initial 

management, seek advice from a 

regional MDT. 

Managing urinary complications 

1.11.11 Refer women who have mesh 

perforating the lower urinary tract to a 

centre for mesh complications for further 

assessment or management. 1.11.12 

For women with urinary symptoms 

after mesh surgery for stress urinary 

incontinence or pelvic organ prolapse 

who are considering mesh removal 

surgery, explain that: 

• urinary symptoms might not improve 

and new symptoms might occur after 

complete or partial removal of the 

mesh 

• stress urinary incontinence might 

recur after mesh removal, and the 

risk of this happening is higher with 

complete than with partial mesh 

removal 

• complete removal of the mesh might 

not be possible 

• further treatment might be needed 

for mesh complications, or recurrent or 

persistent urinary symptoms 

• there is a risk of adverse events such 

as urinary tract fistula. 

1.11.13 Discuss division of mesh sling with 

women who have voiding difficulty after 

mesh sling surgery. 

1.11.14 Refer women considering excision 

of mesh sling for persistent voiding 

dysfunction to a centre specialising 

in the diagnosis and management 

of mesh-related complications for 

assessment and management. 

1.11.15 For women considering surgery 

to alleviate voiding symptoms caused by 

mesh surgery, explain that: 

• the risk of recurrent stress urinary 

incontinence is higher after mesh 

excision than mesh division 

• further surgery might be needed. 

Managing bowel symptoms 

1.11.16 For women who present with 

functional bowel disorders after mesh 

surgery for pelvic organ prolapse, follow 

the recommendations in the NICE 

guideline on faecal incontinence in adults 

for women with faecal incontinence or 

locally agreed protocols for women with 

obstructed defecation. 

1.11.17 For women with bowel 

complications that are directly related 

to mesh placement, such as erosion, 

stricture or fistula, discuss treatment 

with a regional MDT that has expertise 

in complex pelvic floor dysfunction 

and mesh-related problems. Use this 

discussion to formulate an individualised 

treatment plan with the woman. 

1.11.18 Explain to women with bowel 

complications directly related to mesh 

placement that: 


possible 

• bowel symptoms might persist or 

recur after mesh removal 

• they might need a temporary or 

permanent stoma after mesh 

removal. 


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events 

7th Intl meet on rare diseases 

puts India in focus 

Experts highlight the importance of investigating the genetic disorders 

which are largely left undiagnosed 

India is home to an estimated 

70 million people affected by 

undiagnosed or rare diseases. Of 

these, most are carriers of some 

genetic disorder or the other. With 

the advent of the latest sequencing, 

newborn screening and other 

technologies, a few genetic disorders 

such as Down’s syndrome, beta 

thalassemia and sickle cell anaemia 

etc. are being well tracked and have 

been found to be on the rise. Recent 

estimates show that at least 21,400 

children are born every year in India 

with Down’s syndrome and another 

9,000 to 10,000 children with 

thalassemia. While these diseases 

remain inadequately addressed as the 

patients often do not recognize the 

symptoms, the country’s problems 

THE MESSAGE AT THE 7TH 

INTERNATIONAL CONFERENCE 

ON ‘RARE AND UNDIAGNOSED 

DISEASES: ADDRESSING 

PATIENT NEEDS IN INDIA’ WAS 

LOUD AND CLEAR 

with rare and undiagnosed diseases 

continue to be worrying as there aren’t 

enough trained clinicians to detect 

and diagnose them. So, it is anyone’s 

guess as to how bad the scenario is 

in a country of 1.2 billion population 

with widely varied communities and 

subgroups carrying different genetic 

profiles and, potentially, an array of 

known and unknown genetic mutations. 

Not surprisingly, every year, 

thousands of men, women and children 

face uncertainty when healthcare 

providers are unable to discover the 

cause for their symptoms. In India, with 

its low awareness of such diseases, 

a large number of patients are left 

with no treatment and succumb to 

their condition. To make it worse, drug 

researchers and the industry often 

neglect such diseases even if they are 

diagnosed, as the market size for such 

rare disorders are either not estimated 

or comparatively much smaller. 

The message at the 7th International 

Conference on ‘Rare and Undiagnosed 

Diseases: Addressing Patient Needs 


in India’ was loud and clear — to 

make these relevant. The three-day 

event organised in Delhi in April 

by Undiagnosed Disease Network 

International (UDNI), Institute of Medical 

Genetics & Genomics at Sir Ganga 

Ram Hospital, Wilhelm Foundation, 

Organisation of Rare Diseases India 

(ORDI) and Institute of Genomics 

& Integrative Biology (IGIB) of CSIR 

called for the best and most effective 

collaborative efforts both nationally and 

internationally to share such experiences 

and find the way forward to solve and 

help patients with such conditions. 

“In India, the scenario is more 

complex as the volume is enormous and 

it has many communities and different 

subgroups. Because we don’t have 

the frequency of variance of each of 

the subgroups, it becomes much more 

difficult to diagnose new diseases,” said 

William A Gahl from National Human 

Genome Research Institute at the NIH, 

US. 

Dr Gahl, who is also the Director at 

NIH Undiagnosed Diseases Programme, 

added that most of the rare and 

undiagnosed diseases have got some 

or other link with the genetic base. “We 

have seen at the NIH itself about 1,200 

to 1,250 patients and made some 320 

diagnosis. We have discovered about 25 

new diseases in the last ten years where 

a gene is associated with a particular 

phenotype of presentation.” 

According to Dr I C Verma, advisor 

and key member of the scientific 

committee of the Conference, the 

main message of the 7th International 

Conference is that it is worth 

investigating the cause of rare and 

undiagnosed disorders, as this has 

been made easier by the application 

of massively parallel sequencing 

technology. 

“Knowing the diagnosis, one 

proceeds to finding a treatment, which 

is the main concern of the patient and 

the family. Not knowing the diagnosis is 

very frustrating,” quipped Dr Verma. 

“Contrary to usual thinking, rare and 

undiagnosed disorders affect a fairly 

large number of people in India,” added 

In India, the scenario is more 

complex as the volume is 

enormous and it has many 

communities and different 

subgroups. 

Dr William A Gahl 

Director, NIH Undiagnosed Diseases 

Programme 

Verma, Advisor & Senior Consultant and 

Professor of Medical Genetics at Institute 

of Medical Genetics and Genomics, Sir 

Ganga Ram Hospital, while talking to 

Future Medicine in a post-conference 

interview. 

Attended by some 370 registered 

delegates, including practicing 

clinicians, students and researchers, 

the Conference was immensely rich in 

content with about 60 speakers from 

across the world sharing their case 

studies, experiments, ideas and vision. 

“One of the key objectives 

ofconferring here was to communicate 

to our Indian colleagues and medical 

students about patients suffering from 

undiagnosed diseases,” said Dr Ratna 

Dua Puri, organizing chairperson of the 

Conference, in an interview with Future 

Medicine. 

She added: “With a lot of the latest 


sequencing facilities now available 

in the country and a fair number of 

clinical geneticists able to do deep 

phenotyping, we are able to help many 

patients. But, despite all these, there 

are still several cohorts with genetic 

disorders left undiagnosed. So, it is 

important to collaborate with colleagues 

and link the work done here as well as 

at other places and take the initiative 

as a community. This was the other 

main aim of this conference held in 

partnership with Undiagnosed Disease 

Network International.” 

This kind of conferences are also 

a wake-up call for countries like India, 

where genetic and metabolic disorders 

are usually diagnosed with poor 

outcomes. 

“On this front, the major challenges 

in India at present include the small 

number of trained clinicians specialising 

in diagnosing and counselling genetic 

disorders, the few state-funded 

diagnostic and research laboratories, a 

lack of funding for genetic diagnostic 

tests and less accessibility for therapies 

and other interventions,” said Dr 

Meenakshi Bhat, Senior Consultant in 

Clinical Genetics at Centre for Human 

Genetics at Indira Gandhi Institute of 

Child Health, Bangalore. 

According to Dr Seema Kapoor, 

in-charge of Genetics and Metabolism 

Division of Maulana Azad Medical 

College, New Delhi, though India has 

achieved significant milestones towards 

tracking genetic disorders through 

It is worth investigating the 

cause of rare and undiagnosed 

disorders, as this has been 

made easier by the application 

of massively parallel sequencing 

technology. 

Dr I C Verma 

Advisor and key member, 

Scientific Committee 

several government funded initiatives, 

including newborn screening for many 

congenital diseases since 2013, the 

challenges that still invite discussion 

are the feasibility of coverage in less 

developed areas, hilly terrains and home 

deliveries. 

“Besides, the availability of good 

counsellors and a well-integrated followup 

system needs to be developed,” she 

said. 

However, there is light at the end 

of the tunnel. Among others, one of 

the most recent collaborative research 

programmes—The Genomics for 

Understanding Rare Diseases: India 

Alliance Network (GUaRDIAN) initiated 

by the IGIB, has undertaken whole 

exome and genome sequencing for 

identification of variants and genes 

implicated in rare genetic diseases. 

“Using Mitochondrial rare genetic 

disease examples, we will be able 

to share our experiences from the 

GUaRDIAN consortium where we 

apply genome sequencing followed by 

computational analysis and zebrafish 

disease modelling to solve several 

cases of undiagnosed diseases,” said Dr 

Sridhar Sivasubbu, Principal Scientist at 

CSIR-IGIB. 

No doubt, only collaborative models 

will work in such a complex task of 

diagnosing unknown diseases to find 

treatments for them. Dr Gahl concludes 

that since the first meeting of the UDNI 

in Rome in 2014, there have been six 

international meetings, culminating in 

the 2019 conference in Delhi. In the 

past five years, over a dozen countries 

have established Undiagnosed Disease 

Programmes and the Network has 

created several common platforms to 

share experiences, information and 

views. The main focus of the Network 

involves sharing of genotypic and 

phenotypic data and best practices. 

And this, amongst others, can 

ultimately help advance the diagnosis 

and care of rare and undiagnosed 

diseases. 


events 

Cahocon 2019 highlights need for 

patient safety 

5th edition of CAHO conference explores ways and means to minimize medical errors 

DR SUMIT GHOSHAL 

The quality of service provided 

by healthcare providers and 

the related issue of patient 

safety is a major concern of hospital 

managements around the country. 

Mistakes in the treatment and 

healthcare services can not only affect 

the well-being of individual patients 

and their families but also create a trust 

deficit between the healthcare provider 

and the service consumers. 

To discuss these questions and 

to seek ways and means to minimize 

errors at various levels, senior 

management executives of leading 

Indian hospitals got together in 

Mumbai at the 5th national conference 

of CAHO (Consortium of Accredited 

Healthcare Organizations). These are 

hospitals and healthcare organisations 

that have obtained an accreditation 

from the NABH (National Board of 

Accreditation of Hospitals), a quasiofficial 

certification body functioning 

under the aegis of the Quality Council 

of India (QCI). 

The NABH, which was established 

in 2005-06, offers accreditation at 

two levels: An entry-level certificate 

and full-accreditation. The entry level 

certification was instituted along the 

way when NABH leaders realised that 

many hospitals were unable to meet 

With accreditation, though it 

has a cost attached to it, there 

is an element of discipline 

in the healthcare. This has 

resulted in patient safety and 

better treatment outcome 

undoubtedly. 

Dr Rajesndra Patankar 

Chief Operating Officer 

Nanavati Super Specialty Hospital 


the criteria for full-accreditation at the 

start. 

Discussing the healthcare scenario 

before the accreditation system was 

set up in India, Air Marshal (Dr) Pawan 

Kapoor, vice chairman, RUS Education 

and vice chancellor, Lincoln American 

University stated that awareness of 

quality issues in healthcare arose 

when Consumer Protection Act 1986 

was made applicable to doctors and 

hospitals. Till then, mistakes and 

mishaps involving clinicians were 

carefully hidden with the express 

purpose of protecting healthcare 

practitioners from being blamed for 

patient death or injury. 

At present, about 600 large and 

medium healthcare institutions, along 

with about 218 small hospitals, have 

been able to obtain the entry-level 

certification from NABH, Air Marshal 

Kapoor said. He also provided extensive 

statistical data on improvements 

recorded in accredited hospitals in 

terms of fewer mistakes, better patient 

outcomes and so on. 

A highlight of the recent CAHO 

conference was the launch of entry 

level certification by the National 

Accreditation Board for Laboratories 

(NABL), which is a sister organization 

of NABH. Currently, about 1,100 

pathology labs have obtained the full 

accreditation from NABL, which is 

a really small number compared with 

the total of about 50,000 to 

80,000 laboratories present inall 

over the country. 

The NABL has not only launched 

a number of schemes to enable small 

laboratories to join the accreditation 

system, but is also getting ready to 

include the hundreds of radiology and 

imaging laboratories under its ambit. 

Dwelling on the impact of 

The time has come to 

have an accountability 

on healthcare delivery 

standards and accredit 

healthcare organizations 

based on the quality of 

healthcare they provide to 

patients. 

Dr Aparna Jairam 

Founder & Director 

Asavalee Dr Aparna's Pathology 

Laboratory and Co-organising 

Secretary CAHOCon-2019 

errors in patient care, Dr Krishnan 

Sankaranayaranan, Patient Safety 

Officer, with Tawam Hospital in 

Abu Dhabi, pointed out that the 

healthcare workers responsible for a 

serious error wasare often impacted 

almost as severely as the patient 

concerned. In international literature, 

this is being described as “becoming 

the second victim”, the first victim 

of the mistake being the affected 

patient. 

Dr Krishnan emphasized that the 

second victim could suffer severe 

depression and even denial of the 

responsibility, and later self-doubt and 

a loss of self-confidence. There have 

been many instances where such a 

healthcare professional might move 

to a less stressful department in the 

hospital, or in extreme cases move 

away from the healthcare profession 

completely, he said. 

Dr Sanjay Oak, who has held a 

number of top positions in public 

health and education, including 

that of vice chancellor of D Y Patil 

University, Navi Mumbai, pointed out 

that there were several gaps in the 

way medical education was imparted 

in most medical colleges. He said 

there was an urgent need for modern 

teaching methods, including simulation 

modules, that could allow the students 

to appreciate both the structure 

and the functioning of the human 

body without endangering an actual 

human being. 


calendar 

Upcoming conferences 

APR 

26-11 

MAY 

PHYSICAL THERAPY 

FM UQ: Functional Mobilization 

Upper Quadrant 

New Delhi 

2-5 NEPHROLOGY AND 

UROLOGY 

ApEx-Cedars Sinai: The 10th 

Annual Nephrology Board 

Review Course and Urology for 

Nephrologists Workshop 

Mumbai 

3-5 MED EQUIPMENT 

MEDIKO India (MEDIKA) 

Hyderabad 

6-10 ONCOLOGY 

Cardiff-Tata Medical Center FRCR 

2B Oncology Course 

Kolkata 

11 BIOTECHNOLOGY 

Innovative Research in 

Bioscience, Bioinformatics, 

Biomedical Engineering 

Cancer Biology and Applied 

Biotechnology 

Delhi 

23-24 CLINICAL GENETICS 

CRO/Sponsor Summit 2019 

Hyderabad 

24-26 EXPO 

Medical Expo India, Indore (MEI) 

Indore 

26-11 PHYSICAL THERAPY 

FM UQ: Functional Mobilization 

Upper Quadrant 

New Delhi 

28 CLINICAL TRIAL 

10th Annual Clinical Trials 

Summit (Clinical Trials Asia) 

Mumbai 

31-2 NEUROLOGY 

Asian And Oceanian Myology 

Center Meeting (AOMC Meeting) 

Mumbai 

JUNE 

7-9 GYNAECOLOGY 

Annual Conference of the Indian 

Association of Gynaecological 

Endoscopists 

Ahmedabad 

8-9 OPHTHALMOLOGY 

National Conference on 

Community Ophthalmology 

Chennai 

27-30 SONOGRAPHY 

Sono Summit 

Chennai 

28-30 EXPO 

India Med Expo (IME) 

Bengaluru 

JULY 

2-4 DERMATOLOGY 

Congress of Cosmetic 

Dermatology Society 

(COSDERMINDIA) 

Mumbai 


Ophthall (OPH) 

Hyderabad 

3-4 SURGERY 

World Congress & Summit on 

Surgery 

New Delhi 


India International Optical & 

Ophthalmology Expo (IIOO 

EXPO) 

Hyderabad 

9-11 CARDIOLOGY 

Echo Nagpur Summit 

Nagpur 

15-18 TRAUMA S URGERY 

Traumacon 

Mumbai 

23-25 HEMATOLOGY 

Hope Asia 2019 Kolkata 

Kolkata 

AUGUST 


Ophthall (OPH) 

Hyderabad 

3-4 SURGERY 

World Congress & Summit on 

Surgery 

New Delhi 


India International Optical & 

Ophthalmology Expo (IIOO 

EXPO) 

Hyderabad 


Echo Nagpur Summit 

Nagpur 

23-25 HEMATOLOGY 

Hope Asia 2019 

Kolkata 

SEPTEMBER 

5-8 GYNAECOLOGY 

33rd Annual Conference of AICC 

RCOG 2019 

Kolkata 

6-8 ONCOLOGY 

23rd Annual Conference of 

Pediatric Hematology Oncology 

Chapter (PHO) 

Varanasi 


10th National Annual 

Conference of Indian Association 

of Clinical Cardiologists 

Conference (IACCCON 2019) 

Kochi 

10-11 PAEDIATRICS 

World Pediatrics Conference 

Panjim 


World Heart and Cardiothoracic 

Surgery Conference (WHCS 

Heart Conference) 

Cavelossim 

10-11 PULMONARY C ARE 

Pulmonary, Thoracic and Critical 

Care Conference (PTCC) 

Goa 

13-14 ONCOLOGY 

Indo Oncology Summit 

(IOS-Bhubaneswar) 

Bhubaneswar 

13-15 PSYCHOLOGY 

Fortis Annual Psychology 

Conference 

Gurgaon 

20-22 SURGICAL O NCOLOGY 

National Conference of Indian 

Association of Surgical Oncology 

(NATCON IASO) 

Kolkata 

27-29 ARTHROSCOPY 

Conference of Indian 

Arthroscopy Society (IASCON) 

Indore 


Global Cardio Diabetes Conclave 

(GCDC) 

Mumbai 

29- 

Oct 2 

30- 

Oct 2 

TRANSPLANT S URGERY 

CAST 2019 - 16th Congress 

of the Asian Society of 

Transplantation 

Delhi 

NGBT 

2019 Nextgen genomics biology, 

bioinformatics and technologies 

conference 

Mumbai 

The announced dates of the conferences may change 



UNDERSTAND THE FUTURE NOW 

AND APPLY IT IN YOUR PRACTICE 

PROF DR I C VERMA 

Advisor & Senior Consultant, Institute of Medical Genetics, Sir Ganga Ram Hospital, New Delhi 

The age of genomic medicine is upon us and 

we are rapidly moving into the era of precision 

medicine. Young clinicians should spend time to 

understand this technology and learn to interpret the 

results. 

Catching this technology at an early age will also 

help them significantly contribute to the society 

by helping patients who suffer from rare and yet 

undiagnosed diseases. 

Addressing the medical needs of such patients is 

one of the key responsibilities of the advanced medical 

world of today. But, unfortunately, this hasn’t yet got 

due attention from the young and emerging clinicians 

here, unlike in the West. 

In the western world, the need for addressing 

rare and undiagnosed diseases, which are mostly 

connected with genetic causes, has got serious 

attention from the clinician community, especially the 

young who are keen to devote time for research. This 

is not only satisfying intellectually, but also translates 

into financial gains if a new therapy is discovered. 

Genetics and genomic studies have a lot more to 

do in order to address rare and undiagnosed diseases. 

But, sadly the current medical curriculum in India is 

not geared to prepare students to understand or apply 

genomics in healthcare. 

In the UK, they are carrying out genomic studies 

in 100,000 people at present, while in the US it 

is an extensive study in about 1 million people, 

to understand the interplay of genetics and the 

environment to cause diseases. 

Understanding this would lead to the development 

of novel and precise preventive, therapeutic and 

curative approaches. Moving a step ahead, the UK has 

already announced that genomics will henceforth be a 

part and parcel of national health services. 

The younger generation in this profession, if 

equipped with new and emerging technologies, can 

contribute to the critical needs of patients who have 

genetic as well as currently incurable diseases. 

Precision medicine — the concept of tailoring the 

medicine to the genetic as well as environmental 

attributes of the patient —is the future. Be prepared 

for it and apply it in your practice today. 

— As told to CH Unnikrishnan 


Sep 30 th - Oct 2 nd , 2019 - Mumbai, India 

REGISTRATIONS OPEN 

Early bird ends on 

15 th June, 2019 

Abstract submission 

ends on 1 st July, 2019 

NextGen Genomics, Biology, Bioinformatics and Technologies (NGBT) Conference is an international 

meeting organized by SciGenom Research Foundation (SGRF), a not-for-profit organization working to 

promote Science, Research and Education in India and rest of Asia. 

HIGHLIGHTS 

• Learn about cutting edge developments in 

genomics, biology, bioinformatics, drug 

discovery, plant and animal sciences 

• Network with scientists of global repute 

• Meet national and international genomics, 

biology and technology companies 

• Interact with leaders from drug industry 

• Explore collaboration opportunities 

• Scholarship opportunities for students to support 

their participation at the meeting 

KEY FOCUS AREA 

• Genomics technologies 

• Population genomics 

• Clinical/Medical genomics 

• NIPT/Liquid biopsy 

• Precision (personalized) medicine 

• Cancer genomics 

• CRISPR/CAS9 

• Gene editing 

• Signal transduction 

• Cancer immunology 

• Biomarkers 

• Drug discovery 

• Metagenomics 

• Plant genomics/sciences 

• Agriculture genomics/sciences 

• Veterinary genomics/sciences 

• Wildlife genomics/conservation 

100+ 

Speakers 

Ms. Ms. Kamalika Das Das 

+91- 8374 27 4074 

800+ 

Delegates 

ngbt2019@sgrf.org 

300+ 

Posters 

www.sgrfconferences.org 

100+ 

Scholarships & Awards

RNI Number KERENG/2012/44529

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